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NOM DU FICHIER / FILE NAME:
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CA 02863233 2014-07-09
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COMPOSITIONS COMPRISING CROSSLINKED CATION-BINDING
POLYMERS AND USES THEREOF
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of International Patent
Application No.
PCT/US12/20843, filed on January 10, 2012, which is incorporated by reference
herein in
its entirety.
FIELD OF THE DISCLOSURE
[0002] The present disclosure relates generally to compositions
comprising
crosslinked cation-binding polymers comprising monomers containing carboxylic
acid
groups, and a base, wherein said polymers contains less than about 20,000 ppm
or less than
about 50,000 ppm, of non-hydrogen cations, wherein said polymer is crosslinked
with about
0.08 mol.% to about 0.2 mol.% of crosslinker or alternatively from about 0.025
mol.% to
about 3.0 mol% including, for example, from about 0.025 mol.% to about 0.3
mol.% or
from about 0.025 mol.% to about 0.17 mol.% or from about 0.025 mol.% to about
0.34
mol.%, and wherein the base is present in an amount sufficient to provide from
about 0.2
equivalents to about 0.95 equivalents of base per equivalent of carboxylic
acid groups in the
polymer. The present disclosure also relates to methods of preparation of said
compositions
and methods of using such compositions in dosage forms and to treat various
diseases or
disorders.
BACKGROUND
[0003] Numerous diseases and disorders are associated with ion imbalances
(e.g.,
hyperkalemia, hypernatremia, hypercalcemia, and hypermagnesia) and/or
increased
retention of fluid (e.g., heart failure and end stage renal disease (ESRD)).
For example,
patients afflicted with an increased level of potassium (e.g., hyperkalemia)
may exhibit a
variety of symptoms ranging from malaise, palpitations, muscle weakness and,
in severe
cases, cardiac arrhythmias. Patients afflicted with increased levels of sodium
(e.g.,
hypernatremia) may exhibit a variety of symptoms including, lethargy,
weakness,
irritability, edema and in severe cases, seizures and coma. Patients afflicted
with retention
of fluid often suffer from edema (e.g., pulmonary edema, peripheral edema,
edema of the
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legs, etc.) and the buildup of waste products in the blood (e.g., urea,
creatinine, other
nitrogenous waste products, and electrolytes or minerals such as sodium,
phosphate and
potassium).
[0004] Treatments for diseases or disorders associated with ion
imbalances and/or an
increased retention of fluid attempt to restore the ion balance and decrease
the retention of
fluid. For example, treatment of diseases or disorders associated with ion
imbalances may
employ the use of ion exchange resins to restore ion balance. Treatment of
diseases or
disorders associated with an increased retention of fluid may involve the use
of diuretics
(e.g., administration of diuretic agents and/or dialysis, such as hemodialysis
or peritoneal
io dialysis and remediation of waste products that accumulate in the body).
Additionally or
alternatively, treatment for ion imbalances and/or increased retention of
fluid may include
restrictions on dietary consumption of electrolytes and water. However, the
effectiveness
and/or patient compliance with present treatments is less than desired.
SUMMARY
[0005] The present disclosure is directed to compositions
comprising crosslinked
cation-binding polymers comprising monomers containing carboxylic acid groups,
and a
base (e.g., calcium carbonate).
[0006] The present disclosure provides compositions comprising a
crosslinked
cation-binding polymer comprising: monomers that comprise carboxylic acid
groups,
wherein said polymer is crosslinked with about 0.08 mol.% to about 0.2 mol.%
of
crosslinker or alternatively from about 0.025 mol.% to about 3.0 mol%
including, for
example, from about 0.025 mol.% to about 0.3 mol.% or from about 0.025 mol.%
to about
0.17 mol.% or from about 0.025 mol.% to about 0.34 mol.%; and a base (e.g.,
calcium
carbonate), wherein said monomers are acrylic acid or salts thereof, wherein
the polymer
contains less than about 20,000 ppm of non-hydrogen cationsõ and wherein the
base is
present in an amount sufficient to provide from about 0.2 equivalents to about
0.95
equivalents of base (e.g., 0.2 to 0.95 equivalents, 0.2 to 0.9 equivalents,
0.2 to 0.85
equivalents, 0.2 to 0.8 equivalents, 0.2 to 0.75 equivalents, 0.2 to 0.7
equivalents, 0.2 to
0.65 equivalents, 0.2 to 0.6 equivalents, 0.2 to 0.55 equivalents, 0.2 to 0.5
equivalents,
0.2 to 0.45 equivalents, 0.2 to 0.4 equivalents, 0.2 to 0.35 equivalents, 0.2
to 0.3
equivalents, or 0.2 to 0.25 equivalents of base) per equivalent of carboxylic
acid groups in
the polymer. In some embodiments, the composition includes from about 0.5
equivalents to
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0.85 equivalents of base per equivalent of carboxylic acid groups in the
polymer. In some
embodiments, the composition includes from about 0.7 equivalents to 0.8
equivalents of
base per equivalent of carboxylic acid groups in the polymer. In some
embodiments, the
composition includes about 0.75 equivalents of base per equivalent of
carboxylic acid
groups in the polymer. In some embodiments, the composition includes from
about 0.2
equivalents to 0.35 equivalents of base per equivalent of carboxylic acid
groups in the
polymer. In some embodiments, the composition includes from about 0.2
equivalents to 0.3
equivalents of base per equivalent of carboxylic acid groups in the polymer.
In some
embodiments, the composition includes about 0.25 equivalents of base per
equivalent of
carboxylic acid groups in the polymer.
[0007] The present disclosure also provides compositions comprising
a crosslinked
cation-binding polymer comprising: monomers that comprise carboxylic acid
groups,
wherein said polymer is crosslinked with about 0.08 mol.% to about 0.2 mol.%
of
crosslinker or alternatively from about 0.025 mol.% to about 3.0 mol%
including, for
example, from about 0.025 mol.% to about 0.3 mol.% or from about 0.025 mol.%
to about
0.17 mol.% or from about 0.025 mol.% to about 0.34 mol.%, and a base (e.g.,
calcium
carbonate), wherein said monomers are acrylic acid or salts thereof, wherein
the polymer
contains less than about 50,000 ppm of non-hydrogen cations, and wherein the
base is
present in an amount sufficient to provide from about 0.2 equivalents to about
0.95
equivalents of base (e.g., 0.2 to 0.95 equivalents, 0.2 to 0.9 equivalents,
0.2 to 0.85
equivalents, 0.2 to 0.8 equivalents, 0.2 to 0.75 equivalents, 0.2 to 0.7
equivalents, 0.2 to
0.65 equivalents, 0.2 to 0.6 equivalents, 0.2 to 0.55 equivalents, 0.2 to 0.5
equivalents,
0.2 to 0.45 equivalents, 0.2 to 0.4 equivalents, 0.2 to 0.35 equivalents, 0.2
to 0.3
equivalents, or 0.2 to 0.25 equivalents of base) per equivalent of carboxylic
acid groups in
the polymer. In some embodiments, the composition includes from about 0.5
equivalents to
0.85 equivalents of base per equivalent of carboxylic acid groups in the
polymer. In some
embodiments, the composition includes from about 0.7 equivalents to 0.8
equivalents of
base per equivalent of carboxylic acid groups in the polymer. In some
embodiments, the
composition includes about 0.75 equivalents of base per equivalent of
carboxylic acid
groups in the polymer. In some embodiments, the composition includes from
about 0.2
equivalents to 0.35 equivalents of base per equivalent of carboxylic acid
groups in the
polymer. In some embodiments, the composition includes from about 0.2
equivalents to 0.3
equivalents of base per equivalent of carboxylic acid groups in the polymer.
In some
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embodiments, the composition includes about 0.25 equivalents of base per
equivalent of
carboxylic acid groups in the polymer.
[0008] The present disclosure also provides compositions comprising
a crosslinked
cation-binding polymer comprising monomers comprising carboxylic acid groups,
and a
base, wherein no less than about 70% of the polymer has a particle size of
about 212
microns to about 500 microns, wherein said monomers are acrylic acid or salts
thereof,
wherein the polymer comprises less than about 20,000 ppm of non-hydrogen
cations, and
wherein said base is present in an amount sufficient to provide from about 0.2
equivalents to
about 0.95 equivalents of base per equivalent of carboxylic acid groups in
said polymer. In
some embodiments, at least one non-hydrogen cation is present in an amount of
at least
about 5,000 ppm.
[0009] The present disclosure also provides compositions comprising
a crosslinked
cation-binding polymer comprising monomers comprising carboxylic acid groups,
and a
base, wherein no less than about 70% of the polymer has a particle size of
about 212
microns to about 500 microns, wherein said monomers are acrylic acid or salts
thereof,
wherein the polymer comprises less than about 50,000 ppm of non-hydrogen
cations, and
wherein said base is present in an amount sufficient to provide from about 0.2
equivalents to
about 0.95 equivalents of base per equivalent of carboxylic acid groups in
said polymer. In
some embodiments, at least one non-hydrogen cation is present in an amount of
at least
about 5,000 ppm.
[0010] The present disclosure also provides compositions comprising
a crosslinked
cation-binding polymer comprising monomers comprising carboxylic acid groups,
and a
base, wherein no less than about 70% of said polymer has a particle size of 75
microns or
less, wherein the monomers are acrylic acid or salts thereof, wherein the
polymer comprises
less than about 20,000 ppm of non-hydrogen cations, wherein said base is
present in an
amount sufficient to provide from about 0.2 equivalents to about 0.95
equivalents of base
per equivalent of carboxylic acid groups in said polymer. In some embodiments,
at least
one non-hydrogen cation is present in an amount of at least about 5,000 ppm.
[0011] The present disclosure also provides compositions comprising
a crosslinked
cation-binding polymer comprising monomers comprising carboxylic acid groups,
and a
base, wherein no less than about 70% of said polymer has a particle size of 75
microns or
less, wherein the monomers are acrylic acid or salts thereof, wherein the
polymer comprises
less than about 50,000 ppm of non-hydrogen cations, wherein said base is
present in an
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amount sufficient to provide from about 0.2 equivalents to about 0.95
equivalents of base
per equivalent of carboxylic acid groups in said polymer. In some embodiments,
at least
one non-hydrogen cation is present in an amount of at least about 5,000 ppm.
[0012] The present disclosure also provides compositions comprising
polycarbophil,
and a base, wherein wherein the polymer comprises less than about 20,000 ppm
of non-
hydrogen cations, and wherein said base is not sodium bicarbonate and is
present in an
amount sufficient to provide about 0.2 to 0.95 equivalents of base per
equivalent of
carboxylic acid groups in said polycarbophil. In some embodiments, at least
one non-
hydrogen cation is present in an amount of at least about 5,000 ppm.
[0013] The present disclosure also provides compositions comprising
polycarbophil,
and a base, wherein wherein the polymer comprises less than about 50,000 ppm
of non-
hydrogen cations, and wherein said base is not sodium bicarbonate and is
present in an
amount sufficient to provide about 0.2 to 0.95 equivalents of base per
equivalent of
carboxylic acid groups in said polycarbophil. In some embodiments, at least
one non-
hydrogen cation is present in an amount of at least about 5,000 ppm.
[0014] The present disclosure also provides compositions comprising
a crosslinked
cation-binding polymer comprising a crosslinker and monomers that comprise
carboxylic
acid groups, and a base, wherein said monomers are acrylic acid or salts
thereof, wherein
the polymer comprises less than about 20,000 ppm of non-hydrogen cations, and
wherein
said base is present in an amount sufficient to provide from about 0.2
equivalents to about
0.95 equivalents of base per equivalent of carboxylic acid groups in said
polymer. In some
embodiments, at least one non-hydrogen cation is present in an amount of at
least about
5,000 ppm.
[0015] The present disclosure also provides compositions comprising
a crosslinked
cation-binding polymer comprising a crosslinker and monomers that comprise
carboxylic
acid groups, and a base, wherein said monomers are acrylic acid or salts
thereof, wherein
the polymer comprises less than about 50,000 ppm of non-hydrogen cations, and
wherein
said base is present in an amount sufficient to provide from about 0.2
equivalents to about
0.95 equivalents of base per equivalent of carboxylic acid groups in said
polymer. In some
embodiments, at least one non-hydrogen cation is present in an amount of at
least about
5,000 ppm.
[0016] In some embodiments, the crosslinked cation-binding polymer
is a crosslinked
polyacrylate polymer crosslinked with about 0.08 mol.% to about 0.2 mol.% of
crosslinker
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or alternatively from about 0.025 mol.% to about 3.0 mol% including, for
example, from
about 0.025 mol.% to about 0.3 mol.% or from about 0.025 mol.% to about 0.17
mol.% or
from about 0.025 mol.% to about 0.34 mol.%. For example, the polymer may be a
polyacrylate polymer crosslinked with about 0.08 mol% to about 0.2 mol% or
alternatively
from about 0.025 mol.% to about 3.0 mol.% including, for example, from about
0.025
mol.% to about 0.3 mol.% or from about 0.025 mol.% to about 0.17 mol.% or from
about
0.025 mol.% to about 0.34 mol.% crosslinker, and for example, may comprise an
in vitro
saline absorption capacity (e.g., saline holding capacity) of at least about
20 times its weight
(e.g., at least about 20 grams of saline per gram of polymer, or "g/g"), at
least about 30
times its weight, at least about 40 times its weight, at least about 50 times
its weight, at least
about 60 times its weight, at least about 70 times its weight, at least about
80 times its
weight, at least about 90 times its weight, at least about 100 times its
weight, or more. For
the purposes of this disclosure saline absorption capacity (e.g., saline
holding capacity) is
measured in a saline solution buffered to pH 7. In some embodiments, the
crosslinked
polyacrylate polymer is in the form of individual particles or particles that
are agglomerated
(for example, flocculated) to form a larger particle, wherein the diameter of
individual
particles or agglomerated particles is about 1 micron to about 10,000 microns
(alternatively,
about 1 micron to about 10 microns, about 1 micron to about 50 microns, about
10 microns
to about 50 microns, about 10 microns to about 200 microns, about 50 microns
to about 100
microns, about 50 microns to about 200 microns, about 50 microns to about 1000
microns,
about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or
about 5000
microns to about 10,000 microns. In one embodiment, the polyacrylate polymer
is in the
form of small particles that flocculate to form agglomerated particles with a
diameter of
about 1 micron to about 10 microns. Additionally, any suitable base or
combination of two
or more bases may be used to prepare the compositions as disclosed herein. In
some
embodiments, the composition comprises a base such as an alkali earth metal
carbonate, an
alkali earth metal acetate, an alkali earth metal oxide, an alkali earth metal
bicarbonate, an
alkali earth metal hydroxide, an organic base, or combinations thereof.
[0017] In some embodiments, the base is a calcium base such as
calcium carbonate,
calcium acetate, calcium oxide, calcium citrate, or combinations thereof In
some
embodiments, the base is a magnesium base such as magnesium carbonate,
magnesium
hydroxide, magnesium oxide, or combinations thereof In some embodiments, the
base is a
sodium base such as sodium bicarbonate. In some embodiments, the base is a
potassium
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base such as potassium bicarbonate. In some embodiments, the base is an
aluminum base
such as aluminum hydroxide. In some embodiments, the base is an organic base
such as
lysine, choline, histidine, arginine, or combinations thereof.
[0018] The present disclosure also provides formulations and dosage
forms (e.g., oral
dosage forms) that comprise one or more of the compositions disclosed herein.
[0019] The present disclosure also relates to methods of using such
compositions and
or dosage forms comprising the compositions disclosed herein to treat various
diseases or
disorders, including signs and/or symptoms of the diseases or disorders, and
including those
involving ion imbalances and/or fluid imbalances (e.g., overloads). In some
embodiments,
the disease is heart failure. In some embodiments, the disease is heart
failure with chronic
kidney disease. In some embodiments, the disease is end stage renal disease.
In some
embodiments, the disease is end stage renal disease with heart failure. In
some
embodiments, the disease is chronic kidney disease. In some embodiments, the
disease is
hypertension. In some embodiments, the disease is salt-sensitive hypertension.
In some
embodiments, the disease is refractory hypertension. In some embodiments, the
disease
involves an ion imbalance such as hyperkalemia, hypernatremia, hypercalcemia,
etc. In
some embodiments, the disease or disorder involves a fluid maldistribution or
fluid overload
state such as edema or ascites.
[0020] In some embodiments, the disease or disorder is the result
of, or is associated
with, administration of another agent (e.g., drug). For example, compositions
according to
the present disclosure are useful in treating an increase in a subject's
potassium level when
co-administered with an agent (e.g., drug) known to cause increases in
potassium levels,
such as an alpha-adrenergic agonist, a RAAS inhibitor, an ACE inhibitor, an
angiotensin II
receptor blocker, a beta blocker, an aldosterone antagonist, etc. For example,
compositions
according to the present disclosure are useful in treating an increase in a
subject's sodium
level when co-administered with an agent (e.g., drug) known to cause increases
in sodium
levels, such as an anabolic steroid, a birth control pill, an antibiotic,
clonidine, a
corticosteroid, a laxative, lithium, a nonsteroidal anti-inflammatory drug
(NSAID), etc.
[0021] These and other embodiments will be described more fully by
the detailed
description and examples that follow.
DETAILED DESCRIPTION
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[0022] The present disclosure relates generally to compositions
comprising a
crosslinked cation-binding polymer and a base, wherein the polymer comprises
carboxylic
acid-containing monomers, wherein the polymer contains less than about 50,000
ppm, or
less than about 20,000 ppm, of non-hydrogen cations, wherein said polymer is
crosslinked
with about 0.08 mol.% to about 0.2 mol.% of crosslinker or alternatively from
about 0.025
mol.% to about 3.0 mol% including, for example, from about 0.025 mol.% to
about 0.3
mol.% or from about 0.025 mol.% to about 0.17 mol.% or from about 0.025 mol.%
to about
0.34 mol.%, and wherein the base is present in an amount sufficient to provide
from about
0.2 equivalents to about 0.95 equivalents of base per equivalent of carboxylic
acid groups in
the polymer (alternatively, 0.2 to 0.9 equivalents, 0.2 to 0.85 equivalents,
0.2 to 0.8
equivalents, 0.2 to 0.75 equivalents, 0.2 to 0.7 equivalents, 0.2 to 0.65
equivalents, 0.2 to
0.6 equivalents, 0.2 to 0.55 equivalents, 0.2 to 0.5 equivalents, 0.2 to 0.45
equivalents,
0.2 to 0.4 equivalents, 0.2 to 0.35 equivalents, 0.2 to 0.3 equivalents, 0.2
to 0.25
equivalents; alternatively from about 0.5 equivalents to about 0.85
equivalents of base per
equivalent of carboxylic acid groups in the polymer; alternatively, from about
0.7
equivalents to about 0.8 equivalents of base per equivalent of carboxylic acid
groups in the
polymer; or alternatively about 0.75 equivalents of base per equivalent of
carboxylic acid
groups in the polymer). The present disclosure relates generally to
compositions
comprising a crosslinked cation-binding polymer and a base, wherein the
polymer
comprises carboxylic acid-containing monomers, wherein the polymer contains
less than
about 20,000 ppm of non-hydrogen cations, and wherein the base is present in
an amount
sufficient to provide from about 0.2 equivalents to about 0.95 equivalents of
base per
equivalent of carboxylic acid groups in the polymer (alternatively, from about
0.2
equivalents to about 0.35 equivalents of base per equivalent of carboxylic
acid groups in the
polymer; alternatively, from about 0.2 equivalents to about 0.3 equivalents of
base per
equivalent of carboxylic acid groups in the polymer; or alternatively about
0.25 equivalents
of base per equivalent of carboxylic acid groups in the polymer). In some
embodiments, a
composition of the present disclosure comprises a crosslinked cation-binding
polymer
comprising monomers comprising carboxylic acid groups, and a base, wherein
said
monomers are acrylic acid or salts thereof, wherein the polymer comprises less
than about
20,000 ppm of non-hydrogen cations, wherein said base is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of base per
equivalent of
carboxylic acid groups in said polymer, and wherein no less than about 70% of
the polymer
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has a particle size of about 212 microns to about 500 microns. In some
embodiments, a
composition of the present disclosure comprises a crosslinked cation-binding
polymer
comprising monomers comprising carboxylic acid groups, and a base, wherein
said
monomers are acrylic acid or salts thereof, wherein the polymer comprises less
than about
50,000 ppm of non-hydrogen cations, wherein said base is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of base per
equivalent of
carboxylic acid groups in said polymer, and wherein no less than about 70% of
the polymer
has a particle size of about 212 microns to about 500 microns. In some
embodiments, at
least one non-hydrogen cation is present in an amount of at least about 5,000
ppm. In some
embodiments, a composition of the present disclosure comprises a crosslinked
cation-
binding polymer comprising monomers comprising carboxylic acid groups, and a
base,
wherein said monomers are acrylic acid or salts thereof, wherein the polymer
comprises less
than about 20,000 ppm of non-hydrogen cations, wherein said base is present in
an amount
sufficient to provide from about 0.2 equivalents to about 0.95 equivalents of
base per
equivalent of carboxylic acid groups in said polymer, and wherein no less than
about 70%
of the polymer has a particle size of 75 microns or less.
In some embodiments, a
composition of the present disclosure comprises a crosslinked cation-binding
polymer
comprising monomers comprising carboxylic acid groups, and a base, wherein
said
monomers are acrylic acid or salts thereof, wherein the polymer comprises less
than about
50,000 ppm of non-hydrogen cations, wherein said base is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of base per
equivalent of
carboxylic acid groups in said polymer, and wherein no less than about 70% of
the polymer
has a particle size of 75 microns or less. In some embodiments, at least one
non-hydrogen
cation is present in an amount of at least about 5,000 ppm. Such compositions
with
unexpected cation binding or removal and/or fluid binding or removal
properties when
administered to a subject (e.g., a mammal, such as a human) while minimizing
any acidosis
or alkylosis effects from the administration, are useful for the treatment of
a variety of
diseases or disorders, including those involving ion and/or fluid imbalances
(e.g.,
overloads). Surprisingly, ranges of base and polymer in the compositions have
been
discovered and are disclosed herein that are optimized for maintaining the
cation binding
and/or removal properties of the polymer (e.g., for potassium and/or sodium)
and the fluid
binding and/or removal properties of the polymer in humans, while neutralizing
hydrogen
cations released from administration of the polymer. In some embodiments, a
neutral or
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substantially neutral acid/base status (e.g., acid/base balance) is maintained
in the body of a
subject, for example, a human subject. In some embodiments, an acid/base
status (e.g.,
acid/base balance) associated with the subject does not change, for example,
as measured by
serum total bicarbonate, serum total CO2, arterial blood pH, urine pH, urine
phosphorus,
urine ammonium, and/or anion gap. An acid/base status that does not change
includes one
that does not change outside the normal range or outside the normal range for
the subject.
[0023] The present disclosure also relates to methods of
preparation of such
compositions. The present disclosure also relates to methods of using such
compositions,
for example, in dosage forms, for the treatment of various diseases or
disorders as disclosed
1 0 herein, including, for example, heart failure (e.g., with or without
chronic kidney disease),
end stage renal disease (e.g., with or without heart failure), chronic kidney
disease,
hypertension (including, e.g., salt sensitive and refractory), hyperkalemia
(e.g., any origin),
hypernatremia (e.g., any origin), and/or fluid overload states (e.g., edema or
ascities).
[0024] In some embodiments, compositions and/or dosage forms
comprising a base
and a cross-linked cation-binding polymer, including a cross-linked
polyacrylate polymer,
absorb about 20-fold, 30-fold, or 40-fold or more of their mass in a sodium
solution (e.g., a
solution of sodium salts at 0.154 molar total sodium concentration, for
example, a saline
solution or a physiological saline solution). For example, saline holding
capacity for a
disclosed cross-linked cation-binding polymer may be determined in a buffered
saline
solution, e.g., a buffered saline solution that maintains pH at about 7.
[0025] In some embodiments, the polymer is a polycarboxylic acid
polymer, such as
a polyacrylate. In some embodiments, the polymer is derived from
polymerization of
carboxylic acid-containing monomers. Non-limiting examples of suitable
carboxylic acid-
containing monomers include, for example: acrylic acid and its salts,
methacrylic acid and
its salts, crotonic acid and its salts, tiglinic acid and its salts, 2-methyl-
2-butenoic acid (Z)
and its salts, 3-butenoic acid (vinylacetic acid) and its salts, 1-
cyclopentene carboxylic acid
and its salts, 2-cyclopentene carboxylic acid and its salts; and unsaturated
dicarboxylic acids
and their salts, such as maleic acid, fumaric acid, itaconic acid, glutaconic
acid, and their
salts. Copolymers of the above monomers may be included in the polymers. Other
cross-
linked cation-binding polyelectrolyte polymers may be based on sulfonic acids
and their
salts, or phosphonic acids and their salts and amines and their salts, for
example, acrylic
acid with sulfonic acids or salts thereof, phosphonic acids or salts thereof,
or amines and
their salts thereof. Regardless of the choice of monomer, the polymers useful
in the present
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disclosure contain a plurality of carboxylic acid (¨C(0)0H) groups. In some
embodiments,
such carboxylate groups are not bound to a cation other than a proton (H'),
that is,
essentially all, substantially all, or greater than about 99% of the
carboxylate groups of the
polymers are bound to protons. In some embodiments, at least 99%, at least
99.1%, at least
99.2%, at least 99.3%, at least 99.4%, at least 99.5%, at least 99.6%, at
least 99.7%, at least
99.8%, or at least 99.9% of the carboxylate groups in the polymer are bound to
protons. In
some embodiments, less than 2%, less than 1%, less than 0.5%, less than 0.4%,
less than
0.3%, less than 0.2%, or less than 0.1% of the carboxylate groups of the
polymer are bound
to cations other than hydrogen, such as sodium, potassium, calcium, magnesium,
and/or
choline.
[0026] Polymers of the present disclosure are crosslinked. Any
crosslinker known in
the art may be used. Crosslinking agents contemplated for use in the present
disclosure,
include, for example, diethelyeneglycol diacrylate (diacryl glycerol),
triallylamine,
tetraallyloxyethane, allylmethacrylate, 1,1,1-trimethylolpropane triacrylate
(TMPTA),
divinyl benzene, and divinyl glycol. The amount of crosslinking agent used may
vary
depending on the absorbent characteristics desired. In general, increasing
amounts of
crosslinking agent will yield polymers with increasing degrees of
crosslinking. Such
polymers with higher degrees of crosslinking may be preferred over less
crosslinked
polymers when fluid absorption is unnecessary. For polymers of the present
disclosure, an
amount of crosslinking may be chosen that yields a polymer with an in vitro
saline
absorption capacity (e.g., saline holding capacity) of greater than about 20
times its own
weight. For the purposes of this disclosure saline absorption capacity (e.g.,
saline holding
capacity) is measured in a saline solution buffered to pH 7. For example, the
amount of
crosslinker used to crosslink polymers according to the present disclosure may
range from
about 0.08 mol% to about 0.2 mol% or alternatively from about 0.025 mol.% to
about 3.0
mol.% including, for example, from about 0.025 mol.% to about 0.3 mol.% or
from about
0.025 mol.% to about 0.17 mol.% or from about 0.025 mol.% to about 0.34 mol.%.
[0027] In certain exemplary embodiments, the crosslinked cation-
binding polymer, as
described, for example, for inclusion in compositions, formulations, and/or
dosage forms
and/or for use in methods for treatment of various diseases or disorders as
described herein,
and/or for use in methods for cation binding and/or removal, and/or fluid
binding and/or
removal, as described herein, is a crosslinked polyacrylate polymer (i.e.,
derived from
acrylic acid monomers or a salt thereof). For example, the polymer may be a
polyacrylate
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polymer crosslinked with about 0.08 mol% to about 0.2 mol% or alternatively
from about
0.025 mol.% to about 3.0 mol.% including, for example, from about 0.025 mol.%
to about
0.3 mol.% or from about 0.025 mol.% to about 0.17 mol.% or from about 0.025
mol.% to
about 0.34 mol.% crosslinker, and for example, may comprise an in vitro saline
absorption
capacity (e.g., saline holding capacity) of at least about 20 times its weight
(e.g., at least
about 20 grams of saline per gram of polymer, or "g/g"), at least about 30
times its weight,
at least about 40 times its weight, at least about 50 times its weight, at
least about 60 times
its weight, at least about 70 times its weight, at least about 80 times its
weight, at least about
90 times its weight, at least about 100 times its weight, or more. As used
herein an in vitro
saline absorption capacity (e.g., saline holding capacity) is measured in a
saline solution
buffered to pH 7 including as described in Examples 5 and 6). In some
embodiments, the
crosslinked polyacrylate polymer comprises individual particles or particles
that are
agglomerated (for example, flocculated) to form a larger particle, wherein the
individual or
agglomerated particle diameter is about 1 to about 10,000 microns
(alternatively, about 1
micron to about 10 microns, about 1 micron to about 50 microns, about 10
microns to about
50 microns, about 10 microns to about 200 microns, about 50 microns to about
100
microns, about 50 microns to about 200 microns, about 50 microns to about 1000
microns,
about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or
about 5000
microns to about 10,000 microns. In one embodiment, the polyacrylate polymer
is in the
form of small particles that flocculate to form agglomerated particles with a
diameter of
about 1 micron to about 10 microns.
[0028] As used herein, the term non-hydrogen cations refers to
sodium, potassium,
magnesium and calcium cations. In some embodiments, the polymer contains less
than
about 20,000 ppm of non-hydrogen cations. As used herein, the term "about
20,000 ppm of
non-hydrogen cations" refers to a maximum level in the polymer of about 20,000
ppm of
the combination of sodium, potassium, magnesium, and calcium cations; and a
maximum
level in the polymer for each non-hydrogen cation (sodium, potassium,
magnesium and
calcium) of about 5,000 ppm. In some embodiments, the polymer contains less
than about
19,000 ppm of non-hydrogen cations ( e.g., less than or equal to about 4,750
ppm of each
non-hydrogen cation), about 18,000 ppm of non-hydrogen cations (e.g., less
than or equal to
about 4,500 ppm of each non-hydrogen cation), about 17,000 ppm of non-hydrogen
cations
(e.g., less than or equal to about 4,250 ppm of each non-hydrogen cation),
about
16,000 ppm of non-hydrogen cations (e.g., less than or equal to about 4,000
ppm of each
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non-hydrogen cation), about 15,000 ppm of non-hydrogen cations (e.g., less
than or equal to
about 3,750 ppm of each non-hydrogen cation), about 14,000 ppm of non-hydrogen
cations
(e.g., less than or equal to about 3,500 ppm of each non-hydrogen cation),
about
13,000 ppm of non-hydrogen cations (e.g., less than or equal to about 3,250
ppm of each
non-hydrogen cation), about 12,000 ppm of non-hydrogen cations (e.g., less
than or equal to
about 3,000 ppm of each non-hydrogen cation), about 11,000 ppm of non-hydrogen
cations
(e.g., less than or equal to about 2,750 ppm of each non-hydrogen cation),
about
10,000 ppm of non-hydrogen cations (e.g., less than or equal to about 2,500
ppm of each
non-hydrogen cation), about 9,000 ppm of non-hydrogen cations (e.g., less than
or equal to
about 2,250 ppm of each non-hydrogen cation), about 8,000 ppm of non-hydrogen
cations
(e.g., less than or equal to about 2,000 ppm of each non-hydrogen cation),
about 7,000 ppm
of non-hydrogen cations (e.g., less than or equal to about 1,750 ppm of each
non-hydrogen
cation), about 6,000 ppm of non-hydrogen cations (e.g., less than or equal to
about
1,500 ppm of each non-hydrogen cation), about 5,000 ppm of non-hydrogen
cations (e.g.,
less than or equal to about 1,250 ppm of each non-hydrogen cation), about
4,000 ppm of
non-hydrogen cations (e.g., less than or equal to about 1,000 ppm of each non-
hydrogen
cation), about 3,000 ppm of non-hydrogen cations (e.g., less than or equal to
about 750 ppm
of each non-hydrogen cation), about 2,000 ppm of non-hydrogen cations (e.g.,
less than or
equal to about 500 ppm of each non-hydrogen cation), about 1,000 ppm of non-
hydrogen
cations (e.g., less than or equal to about 250 ppm of each non-hydrogen
cation), about
500 ppm of non-hydrogen cations (e.g., less than or equal to about 125 ppm of
each non-
hydrogen cation), about 400 ppm of non-hydrogen cations (e.g., less than or
equal to about
100 ppm of each non-hydrogen cation), about 300 ppm of non-hydrogen cations
(e.g., less
than or equal to about 75 ppm of each non-hydrogen cation), about 200 ppm of
non-
hydrogen cations (e.g., less than or equal to about 50 ppm of each non-
hydrogen cation), or
about 100 ppm of non-hydrogen cations (e.g., less than or equal to about 25
ppm of each
non-hydrogen cation.
[0029] In some embodiments, the polymer contains less than about
50,000 ppm of
non-hydrogen cations. As used herein, the term "about 50,000 ppm of non-
hydrogen
cations" refers to a maximum level in the polymer of about 50,000 ppm of the
combination
of sodium, potassium, magnesium, and calcium cations. In some embodiments, the
polymer contains less than about 50,000 ppm of all non-hydrogen cations
combined, and at
least about 5,000 ppm of one non-hydrogen cation; at least about 5,000 ppm
each of two
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non-hydrogen cations (e.g., calcium and sodium, calcium and magnesium, calcium
and
potassium, sodium and magnesium, sodium and potassium, or magnesium and
potassium);
at least about 5,000 ppm each of two non-hydrogen cations (e.g., calcium,
sodium and
magnesium; calcium, sodium and potassium; calcium, magnesium and potassium; or
sodium, magnesium and potassium); or at least about 5,000 ppm of each non-
hydrogen
cation.
[0030] In some embodiments, the polymer contains less than about
5,000 ppm of any
single non-hydrogen cation, for example about 5,000 ppm, about 4,000 ppm,
about
3,000 ppm, about 2,000 ppm, about 1,000 ppm, about 900 ppm, about 800 ppm,
about
700 ppm, about 600 ppm, about 500 ppm, about 400 ppm, about 300 ppm, about 200
ppm,
about 100 ppm, or less than about 100 ppm of any single non-hydrogen cation.
[0031] In some embodiments, the polymer contains less than about
5,000 ppm of
sodium, for example about 5,000 ppm, about 4,000 ppm, about 3,000 ppm, about
2,000 ppm, about 1,000 ppm, about 900 ppm, about 800 ppm, about 700 ppm, about
600 ppm, about 500 ppm, about 400 ppm, about 300 ppm, about 200 ppm, about 100
ppm,
or less than about 100 ppm of sodium.
[0032] In some embodiments, the polymer contains less than about
5,000 ppm of
potassium, for example about 5,000 ppm, about 4,000 ppm, about 3,000 ppm,
about
2,000 ppm, about 1,000 ppm, about 900 ppm, about 800 ppm, about 700 ppm, about
600 ppm, about 500 ppm, about 400 ppm, about 300 ppm, about 200 ppm, about 100
ppm,
or less than about 100 ppm of potassium.
[0033] In some embodiments, the polymer contains less than about
5,000 ppm of
magnesium, for example about 5,000 ppm, about 4,000 ppm, about 3,000 ppm,
about
2,000 ppm, about 1,000 ppm, about 900 ppm, about 800 ppm, about 700 ppm, about
600 ppm, about 500 ppm, about 400 ppm, about 300 ppm, about 200 ppm, about 100
ppm,
or less than about 100 ppm of magnesium.
[0034] In some embodiments, the polymer contains less than about
5,000 ppm of
calcium, for example about 5,000 ppm, about 4,000 ppm, about 3,000 ppm, about
2,000 ppm, about 1,000 ppm, about 900 ppm, about 800 ppm, about 700 ppm, about
600 ppm, about 500 ppm, about 400 ppm, about 300 ppm, about 200 ppm, about 100
ppm,
or less than about 100 ppm of calcium.
[0035] The present disclosure relates generally to compositions
comprising a
crosslinked cation-binding polymer and a base, wherein the polymer comprises
carboxylic
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acid-containing monomers, wherein the polymer contains less than about 20,000
ppm of
non-hydrogen cations, and wherein the base is present in an amount sufficient
to provide
from about 0.2 equivalents to about 0.95 equivalents of base per equivalent of
carboxylic
acid groups in the polymer (alternatively, from about 0.2 equivalents to about
0.35
equivalents of base per equivalent of carboxylic acid groups in the polymer;
alternatively,
from about 0.2 equivalents to about 0.3 equivalents of base per equivalent of
carboxylic
acid groups in the polymer; or alternatively about 0.25 equivalents of base
per equivalent of
carboxylic acid groups in the polymer).
[0036] In some embodiments, a composition of the present disclosure
comprises a
crosslinked cation-binding polymer comprising monomers comprising carboxylic
acid
groups, and a base, wherein no less than about 70% of the polymer has a
particle size of
about 212 microns to about 500 microns, wherein said monomers are acrylic acid
or salts
thereof, wherein the polymer comprises less than about 20,000 ppm of non-
hydrogen
cations, and wherein said base is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of base per equivalent of carboxylic
acid groups in
said polymer.
[0037] In some embodiments, a composition of the present disclosure
comprises a
crosslinked cation-binding polymer comprising monomers comprising carboxylic
acid
groups, and a base, wherein no less than about 70% of the polymer has a
particle size of
about 212 microns to about 500 microns, wherein said monomers are acrylic acid
or salts
thereof, wherein the polymer comprises less than about 50,000 ppm of non-
hydrogen
cations, and wherein said base is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of base per equivalent of carboxylic
acid groups in
said polymer. In some embodiments, at least one non-hydrogen cation is present
in an
amount of at least about 5,000 ppm.
[0038] In some embodiments, a composition of the present disclosure
comprises a
crosslinked cation-binding polymer comprising monomers comprising carboxylic
acid
groups, and a base, wherein no less than about 70% of the polymer has a
particle size of 75
microns or less, wherein said monomers are acrylic acid or salts thereof,
wherein the
polymer comprises less than about 20,000 ppm of non-hydrogen cations, and
wherein said
base is present in an amount sufficient to provide from about 0.2 equivalents
to about 0.95
equivalents of base per equivalent of carboxylic acid groups in said polymer.
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[0039] In some embodiments, a composition of the present disclosure
comprises a
crosslinked cation-binding polymer comprising monomers comprising carboxylic
acid
groups, and a base, wherein no less than about 70% of the polymer has a
particle size of 75
microns or less, wherein said monomers are acrylic acid or salts thereof,
wherein the
polymer comprises less than about 50,000 ppm of non-hydrogen cations, and
wherein said
base is present in an amount sufficient to provide from about 0.2 equivalents
to about 0.95
equivalents of base per equivalent of carboxylic acid groups in said polymer.
In some
embodiments, at least one non-hydrogen cation is present in an amount of at
least about
5,000 ppm.
[0040] In some embodiments, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid, and
further wherein: the polymer contains no more than about 5,000 ppm of sodium,
no more
than about 20 ppm of heavy metals, no more than about 1,000 ppm of residual
monomer, no
more than about 20 wt.% of soluble polymer, and loses less than about 5% of
its weight
upon drying; the polymer contains no more than about 1,000 ppm of sodium, no
more than
about 20 ppm of heavy metals, no more than about 500 ppm of residual monomer,
no more
than about 10 wt.% of soluble polymer, and loses less than about 5% of its
weight upon
drying; the polymer contains no more than about 500 ppm of sodium, no more
than about
20 ppm of heavy metals, no more than about 100 ppm of residual monomer, no
more than
about 10 wt.% of soluble polymer, and loses less than about 5% of its weight
upon drying;
the polymer contains no more than about 500 ppm of sodium, no more than about
20 ppm
of heavy metals, no more than about 50 ppm of residual monomer, no more than
about
10 wt.% of soluble polymer, and loses less than about 5% of its weight upon
drying; the
polymer contains about 430 ppm of sodium, less than about 20 ppm of heavy
metals, less
than about 2 ppm of residual monomer, about 3 wt.% of soluble polymer, and
loses about
2% of its weight upon drying; the polymer contains about 160 ppm of sodium,
less than
about 20 ppm of heavy metals, about 4 ppm of residual monomer, about 4 wt.% of
soluble
polymer, and loses about 3% of its weight upon drying; the polymer contains
about
335 ppm of sodium, less than about 20 ppm of heavy metals, about 36 ppm of
residual
monomer, about 4 wt.% of soluble polymer, and loses about 2% of its weight
upon drying;
the polymer contains about 300 ppm of sodium, less than about 20 ppm of heavy
metals,
about 14 ppm of residual monomer, about 7 wt.% of soluble polymer, and loses
about 2%
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of its weight upon drying; or the polymer contains about 153 ppm of sodium,
less than
about 20 ppm of heavy metals, less than about 40 ppm of residual monomer,
about 3 wt.%
of soluble polymer, and loses about 1% of its weight upon drying. In any of
the above
composition embodiments, the base is calcium carbonate and the calcium
carbonate is
present in an amount sufficient to provide from about 0.2 equivalents to about
0.95
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer
(e.g., from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer, from about 0.25
equivalents to about
0.50 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer, from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer, from about 0.5
equivalents to about
0.55 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer, from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer, from about 0.7
equivalents to about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer, from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer, from about 0.7
equivalents to about
0.80 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer, or about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer).
[0041] Determination of the content of non-hydrogen cations (e.g.,
parts per million,
weight percent, etc.) can be accomplished by any suitable means known in the
art (e.g., ICP
spectroscopy, atomic absorption spectroscopy, ion chromatography, or similar
analytic
methods). For example and without limitation, the polymer may be analyzed with
an
inductively coupled plasma ("ICP") spectrometer (e.g., by mass spectroscopy
(ICP-MS),
atomic emission spectroscopy (ICP-AES), or optical emission spectroscopy (ICP-
OES))
using methods known to those skilled in the art. Such methods include methods
of sample
preparation wherein the polymer is completely digested.
[0042] Compositions and/or dosage forms comprising a polymer as
disclosed herein
additionally comprise a base (alternatively termed an alkali). As used with
respect to a
component of the compositions and dosage forms disclosed herein, the term base
refers to
any suitable compound or mixture of compounds that is capable of increasing
the pH of the
blood or other bodily fluids. Preferred bases include calcium carbonate,
calcium acetate,
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magnesium oxide, calcium oxide, potassium citrate, potassium acetate, and
sodium
bicarbonate. Generally, inorganic and organic bases can be used, provided they
are
acceptable, for example, pharmaceutically and/or physiologically acceptable.
To be
acceptable, the dose and route of administration of the specific base are
important
considerations. For example, oral administration of even small amounts of
sodium
hydroxide would cause local tissue damage and would not be acceptable on this
basis while
administration of intermittent, small amounts of sodium hydroxide
intravenously is
performed routinely. Similarly, though lithium carbonate or rubidium acetate
would be an
acceptable base, only small amounts could be used due to the effects of the
lithium or the
1 o rubidium, regardless of the route of administration.
[0043] In some embodiments, the base is one or more of: an alkali
metal hydroxide,
an alkali metal acetate, an alkali metal carbonate, an alkali metal
bicarbonate, an alkali
metal oxide, an alkaline earth metal hydroxide, an alkaline earth metal
acetate, an alkaline
earth metal carbonate, an alkaline earth metal bicarbonate, an alkaline earth
metal oxide,
and an organic base. In some embodiments, the base is choline, lysine,
arginine, histidine, a
pharmaceutically acceptable salt thereof, or a combination thereof In some
embodiments,
the base is an acetate, a butyrate, a propionate, a lactate, a succinate, a
citrate, an isocitrate,
a fumarate, a malate, a malonate, an oxaloacetate, a pyruvate, a phosphate, a
carbonate, a
bicarbonate, a lactate, a benzoate, a sulfate, a lactate, a silicate, an
oxide, an oxalate, a
hydroxide, an amine, a dihydrogen citrate, or a combination thereof In some
embodiments,
the base is a bicarbonate, a carbonate, an oxide, or a hydrochloride. In
related
embodiments, the base is one or more of: calcium bicarbonate, calcium
carbonate, calcium
oxide, and calcium hydroxide. In some embodiments, the base is a lithium salt,
a sodium
salt, a potassium salt, a magnesium salt, a calcium salt, an aluminum salt, a
rubidium salt, a
barium salt, a chromium salt, a manganese salt, an iron salt, a cobalt salt, a
nickel salt, a
copper salt, a zinc salt, an ammonium salt, a lanthanum salt, a choline salt,
or a serine salt of
any of the foregoing anions or anion combinations.
[0044] In some embodiments, the base may be selected to avoid
increasing a level of
a particular cation associated with the subject. For example, a composition
according to the
present disclosure intended to treat hyperkalemia in a subject would
preferably contain a
base that does not include potassium cations. Similarly, a composition
according to the
present disclosure intended to treat hypernatremia in a subject would
preferably contain a
base that does not include sodium cations.
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[0045] In some embodiments, the base is present in an amount
sufficient to provide
an equivalents ratio of from about 0.2 equivalents to 0.95 equivalents of base
per equivalent
(e.g., mole) of carboxylic acid groups in the polymer. As used herein, the
term "equivalents
ratio" ("ER") refers to the ratio between the number of units (e.g.,
equivalents) of base
present in the composition and the number of units (e.g., moles) of carboxylic
acid groups
in the polymer. A monobasic base provides one equivalent of base per mole of
monobasic
base. A dibasic base provides two equivalents of base per mole of dibasic
base. A tribasic
base provides three equivalents of base per mole of tribasic base. For
example, a
composition comprising a polymer derived from polymerization and crosslinking
of 1.0
mole of acrylic acid monomers may contain from about 0.2 moles to 0.95 moles
of a
monobasic base, such as a bicarbonate. If a dibasic base is used, such as a
carbonate, a
composition comprising 1.0 mole of carboxylic acid groups may contain from
about 0.1 to
about 0.475 equivalents of the dibasic base.
[0046] In some embodiments, compositions of the present disclosure
comprise a
monobasic base present in an amount sufficient to provide from about 0.2 to
about 0.95
moles of base per mole of carboxylic acid groups in the polymer, for example
about 0.2
moles of base, about 0.25 moles of base, about 0.3 moles of base, about 0.35
moles of base,
about 0.4 moles of base, about 0.45 moles of base, about 0.5 moles of base,
about 0.55
moles of base, about 0.6 moles of base, about 0.65 moles of base, about 0.7
moles of base,
about 0.75 moles of base, about 0.8 moles of base, about 0.85 moles of base,
about 0.9
moles of base, or about 0.95 moles of base per mole of carboxylic acid groups
in the
polymer. In some embodiments, compositions of the present disclosure comprise
a
monobasic base present in an amount sufficient to provide from about 0.5 moles
of base to
about 0.85 moles of base of base, for example about 0.5 moles of base, about
0.55 moles of
base, about 0.6 moles of base, about 0.65 moles of base, about 0.7 moles of
base, about 0.75
moles of base, about 0.8 moles of base, or about 0.85 moles of base per mole
of carboxylate
groups in the polymer. In some embodiments, the composition includes from
about 0.2
equivalents to 0.35 moles of base per mole of carboxylic acid groups in the
polymer, for
example about 0.2 moles of base to about 0.3 moles of base, about 0.2 moles of
base, about
0.25 moles of base, about 0.3 moles of base, or about 0.35 moles of base per
mole of
carboxylic acid groups in the polymer. In some embodiments, compositions of
the present
disclosure comprise a monobasic base present in an amount sufficient to
provide from about
0.7 moles of base to about 0.8 moles of base of base, for example about 0.7
moles of base,
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about 0.75 moles of base, about or 0.8 moles of base per mole of carboxylate
groups in the
polymer. In some embodiments, compositions of the present disclosure comprise
a
monobasic base present in an amount sufficient to provide about 0.75 moles of
base per
mole of carboxylate groups in the polymer.
[0047] In some embodiments, compositions of the present disclosure comprise
a
dibasic base present in an amount sufficient to provide from about 0.1 to
about 0.475 moles
of base per mole of carboxylic acid groups in the polymer, for example about
0.1 moles of
base, about 0.125 moles of base, about 0.15 moles of base, about 0.175 moles
of base, about
0.2 moles of base, about 0.225 moles of base, about 0.25 moles of base, about
0.275 moles
of base, about 0.3 moles of base, about 0.325 moles of base, about 0.35 moles
of base, about
0.375 moles of base, about 0.4 moles of base, about 0.425 moles of base, about
0.45 moles
of base, or about 0.475 moles of base per mole of carboxylic acid groups in
the polymer. In
some embodiments, compositions of the present disclosure comprise a dibasic
base present
in an amount sufficient to provide from about 0.25 moles of base to about
0.425 moles of
base of base, for example about 0.25 moles of base, about 0.275 moles of base,
about 0.3
moles of base, about 0.325 moles of base, about 0.35 moles of base, about
0.375 moles of
base, about 0.4 moles of base, or about 0.425 moles of base per mole of
carboxylate groups
in the polymer. In some embodiments, compositions of the present disclosure
comprise a
dibasic base present in an amount sufficient to provide from about 0.35 moles
of base to
about 0.4 moles of base of base, for example about 0.35 moles of base, about
0.375 moles
of base, about or 0.4 moles of base per mole of carboxylate groups in the
polymer. In some
embodiments, compositions of the present disclosure comprise a dibasic base
present in an
amount sufficient to provide about 0.375 moles of base per mole of carboxylate
groups in
the polymer.
[0048] In some embodiments, compositions of the present disclosure comprise
a
tribasic base present in an amount sufficient to provide from about 0.065 to
about 0.32
moles of base per mole of carboxylic acid groups in the polymer, for example
about 0.065
moles of base, about 0.07 moles of base, about 0.075 moles of base, about 0.08
moles of
base, about 0.085 moles of base, about 0.09 moles of base, about 0.095 moles
of base, about
0.1 moles of base, about 0.105 moles of base, about 0.11 moles of base, about
0.115 moles
of base, about 0.12 moles of base, about 0.125 moles of base, about 0.13 moles
of base,
about 0.135 moles of base, about 0.14 moles of base, about 0.145 moles of
base, about 0.15
moles of base, about 0.155 moles of base, about 0.16 moles of base, about
0.165 moles of
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base, about 0.17 moles of base, about 0.175 moles of base, about 0.18 moles of
base, about
0.185 moles of base, about 0.19 moles of base, about 0.195 moles of base,
about 0.2 moles
of base, about 0.205 moles of base, about 0.21 moles of base, about 0.215
moles of base,
about 0.22 moles of base, about 0.225 moles of base, about 0.23 moles of base,
about 0.235
moles of base, about 0.24 moles of base, about 0.245 moles of base, about 0.25
moles of
base, about 0.255 moles of base, about 0.26 moles of base, about 0.265 moles
of base, about
0.27 moles of base, about 0.275 moles of base, about 0.28 moles of base, about
0.285 moles
of base, about 0.29 moles of base, about 0.295 moles of base, about 0.3 moles
of base, about
0.305 moles of base, about 0.31 moles of base, about 0.315 moles of base, or
about 0.32
moles of base per mole of carboxylic acid groups in the polymer. In some
embodiments,
compositions of the present disclosure comprise a tribasic base present in an
amount
sufficient to provide from about 0.165 moles of base to about 0.285 moles of
base of base,
for example about 0.065 moles of base, about 0.07 moles of base, about 0.075
moles of
base, about 0.08 moles of base, about 0.085 moles of base, about 0.09 moles of
base, about
0.095 moles of base, about 0.1 moles of base, about 0.105 moles of base, about
0.11 moles
of base, about 0.115 moles of base, about 0.12 moles of base, about 0.125
moles of base,
about 0.13 moles of base, about 0.135 moles of base, about 0.14 moles of base,
about 0.145
moles of base, about 0.15 moles of base, about 0.155 moles of base, about 0.16
moles of
base, about 0.165 moles of base, about 0.17 moles of base, about 0.175 moles
of base, about
0.18 moles of base, about 0.185 moles of base, about 0.19 moles of base, about
0.195 moles
of base, about 0.2 moles of base, about 0.205 moles of base, about 0.21 moles
of base, about
0.215 moles of base, about 0.22 moles of base, about 0.225 moles of base,
about 0.23 moles
of base, about 0.235 moles of base, about 0.24 moles of base, about 0.245
moles of base,
about 0.25 moles of base, about 0.255 moles of base, about 0.26 moles of base,
about 0.265
moles of base, about 0.27 moles of base, about 0.275 moles of base, about 0.28
moles of
base, or about 0.285 moles of base per mole of carboxylate groups in the
polymer. In some
embodiments, compositions of the present disclosure comprise a tribasic base
present in an
amount sufficient to provide from about 0.235 moles of base to about 0.265
moles of base
of base, for example about 0.235 moles of base, about 0.24 moles of base,
about 0.245
moles of base, about 0.25 moles of base, about 0.255 moles of base, about 0.26
moles of
base, or about 0.265 moles of base per mole of carboxylate groups in the
polymer. In some
embodiments, compositions of the present disclosure comprise a tribasic base
present in an
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amount sufficient to provide about 0.25 moles of base per mole of carboxylate
groups in the
polymer.
[0049] In some embodiments, compositions of the present disclosure
comprise more
than one base (e.g., one or more monobasic bases, one or more dibasic bases,
one or more
tribasic bases, etc.). In such embodiments, the compositions comprise an
amount of each
base such that the total number of equivalents of base present is between
about 0.2 and
about 0.95 equivalents per mole of carboxylic acid groups in the polymer. For
example, a
composition comprising 1.0 moles of carboxylic acid groups in the polymer may
further
comprise a total amount of base according to the following Equation 1:
(about 0.2)(NcooH) (Nmonobasic) +
(2)(Ndibasic) + (3)(Ntribasic) + (4)(Ntetrabasic) + = = = ..
(about 0.95)(NcooH),
wherein:
Nc00H is the number of moles of carboxylate groups in the polymer;
Nmonobasic is the number of moles of all monobasic bases present in the
composition;
Ndibasie is the number of moles of all dibasic bases present in the
composition;
Ntribasic is the number of moles of all tribasic bases present in the
composition; and
Ntetrabasic is the number of moles of all tetrabasic bases present in the
composition.
[0050] Thus, as one example embodiment, a composition according to
the present
invention that comprises 1.0 mole of carboxylic acid groups and 0.1 moles of
sodium
bicarbonate may also comprise from about 0.05 moles to about 0.425 moles of a
dibasic
base such as magnesium carbonate. In such an embodiment, the total equivalents
of base
would be equal to 0.1 + (2) (about 0.05 to about 0.425), or about 0.2 to about
0.95
equivalents of base.
[0051] In some embodiments, the base is present in an amount
sufficient to provide
from about 0.2 to about 0.95 equivalents of base, for example about 0.2
equivalents, about
0.25 equivalents, about 0.3 equivalents, about 0.35 equivalents, about 0.4
equivalents, about
0.45 equivalents, about 0.5 equivalents, about 0.55 equivalents, about 0.6
equivalents, about
0.65 equivalents, about 0.7 equivalents, about 0.75 equivalents, about 0.8
equivalents, about
0.85 equivalents, about 0.9 equivalents, or about 0.95 equivalents of base per
equivalent of
carboxylic acid groups in the polymer. In some embodiments, the base is
present in an
amount sufficient to provide from about 0.2 equivalents to about 0.35
equivalents of base,
for example about 0.2 equivalents, about 0.25 equivalents, about 0.3
equivalents, or about
0.35 equivalents of base per equivalent of carboxylate groups in the polymer.
In some
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embodiments, the base is present in an amount sufficient to provide from about
0.5
equivalents to about 0.85 equivalents of base, for example about 0.5
equivalents, about 0.55
equivalents, about 0.6 equivalents, about 0.65 equivalents, about 0.7
equivalents, about 0.75
equivalents, about 0.8 equivalents, or about 0.85 equivalents of base per
equivalent of
carboxylate groups in the polymer. In some embodiments, the base is present in
an amount
sufficient to provide from about 0.7 equivalents to about 0.8 equivalents of
base, for
example about 0.7 equivalents, about 0.75 equivalents, about or 0.8
equivalents of base per
equivalent of carboxylate groups in the polymer. In some embodiments, the base
is present
in an amount sufficient to provide about 0.75 equivalents of base per
equivalent of
carboxylate groups in the polymer.
[0052] In some embodiments, a composition of the present disclosure
has an in vitro
saline absorption capacity (e.g., saline holding capacity) of greater than
about 20 times its
own weight (e.g., greater than about 20 grams of saline per gram of
composition, or "g/g").
In related embodiments, the composition has an in vitro saline absorption
capacity (e.g.,
saline holding capacity) of about 20 times, about 25 times, about 30 times,
about 35 times,
about 40 times, about 45 times, about 50 times, about 55 times, about 60
times, about
65 times, about 70 times, about 75 times, about 80 times, about 85 times,
about 90 times,
about 95 times, or about 100 times its own weight, or more.
[0053] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer comprising (e.g., acrylic acid) monomers that comprise carboxylic acid
groups,
wherein said polymer is crosslinked with about 0.08 mol% to about 0.2 mol% or
alternatively from about 0.025 mol.% to about 3.0 mol.% including, for
example, from
about 0.025 mol.% to about 0.3 mol.% or from about 0.025 mol.% to about 0.17
mol.% or
from about 0.025 mol.% to about 0.34 mol.%, and a base, wherein said monomers
are
acrylic acid or salts thereof, wherein said polymer comprises less than about
20,000 ppm of
non-hydrogen cations, and wherein base (e.g., calcium carbonate) is present in
an amount
sufficient to provide from about 0.2 equivalents to about 0.95 equivalents of
calcium
carbonate per equivalent of carboxylic acid groups of said polymer.
[0054] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0055] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0056] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0057] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[0058] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0059] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0060] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0061] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0062] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0063] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[0064] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0065] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
20,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[0066] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0067] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0068] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0069] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0070] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[0071] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0072] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0073] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0074] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0075] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0076] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0077] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[0078] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
15,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[0079] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0080] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0081] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0082] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[0083] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0084] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0085] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0086] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0087] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0088] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0089] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0090] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0091] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[0092] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0093] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0094] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0095] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[0096] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0097] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0098] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[0099] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00100] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00101] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00102] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00103] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00104] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00105] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[00106] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00107] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00108] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00109] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00110] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00111] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00112] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00113] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00114] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00115] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00116] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00117] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00118] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00119] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[00120] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00121] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00122] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00123] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00124] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00125] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00126] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00127] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00128] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00129] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00130] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00131] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00132] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00133] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[00134] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00135] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00136] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00137] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00138] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00139] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00140] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00141] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00142] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00143] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00144] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00145] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00146] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00147] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00148] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00149] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00150] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00151] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00152] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00153] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00154] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00155] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00156] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00157] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00158] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
io provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00159] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00160] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00161] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[00162] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00163] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00164] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00165] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00166] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00167] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00168] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00169] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00170] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00171] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00172] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00173] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00174] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00175] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[00176] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00177] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00178] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00179] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00180] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00181] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00182] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00183] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00184] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00185] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00186] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00187] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00188] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00189] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[00190] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00191] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00192] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00193] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00194] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00195] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00196] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00197] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00198] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00199] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00200] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00201] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00202] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00203] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[00204] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00205] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00206] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00207] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00208] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
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provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00209] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00210] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.3 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00211] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.35 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00212] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00213] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.25 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00214] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.25 equivalents to about 0.50 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00215] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00216] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.5 equivalents to about 0.55 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00217] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.6 equivalents to about 0.65 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
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[00218] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.75 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00219] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.8 equivalents to about 0.85 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00220] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide from about 0.7 equivalents to about 0.80 equivalents of calcium
carbonate per
equivalent of carboxylic acid groups of said polymer.
[00221] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein calcium carbonate is present in an amount
sufficient to
provide about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00222] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
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about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00223] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00224] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00225] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00226] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00227] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00228] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00229] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00230] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00231] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
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[00232] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00233] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
[00234] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00235] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00236] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
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about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00237] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00238] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00239] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00240] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00241] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00242] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00243] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00244] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00245] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
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[00246] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00247] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00248] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00249] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00250] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
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about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00251] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00252] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00253] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00254] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00255] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00256] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00257] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
[00258] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00259] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
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[00260] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00261] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00262] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00263] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00264] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
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about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00265] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00266] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00267] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00268] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00269] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
[00270] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00271] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00272] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00273] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
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[00274] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00275] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00276] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00277] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00278] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
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about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00279] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00280] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00281] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00282] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
[00283] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00284] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00285] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00286] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00287] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
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[00288] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00289] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00290] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00291] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00292] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
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about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00293] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00294] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
[00295] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00296] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00297] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00298] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00299] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00300] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00301] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
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[00302] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00303] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00304] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00305] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00306] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
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0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
[00307] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00308] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00309] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00310] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00311] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00312] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00313] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00314] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00315] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
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[00316] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00317] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00318] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
[00319] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00320] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
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about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00321] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00322] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00323] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00324] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00325] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00326] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00327] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00328] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00329] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
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[00330] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
[00331] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.95 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00332] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.25 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00333] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.2 equivalents to about 0.3 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00334] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
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about 0.2 equivalents to about 0.35 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00335] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.25 equivalents to about 0.50 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00336] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00337] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.5 equivalents to about 0.55 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00338] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.6 equivalents to about 0.65 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00339] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.75 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00340] In one embodiment, a composition comprises a crosslinked cation-
binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.8 equivalents to about 0.85 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00341] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.80 equivalents of calcium carbonate per
equivalent of
carboxylic acid groups of said polymer.
[00342] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein calcium carbonate is present in an amount sufficient to
provide about
0.75 equivalents of calcium carbonate per equivalent of carboxylic acid groups
of said
polymer.
[00343] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
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equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00344] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00345] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00346] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00347] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00348] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00349] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00350] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00351] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00352] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
10,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00353] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00354]
In one embodiment, a composition comprises a crosslinked cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00355]
In one embodiment, a composition comprises a crosslinked cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00356]
In one embodiment, a composition comprises a crosslinked cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00357] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00358] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00359] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00360] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00361] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00362] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00363] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00364] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00365] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00366] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00367] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00368] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00369] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00370] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00371] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00372] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00373] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00374] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00375] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00376] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00377] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00378] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00379] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00380] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00381] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00382] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00383] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00384] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00385] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00386] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00387] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00388] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00389] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00390] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00391] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00392] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00393] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00394] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00395] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00396] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00397] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00398] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00399] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00400] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00401] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00402] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00403] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00404] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00405] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00406] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00407] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00408] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00409] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00410] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00411]
In one embodiment, a composition comprises a crosslinked cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00412]
In one embodiment, a composition comprises a crosslinked cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00413]
In one embodiment, a composition comprises a crosslinked cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00414] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00415] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00416] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00417] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00418] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00419] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00420] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00421] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00422] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00423] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00424] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00425] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00426] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00427] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00428] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00429] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00430] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00431] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00432] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00433] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00434] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00435] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00436] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00437] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00438] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00439] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00440] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00441] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00442] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00443] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
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and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.95 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00444] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.2
equivalents to about 0.25 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00445] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.25
equivalents to about 0.50 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00446] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
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[00447] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.5
equivalents to about 0.55 equivalents of calcium carbonate per equivalent of
carboxylic acid
io groups of said polymer.
[00448] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.6
equivalents to about 0.65 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00449] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.75 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00450] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.8
equivalents to about 0.85 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00451] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
from about 0.7
equivalents to about 0.80 equivalents of calcium carbonate per equivalent of
carboxylic acid
groups of said polymer.
[00452] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
non-hydrogen cations, and wherein at least about 98% or 99% (e.g., 98.1%,
98.2%, 98.3%,
98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%,
99.6%,
99.7%, 99.8%, or 99.9%) of the carboxylate groups of said polymer are bound to
hydrogen,
and wherein calcium carbonate is present in an amount sufficient to provide
about 0.75
equivalents of calcium carbonate per equivalent of carboxylic acid groups of
said polymer.
[00453] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00454] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00455] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00456] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00457] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00458] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00459] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00460] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00461] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00462] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
5,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00463] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00464] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00465] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00466] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00467] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00468] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00469] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00470] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00471] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00472] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
4,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00473] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00474] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00475] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00476] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00477] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00478] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00479] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00480] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00481] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00482] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
3,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00483] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00484] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00485] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00486] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00487] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00488] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00489] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00490] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00491] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00492] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
2,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00493] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00494] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00495] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00496] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00497] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00498] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00499] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00500] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00501] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00502] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
1,000 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00503] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00504] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00505] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00506] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00507] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00508] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00509] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00510] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00511] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00512] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
500 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00513] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00514] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00515] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00516] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00517] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00518] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00519] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00520] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00521] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00522] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
400 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00523] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00524] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00525] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00526] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00527] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00528] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00529] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00530] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00531] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00532] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
300 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00533] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00534] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00535] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00536] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00537] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00538] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00539] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00540] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00541] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00542] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
200 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00543] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
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calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.95 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00544]
In one embodiment, a composition comprises a crosslinked cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.2
equivalents
to about 0.25 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00545]
In one embodiment, a composition comprises a crosslinked cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about
0.25 equivalents
to about 0.50 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00546]
In one embodiment, a composition comprises a crosslinked cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
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[00547] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.5
equivalents
to about 0.55 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00548] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.6
equivalents
to about 0.65 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00549] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.75 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00550] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
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the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.8
equivalents
to about 0.85 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00551] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
io (e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide from about 0.7
equivalents
to about 0.80 equivalents of calcium carbonate per equivalent of carboxylic
acid groups of
said polymer.
[00552] In one embodiment, a composition comprises a crosslinked
cation-binding
polymer and a base, wherein the crosslinked cation-binding polymer comprising
monomers
(e.g., acrylic acid) containing carboxylic acid groups is a crosslinked
polyacrylic acid; and
the base is calcium carbonate, wherein said polymer contains less than about
100 ppm of
sodium, and wherein at least about 98% or 99% (e.g., 98.1%, 98.2%, 98.3%,
98.4%, 98.5%,
98.6%, 98.7%, 98.8%, 98.9%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%,
99.8%,
or 99.9%) of the carboxylate groups of said polymer are bound to hydrogen, and
wherein
calcium carbonate is present in an amount sufficient to provide about 0.75
equivalents of
calcium carbonate per equivalent of carboxylic acid groups of said polymer.
[00553] The present disclosure also relates to methods of using the
polymers, and
compositions, formulations, and/or dosage forms containing the polymers
disclosed herein,
with or without added base, to treat various diseases and disorders, ion
imbalances, and
fluid imbalances.
[00554] In some embodiments, the disease or disorder is one or more
of: heart failure,
a renal insufficiency disease, end stage renal disease, liver cirrhosis,
chronic renal
insufficiency, chronic kidney disease, fluid overload, fluid maldistribution,
edema,
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pulmonary edema, peripheral edema, lymphedema, nephrotic edema, idiopathic
edema,
ascites, cirrhotic ascites, interdialytic weight gain, high blood pressure,
hyperkalemia,
hypernatremia, abnormally high total body sodium, hypercalcemia, tumor lysis
syndrome,
head trauma, an adrenal disease, hyporeninemic hypoaldosteronism,
hypertension, salt-
sensitive hypertension, refractory hypertension, renal tubular disease,
rhabdomyolysis,
crush injuries, renal failure, acute tubular necrosis, insulin insufficiency,
hyperkalemic
periodic paralysis, hemolysis, malignant hyperthermia, pulmonary edema
secondary to
cardiogenic pathophysiology, pulmonary edema with non-cardiogenic origin,
drowning,
acute glomerulonephritis, allergic pulmonary edema, high altitude sickness,
Adult
Respiratory Distress Syndrome, traumatic edema, cardiogenic edema, acute
hemorrhagic
edema, heatstroke edema, facial edema, eyelid edema, angioedema, cerebral
edema, scleral
edema, nephritis, nephrosis, nephrotic syndrome, glomerulonephritis, and/or
renal vein
thrombosis.
[00555] In some embodiments, the disease or disorder is the result
of, or is associated
with, administration of another drug. For example, compositions and/or dosage
forms as
disclosed herein are useful in treating an increase in a subject's potassium
level when co-
administered with a drug known to cause increases in potassium levels. In some
embodiments, such a drug is an alpha-adrenergic agonist, a RAAS inhibitor, an
ACE
inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone
antagonist, etc.
Preparation of Crosslinked Cation-Binding Polymers
[00690] Crosslinked cation-binding polymers, including, for example,
polyelectrolyte
polymers, such as polyacrylate polymers, etc., may be prepared by methods
known in the
art, including by suspension methods, aqueous one-phase methods (e.g.,
Buchholz, F. L.
and Graham, A. T., "Modern Superabsorbent Polymer Technology," John Wiley &
Sons
(1998)) and by precipitation polymerization (see, e.g., European Patent
Application No.
EP0459373A2). Polymers with differential properties may be prepared that are
useful as
therapeutics for different diseases and disorders, including those involving
an ion imbalance
and/or a fluid imbalance. For example, methods are provided for washing the
cross-linked
polymer with an acid to replace bound counterions other than hydrogen with
hydrogen. The
polymeric material, including for example polymeric beads, may be further
processed by
milling or grinding the polymeric material into particles. A polymer as
described herein
may contain many carboxylic acid groups, for example, polyacrylic acid, which
may be
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reacted with alkali metals to produce a polycarboxylate, for example,
polyacrylate. Many
of these polycarboxylates act as superabsorbent polymers and have a saline
absorption
capacity (e.g., saline holding capacity) of over twenty times their mass in
vitro (e.g., about
40 times its mass) as measured in 0.9% saline solution (e.g., 0.15 M sodium
chloride
solution) buffered to pH 7 (see, e.g., Examples 5 and 6). Exemplary methods
are provided
below.
1. Manufacture of Crosslinked Cation-Binding Polymers
[00691] Cross-linked cation-binding polymers, including cross-linked
polyacrylate and/or
polyacrylic acid polymers, may be prepared by commonly known methods in the
art. In an
exemplary method, cross-linked polyelectrolyte polymers may be prepared as a
suspension
of drops of aqueous solution in a hydrocarbon, for example, a liquid
hydrocarbon (e.g., by
inverse suspension polymerization).
[00692] Cross-linked polyacrylate polymers may be prepared by polymerization
of
partially neutralized acrylic acid in an aqueous environment where an
appropriate cross-
linker is present in small quantities. Given that there is an inverse
relationship between the
amount of fluid the polymer will absorb and the degree of cross-linking of the
polymer, it
may be desirable to have a low level of cross-linking to obtain a fluid
absorption capacity of
at least 20 g/g (e.g. 20 g/g, 30 g/g, 40 g/g, 50 g/g, 60 g/g, 70 g/g, 80 g/g,
90 g/g, or 100 g/g
polymer), for use in methods as described herein. However, there is also an
inverse
relationship between the degree of cross-linking and the percentage of polymer
chains that
do not cross-link. Non-crosslinked polymer is soluble and may not contribute
to the
absorbency of the polymer since it dissolves in the fluid. For example,
polyacrylates can be
designed to absorb about 35 times their mass in pH 7 buffered physiological
saline as a
compromise between high absorbency and minimal soluble polymer.
[00693] Since the amount of reactants used in a polymerization reaction varies
depending
upon the size of the reactor and other factors, the precise amount of each
reactant used in
the preparation of cross-linked polyelectrolyte polymer, such as polyacrylate,
may be
determined by one of skill in the art. For example, in a five-hundred gallon
reactor, about
190 to 200 pounds (roughly 85 to 90 kg) of acrylic acid may be used while in a
three liter
reactor 150 to 180 g of acrylic acid may be used. Accordingly, the amount of
each reactant
used for the preparation of an exemplary cross-linked polyacrylate may be
expressed as a
weight ratio to acrylic acid. Thus, acrylic acid weight may be taken as 1.0000
and other
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compounds are represented in relation to this value. Exemplary amounts of
reactants used
for the preparation of such a cross-linked polyacrylate by an inverse
suspension
polymerization are presented in Table 1.
[00694] Table 1: Exemplary amounts of reactants in an inverse suspension
polymerization
Substance Low value Hi211 Value
Acrylic acid 1.0000 1.0000
Water 0.5000 3.0000
Hydrophobic solvent 1.2000 12.0000
Base (expressed as 50% NaOH) 0.6600 (60% neutral) 1.1100 (100% neutralized)
Crosslinker 0.0030 0.0080
Initiator 0.0005 0.0200
Chelating agent 0.0000 0.0050
Surfactant 0.0050 0.0400
[00695] An exemplary inverse suspension reaction to form a crosslinked polymer
may
involve preparation of two mixtures (e.g., a hydrophobic mixture and an
aqueous mixture)
in two different vessels followed by combination of the mixtures to form a
reaction mixture.
One vessel may be designated as a hydrophobic compound vessel and the other
may be
designated as an aqueous solution vessel. The hydrophobic compounds may be
mixed in a
larger vessel that will become a reaction vessel, while an aqueous solution
may be prepared
in a smaller vessel that may be discharged into the reaction vessel. In an
exemplary
embodiment, the hydrophobic mixture may contain solvent, surfactant, and
crosslinking
agent, and the aqueous mixture may contain water, base, monomer (e.g., acrylic
acid),
initiator, and optional chelating agent.
[00696] A hydrophobic solvent may be introduced into the reaction vessel. As
will be
appreciated by one of skill in the art, a hydrophobic solvent (also referred
to herein as the
"oil phase") may be chosen based upon one or more considerations, including,
for example,
the density and viscosity of the oil phase, the solubility of water in the oil
phase, the
partitioning of the neutralized and unneutralized ethylenically unsaturated
monomers
between the oil phase and the aqueous phase, the partitioning of the
crosslinker and the
initiator between the oil phase and the aqueous phase and/or the boiling point
of the oil
phase.
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[00697] Hydrophobic solvents contemplated for use in the present disclosure
include, for
example, IsoparTM L (isoparaffin fluid), toluene, benzene, dodecane,
cyclohexane, n-
heptane and/or cumene. Preferably, IsoparTM L is chosen as a hydrophobic
solvent due to
its low viscosity, high boiling point and low solubility for neutralized
monomers such as
sodium acrylate and/or potassium acrylate. One of skill in the art will
appreciate that a large
enough volume of hydrophobic solvent is used to ensure that the aqueous phase
is
suspended as droplets in the oil rather than the reverse and that the aqueous
phase droplets
are sufficiently separated to prevent coalescence into large masses of aqueous
phase.
[00698] One or more surfactants and one or more cross-linkers may be added to
the oil
(hydrophobic) phase. The oil phase may then be agitated and sparged with an
inert gas,
such as nitrogen or argon to remove oxygen from the oil phase. It will be
appreciated that
the amount of surfactant used in the reaction depends on the size of the
desired polymer
particles and the agitator stir rate. This addition of surfactant is designed
to coat the water
droplets formed in the initial reaction mixture before the reaction starts.
Higher amounts of
surfactant and higher agitation rates produce smaller droplets with more total
surface area.
It will be understood by those of skill in the art that an appropriate choice
of cross-linker
and initiator may be used to prepare spherical to ellipsoid shaped beads. One
of skill in the
art will be capable of determining an appropriate cross-linker for the
preparation of a
specified cross-linked cation-binding polymer. For example, cross-linker
choice depends
on whether it needs to be hydrophobic or hydrophilic polymer or whether it
needs to resist
acidic or basic external conditions. An amount of cross-linker depends on how
much
soluble polymer is permissible and how much saline holding capacity is
desired.
[00699] Exemplary surfactants include hydrophobic agents that are solids at
room
temperature, including, for example, hydrophobic silicas (such as Aerosil or
Perform-0-
Si1TM) and glycolipids (such as polyethylene glycol distearate, polyethylene
glycol dioleate,
sorbitan monostearate, sorbitan monooleate or octyl glucoside).
[00700] Crosslinking agents with two or more vinyl groups, each group of which
is
independently polymerizable, may be used, allowing for a wide variety in
molecular weight,
aqueous solubility and/or lipid (e.g., oil) solubility. Crosslinking agents
contemplated for
use in the present disclosure, include, for example, diethyleneglycol
diacrylate, diacryl
glycerol, triallylamine, tetraallyloxyethane, allylmethacrylate, 1,1,1-
trimethylolpropane
triacrylate (TMPTA), divinyl benzene and divinyl glycol.
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[00701] In some embodiments, the crosslinker is one or more compounds having
(in one
molecule) 2-4 groups selected from the group consisting of CH2=CHCO¨,
CH=C(CH3)C0¨ and CH2=CH¨CH2¨, for example and without limitation: diacrylates
and
dimethacrylates of ethylene glycol, glycerol, diethylene glycol, triethylene
glycol,
tetraethyleneglycol, propylene glycol,
dipropyleneglycol, tripropyleneglycol,
tetrapropyleneglycol, polyoxyethylene glycols and polyoxypropylene glycols,
1,4-
butanediol, 1,5-pentanediol, 1,6-hexanediol, neopentyl glycol, trimethylol
propane, and
pentaerythritol; triacrylates and trimethacrylates of trimethylolpropane and
pentaerythritol;
highly ethoxylated trimethylol propane triacrylate; tetracrylate and
tetramethacrylate of
io pentaerythritol; allyl methacrylate, triallylamine, triallylcitrate and
tetraallyloxyethane.
[00702] In some embodiments, a heat activated crosslinker may be used in the
preparation
of crosslinked polymers according to the present disclosure. Non-limiting
examples of
heat-activated crosslinkers include hydroxyl-containing crosslinking agents,
amine-
containing crosslinking agents, or epoxy-containing crosslinking agents
containing at least
one functionality suitable to react with a carboxyl group on the polymer and
containing at
least two functional groups capable of forming covalent bonds with the
polymer. Some non-
limiting examples of heat-activated crosslinkers suitable for such use is the
class of
compounds commonly referred to as polyols or polyhydroxy compounds. Some non-
limiting examples of polyols include: glycerin, ethylene glycol, diethylene
glycol,
triethylene glycol, propylene glycol, 1,4-butanediol, 1,5-pentanediol, 1,6-
hexanediol,
neopentyl glycol, polyglycerin, trimethylolpropane, polyethylene glycol, and
polypropylene
glycol-polyethylene glycol copolymers. Masked polyols, such as ethyleneglycol
diacetate
may also be used. Some non-limiting examples of heat-activated crosslinkers
containing
amine functionality are ethylenediamine, diethylenetriamine,
triethylenetetramine,
monoethanolamine, and aminoethylethanolamine. Some non-limiting examples of
heat-
activated crosslinkers containing epoxy functionality are glycidyl acrylate,
glycidylmethacrylate, and ethyleneglycol diglycidylether,
[00703] In some embodiments, dimodal crosslinkers may be used in the
preparation of
crosslinked polymers according to the present disclosure. Dimodal crosslinkers
contain one
or more carboxylic acid-reactive groups and one or more ethylenically
unsaturated groups
in the same compound. Non-limiting examples of dimodal crosslinkers suitable
for use to
crosslink polymers according to the present disclosure include: 2-
hydroxyethyl(meth)acrylate, polyethylene glycol monomethacrylate, glycidyl
methacrylate,
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allyl glycidyl ether, hydroxypropyl methacrylate, hydroxyethyl methacrylate,
and
hexapropylene glycol monomethacrylate.
[00704] In some embodiments, polyvinyl compounds may be used in the
preparation of
crosslinked polymers according to the present disclosure. Non-limiting
examples of
polyvinyl crosslinkers include divinyl compounds or polyvinyl compounds such
as: divinyl
glycol, divinyl benzene, divinyl toluene, divinyl xylene, divinyl ether,
divinyl ketone,
trivinyl benzene; unsaturated polyesters that can be obtained by reacting an
unsaturated acid
such as maleic acid with polyols such as: ethylene glycol, glycerol,
diethylene glycol,
triethylene glycol, tetraethyleneglycol, propylene glycol, dipropyleneglycol,
tripropyleneglycol, tetrapropyleneglycol, polyoxyethylene glycols and
polyoxypropylene
glycols, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, neopentyl glycol,
trimethylol
propane, and pentaerythritol; diesters or polyesters of unsaturated mono-or
polycarboxylic
acids with polyols derived from reaction of c2¨C10 polyhydric alcohols with 2-
8 C2¨C4
alkylene oxide units per hydroxyl group, such as tri methylol propane
hexaethoxyl
triacrylate; di-methacrylic acid or tri-methacrylic acid esters that can be
obtained by
reacting polyepoxide with methacrylic acid; bis(meth)acrylamides such as N,N-
methylene-
bisacrylamide; carbamyl esters that can be obtained by reacting
polyisocyanates, such as
tolylene diisocyanate, hexamethylene diisocyanate, 4,4'-diphenyl methane
diisocyanate; and
NCO-containing prepolymers obtained by reacting such diisocyanates with active
hydrogen
atom-containing compounds with hydroxyl group-containing monomers, such as di-
methacrylic acid carbamyl esters obtainable by reacting the above-mentioned
diisocyanates
with hydroxyethyl(meth)acrylate; di(meth)allyl ethers or poly(meth)allyl
ethers of polyols
such as alkylene glycols, glycerol, polyalkylene glycols, polyoxyalkylene
polyols and
carbohydrates such as polyethylene glycol diallyl ether, allylated starch, and
allylated
cellulose; di-allyl or poly-allyl esters of polycarboxylic acids, such as
diallyl phthalate and
diallyl adipate; and esters of unsaturated monocarboxylic acids or
polycarboxylic acids with
mono(meth)allyl ester of polyols, such as allyl methacrylate or (meth)acrylic
acid ester of
polyethylene glycol monoallyl ether.
[00705] In some embodiments, the crosslinker may be one or more compound
consistent
with the following formula:
wherein:
Rl is a straight-chain or branched-chain c,¨c,0 polyalkoxy radical, optionally
substituted
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with one or more oxygen atoms in the backbone, having x valences;
each R2 is independently a c2¨C4 alkylene group;
each R3 is independently a straight-chain or branched-chain C2¨C10 alkenyl
moiety;
n is a positive integer from 1-20; and
x is a positive integer from 2-8.
[00706] An aqueous phase mixture may be prepared in another vessel (e.g., a
vessel that is
separate from that used to prepare the hydrophobic phase) that contains water.
For
example, preparation of neutralized or partially neutralized polymer, base and
monomer are
added to the water. For preparation of non-neutralized (acid form) polymer,
monomer is
added to the water without base. It will be appreciated by one of skill in the
art that the
amount of base used in the vessel is determined by the degree of
neutralization of the
monomer desired. For neutralized or partially neutralized polymer, a
degree of
neutralization between about 60% and 100% is preferred. Without wishing to be
bound by
a theory or mechanism, it is believed that one-hundred percent neutralization
minimizes the
chance of suspension failure, but the highly charged monomer may not react as
rapidly and
may not pull hydrophobic crosslinkers into the forming polymer. Considerations
in
choosing the degree of neutralization may be determined by one of skill in the
art and
include, for example, the effect of monomer charge (e.g., as determined by
ionization of the
cation from the neutralized molecules) on reaction rate, partitioning of the
monomer and
neutralized monomer between oil phase and aqueous phase and/or tendency of the
aqueous
droplets to coalesce during the reaction. The solubilities of sodium acrylate
and sodium
methacrylate in water are limited and are lower at lower temperatures (e.g.,
sodium acrylate
is soluble at about 45% at 70 C but less than 40% at 20 C). This solubility
may establish
the lower limit of the amount of water needed in the neutralization step. The
upper limit of
the amount of water may be based on reactor size, amount of oil phase needed
to reliably
suspend the aqueous phase as droplets and/or the desired amount of polymer
produced per
batch.
[00707] Bases contemplated for use in methods of making the crosslinked
polymers of the
present disclosure include, for example, hydroxides, bicarbonates, or
carbonates. Use of
these bases allows neutralization of the acid monomer without residual anions
left in the
reaction mixture as the anions react to form water or CO2. Frequently, sodium
bases are
chosen in the method of making the crosslinked polymers. However, potassium
bases,
ammonium bases, and bases of other cations, including calcium bases, are
contemplated for
use in the present disclosure.
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[00708] The water used in the reaction may be purified water or water from
other sources
such as city water or well water. If the water used is not purified water,
chelating agents
may be needed to control metals, e.g., heavy metal ions, such as iron,
calcium, and/or
magnesium from destroying the initiator. Chelating agents contemplated for use
with the
present disclosure include, for example, diethylenetriaminepentaacetic acid
pentasodium
(VersenexTM 80). The amount of chelating agent added to the reaction mixture
may be
determined by one of skill in the art from a determination of the amount of
undesirable
metal in the water.
[00709] In some instances a metal may be added to catalyze the polymerization
reaction
(e.g., iron).
[00710] Once base is added to the water, the aqueous phase solution may be
cooled to
remove the heat released from dilution of the base, and one or more classes of
monomers
may be added, to react with the base, for example, monomers which will be
neutralized by
the base. As will be appreciated by one of skill in the art, the monomers will
be neutralized
to the degree dictated by the amount of base in the reaction. The aqueous
phase solution
may be kept cool (e.g., below 35 to 40 C) and preferably around 20 C to
prevent formation
of prepolymer strands, dimers and/or possible premature polymerization.
[00711] Monomers are dissolved in water at concentrations of 10-70 wt% or 20-
40 wt%
and polymerization may subsequently be initiated by free radicals in the
aqueous phase.
Monomers may be polymerized either in the acid form or as a partially
neutralized salt. For
an inverse suspension process, monomers in the acid form may be less desirable
due to high
solubility in the oil phase. The amount of water used to dissolve the monomer
is minimally
set so that all of the monomer (e.g., sodium acrylate) is dissolved in the
water rather than
crystallizing and maximally set so that there is the smallest volume of
reaction mixture
possible (to minimize the amount of distillation and allow the maximum yield
per batch).
[00712] Exemplary monomer units contemplated for use in the present
disclosure,
include, for example, acrylic acid and its salts, methacrylic acid and its
salts, crotonic acid
and its salts, tiglinic acid and its salts, 2-methyl-2-butenoic acid (Z) and
its salts, 3-butenoic
acid (vinylacetic acid) and its salts, 1-cyclopentene carboxylic acid, and 2-
cyclopentene
carboxylic acid and their salts; and unsaturated dicarboxylic acids and their
salts, such as
maleic acid, fumaric acid, itaconic acid, glutaconic acid, and their salts.
Other cross-linked
polyelectrolyte superabsorbent polymers may be based on sulfonic acids and
their salts, or
phosphonic acids and their salts. In other non-limiting embodiments,
additional monomers
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may be contemplated for use. The additional monomers are those from which the
desired
carboxylic acid, sulfonic acid, or phosphonic acid functionality may be
derived by known
chemical reactions, for example by hydrolysis. In these embodiments, the
monomer, for
example, acrylonitrile, acrylamide, methacrylamide, lower alcohol esters of
unsaturated,
polymerizable carboxylic acids (such as those mentioned in the paragraph
above) or their
mixtures, and the like may be polymerized with a suitable crosslinker to an
intermediate
crosslinked polymer, which is then subjected to chemical reaction (so-called
"polymer
analogous reaction") to convert the functional groups of the polymer into
carboxylic
functionality. For example, ethyl acrylate may be polymerized with a non-
hydrolysis-
susceptible crosslinker (e.g. tetraallyloxyethane) to form a crosslinked
intermediate
polymer, which is then subjected to hydrolysis conditions to convert the ester
functionality
to carboxylic acid functionality by means known in the art. In another
example, acrylonitrile
is graft polymerized to starch with a crosslinker as necessary to form a
crosslinked starch-
graft intermediate polymer, which is then treated with aqueous base to
hydrolyze the nitrile
functionality to carboxylic acid functionality (see, e.g., U.S. Patent Nos.
3,935,099,
3,991,100, 3,997,484, and 4,134,863).
[00713] One or more initiators, such as free radical producers, may be added
to the
aqueous phase just before the aqueous phase is transferred into the oil phase.
As will be
appreciated by one of skill in the art, the initiator amount and type used in
the
polymerization reaction depends on oil versus water solubility and whether
longer chain
lengths are desired. For example, a lower amount of initiator may be used in
the
polymerization reaction when longer chain lengths are desired.
[00714] In some embodiments, one of the initiators may be a thermally
sensitive
compound such as a persulfate, 2,2'-azobis(2-amidino-propane)-dihydrochloride,
2,2'-
azobis (2-amidino-propane)-dihydrochloride and/or 2,2'-azobis (4-
cyanopentanoic acid).
With thermally sensitive initiators polymerization does not begin until an
elevated
temperature is reached. For persulfates, this temperature is approximately 50
to 55 C.
Since the reaction is highly exothermic, vigorous removal of the heat of
reaction is required
to prevent boiling of the aqueous phase. It is preferred that the reaction
mixture be
maintained at approximately 65 C. As will be appreciated by one of skill in
the art, thermal
initiators have the advantage of allowing control of the start of the reaction
when the
reaction mixture is adequately sparged of oxygen.
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[00715] In some embodiments, one of the initiators may be a redox pair such as
persulfate/bisulfate, p ersulfate/thio sulfate,
persulfate/ascorbate, hydrogen
peroxide/ascorbate, sulfur dioxide/tert-butylhydroperoxide,
persulfate/erythorbate, tert-
butylhydroperoxide/erythorbate and/or tert-butylperbenzoate/erythorbate. These
initiators
are able to initiate the reaction at room temperature, thereby minimizing the
chance of
heating the reaction mixture to the boiling point of the aqueous phase as heat
is removed
through the jacket around the reactor.
[00716] In some embodiments, the reaction is not started immediately after the
mixing of
the aqueous phase into the oil phase in the final reactor because the aqueous
phase still has
io an excessive amount of oxygen dissolved in the water. It will be
appreciated by one of skill
in the art that an excessive amount of oxygen may cause poor reactivity and
inadequate
mixing may prevent the establishment of uniform droplet sizes. Instead, the
final reaction
mixture is first sparged with an inert gas for ten to sixty minutes after all
reagents (except
the redox pair if that initiator system is used) have been placed in the
reactor. The reaction
may be initiated when a low oxygen content (e.g., below 15 ppm) is measured in
the inert
gas exiting the reactor.
[00717] It will be appreciated by those of skill in the art that with acrylate
and
methacrylate monomers, polymerization begins in the droplets and progresses to
a point
where coalescence of the particles becomes more likely (the "sticky phase").
It may be
necessary that a second addition of surfactant (e.g., appropriately degassed
to remove
oxygen) be added during this phase or that the agitation rate be increased.
For persulfate
thermal initiation, this sticky phase may occur at about 50 to 55 C. For
redox initiation
systems, the need for additional surfactant may be lessened by the initial
surface
polymerization, but if additional surfactant is needed, it should be added as
soon as an
exotherm is noted.
[00718] The reaction may be continued for four to six hours after the peak
exotherm is
seen to allow for maximal consumption of the monomer into the polymer.
Following the
reaction, the polymeric material may be isolated by either transferring the
entire reaction
mixture to a centrifuge or filter to remove the fluids or by initially
distilling the water and
some of the oil phase (e.g., frequently as an azeotrope) until no further
removal of water is
possible and the distillation temperature rises significantly above 100 C,
followed by
isolating the polymeric material by either centrifugation or filtering. The
isolated
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crosslinked cation-binding polymeric material is then dried to a desired
residual moisture
content (e.g., less than 5%).
[00719] An exemplary cross-linked cation-binding polymer, polyacrylate, may be
formed
by copolymerizing an ethylenically unsaturated carboxylic acid with a
multifunctional
cross-linking monomer. The acid monomer or polymer may be substantially or
partially
neutralized with an alkali metal salt such as an oxide, a hydroxide, a
carbonate, or a
bicarbonate and polymerized by the addition of an initiator. One such
exemplary polymer
gel is a copolymer of acrylic acid/sodium acrylate and any of a variety of
cross-linkers.
[00720] The reactants for the synthesis of an exemplary cross-linked cation-
binding
polymer, cross-linked polyacrylate, is provided in Table 2 below. This cross-
linked cation-
binding polymer may be produced as a one-hundred kilogram batch in a five-
hundred gallon
vessel.
Table 2: List of Components Used in the Manufacture of an Exemplary Cross-
linked
Polyacrylate Polymer
Component Function
Amount/batch
(kg)
Acrylic Acid Monomer 88
Water Solvent 90
50% Sodium Hydroxide Neutralization of acrylic 79
acid monomer
Naphtha [petroleum], hydrotreated heavy, Continuous phase for
As needed
(IsoparTM L) Suspension
Fumed silica (Aerosil R972) Suspending agent (Surfactant) 0.9
Diethylenetriaminepentaacetic Acid Control of metal ions in 0.9
Pentasodium (VersenexTM 80) reagents, solvents, or
Sodium Persulfate Polymerization initiator 0.06
Cross-linking agent 0.3
Trimethylolpropane Triacrylate, (TMPTA)
[00721] In addition to inverse (water-in-oil) suspension methods, cation-
binding polymers
may be prepared by other methods known in the art (e.g., Buchholz, F. L. and
Graham, A.
T., "Modern Superabsorbent Polymer Technology," John Wiley & Sons (1998)), for
example by aqueous one-phase methods, by precipitation polymerization (see,
e.g.,
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European Patent Application No. EP0459373A2), and by crosslinking of soluble
polymer
using monomers, crosslinkers, surfactants, initiators, neutralizing agents,
solvents,
suspending agents, and chelators as described herein. For example, cation-
binding
polymers containing carboxyl groups formed from monomers as described herein
may be
polymerized to form soluble polymer which may then be crosslinked. In some
embodiments, it may be possible to incorporate the crosslinker either into the
intermediate
polymer, or into the chemically-reacted carboxylic acid functional polymer.
For example,
crosslinker may be incorporated by copolymerization of the contemplated
monomers with a
crosslinker as described herein, and then the crosslinked polymer may be
converted by, for
io example hydrolysis, to the desired crosslinked carboxylic acid-
functional product.
Alternatively, the contemplated additional monomers may be polymerized to a
non-
crosslinked polymer, then converted to the carboxylic acid-functional polymer
and
subsequently reacted with a suitable crosslinker (for example, one of the heat-
activated
crosslinkers in the list) to provide the desired, crosslinked, carboxylic acid-
functional
polymer. Because it is difficult to thoroughly mix a small amount of
crosslinker into a high
molecular weight polymer, it is desirable to add a heat-activated crosslinker
to the
monomer-containing reaction mixture, under conditions in which the crosslinker
is inactive
toward reaction. The polymerization is accomplished in the normal way to yield
an
uncrosslinked polymer that also contains the molecularly dispersed, heat-
activated
crosslinker. When it is desired to form the crosslinks, the polymer system is
heated to a
temperature that is suitable to cause the reaction between polymer functional
groups and the
crosslinker molecules, thereby crosslinking the polymer.
2. Preparation of Crosslinked Cation-Binding Polymers with Hydrogen
Counterions
from Neutralized or Partially Neutralized Crosslinked Cation-Binding Polymers
[00722] Partially neutralized or fully neutralized crosslinked cation-binding
polymers may
be acidified by washing the polymer with acid. Suitable acids contemplated for
use with the
present disclosure, include, for example, hydrochloric acid, acetic acid and
phosphoric acid.
[00723] Those skilled in the art will recognize that the replacement of the
counterions,
including cations such as sodium atoms, by hydrogen atoms can be performed
with many
different acids and different concentrations of acid. However, care must be
taken in choice
of acid and concentration to avoid damage to the polymer or the cross-linkers.
For instance,
nitric and sulfuric acids would be avoided.
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[00724] Acid-washed crosslinked cation-binding polymers may be additionally
rinsed
with water and then dried in, for example, a vacuum oven or inert atmosphere
until, for
example, less than 5% moisture remains, to produce a substantially free acid
form of cross-
linked polyacrylic acid. Any particle form of partially or fully neutralized
cross-linked
cation-binding polymer may be used as the starting point, for example,
particles, powders,
or bead-form particles, or milled bead-form particles.
3. Preparation of Crosslinked Cation-Binding Polymers with Hydrogen
Counterions
[00725] Acid form cross-linked cation-binding polymers may be prepared by any
method
known by those skilled in the art (e.g., Buchholz, F. L. and Graham, A. T.,
"Modern
Superabsorbent Polymer Technology," John Wiley & Sons (1998)), for example by
inverse
suspension, aqueous one-phase polymerization, by precipitation polymerization
(see, e.g.,
European Patent Application No. EP0459373A2), and by crosslinking of soluble
polymer.
Any of the methods, monomers, crosslinkers, surfactants, initiators,
neutralizing agents,
solvents, suspending agents, chelators, catalysts, and other agents as
described herein may
be used.
[00726] Crosslinked cation-binding polymers may be prepared from monomers with
unneutralized carboxylic acid groups. For example, a crosslinked polyacrylate
can be
prepared from acrylic acid. A monomer solution is prepared in a reactor by
dissolving an
unsaturated carboxylic acid monomer (e.g., acrylic acid) in water. Optionally,
a chelating
agent (e.g., VersenexTM 80) may be added to control metal ions and/or a metal
added to
catalyze the polymerization reaction (e.g., iron). A suitable crosslinking
agent (e.g.,
trimethylolpropane triacrylate) is added to the reactor. The solution may be
agitated and
oxygen may be removed using nitrogen, argon or by other means known in the
art. The
temperature of the solution may be adjusted as desired. One or more
polymerization
initiators may be added to the reactor and the oxygen tension may be reduced
or the
temperature may be increased to initiate polymerization. The reaction is
allowed to proceed
through the exothermic heating that occurs during reaction. Reaction heat can
be removed
and/or controlled as desired by methods known to those skilled in the art. The
reaction
vessel may then be heated and oxygen tension in the reaction vessel may be
kept low to
continue the polymerization to low levels of residual monomer. Once the
reaction is
completed, the polymerization reaction product can be removed from the reactor
and the
wet polymer may be reduced in size (e.g. by cutting or by methods known to
those skilled in
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the art) into pieces of appropriate size for drying. The polymer pieces can
then be dried in a
vacuum oven or other equipment known to those skilled in the art. Conditions
during
drying may be adjusted (e.g. humidity level, rate of drying) so that
polymerization and
reduction of residual monomer continues during the drying process. After
drying, the
particles can be separated by size and/or milled and/or sieved to produce the
desired particle
size. Other examples of the polymerization of aqueous acrylic acid solutions
with
crosslinkers are disclosed in Buchholz, F. L. and Graham, A. T., "Modern
Superabsorbent
Polymer Technology," John Wiley & Sons (1998), U.S. Patent No. 4,654,039; U.S.
Patent
No. 4,295,987; U.S. Patent No. 5,145,906; and U.S. Patent No. 4,861,849, the
contents of
which are incorporated herein by reference.
4. Preparation of Crosslinked Cation-Binding Polymers with Calcium and/or
Magnesium Counterions
[00727] Crosslinked, cation-binding polymers with calcium and/or magnesium
ions may
be prepared by ion-exchange from a partially neutralized crosslinked, cation-
binding
polymer, by the addition of a calcium and/or magnesium base to an acid form of
a
crosslinked, cation-binding polymer, by using a calcium or magnesium base to
neutralize
acrylic acid prior to polymerization, or by other methods known by those
skilled in the art.
Any particle form of partially or fully neutralized cross-linked cation-
binding polymer may
be used as the starting point, for example, particles, powders, or bead-form
particles, or
milled bead-form particles.
[00728] Partially neutralized crosslinked cation-binding polymers (e.g. sodium
acrylate)
may be hydrated and equilibrated with several washes of a salt solution of
calcium and/or
magnesium (e.g. CaC12, MgC12) of a concentration high enough to exchange the
original
counterions on the polymer with the calcium and/or magnesium cations and
remove the
original counterions from the solution. For polymer more highly neutralized
than the desired
calcium or magnesium polymer, an appropriate amount of acid may be added with
the
calcium and/or magnesium salt to bring the neutralization level down to the
desired level.
Those skilled in the art will recognize that the replacement of the
counterions (ion-
exchange), including cations such as sodium atoms, by calcium and/or magnesium
cations
can be performed with many different calcium and/or magnesium salts and salt
concentrations. The calcium and/or magnesium crosslinked cation-binding
polymers may
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be additionally rinsed with water and then dried in, for example, a vacuum
oven or inert
atmosphere until, for example, less than 5% moisture remains.
[00729] Crosslinked cation-binding polymers with calcium and/or magnesium
counterions
may be produced from the acid form of the polymer through the addition of a
calcium
and/or magnesium base (e.g, CaCO3, MgO). The base may be added to the polymer
as a
solid or solution and the polymer may be hydrated prior to addition of the
base. The
polymer and base may be stirred and/or heated to facilitate neutralization of
the polymer
with the base. The calcium and/or magnesium crosslinked cation-binding
polymers may be
additionally rinsed with water and then dried in, for example, a vacuum oven
or inert
atmosphere until, for example, less than 5% moisture remains.
[00730] Crosslinked cation-binding polymers with calcium and magnesium
counterions
may be prepared from monomers with unneutralized carboxylic acid groups (acid
form) and
a calcium or magnesium base. A solution of the calcium or magnesium base is
prepared by
adding the appropriate base slowly to water (e.g. CaCO3, MgO). Cooling may be
used to
control the solution temperature. The monomer solution is then prepared in a
reactor by
adding the monomer (e.g., acrylic acid), water and the base solution and then
stirring.
Alternatively, the solid base can be added to the reactor with the monomer and
water. Care
should be taken to ensure that the base does not precipitate. Optionally, a
chelating agent
(e.g., VersenexTM 80) may be added to control metal ions and/or a metal added
to catalyze
the polymerization reaction (e.g., iron). A
suitable crosslinking agent (e.g.,
trimethylolpropane triacrylate) is added to the reactor and the mixture
stirred. Oxygen may
be removed using a nitrogen or argon sparge, or by other means known in the
art. The
temperature of the solution may be adjusted. One or more polymerization
initiators (e.g.
sodium persulfate) are added to the reactor and the reaction mixture is
bubbled with an inert
gas (e.g., nitrogen) and agitated until adequate removal of oxygen is
achieved. The reaction
is then initiated either by reaching an oxygen concentration where a redox
couple (e.g.,
tertiary butylhydroperoxide/thiosulfate, or hydrogen peroxide/erythorbic acid)
produces
enough radicals that are not quenched by oxygen, or by adding heat to cause a
temperature
dependent initiator (e.g., sodium persulfate) to produce radicals. The
reaction is allowed to
proceed through the exothermic heating that occurs during reaction. Reaction
heat can be
removed and/or controlled as desired by methods known to those skilled in the
art. The
reaction vessel may then be heated and oxygen tension in the reaction vessel
may be kept
low to continue the polymerization to low levels of residual monomer. Once the
reaction is
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completed, the polymerization reaction product can be removed from the reactor
and the
wet polymer may be reduced in size (e.g. by cutting or by methods known to
those skilled in
the art) into pieces of appropriate size for drying. The polymer pieces can
then be dried in a
vacuum oven or other equipment known to those skilled in the art. Conditions
during
drying may be adjusted (e.g. humidity level, rate of drying) so that
polymerization and
reduction of residual monomer continues during the drying process. After
drying, the
particles can be separated by size and/or milled and/or sieved to produce the
desired particle
size.
[00731] Exemplary crosslinked cation-binding polymers, including for example
those
prepared according to Examples 1-4, generally have a pH 7 buffered saline
holding
capacity of about 20 g/g or greater, including, for example, greater than
about 40 g/g as
described in Examples 5 and 6; and contain less than about 5,000 ppm of
sodium, less than
about 20 ppm of heavy metals, less than about 1000 ppm (e.g., less than about
500 ppm) of
residual monomer, less than about 2,000 ppm of residual chloride, and less
than about 20 wt
% of soluble polymer. Preferably, acidified polymers useful as crosslinked
cation-binding
polymers prepared according to this disclosure have a saline holding capacity
of preferably
greater than about 40 g/g, (e.g., 80 g/g) contain less than about 500 ppm of
sodium, less
than about 20 ppm of heavy metals, less than about 500 ppm of residual
monomer, less than
about 1,500 ppm of residual chloride, and less than about 10 wt.% of soluble
polymer.
[00732] Crosslinked cation-binding polymers prepared, for example, according
to the
method of Example 1 or 2 using acrylic acid monomers, followed by
acidification as
described in Example 3, or crosslinked cation-binding polymers prepared, for
example, as
described in Example 4, are referred to as "H-CLP" or "HCLP" in Examples 7 to
15.
[00733] The polymer particles may be reduced in size by milling or grinding or
other
means known to those skilled in the art. Particles of certain size ranges or a
particle size
distribution may be obtained by means known to those of skill in the art, for
example, by
sieving through sieves or screens. Seives may be stacked vertically starting
with the
smallest pore size at the bottom (largest mesh size) to largest pore size at
the top (smallest
mesh size). The material is placed on top of the screen and the screens are
shaken to allow
particles to pass through screens until they are caught on a screen smaller
than diameter.
The material on each screen will then be smaller than the screen above, but
larger than the
screen below. For example, particles that pass through an 18 Mesh screen and
are caught on
a 20 Mesh screen are between 850 and 1000 microns in diameter. Screen mesh and
the
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corresponding maximum particle size allowed to pass through the mesh include,
18 mesh,
1000 microns; 20 mesh, 850 microns; 25 mesh, 710 microns; 30 mesh, 600
microns; 35
mesh, 500 microns, 40 mesh, 425 microns; 45 mesh, 35 microns; 50 mesh, 300
microns; 60
mesh, 250 microns; 70 mesh, 212 microns; 80 mesh, 180 microns; 100 mesh, 150
microns;
120 mesh, 125 microns; 140 mesh, 106 microns; 170 mesh, 90 microns; 200 mesh,
75
microns; 230 mesh, 63 microns; and 270 mesh, 53 microns. Thus particles of
varying sizes
may be obtained through the use of one or more screens.
[00734] The particle size range may be characterized, for example, by sieves
or screens,
a particle size distribution determined, for example, by laser light
diffraction, by an average
size, or other measures. A particles size distribution for material passing
through a 35 mesh
(500 um) screen but captured on a 70 mesh (210 um) screen may be characterized
as the
weight % of the polymer greater than 500 um, the fraction between 210 to 500
um, and the
fraction below 210 um. In an exemplary polymer fraction collected using 35 and
70 mesh
screens, the fraction between 210-500um would preferably be greater than 70%.
The
particle size distribution can also be characterized by describing particle
diameters where
10% (D0.1), 50% (D0.5), or 90% (D0.9) of the particles are smaller than that
particle size.
Pharmaceutical Compositions and Dosage Forms
[00735] Pharmaceutical compositions are disclosed comprising a cross-linked
cation-
binding polymer (e.g., a cross-linked polyacrylic acid polymer). These
compositions may
be delivered to a subject, including using a wide variety of routes or modes
of
administration. Preferred routes for administration are oral or intestinal.
[00736] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, comprise a crosslinked cation-
binding
polymer comprising: monomers that comprise carboxylic acid groups, wherein
said polymer
is crosslinked with about 0.08 mol.% to about 0.2 mol.% of crosslinker or
alternatively from
about 0.025 mol.% to about 3.0 mol% including, for example, from about 0.025
mol.% to
about 0.3 mol.% or from about 0.025 mol.% to about 0.17 mol.% or from about
0.025
mol.% to about 0.34 mol.%; and a base (e.g., calcium carbonate), wherein said
monomers
are acrylic acid or salts thereof, wherein the polymer contains less than
about 20,000 ppm
of non-hydrogen cationsõ and wherein the base is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of base (e.g.,
0.2 to 0.95
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equivalents, 0.2 to 0.9 equivalents, 0.2 to 0.85 equivalents, 0.2 to 0.8
equivalents, 0.2 to
0.75 equivalents, 0.2 to 0.7 equivalents, 0.2 to 0.65 equivalents, 0.2 to 0.6
equivalents,
0.2 to 0.55 equivalents, 0.2 to 0.5 equivalents, 0.2 to 0.45 equivalents, 0.2
to 0.4
equivalents, 0.2 to 0.35 equivalents, 0.2 to 0.3 equivalents, or 0.2 to 0.25
equivalents of
base) per equivalent of carboxylic acid groups in the polymer. In some
embodiments, the
composition includes from about 0.5 equivalents to 0.85 equivalents of base
per equivalent
of carboxylic acid groups in the polymer. In some embodiments, the composition
includes
from about 0.7 equivalents to 0.8 equivalents of base per equivalent of
carboxylic acid
groups in the polymer. In some embodiments, the composition includes about
0.75
equivalents of base per equivalent of carboxylic acid groups in the polymer.
In some
embodiments, the composition includes from about 0.2 equivalents to 0.35
equivalents of
base per equivalent of carboxylic acid groups in the polymer. In some
embodiments, the
composition includes from about 0.2 equivalents to 0.3 equivalents of base per
equivalent of
carboxylic acid groups in the polymer. In some embodiments, the composition
includes
about 0.25 equivalents of base per equivalent of carboxylic acid groups in the
polymer.
[00737] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, comprise a crosslinked cation-
binding
polymer comprising: monomers that comprise carboxylic acid groups, wherein
said polymer
is crosslinked with about 0.08 mol.% to about 0.2 mol.% of crosslinker or
alternatively from
about 0.025 mol.% to about 3.0 mol% including, for example, from about 0.025
mol.% to
about 0.3 mol.% or from about 0.025 mol.% to about 0.17 mol.% or from about
0.025
mol.% to about 0.34 mol.%, and a base (e.g., calcium carbonate), wherein said
monomers
are acrylic acid or salts thereof, wherein the polymer contains less than
about 50,000 ppm
of non-hydrogen cations, and wherein the base is present in an amount
sufficient to provide
from about 0.2 equivalents to about 0.95 equivalents of base (e.g., 0.2 to
0.95 equivalents,
0.2 to 0.9 equivalents, 0.2 to 0.85 equivalents, 0.2 to 0.8 equivalents, 0.2
to 0.75
equivalents, 0.2 to 0.7 equivalents, 0.2 to 0.65 equivalents, 0.2 to 0.6
equivalents, 0.2 to
0.55 equivalents, 0.2 to 0.5 equivalents, 0.2 to 0.45 equivalents, 0.2 to 0.4
equivalents,
0.2 to 0.35 equivalents, 0.2 to 0.3 equivalents, or 0.2 to 0.25 equivalents of
base) per
equivalent of carboxylic acid groups in the polymer. In some embodiments, the
composition
includes from about 0.5 equivalents to 0.85 equivalents of base per equivalent
of carboxylic
acid groups in the polymer. In some embodiments, the composition includes from
about 0.7
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equivalents to 0.8 equivalents of base per equivalent of carboxylic acid
groups in the
polymer. In some embodiments, the composition includes about 0.75 equivalents
of base
per equivalent of carboxylic acid groups in the polymer. In some embodiments,
the
composition includes from about 0.2 equivalents to 0.35 equivalents of base
per equivalent
of carboxylic acid groups in the polymer. In some embodiments, the composition
includes
from about 0.2 equivalents to 0.3 equivalents of base per equivalent of
carboxylic acid
groups in the polymer. In some embodiments, the composition includes about
0.25
equivalents of base per equivalent of carboxylic acid groups in the polymer.
[00738] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, comprise a crosslinked cation-
binding
polymer comprising monomers comprising carboxylic acid groups, and a base,
wherein no
less than about 70% of the polymer has a particle size of about 212 microns to
about 500
microns, wherein said monomers are acrylic acid or salts thereof, wherein the
polymer
comprises less than about 20,000 ppm of non-hydrogen cations, and wherein said
base is
present in an amount sufficient to provide from about 0.2 equivalents to about
0.95
equivalents of base per equivalent of carboxylic acid groups in said polymer.
In some
embodiments, at least one non-hydrogen cation is present in an amount of at
least about
5,000 ppm.
[00739] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, comprise a crosslinked cation-
binding
polymer comprising monomers comprising carboxylic acid groups, and a base,
wherein no
less than about 70% of the polymer has a particle size of about 212 microns to
about 500
microns, wherein said monomers are acrylic acid or salts thereof, wherein the
polymer
comprises less than about 50,000 ppm of non-hydrogen cations, and wherein said
base is
present in an amount sufficient to provide from about 0.2 equivalents to about
0.95
equivalents of base per equivalent of carboxylic acid groups in said polymer.
In some
embodiments, at least one non-hydrogen cation is present in an amount of at
least about
5,000 ppm.
[00740] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, comprise a crosslinked cation-
binding
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polymer comprising monomers comprising carboxylic acid groups, and a base,
wherein no
less than about 70% of said polymer has a particle size of 75 microns or less,
wherein the
monomers are acrylic acid or salts thereof, wherein the polymer comprises less
than about
20,000 ppm of non-hydrogen cations, wherein said base is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of base per
equivalent of
carboxylic acid groups in said polymer. In some embodiments, at least one non-
hydrogen
cation is present in an amount of at least about 5,000 ppm.
[00741] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
io use in methods of treatment disclosed herein, comprise a crosslinked
cation-binding
polymer comprising monomers comprising carboxylic acid groups, and a base,
wherein no
less than about 70% of said polymer has a particle size of 75 microns or less,
wherein the
monomers are acrylic acid or salts thereof, wherein the polymer comprises less
than about
50,000 ppm of non-hydrogen cations, wherein said base is present in an amount
sufficient to
provide from about 0.2 equivalents to about 0.95 equivalents of base per
equivalent of
carboxylic acid groups in said polymer. In some embodiments, at least one non-
hydrogen
cation is present in an amount of at least about 5,000 ppm.
[00742] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, comprise polycarbophil, and a
base, wherein
wherein the polymer comprises less than about 20,000 ppm of non-hydrogen
cations, and
wherein said base is not sodium bicarbonate and is present in an amount
sufficient to
provide about 0.2 to 0.95 equivalents of base per equivalent of carboxylic
acid groups in
said polycarbophil. In some embodiments, at least one non-hydrogen cation is
present in an
amount of at least about 5,000 ppm.
[00743] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, comprise polycarbophil, and a
base, wherein
wherein the polymer comprises less than about 50,000 ppm of non-hydrogen
cations, and
wherein said base is not sodium bicarbonate and is present in an amount
sufficient to
provide about 0.2 to 0.95 equivalents of base per equivalent of carboxylic
acid groups in
said polycarbophil. In some embodiments, at least one non-hydrogen cation is
present in an
amount of at least about 5,000 ppm.
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[00744] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, comprise a crosslinked cation-
binding
polymer comprising a crosslinker and monomers that comprise carboxylic acid
groups, and
a base, wherein said monomers are acrylic acid or salts thereof, wherein the
polymer
comprises less than about 20,000 ppm of non-hydrogen cations, and wherein said
base is
present in an amount sufficient to provide from about 0.2 equivalents to about
0.95
equivalents of base per equivalent of carboxylic acid groups in said polymer.
In some
embodiments, at least one non-hydrogen cation is present in an amount of at
least about
5,000 ppm.
[00745] In some embodiments, the polymers disclosed herein for inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, comprise a crosslinked cation-
binding
polymer comprising a crosslinker and monomers that comprise carboxylic acid
groups, and
a base, wherein said monomers are acrylic acid or salts thereof, wherein the
polymer
comprises less than about 50,000 ppm of non-hydrogen cations, and wherein said
base is
present in an amount sufficient to provide from about 0.2 equivalents to about
0.95
equivalents of base per equivalent of carboxylic acid groups in said polymer.
In some
embodiments, at least one non-hydrogen cation is present in an amount of at
least about
5,000 ppm.
[00746] In some embodiments, the dosage form comprises a crosslinked cation-
binding
polymer comprising repeat units containing carboxylic acid groups, and a base,
wherein less
than 1% of carboxylic acid groups are neutralized by non-hydrogen cations; and
said base is
present in an amount sufficient to provide from about 0.2 equivalents to about
0.95
equivalents of base per equivalent of carboxylic acid groups in the polymer
(e.g., moles of
carboxylic acid groups in the polymer). In a related example the dosage form
contains
about 0.2 equivalents, about 0.25 equivalents, about 0.3 equivalents, about
0.35 equivalents,
about 0.4 equivalents, about 0.45 equivalents, about 0.5 equivalents, about
0.55 equivalents,
about 0.6 equivalents, about 0.65 equivalents, about 0.7 equivalents, about
0.75 equivalents,
about 0.8 equivalents, about 0.85 equivalents, about 0.9 equivalents, or about
0.95
equivalents of base per equivalent of carboxylic acid groups in the polymer.
In some
embodiments, hydrogen cations, i.e., protons (H), are bound to at least 98%,
at least 98.1%,
at least 98.2%, at least 98.3%, at least 98.4%, at least 98.5%, at least
98.6%, at least 98.7%,
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at least 98.8%, at least 98.9%, at least 99%, at least 99.1%, at least 99.2%,
at least 99.3%, at
least 99.4%, at least 99.5%, at least 99.6%, at least 99.7%, at least 99.8%,
or at least 99.9%
of the carboxylate groups in the polymer. In some embodiments, less than 5%,
less than
4%, less than 3%, less than 2%, less than 1%, less than 0.5%, less than 0.4%,
less than
0.3%, less than 0.2%, or less than 0.1% of the carboxylate groups of the
polymer are bound
to cations other than hydrogen (e.g., non-hydrogen cations), such as sodium,
potassium,
calcium, magnesium, choline, etc.
[00556] In some embodiments, the polymers disclosed herein for
inclusion in a
composition, formulation, or dosage form, e.g., for administration to an
individual, e.g., for
use in methods of treatment disclosed herein, are individual particles or
particles
agglomerated to form a larger particle (for example, flocculated particles),
and have a
diameter of about 1 to about 10,000 microns (alternatively, about 1 micron to
about 50
microns, about 10 microns to about 50 microns, about 10 microns to about 200
microns,
about 50 microns to about 100 microns, about 50 microns to about 200 microns,
about 50
microns to about 1000 microns, about 500 microns to about 1000 microns, about
1000 to
about 5000 microns, or about 5000 microns to about 10,000 microns). In some
embodiments, the particles or agglomerated particles have a diameter of about
1, about 5,
about 10, about 20, about 30, about 40, about 50, about 60, about 70, about
80, about 90,
about 100, about 110, about 120, about 130, about 140, about 150, about 160,
about 170,
about 180, about 190, about 200, about 250, about 300, about 350, about 400,
about 450,
about 500, about 550, about 600, about 650, about 700, about 750, about 800,
about 850,
about 900, about 950, about 1000 , about 1500, about 2000, about 2500, about
3000, about
3500, about 4000, about 4500, about 5000, about 5500, about 6000, about 7000,
about
7500, about 8000, about 8500, about 9000, about 9500, or about 10,000 microns.
[00557] In some embodiments, the crosslinked cation-binding polymer
disclosed
herein for inclusion in a composition, formulation, or dosage form, e.g., for
administration
to an individual, e.g., for use in methods of treatment disclosed herein is a
crosslinked
polyacrylate polymer. For example, the polymer may be a polyacrylate polymer
crosslinked with about 0.08 mol% to about 0.2 mol% or alternatively from about
0.025
mol.% to about 3.0 mol.% including, for example, from about 0.025 mol.% to
about 0.3
mol.% or about 0.025 mol.% to about 0.17 mol.% or from about 0.025 mol.% to
about 0.34
mol.% crosslinker, and for example, may comprise an in vitro saline absorption
capacity
(e.g., saline holding capacity) of at least about 20 times its weight (e.g.,
at least about 20
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grams of saline per gram of polymer, or "g/g"), at least about 30 times its
weight, at least
about 40 times its weight, at least about 50 times its weight, at least about
60 times its
weight, at least about 70 times its weight, at least about 80 times its
weight, at least about 90
times its weight, at least about 100 times its weight, or more. In some
embodiments, the
crosslinked polyacrylate polymer is in the form of individual particles or
particles that are
agglomerated (for example, flocculated) to form a larger particle, wherein the
diameter of
individual particles or agglomerated particles is about 1 micron to about
10,000 microns
(alternatively, about 1 micron to about 10 microns, about 1 micron to about 50
microns,
about 10 microns to about 50 microns, about 10 microns to about 200 microns,
about 50
microns to about 100 microns, about 50 microns to about 200 microns, about 50
microns to
about 1000 microns, about 500 microns to about 1000 microns, about 1000 to
about 5000
microns, or about 5000 microns to about 10,000 microns. In one embodiment, the
polyacrylate polymer is in the form of small particles that flocculate to form
agglomerated
particles with a diameter of about 1 micron to about 10 microns.
[00558] In some
embodiments, the above dosage forms additionally comprise one or
more excipients, carriers, or diluents. Compositions for use in accordance
with the present
disclosure may be formulated in conventional manner using one or more
physiologically
acceptable carriers comprising excipients, diluents, and auxiliaries which
facilitate
processing of the polymer into preparations which may be used
pharmaceutically. Proper
formulation is dependent upon the route of administration chosen. Such
compositions may
contain a therapeutically effective amount of polymer and may include a
pharmaceutically
acceptable carrier, excipient, and/or diluent.
Pharmaceutically acceptable carriers,
additives, and formulation ingredients include those approved by a regulatory
agency of the
Federal or a state government or listed in the U.S. Pharmacopeia or other
generally
recognized pharmacopeia for use in animals, and more particularly, in humans.
Carriers can
include an active ingredient in which the disclosed compositions are
administered.
[00559]
In some embodiments, dosage forms according to the present disclosure
comprise a crosslinked cation-binding polymer comprising carboxylic acid
monomers, and
a base. In related embodiments, the compositions contain less than about
20,000 ppm of
non-hydrogen cations. In some embodiments, the dosage form comprises an amount
of the
base sufficient to provide from about 0.2 to about 0.95 equivalents of base
per equivalent of
carboxylic acid groups on the polymer. In some embodiments, the dosage form
includes an
amount of base sufficient to ameliorate or prevent acidosis in a subject to
whom the
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polymer is administered. Monomers, crosslinkers, and bases useful in the
preparation of the
crosslinked cation-binding polymers as described above are also suitable for
the dosage
forms of the present disclosure.
[00560] In some embodiments, the dosage form is a capsule, a tablet,
a chewable
tablet, a suspension, an oral suspension, a powder, a gel block, a gel pack, a
confection, a
chocolate bar, a pudding, a flavored bar, or a sachet. In some embodiments,
the dosage
form contains about 0.25 g, 0.5 g, or 1 g to about 7.5 g, 15 g, 30 g, or about
100 g of a
disclosed cation-binding polymer. For example and without limitation, the
composition,
formulation, or dosage form may include about 0.25 g, about 0.5 g, about 1 g,
about 1.5 g,
about 2 g, about 2.5 g, about 3 g, about 3.5 g, about 4 g, about 4.5 g, about
5 g, about 5.5 g,
about 6 g, about 6.5 g, about 7 g, about 7.5 g, about 8 g, about 8.5 g, about
9 g, about 9.5 g,
about 10 g, about 11 g, about 12 g, about 13 g, about 14 g, about 15 g, about
16 g, about 17
g, about 18 g, about 19 g, about 20 g, about 21 g, about 22 g, about 23 g,
about 24 g, about
25 g, about 26 g, about 27 g, about 28 g, about 29 g, about 30 g, about 35 g,
about 40 g,
about 45 g, about 50 g, about 55 g, about 60 g, about 65 g, about 70 g, about
75 g, about 80
g, about 85 g, about 90 g, about 95 g, or about 100 g, or more of the cation-
binding
polymer. For example and without limitation, the dosage form may include an
amount of
the composition to provide about 1 g, about 1.5 g, about 2 g, about 2.5 g,
about 3 g, about
3.5 g, about 4 g, about 4.5 g, about 5 g, about 5.5 g, about 6 g, about 6.5 g,
about 7 g, about
7.5 g, about 8 g, about 8.5 g, about 9 g, about 9.5 g, about 10 g, about 11 g,
about 12 g,
about 13 g, about 14 g, about 15 g, about 16 g, about 17 g, about 18 g, about
19 g, about
20 g, about 21 g, about 22 g, about 23 g, about 24 g, about 25 g, about 26 g,
about 27 g,
about 28 g, about 29 g, or about 30 g, about 35 g, about 40 g, about 45 g,
about 50 g, about
55 g, about 60 g, about 65 g, about 70 g, about 75 g, about 80 g, about 85 g,
about 90 g,
about 95 g, or about 100 g, or more of the cation-binding polymer. Regardless
of the
amount of polymer present in the dosage form, the dosage forms of the present
disclosure
also include from about 0.2 to about 0.95, about 0.5 to about 0.9, or about
0.6 to about 0.8
equivalents of base per equivalent of carboxylate groups in the polymer, for
example, about
0.2 equivalents, about 0.25 equivalents, about 0.3 equivalents, about 0.35
equivalents, about
0.4 equivalents, about 0.45 equivalents, about 0.5 equivalents, about 0.55
equivalents, about
0.6 equivalents, about 0.65 equivalents, about 0.7 equivalents, about 0.75
equivalents, about
0.8 equivalents, about 0.85 equivalents, about 0.9 equivalents, or about 0.95
equivalents of
base per equivalent of carboxylic acid groups in the polymer. In some
embodiments, the
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base is present in an amount sufficient to provide from about 0.5 equivalents
to about 0.85
equivalents of base, for example about 0.5 equivalents, about 0.55
equivalents, about 0.6
equivalents, about 0.65 equivalents, about 0.7 equivalents, about 0.75
equivalents, about 0.8
equivalents, or about 0.85 equivalents of base per equivalent of carboxylate
groups in the
polymer. In other embodiments, the base is present in an amount sufficient to
provide from
about 0.7 equivalents to about 0.8 equivalents of base, for example about 0.7
equivalents,
about 0.75 equivalents, about or 0.8 equivalents of base per equivalent of
carboxylate
groups in the polymer. In some embodiments, the base is present in an amount
sufficient to
provide about 0.75 equivalents of base per equivalent of carboxylate groups in
the polymer.
[00561] In some embodiments, the base component of the dosage form is one
or more
of: an alkali metal hydroxide, an alkali metal acetate, an alkali metal
carbonate, an alkali
metal bicarbonate, an alkali metal oxide, an alkali earth metal hydroxide, an
alkali earth
metal acetate, an alkali earth metal carbonate, an alkali earth metal
bicarbonate, an alkali
earth metal oxide, an organic base, choline, lysine, arginine, histidine, an
acetate, a butyrate,
a propionate, a lactate, a succinate, a citrate, an isocitrate, a fumarate, a
malate, a malonate,
an oxaloacetate, a pyruvate, a phosphate, a carbonate, a bicarbonate, a
lactate, a benzoate, a
sulfate, a lactate, a silicate, an oxide, an oxalate, a hydroxide, an amine, a
dihydrogen
citrate, calcium bicarbonate, calcium carbonate, calcium oxide, calcium
hydroxide,
magnesium oxide, magnesium carbonate, magnesium hydrochloride, sodium
bicarbonate,
and potassium citrate, or a combination thereof
[00562] For oral administration, the disclosed compositions may be
formulated readily
by combining them with pharmaceutically acceptable carriers well known in the
art. Such
carriers enable the compositions of the disclosure to be formulated,
preferably in capsules
but alternatively in other dosage forms such as tablets, chewable tablets,
pills, dragees,
capsules, liquids, gel packs, gel blocks, syrups, slurries, suspensions,
wafers, sachets,
powders, dissolving tablets and the like, for oral ingestion by a subject,
including a subject
to be treated. In some embodiments, the compositions or capsules containing
the
compositions have an enteric coating. In other embodiments, the compositions
or capsules
containing the compositions, do not have an enteric coating.
[00563] In some embodiments, the dosage form comprises a base and an
unneutralized
crosslinked polycarboxylate polymer as described herein, and is administered
in an amount
sufficient to provide from about 0.01 moles of carboxylate groups to about 0.5
moles or
about 0.56 moles of carboxylate groups to the subject per day, for example,
about 0.01
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moles, about 0.02 moles, about 0.03 moles, about 0.04 moles, about 0.05 moles,
about 0.06
moles, about 0.07 moles, about 0.08 moles, about 0.09 moles, about 0.1 moles,
about 0.11
moles, about 0.12 moles, about 0.13 moles, about 0.14 moles, about 0.15 moles,
about 0.16
moles, about 0.17 moles, about 0.18 moles, about 0.19 moles, about 0.2 moles,
about 0.21
moles, about 0.22 moles, about 0.23 moles, about 0.24 moles, about 0.25 moles,
about 0.26
moles, about 0.27 moles, about 0.28 moles, about 0.29 moles, about 0.3 moles,
about 0.31
moles, about 0.32 moles, about 0.33 moles, about 0.34 moles, about 0.35 moles,
about 0.36
moles, about 0.37 moles, about 0.38 moles, about 0.39 moles, about 0.4 moles,
about 0.41
moles, about 0.42 moles, about 0.43 moles, about 0.44 moles, about 0.45 moles,
about 0.46
moles, about 0.47 moles, about 0.48 moles, about 0.49 moles, or about 0.5
moles of
carboxylate groups to the subject per day. In a preferred embodiment, the
dosage forms are
administered in an amount sufficient to provide from about 0.01 to about 0.25
moles of
carboxylate groups per day. In a more preferred embodiment, the dosage forms
are
administered in an amount sufficient to provide from about 0.1 to about 0.25
moles of
carboxylate groups per day.
[00564] In some embodiments, the dosage form comprises a base and an
unneutralized
crosslinked polyacrylate polymer as described herein, and is administered in
an amount
sufficient to provide from about 1 g to about 30 g or 100 g of polymer per
day, for example,
about 1 g per day, about 2 g per day, about 3 g per day, about 4 g per day,
about 5 g per day,
about 6 g per day, about 7 g per day, about 8 g per day, about 9 g per day,
about 10 g per
day, about 11 g per day, about 12 g per day, about 13 g per day, about 14 g
per day, about
15 g per day, about 16 g per day, about 17 g per day, about 18 g per day,
about 19 g per day,
about 20 g per day, about 21 g per day, about 22 g per day, about 23 g per
day, about 24 g
per day, about 25 g per day, about 26 g per day, about 27 g per day, about 28
g per day,
about 29 g per day, or about 30 g per day, about 35 g per day, about 40 g per
day, about 45
g per day, about 50 g per day, about 55 g per day, about 60 g per day, about
65 g per day,
about 70 g per day, about 75 g per day, about 80 g per day, about 85 g per
day, about 90 g
per day, about 95 g per day, or about 100 g of polymer per day or more.
[00565] In some embodiments, the dosage form is a sachet and
contains a composition
according to the present disclosure in sufficient amount to provide from about
1 g to about
30 g of the polymer. For example, a sachet may contain a composition according
to the
present disclosure in sufficient amount to provide about 1 g, about 1.5 g,
about 2 g, about
2.5 g, about 3 g, about 3.5 g, about 4 g, about 4.5 g, about 5 g, about 5.5 g,
about 6 g, about
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6.5 g, about 7 g, about 7.5 g, about 8 g, about 8.5 g, about 9 g, about 9.5 g,
about 10 g,
about 10.5 g, about 11 g, about 11.5 g, about 12 g, about 12.5 g, about 13 g,
about 13.5 g,
about 14 g, about 14.5 g, about 15 g, about 15.5 g, about 16 g, about 16.5 g,
about 17 g,
about 17.5 g, about 18 g, about 18.5 g, about 19 g, about 19.5 g, about 20 g,
about 20.5 g,
about 21 g, about 21.5 g, about 22 g, about 22.5 g, about 23 g, about 23.5 g,
about 24 g,
about 24.5 g, about 25 g, about 25.5 g, about 26 g, about 26.5 g, about 27 g,
about 27.5 g,
about 28 g, about 28.5 g, about 29 g, about 29.5 g, or about 30 g of polymer.
[00566] In some embodiments, the dosage form is a capsule containing
an amount of a
composition according to the present disclosure sufficient to provide from
about 0.1 g to
about 1 g of the polymer. For example, a capsule may contain an amount of a
composition
according to the present disclosure that is sufficient to provide about 0.1 g,
about 0.15 g,
about 0.2 g, about 0.25 g, about 0.3 g, about 0.35 g, about 0.4 g, about 0.45
g, about 0.5 g,
about 0.55 g, about 0.6 g, about 0.65 g, about 0.7 g, about 0.75 g, about 0.8
g, about 0.85 g,
about 0.9 g, about 0.95 g, or about 1 g of polymer.
[00567] In some embodiments, the dosage form is a tablet that contains an
amount of a
composition according to the present disclosure to provide from about 0.3 g to
about 1 g of
the polymer. For example, the tablet may contain about 0.3 g, about 0.35 g,
about 0.4 g,
about 0.45 g, about 0.5 g, about 0.55 g, about 0.6 g, about 0.65 g, about 0.7
g, about 0.75 g,
about 0.8 g, about 0.85 g, about 0.9 g, about 0.95 g, or about 1 g of polymer.
In some
embodiments, a disclosed composition is formulated as a tablet that is
spherical or
substantially spherical.
[00568] In some embodiments, the dosage form is a sachet, flavored
bar, gel block, gel
pack, pudding, or powder that contains an amount of a composition according to
the present
disclosure to provide from about lg or about 2 g to about 30 g of the polymer.
For example,
the sachet, flavored bar, gel block, gel pack, pudding, or powder may contain
an amount of
a composition according to the present disclosure to provide about 2 g, about
3 g, about 4 g,
about 5 g, about 6 g, about 7 g, about 8 g, about 9 g, about 10 g, about 11 g,
about 12 g,
about 13 g, about 14 g, about 15 g, about 16 g, about 17 g, about 18 g, about
19 g, about
20 g, about 21 g, about 22 g, about 23 g, about 24 g, about 25 g, about 26 g,
about 27 g,
about 28 g, about 29 g, or about 30 g of the polymer.
[00569] In some embodiments, the dosage form is a suspension or an
oral suspension
that contains an amount of a composition according to the present disclosure
to provide
from about lg or about 2 g to about 30 g of the polymer. For example, the
suspension or
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oral suspension may contain an amount of a composition according to the
present disclosure
to provide about 2 g, about 3 g, about 4 g, about 5 g, about 6 g, about 7 g,
about 8 g, about
9 g, about 10 g, about 11 g, about 12 g, about 13 g, about 14 g, about 15 g,
about 16 g,
about 17 g, about 18 g, about 19 g, about 20 g, about 21 g, about 22 g, about
23 g, about
24 g, about 25 g, about 26 g, about 27 g, about 28 g, about 29 g, or about 30
g of the
polymer.
[00570] In some embodiments, dosage forms according to the present
disclosure
further include an additional agent. In related embodiments, the additional
agent is one that
causes, routinely causes, typically causes, is known to cause, or is suspected
of causing an
increase in an ion level in at least some subjects upon administration. For
example and
without limitation, the additional agent may be an agent known to cause an
increase in
serum potassium levels in at least some subjects upon administration. For
example and
without limitation, the additional agent may be an agent known to cause an
increase in
serum sodium levels in at least some subjects upon administration. In related
embodiments,
the additional agent may be one or more of: a tertiary amine, spironolactone,
fluoxetine,
pyridinium and its derivatives, metoprolol, quinine, loperamide,
chlorpheniramine,
chlorpromazine, ephedrine, amitryptyline, imipramine, loxapine, cinnarizine,
amiodarone,
nortriptyline, a mineralocorticosteroid, propofol, digitalis, fluoride,
succinylcholine,
eplerenone, an alpha-adrenergic agonist, a RAAS inhibitor, an ACE inhibitor,
an
angiotensin II receptor blocker, a beta blocker, an aldosterone antagonist,
benazepril,
captopril, enalapril, fosinopril, lisinopril, moexipril, perindopril,
quinapril, ramipril,
trandolapril, candesartan, eprosartan, irbesartan, losartan, valsartan,
telmisartan, acebutolol,
atenolol, betaxolol, bisoprolol, carteolol, nadolol, propranolol, sotalol,
timolol, canrenone,
aliskiren, aldosterone synthesis inhibitors, VAP antagonists, amiloride,
triamterine, a
potassium supplement, heparin, a low molecular weight heparin, a non-steroidal
anti-
inflammatory drug, ketoconazole, trimethoprim, pentamide, a potassium sparing
diuretic,
amiloride, and/or triamterene. For example, in some embodiments, the
additional agent
may cause fluid retention and/or maldistribution in at least some subjects
upon
administration.
[00571] The compositions of the present disclosure may be administered in
combination with other therapeutic agents. The choice of therapeutic agents
that may be co-
administered with the compositions of the disclosure will depend, in part, on
the condition
being treated.
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[00572]
Compositions of the present disclosure may be administered in combination
with a therapeutic agent that causes an increase, or is known to commonly
cause an
increase, in one or more ions in the subject. By way of example only, the
crosslinked
cation-binding polymer of the present disclosure may be administered with a
therapeutic
agent that causes an increase, or is known to commonly cause an increase, in
the potassium
and/or sodium level of a subject.
Therapeutic Uses
[00573]
The disclosed polymers, compositions comprising the disclosed polymers,
and/or dosage forms comprising the disclosed polymers may be used to treat a
subject with
a disease and/or disorder.
Additionally or alternatively, the disclosed polymers,
compositions comprising the disclosed polymers and/or oral dosage forms
comprising the
disclosed polymers may be used to prevent a subject from becoming afflicted
with a disease
and/or disorder. In any of the methods of treatment or prophylaxis described
herein, a base
may be co-administered along with the polymer, composition comprising a
polymer, and/or
dosage form comprising a polymer, either simultaneously (e.g., at the same
time) or
sequentially (e.g.õ before or after administration of the polymer). When
administering the
polymer in a dosage form, the base may be included in the same dosage form or
separate
from the dosage form containing the polymer, for example in a separate dosage
form which
is co-administered at the same time or before or after the dosage form that
contains the
polymer.
[00574]
The disclosed polymers, compositions comprising the disclosed polymers,
and/or dosage forms comprising the disclosed polymers may be used in methods
for the
removal of fluid from a subject.
[00575] The
disclosed polymers, compositions comprising the disclosed polymers,
and/or dosage forms comprising the disclosed polymers may also be used in
methods for
treating diseases or disorders associated with increased retention of fluid
and/or ion
imbalances.
[00576]
The disclosed polymers, compositions comprising the disclosed polymers,
and/or dosage forms comprising the disclosed polymers may also be used in
methods to
treat end stage renal disease (ESRD), chronic kidney disease (CKD), congestive
heart
failure (CHF), hyperkalemia, hypernatremia, or hypertension.
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[00577] The polymers, compositions comprising the disclosed
polymers, and/or
dosage forms comprising the disclosed polymers as disclosed herein may be used
to remove
one or more ions selected from the group consisting of: sodium, potassium,
calcium,
magnesium and/or ammonium.
[00578] In some embodiments, the polymers, compositions comprising the
disclosed
polymers, and/or dosage forms comprising the disclosed polymers as disclosed
herein may
be substantially coated with a coating (e.g., an enteric coating) that allows
it to pass through
the gut and open in the intestine where the polymer may absorb fluid and/or
specific ions
that are concentrated in that particular portion of the intestine. In other
embodiments, the
polymers, compositions comprising the disclosed polymers, and/or dosage forms
comprising the disclosed polymers disclosed herein do not comprise such a
coating. In
some embodiments, the absorbent material, (i.e., polymer as disclosed herein)
may be
encapsulated in a capsule. In one embodiment, the capsule may be substantially
coated with
a coating (e.g., an enteric coating) that allows it to pass through the gut
and open in the
intestine where the capsule may release the polymer to absorb fluid or
specific ions that are
concentrated in that particular position of the intestine. In another
embodiment, the capsule
does not contain such a coating. Individual particles of polymer or groups of
particles may
be encapsulated or alternatively, larger quantities of beads or particles may
be encapsulated
together.
[00579] In some embodiments, polymers as disclosed herein may be milled to
give
finer particles in order to increase drug loading of capsules, or to provide
better palatability
for formulations such as gels, bars, puddings, or sachets. In addition, milled
particles or
groups of particles, or unmilled polymeric material (e.g., beads) may be
coated with various
common pharmaceutical coatings. These coatings may or may not have enteric
properties
but will have the common characteristic that they will separate the polymer
from the tissues
of the mouth and prevent the polymer from adhering to tissue. For example,
such coatings
may include, but are not limited to: a single polymer or mixtures thereof,
such as may be
selected from polymers of ethyl cellulose, polyvinyl acetate, cellulose
acetate, polymers
such as cellulose phthalate, acrylic based polymers and copolymers or any
combination of
soluble, insoluble polymers or polymer systems, waxes and wax based coating
systems.
[00580] In some embodiments, the polymers disclosed herein for
administration to an
individual or inclusion in a composition, formulation, or dosage form for
administration to
an individual, e.g., for use in a method of treatment as disclosed herein, are
individual
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particles or particles agglomerated to form a larger particle (for example,
flocculated
particles), and have a diameter of about 1 to about 10,000 microns
(alternatively, about 1
micron to about 50 microns, about 10 microns to about 50 microns, about 10
microns to
about 200 microns, about 50 microns to about 100 microns, about 50 microns to
about 200
microns, about 50 microns to about 1000 microns, about 500 microns to about
1000
microns, about 1000 to about 5000 microns, or about 5000 microns to about
10,000
microns). In some embodiments, the particles or agglomerated particles have a
diameter of
about 1, about 5, about 10, about 20, about 30, about 40, about 50, about 60,
about 70, about
80, about 90, about 100, about 110, about 120, about 130, about 140, about
150, about 160,
about 170, about 180, about 190, about 200, about 250, about 300, about 350,
about 400,
about 450, about 500, about 550, about 600, about 650, about 700, about 750,
about 800,
about 850, about 900, about 950, about 1000 , about 1500, about 2000, about
2500, about
3000, about 3500, about 4000, about 4500, about 5000, about 5500, about 6000,
about
7000, about 7500, about 8000, about 8500, about 9000, about 9500, or about
10,000
microns. In one embodiment, the particles with a diameter of about 1 micron to
about 10
microns.
[00581] In certain exemplary embodiments, the crosslinked cation-
binding polymer, as
described, for example, for administration to an individual or inclusion in a
composition,
formulation, or dosage form for administration to an individual, e.g., for use
in a method of
treatment as disclosed herein, is a crosslinked polyacrylate polymer (i.e.,
derived from
acrylic acid monomers or a salt thereof). For example, the polymer may be a
polyacrylate
polymer crosslinked with about 0.08 mol% to about 0.2 mol% or alternatively
from about
0.025 mol.% to about 3.0 mol.% including, for example, from about 0.025 mol.%
to about
0.3 mol.% or about 0.025 mol.% to about 0.17 mol.% or from about 0.025 mol.%
to about
0.34 mol.% crosslinker, and for example, may comprise an in vitro saline
absorption
capacity (e.g., saline holding capacity) of at least about 20 times its weight
(e.g., at least
about 20 grams of saline per gram of polymer, or "g/g"), at least about 30
times its weight,
at least about 40 times its weight, at least about 50 times its weight, at
least about 60 times
its weight, at least about 70 times its weight, at least about 80 times its
weight, at least about
90 times its weight, at least about 100 times its weight, or more. In some
embodiments, the
crosslinked polyacrylate polymer comprises individual particles or particles
that are
agglomerated (for example, flocculated) to form a larger particle, wherein the
individual or
agglomerated particle diameter is about 1 to about 10,000 microns
(alternatively, about 1
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micron to about 10 microns, about 1 micron to about 50 microns, about 10
microns to about
50 microns, about 10 microns to about 200 microns, about 50 microns to about
100
microns, about 50 microns to about 200 microns, about 50 microns to about 1000
microns,
about 500 microns to about 1000 microns, about 1000 to about 5000 microns, or
about 5000
microns to about 10,000 microns.
[00582] In some embodiments, the polymer may be mixed with base in
the same
dosage form and may be in contact with fluid within the dosage from, such as
suspensions
or gels. To prevent interaction of the crosslinked cation-binding polymer and
the base
component before administration to a subject, pharmaceutical coatings known in
the art can
be used to coat the polymer, the base, or both to prevent or impede
interaction of the
polymer and the base. In some embodiments, the pharmaceutical coating may have
enteric
properties. As example, pharmaceutical coatings may include but are not
limited to: a
single polymeric coating or mixtures of more than one pharmaceutical coating,
such as may
be selected from polymers of ethyl cellulose, polyvinyl acetate, cellulose
acetate; polymers
such as cellulose phthalate, acrylic based polymers and copolymers, or any
combination of
soluble polymers, insoluble polymers and/or polymer systems, waxes and wax
based
coating systems. In alternate embodiments, the polymer and base are
administered in
separate dosage forms.
[00583] A subject (e.g., an individual or patient), as disclosed
herein, includes a
vertebrate, preferably a mammal, more preferably a human. Mammals include, but
are not
limited to, farm animals (such as cows), sport animals, pets (such as cats,
dogs and horses),
primates, and rodents (such as mice and rats). For purposes of treatment,
prognosis and/or
diagnosis, a subject includes any animal such as those classified as a mammal,
including
humans, domestic and farm animals, and zoo, wild, sports, or pet animals, such
as dogs,
horses, cats, cows, etc. Preferably, the subject for treatment, prognosis
and/or diagnosis is
human.
[00584] A disease or disorder includes any condition that would
benefit from treatment
with a composition as disclosed herein. This includes both chronic and acute
diseases or
disorders, including those pathological conditions which predispose the
subject to the
disease or disorder in question.
[00585] As used herein, treatment refers to clinical intervention in
an attempt to alter
the natural course of the subject being treated, and can be performed either
for prophylaxis
(e.g., prevention) or during the course of clinical pathology (e.g., after the
subject is
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identified as having a disease or disorder or the symptoms of a disease or
disorder).
Desirable effects of treatment include preventing occurrence or recurrence of
disease,
alleviation of symptoms, diminishment of any direct or indirect pathological
consequences
of the disease or disorder, decreasing the rate of disease progression,
amelioration or
palliation of the disorder, and remission or improved prognosis. Terms such as
treating/treatment/to treat or alleviating/to alleviate refer to both 1)
therapeutic measures
that cure, slow down, lessen symptoms of, and/or halt progression of a
diagnosed disease or
disorder (e.g., a pathologic condition or disorder) and 2) prophylactic or
preventative
measures that prevent and/or slow the development of a disease or disorder
(e.g., a targeted
io pathologic condition or disorder). Thus, those in need of treatment may
include those
already with the disease or disorder; those prone to have the disease or
disorder; and those
in whom the disease or disorder is to be prevented.
[00586]
An effective amount refers to an amount effective, at dosages and for
periods
of time necessary, to achieve the desired therapeutic or prophylactic result.
A
therapeutically effective amount of a composition disclosed herein, may vary
according to
factors such as the disorder, age, sex, and weight of the subject, and the
ability of the
composition to elicit a desired response in the individual. A therapeutically
effective amount
is also one in which any toxic or detrimental effects of the composition are
outweighed by
the therapeutically beneficial effects. A prophylactically effective amount
refers to an
amount effective, at dosages and for periods of time necessary, to achieve the
desired
prophylactic result. Typically but not necessarily, since a prophylactic dose
is used in
subjects prior to or at an earlier stage of disease, the prophylactically
effective amount may
be less than the therapeutically effective amount. For example, a
therapeutically or
prophylactically effective amount includes administration of about 1 g to
about 30 g, about
15g to about 25g, or about 15g to about 30g, for example, about 15g per day of
a disclosed
cross-linked polymer to an individual. In various embodiments, base is co-
administered at
about 0.2 equivalents to about 0.95 equivalents, for example, about 0.5
equivalents to about
0.85 equivalents, about 0.7 equivalents to about 0.8 equivalents, or about
0.75 equivalents,
with respect to carboxylic acid groups on the polymer.
A therapeutically or
prophylactically effective amount of polymer and base may be administered in a
single
dosage or multiple doses, for example, administered once per day or
administered 2-4 or
more times daily, i.e., divided into and administered as 1, 2, 3, 4, or more
doses per day, or
administered at intervals of 2, 3, 4, 5, or 6 days, weekly, bi-weekly, etc..
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[00587]
Pharmaceutically acceptable includes approved or approvable by a regulatory
agency of the Federal or a state government or listed in the U.S. Pharmacopeia
or other
generally recognized pharmacopeia for use in animals, including humans.
A
pharmaceutically acceptable salt includes a salt of a compound that is
pharmaceutically
acceptable and that possesses the desired pharmacological activity of the
parent compound.
A pharmaceutically acceptable excipient, carrier or adjuvant includes an
excipient, carrier or
adjuvant that can be administered to a subject, together with at least one
composition of the
present disclosure, and which does not destroy the pharmacological activity
thereof and is
nontoxic when administered in doses sufficient to deliver a therapeutic or
prophylactic
amount of the composition. A pharmaceutically acceptable vehicle includes a
diluent,
adjuvant, excipient, or carrier with which at least one composition of the
present disclosure
is administered.
[00588]
Compositions comprising cross-linked cation binding polymers as disclosed
herein can be used either alone or in combination with one or more other
agents for
administration to a subject (e.g., in a therapy or prophylaxis). As described
herein, such
combined therapies or prophylaxis include combined administration (where the
composition
and one or more agents are included in the same or separate formulations) and
separate
administration, in which case, administration of the composition disclosed
herein can occur
prior to, contemporaneous with and/or following, administration of the one or
more other
agents (e.g., for adjunct therapy or intervention). Thus, co-administered or
co-administration
includes administration of the compositions of the present disclosure before,
during and/or
after the administration of one or more additional agents or therapies.
[00589]
In some embodiments, the polymers, compositions comprising the disclosed
polymers, and/or dosage forms comprising the disclosed polymers are useful for
treating a
disease or disorder. For example, the disclosed polymers, compositions
comprising the
disclosed polymers, and/or dosage forms comprising the disclosed polymers are
co-
administered with a base, as described herein. In some embodiments in which a
composition and/or dosage form comprising the polymer is administered, the
base may be
included in the same composition and/or dosage form as the polymer. In other
embodiments, the base may be administered separately from the composition
and/or dosage
form.
In some embodiments, the disease or disorder is one or more of: heart
failure, a
renal insufficiency disease, end stage renal disease, liver cirrhosis, chronic
renal
insufficiency, chronic kidney disease, fluid overload, fluid maldistribution,
edema,
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pulmonary edema, peripheral edema, lymphedema, nephrotic edema, idiopathic
edema,
ascites, cirrhotic ascites, interdialytic weight gain, high blood pressure,
hyperkalemia,
hypernatremia, abnormally high total body sodium, hypercalcemia, tumor lysis
syndrome,
head trauma, an adrenal disease, hyporeninemic hypoaldosteronism,
hypertension, salt-
sensitive hypertension, refractory hypertension, renal tubular disease,
rhabdomyolysis,
crush injuries, renal failure, acute tubular necrosis, insulin insufficiency,
hyperkalemic
periodic paralysis, hemolysis, malignant hyperthermia, pulmonary edema
secondary to
cardiogenic pathophysiology, pulmonary edema with non-cardiogenic origin,
drowning,
acute glomerulonephritis, allergic pulmonary edema, high altitude sickness,
Adult
io Respiratory Distress Syndrome, traumatic edema, cardiogenic edema, acute
hemorrhagic
edema, heatstroke edema, facial edema, eyelid edema, angioedema, cerebral
edema, scleral
edema, nephritis, nephrosis, nephrotic syndrome, glomerulonephritis, and/or
renal vein
thrombosis.
[00590] In some embodiments, the polymers, compositions comprising
the disclosed
polymers, and/or dosage forms comprising the disclosed polymers as disclosed
herein are
useful for treating a disease or disorder involving an ion imbalance in a
subject by
administering to the subject an effective amount of a polymer, a composition
comprising a
disclosed polymer, and/or a dosage form comprising a disclosed polymer (e.g.,
an effective
amount) as disclosed herein. For example, the disclosed polymers, compositions
comprising the disclosed polymers, and/or dosage forms comprising the
disclosed polymers
are co-administered with a base, as described herein. In some embodiments, the
disease or
disorder is hyperkalemia. In some embodiments, the disease or disorder is
hypernatremia.
In some embodiments, the disease or disorder is a high sodium level. In some
embodiments, the disease or disorder is an abnormally high potassium level. In
some
embodiments, the disease or disorder is hypernatremia and hyperkalemia.
[00591] In some embodiments, the polymers, compositions comprising
the disclosed
polymers, and/or dosage forms comprising the disclosed polymers as disclosed
herein are
useful for treating a subject with heart failure by administering to the
subject an effective
amount of a polymer, composition comprising a disclosed polymer, and/or a
dosage form
comprising a disclosed polymer as disclosed herein. For example, the disclosed
polymers,
compositions comprising the disclosed polymers, and/or dosage forms comprising
the
disclosed polymers are co-administered with a base, as described herein. In
some
embodiments, the subject has both heart failure and chronic kidney disease. In
some related
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embodiments, the methods further comprise reducing one or more symptoms of a
fluid
overload state in the subject. Symptoms of a fluid overload state in a subject
are known to
those skilled in the art, and may include, for example and without limitation,
difficulty
breathing when lying down, ascites, fatigue, shortness of breath, increased
body weight,
peripheral edema, and/or pulmonary edema. In some related embodiments, the
subject may
be on concomitant dialysis therapy. In some further related embodiments, the
dialysis
therapy may be reduced or discontinued after administration of the polymer,
the
composition comprising the disclosed polymer, and/or the dosage form
comprising the
disclosed polymer as disclosed herein. In some related embodiments, the method
further
comprises identifying the subject as having heart failure before administering
the polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer. In some embodiments, administration of the disclosed polymers,
compositions
comprising the disclosed polymers, and/or dosage forms comprising the
disclosed polymers,
as described herein, improves or ameliorates at least one symptom of heart
failure, for
example, at least one symptom that impacts the subject's quality of life
and/or physical
function. For example, administration may result in body weight reduction,
dyspnea
improvement (for example, overall and dyspnea at exertion), six minute walk
test
improvement, and/or improvement or absence of edema (e.g., peripheral edema).
In some
embodiments, administration of the disclosed polymers, compositions comprising
the
disclosed polymers, and/or dosage forms comprising the disclosed polymers, as
described
herein, results in reduction of patient classification by at least one heart
failure class,
according to the New York Heart Association Class I, II, III, IV functional
classification
system.
[00592] In some embodiments, the polymers, compositions comprising
the disclosed
polymers, and/or dosage forms comprising the disclosed polymers as disclosed
herein are
useful for treating a subject with end stage renal disease (ESRD) by
administering to the
subject an effective amount of a polymer, a composition comprising a disclosed
polymer,
and/or a dosage form comprising a disclosed polymer as disclosed herein. For
example, the
disclosed polymers, compositions comprising the disclosed polymers, and/or
dosage forms
comprising the disclosed polymers are co-administered with a base, as
described herein. In
some related embodiments, the subject is on concomitant dialysis therapy. In
some
embodiments, the method reduces blood pressure in an ESRD subject on
concomitant
dialysis therapy, for example, pre-dialysis, post-dialysis, and/or
interdialytic systolic and
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diastolic blood pressure may be reduced. In some embodiments, the method
reduces
interdialytic weight gain in an ESRD subject on concomitant dialysis therapy.
In some
embodiments, the subject also has heart failure. In some embodiments, one or
more
symptoms of intradialytic hypotension are improved after administration of a
polymer, a
composition comprising a disclosed polymer, and/or a dosage form comprising a
disclosed
polymer as disclosed herein. For example and without limitation, incidences of
vomiting,
fainting and/or drops in blood pressure levels are reduced or eliminated. In
some
embodiments, the subject experiences one or more of: a reduced frequency of
emergency
dialysis sessions, a reduced frequency of inadequate dialysis sessions, a
reduced frequency
io of dialysis sessions on low-potassium dialysis bath, and/or reduced
frequency or reduced
severity of EKG signs during dialysis sessions. In some embodiments, one or
more
symptom of intradialytic hypotension are reduced or eliminated after
administration of a
polymer, a composition comprising a disclosed polymer, and/or a dosage form
comprising a
disclosed polymer. Symptoms of intradialytic hypotension are known to those
skilled in the
art and may include, for example, vomiting, fainting, an abrupt decrease in
blood pressure,
seizures, dizziness, severe abdominal cramping, severe leg or arm muscular
cramping,
intermittent blindness, infusion, medication, and dialysis session
interruption or
discontinuation. In some embodiments, ESRD subjects may experience an
improvement in
physical function as expressed by increaseas in the 6 Minute Walk Test.
[00593] In some embodiments, polymers, compositions comprising the
disclosed
polymers, and/or dosage forms comprising the disclosed polymers as disclosed
herein are
useful for treating a subject having a chronic kidney disease. In some
embodiments, the
methods comprise administering to the subject an effective amount of a
polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer as disclosed herein. For example, the disclosed polymers, compositions
comprising the disclosed polymers, and/or dosage forms comprising the
disclosed polymers
are co-administered with a base, as described herein. In some embodiments, the
methods
further comprise identifying the subject as having a chronic kidney disease
before
administration of the polymer, composition comprising a disclosed polymer,
and/or dosage
form comprising a disclosed polymer as disclosed herein. In some related
embodiments, the
methods further comprise reducing one or more symptoms of a fluid overload
state in the
subject. In some embodiments, a comorbidity of chronic kidney disease is
reduced,
alleviated, and/or eliminated after administration of a polymer, a composition
comprising a
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disclosed polymer, and/or a dosage form comprising a disclosed polymer.
Comorbidities of
chronic kidney disease are known to those skilled in the art and include, for
example, fluid
overload, edema, pulmonary edema, hypertension, hyperkalemia, excess total
body sodium,
heart failure, ascites, and/or uremia. In some embodiments, CKD patients may
experience
prevention of doubling of serum creatinine over the duration of a study (for
example, 1 to 2
years), prevention of disease progression to dialysis, and/or prevention of
death and CKD
related hospitalizations and/or complications.
[00594] In some embodiments, polymers, compositions comprising a
disclosed
polymer, and/or dosage forms comprising a disclosed polymer as disclosed
herein are useful
for treating a subject having hypertension. In some embodiments, the methods
comprise
administering to the subject an effective amount of a polymer, composition
comprising a
disclosed polymer, and/or dosage form comprising a disclosed polymer as
disclosed herein.
For example, the disclosed polymers, compositions comprising the disclosed
polymers,
and/or dosage forms comprising the disclosed polymers are co-administered with
a base, as
described herein. In some embodiments, the methods further comprise
identifying that the
subject has hypertension before administering the polymer, composition
comprising a
disclosed polymer, and/or dosage form comprising a disclosed polymer as
disclosed herein.
As used herein, the term hypertension includes the various subtypes of
hypertension known
to those skilled in the art, for example and without limitation: primary
hypertension,
secondary hypertension, salt sensitive hypertension, and refractory
hypertension and
combinations thereof. In some embodiments, the method is effective in reducing
the
subject's blood pressure. In related embodiments, the method may further
comprise
determining a blood pressure level before, after, or both before and after
administration of
the polymer, composition comprising a disclosed polymer, and/or dosage form
comprising a
disclosed polymer as disclosed herein. For example, the method may further
comprise
determining the subject's diastolic blood pressure, systolic blood pressure,
and/or mean
arterial pressure ("MAP") before, after, or both before and after
administration of the
polymer, composition comprising a disclosed polymer, and/or dosage form
comprising a
disclosed polymer as disclosed herein. In some embodiments, one or more
symptom of a
fluid overload state is reduced, improved, or alleviated by administering a
polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer as disclosed herein. In some related embodiments, the method may
further
comprise determining a fluid overload state symptom before, after, or both
before and after
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administration of the polymer, composition comprising a disclosed polymer,
and/or dosage
form comprising a disclosed polymer as disclosed herein. For example, the
method may
further comprise observing an improvement in the subject's breathing while
lying down,
ascites, fatigue, shortness of breath, body weight, peripheral edema, and/or
pulmonary
edema. In some embodiments, the subject is on concomitant diuretic therapy. As
used
herein, the term diuretic therapy refers to administration of pharmaceutical
compositions
(e.g., diuretic agents), and non-chemical intervention, such as dialysis or
restriction of fluid
intake. Diuretic agents are known to those skilled in the art and include, for
example,
furosemide, bumetanide, torsemide, hydrochlorthiazide, amiloride and/or
spironolactone. In
io some related embodiments, the diuretic therapy may be reduced or
discontinued following
administration of the polymer, composition comprising a disclosed polymer,
and/or dosage
form comprising a disclosed polymer as disclosed herein.
[00595] In some embodiments, the polymers, compositions comprising a
disclosed
polymer, and/or dosage forms comprising a disclosed polymer as disclosed
herein of the
present disclosure are useful for treating hyperkalemia in a subject. In some
embodiments,
the method comprises administering to the subject an effective amount of a
polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer according to the present disclosure. For example, the disclosed
polymers,
compositions comprising the disclosed polymers, and/or dosage forms comprising
the
disclosed polymers are co-administered with a base, as described herein. In
some
embodiments, the method further comprises identifying the subject as having
hyperkalemia,
or as having a risk of developing hyperkalemia, before administering the
polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer as disclosed herein. In some embodiments, the method may further
comprise
determining a potassium ion level in the subject before administering the
polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer as disclosed herein. In some related embodiments, the potassium ion
level may be
within a normal range, slightly elevated, or elevated before administering the
polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer as disclosed herein. In some embodiments, the subject has been
prescribed or will
be administered a drug known to increase potassium levels. In some
embodiments, the
subject has already ingested a drug known to increase potassium levels. In
some
embodiments, the method may further comprise determining a second, reduced
potassium
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ion level in the subject after administration of the polymer, composition
comprising a
disclosed polymer, and/or dosage form comprising a disclosed polymer as
disclosed herein.
In some embodiments, an acid/base status (e.g., acid/base balance) associated
with the
subject does not change, for example, as measured by serum total bicarbonate,
serum total
CO2, arterial blood pH, urine pH, urine phosphorus, urine ammonium, and/or
anion gap.
An acid/base status that does not change includes one that does not change
outside the
normal range or outside the normal range for the subject.
[00596] In some embodiments, the polymers, compositions comprising a
disclosed
polymer, and/or dosage forms comprising a disclosed polymer as disclosed
herein of the
present disclosure are useful for treating an high sodium level, e.g.,
hypernatremia, in a
subject. In some embodiments, the method comprises administering to the
subject an
effective amount of a polymer, composition comprising a disclosed polymer,
and/or dosage
form comprising a disclosed polymer as disclosed herein. For example, the
disclosed
polymers, compositions comprising the disclosed polymers, and/or dosage forms
comprising the disclosed polymers are co-administered with a base, as
described herein. In
some embodiments, the method further comprises identifying the subject as
having an high
sodium level, or as having a risk of developing an high sodium level, before
administering
the polymer, composition comprising a disclosed polymer, and/or dosage form
comprising a
disclosed polymer as disclosed herein. In some embodiments, the method may
further
comprise determining a sodium ion level in the subject before administering
the polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer as disclosed herein. In some related embodiments, the sodium ion level
may be
within a normal range, slightly elevated, or elevated before administering the
polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer as disclosed herein. In some embodiments, the method may further
comprise
determining a second, reduced sodium ion level in the subject after
administration of the
polymer, composition comprising a disclosed polymer, and/or dosage form
comprising a
disclosed polymer as disclosed herein. In some embodiments, an acid/base
status (e.g.,
acid/base balance) associated with the subject does not change, for example,
as measured by
serum total bicarbonate, serum total CO2, arterial blood pH, urine pH, urine
phosphorus,
urine ammonium, and/or anion gap. An acid/base status that does not change
includes one
that does not change outside the normal range or outside the normal range for
the subject.
In some embodiments, the subject has taken or will take a drug known to
increase sodium
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levels, for example and without limitation: estrogen containing compositions,
mineralocorticoids, osmotic diuretics (e.g., glucose or urea), vaptans (e.g.,
tolvaptan,
lixivaptan), lactulose, cathartics (e.g., phenolphthalein), phenytoin,
lithium, Amphotericin
B, demeclocycline, dopamine, ofloxacin, orlistat, ifosfamide,
cyclophosphamide,
hyperosmolar radiographic contrast agents (e.g., gastrographin, renographin),
cidofovir,
ethanol, foscarnet, indinavir, libenzapril, mesalazine, methoxyflurane,
pimozide, rifampin,
streptozotocin, tenofir, triamterene, and/or cholchicine. In some
embodiments,
administration of the polymers, compositions comprising the disclosed
polymers, and/or
dosage forms comprising the disclosed polymers may further comprise increasing
a dose of
1(1 one or more additional agents, for example, an agent known to cause an
increase in sodium
levels. In some embodiments, the method further comprises increasing a dose of
one or
more of: an aldosterone antagonist, an angiotensin II receptor blocker, and/or
an
angiotensin-converting enzyme inhibitor before, concomitantly, and/or after
administering a
polymer, a composition comprising a disclosed polymer, and/or a dosage form
comprising a
disclosed polymer. In some embodiments, administration of the polymers,
compositions
comprising the disclosed polymers, and/or dosage forms comprising the
disclosed polymers
may further comprise decreasing a dose or discontinuing administration or co-
administration of a diuretic.
[00597]
In some embodiments, the polymers, compositions comprising a disclosed
polymer, and/or dosage forms comprising a disclosed polymer as disclosed
herein are useful
for treating a subject with a disease or disorder involving fluid overload
(e.g., a fluid
overload state such as heart failure, end stage renal disease, ascites, renal
failure (for
example, acute renal failure), nephritis, and nephrosis). In some embodiments,
the method
comprises administering to the subject an effective amount of a polymer,
composition
comprising a disclosed polymer, and/or dosage form comprising a disclosed
polymer as
disclosed herein. For example, the disclosed polymers, compositions comprising
the
disclosed polymers, and/or dosage forms comprising the disclosed polymers are
co-
administered with a base, as described herein. In some embodiments, the
subject may be on
concomitant diuretic therapy. In some embodiments, the method may further
comprise
identifying a fluid overload state in the subject, or identifying a risk that
the subject will
develop a fluid overload state before administration of a polymer, composition
comprising a
disclosed polymer, and/or dosage form comprising a disclosed polymer. Methods
of
identifying a fluid overload state or a risk of developing a fluid overload
state are known to
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those skill in the art and may include, for example and without limitation:
assessing
difficulty breathing when lying down, ascites, fatigue, shortness of breath,
increased body
weight, peripheral edema, and/or pulmonary edema associated with the subject.
In some
embodiments, an acid/base status (e.g., acid/base balance) associated with the
subject does
not change, for example, as measured by serum total bicarbonate, serum total
CO2, arterial
blood pH, urine pH, urine phosphorus, urine ammonium, and/or anion gap. An
acid/base
status that does not change includes one that does not change outside the
normal range or
outside the normal range for the subject.
[00598] In some embodiments, the polymers, compositions comprising a
disclosed
polymer, and/or dosage forms comprising a disclosed polymer as disclosed
herein according
to the present disclosure are useful for treating a subject with a disease or
disorder involving
fluid maldistribution (e.g., a fluid maldistribution state such as pulmonary
edema,
angioneurotic edema, ascites, high altitude sickness, adult respiratory
distress syndrome,
uticarial edema, papille edema, facial edema, eyelid edema, cerebral edema,
and scleral
edema). In some embodiments, the method comprises administering to the subject
an
effective amount of a polymer, composition comprising a disclosed polymer,
and/or dosage
form comprising a disclosed polymer as disclosed herein. For example, the
disclosed
polymers, compositions comprising the disclosed polymers, and/or dosage forms
comprising the disclosed polymers are co-administered with a base, as
described herein. In
some embodiments, the method may further comprise identifying a fluid
maldistribution
state or a risk of developing a fluid maldistribution state in the subject
before administering
to the subject a polymer, composition comprising a disclosed polymer, and/or
dosage form
comprising a disclosed polymer.
[00599] In some embodiments, the polymers, compositions comprising a
disclosed
polymer, and/or dosage forms comprising a disclosed polymer as disclosed
herein are useful
for treating edema in a subject. In some embodiments, the method comprises
administering
to the subject an effective amount of a polymer, composition comprising a
disclosed
polymer, and/or dosage form comprising a disclosed polymer as disclosed
herein. For
example, the disclosed polymers, compositions comprising the disclosed
polymers, and/or
dosage forms comprising the disclosed polymers are co-administered with a
base, as
described herein. In some embodiments, the method may further comprise
identifying an
edematous state or a risk of developing an edematous state in the subject
before
administering a polymer, composition comprising a disclosed polymer, and/or
dosage form
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comprising a disclosed polymer as disclosed herein. In some embodiments, the
edematous
state is nephritic edema, pulmonary edema, peripheral edema, lymphedema,
and/or
angioneurotic edema. In some embodiments, the subject is on concomitant
diuretic therapy.
In some related embodiments, the diuretic therapy may be reduced or
discontinued after
administration of the polymer, composition comprising a disclosed polymer,
and/or dosage
form comprising a disclosed polymer as disclosed herein. In some embodiments,
the
method may further comprise, before administering a polymer, composition
comprising a
disclosed polymer, and/or dosage form comprising a disclosed polymer as
disclosed herein,
determining one or more of: a baseline level of one or more ions (e.g.,
sodium, potassium,
io lithium and/or magnesium) in the subject, a baseline total body weight
associated with the
subject, a baseline total body water level associated with the subject, a
baseline total
extracellular water level associated with the subject, and/or a baseline total
intracellular
water level associated with the subject. In some embodiments, the method may
further
comprise, after administering a polymer, composition comprising a disclosed
polymer,
and/or dosage form comprising a disclosed polymer as disclosed herein,
determining one or
more of: a second level of one or more ions in the subject, a second total
body weight
associated with the subject, a second total body water level associated with
the subject, a
second total extracellular water level associated with the subject, and/or a
second total
intracellular water level associated with said subject. In some embodiments,
the second
level is lower than the corresponding baseline level. In some embodiments, an
acid/base
status (e.g., acid/base balance) associated with the subject does not change,
for example, as
measured by serum total bicarbonate, serum total CO2, arterial blood pH, urine
pH, urine
phosphorus, urine ammonium, and/or anion gap. An acid/base status that does
not change
includes one that does not change outside the normal range or outside the
normal range for
the subject. In some embodiments, a blood pressure level associated with the
subject after
administration of the polymer, composition comprising a disclosed polymer,
and/or dosage
form comprising a disclosed polymer is substantially lower than a baseline
blood pressure
level associated with the subject determined before administration of the
polymer,
composition comprising a disclosed polymer, and/or dosage form comprising a
disclosed
polymer. In some embodiments, one or more symptoms of edema are reduced and/or
eliminated following administration of a polymer, composition comprising a
disclosed
polymer, and/or dosage form comprising a disclosed polymer as disclosed
herein.
Symptoms of edema are known to those skilled in the art; some non-limiting
examples
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include: difficulty breathing when lying down, shortness of breath, peripheral
edema, and
leg edema.
[00600] In some embodiments, the polymers, compositions comprising
the disclosed
polymers, and/or dosage forms comprising the disclosed polymers according to
the present
disclosure are useful for treating ascites in a subject. In some embodiments,
the method
comprises administering to the subject an effective amount of a polymer
composition
comprising a disclosed polymer, and/or a dosage form comprising a disclosed
polymer
according to the present disclosure. For example, the disclosed polymers,
compositions
comprising the disclosed polymers, and/or dosage forms comprising the
disclosed polymers
are co-administered with a base, as described herein. In some embodiments, the
method
may further comprise identifying an ascitic state or a risk of developing an
ascitic state in
the subject. In some embodiments, the subject is on concomitant diuretic
therapy. In some
related embodiments, the diuretic therapy may be reduced or discontinued after
administration of the composition. In some embodiments, the subject may have
taken, or
will take, a drug known to increase potassium levels.
[00601] In some embodiments, the polymers, compositions comprising
the disclosed
polymers, and/or dosage forms comprising the disclosed polymers as disclosed
herein are
useful for treating nephrotic syndrome in a subject. In some embodiments, the
method
comprises administering to said subject an effective amount of a polymer, a
composition
comprising a disclosed polymer, and/or a dosage form comprising a disclosed
polymer as
disclosed herein. For example, the disclosed polymers, compositions comprising
the
disclosed polymers, and/or dosage forms comprising the disclosed polymers are
co-
administered with a base, as described herein. In some embodiments, the method
further
comprises identifying the subject as having nephrotic syndrome, or as having a
risk of
developing nephrotic syndrome, before administering the polymer, the
composition
comprising a disclosed polymer, and/or the dosage form comprising a disclosed
polymer.
In some embodiments, the method may further comprise determining one or more
of: a
level of one or more ions (e.g., sodium, potassium calcium, lithium, and/or
magnesium) in
the subject, a total body weight associated with the subject, a total body
water level
associated with the subject, a total extracellular water level associated with
the subject,
and/or a total intracellular water level associated with the subject before
administering the
polymer, the composition comprising a disclosed polymer, and/or the dosage
form
comprising a disclosed polymer. In some embodiments, the method may further
comprise
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determining a second, lower level of one or more of: a level of one or more
ions in the
subject, a total body weight associated with the subject, a total body water
level associated
with the subject, a total extracellular water level associated with the
subject, and/or a total
intracellular water level associated with the subject after administering the
polymer, the
composition comprising a disclosed polymer, and/or the dosage form comprising
a
disclosed polymer. In some embodiments, an acid/base status (e.g., acid/base
balance)
associated with the subject does not change, for example, as measured by serum
total
bicarbonate, serum total CO2, arterial blood pH, urine pH, urine phosphorus,
urine
ammonium, and/or anion gap. An acid/base status that does not change includes
one that
1(1 does not change outside the normal range or outside the normal range
for the subject. In
some embodiments, a blood pressure level associated with the subject after
administration
of the polymer, the composition comprising a disclosed polymer, and/or the
dosage form
comprising a disclosed polymer is substantially lower than a baseline blood
pressure level
associated with the subject before the administration(s). In some embodiments,
one or more
symptoms of fluid overload is alleviated, reduced, or eliminated after
administration of
polymer, the composition comprising a disclosed polymer, and/or the dosage
form
comprising a disclosed polymer. In some related embodiments, the symptom may
be one or
more of: difficulty breathing when lying down, shortness of breath, peripheral
edema,
and/or leg edema. In some embodiments, the subject may be on concomitant
diuretic
therapy. In some related embodiments, the diuretic therapy may be reduced or
eliminated
after administration of the polymer, the composition comprising a disclosed
polymer, and/or
the dosage form comprising a disclosed polymer.
[00602] In some embodiments, methods according to the present
disclosure may
further comprise administering to the subject an additional agent, for
example, a drug or
agent for treatment of a condition such as end stage renal disease, including,
for example,
phosphate binders. Non-limiting examples of additional agents include
mannitol, sorbitol,
calcium acetate, sevelamer carbonate (Renvelac)), and/or sevelamer
hydrochloride.
[00603] In some embodiments, methods according to the present
disclosure may
further comprise administering to the subject an agent known to increase
potassium levels.
As used herein, the term "an agent known to increase potassium levels" refers
to agents that
are known to cause an increase, are suspected of causing an increase, or are
correlated with
an increase in potassium levels upon administration. For example and without
limitation,
agents known to cause an increase in potassium levels may include: a tertiary
amine,
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spironolactone, fluoxetine, pyridinium and its derivatives, metoprolol,
quinine, loperamide,
chlorpheniramine, chlorpromazine, ephedrine, amitryptyline, imipramine,
loxapine,
cinnarizine, amiodarone, nortriptyline, a mineralocorticosteroid, propofol,
digitalis, fluoride,
succinylcholine, eplerenone, an alpha-adrenergic agonist, a RAAS inhibitor, an
ACE
inhibitor, an angiotensin II receptor blocker, a beta blocker, an aldosterone
antagonist,
benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril,
perindopril, quinapril,
ramipril, trandolapril, candesartan, eprosartan, irbesartan, losartan,
valsartan, telmisartan,
acebutolol, atenolol, betaxolol, bisoprolol, carteolol, nadolol, propranolol,
sotalol, timolol,
canrenone, aliskiren, aldosterone synthesis inhibitors, and/or VAP
antagonists. In some
embodiments, administration of the polymers, compositions comprising the
disclosed
polymers, and/or dosage forms comprising the disclosed polymers may further
comprise
increasing a dose of one or more additional agents, for example, an agent
known to cause an
increase in potassium levels. In some embodiments, administration of the
polymers,
compositions comprising the disclosed polymers, and/or dosage forms comprising
the
disclosed polymers may further comprise decreasing a dose or discontinuing
administration
or co-administration of a diuretic.
[00604] In some embodiments, methods according to the present
disclosure may
further comprise administering to the subject an agent known to increase
sodium levels. As
used herein, the term "an agent known to increase sodium levels" refers to
agents that are
known to cause an increase, are suspected of causing an increase, or are
correlated with an
increase in sodium levels upon administration. For example and without
limitation, agents
known to cause an increase in sodium levels may include: estrogen containing
compositions, mineralocorticoids, osmotic diuretics (e.g., glucose or urea),
lactulose,
cathartics (e.g., phenolphthalein), phenytoin, lithium, Amphotericin B,
demeclocycline,
dopamine, ofloxacin, orlistat, ifosfamide, cyclophosphamide, hyperosmolar
radiographic
contrast agents (e.g., gastrographin, renographin), cidofovir, ethanol,
foscarnet, indinavir,
libenzapril, mesalazine, methoxyflurane, pimozide, rifampin, streptozotocin,
tenofir,
triamterene, and/or cholchicine. In some embodiments, administration of the
polymers,
compositions comprising the disclosed polymers, and/or dosage forms comprising
the
disclosed polymers may further comprise increasing a dose of one or more
additional
agents, for example, an agent known to cause an increase in sodium levels. In
some
embodiments, administration of the polymers, compositions comprising the
disclosed
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polymers, and/or dosage forms comprising the disclosed polymers may further
comprise
decreasing a dose or discontinuing administration or co-administration of a
diuretic.
[00605] In some embodiments, methods according to the present
disclosure may
further comprise determining a baseline level of one or more ions in a subject
before
administering a polymer, the composition comprising a disclosed polymer,
and/or the
dosage form comprising a disclosed polymer as disclosed herein, and
determining a second
level of said one or more ions in the subject after administering a polymer,
the composition
comprising a disclosed polymer, and/or the dosage form comprising a disclosed
polymer as
disclosed herein. Ion levels may be determined in a subject, for example, in
serum, urine,
io and/or feces. Non-limiting examples of methods that may be used to
measure ions include
atomic absorption, clinical laboratory blood and urine tests, ion
chromatography, and ICP
(inductively coupled plasma mass spectroscopy). In related embodiments, a
baseline level
of potassium is determined in a subject. In another embodiment, a baseline
level of sodium
is determined in a subject. Thereafter, a polymer, the composition comprising
a disclosed
polymer, and/or the dosage form comprising a disclosed polymer as disclosed
herein is
administered to the subject, followed by a determination of a second potassium
and/or
sodium level. In some embodiments, the second potassium and/or sodium level is
lower
than the baseline potassium level.
[00606] In some embodiments, methods according to the present
disclosure may
further comprise determining a baseline total body weight associated with a
subject before
administering a polymer, the composition comprising a disclosed polymer,
and/or the
dosage form comprising a disclosed polymer as disclosed herein, and
determining a second
total body weight associated with the subject after administering a polymer,
the composition
comprising a disclosed polymer, and/or the dosage form comprising a disclosed
polymer as
disclosed herein. In some embodiments, the second total body weight is lower
than the
baseline total body weight. Any suitable method for determining the total body
weight
associated with a subject may be used.
[00607] In some embodiments, methods according to the present
disclosure may
further comprise determining a baseline total water level associated with a
subject before
administering a polymer, the composition comprising a disclosed polymer,
and/or the
dosage form comprising a disclosed polymer as disclosed herein, and
determining a second
total water level associated with the subject after administering a polymer,
the composition
comprising a disclosed polymer, and/or the dosage form comprising a disclosed
polymer as
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disclosed herein. In some embodiments, the second total water level is lower
than the
baseline total water level. Any suitable method for determining a total water
level
associated with a subject may be used, for example, by bioimpedance
measurement, or
through invasive procedures, such as central vein catheters for measurement of
pulmonary
wedge pressure.
[00608] In some embodiments, methods according to the present
disclosure may
further comprise determining a baseline total extracellular water level
associated with a
subject before administering a polymer, the composition comprising a disclosed
polymer,
and/or the dosage form comprising a disclosed polymer as disclosed herein, and
determining a second total extracellular water level associated with the
subject after
administering a polymer, the composition comprising a disclosed polymer,
and/or the
dosage form comprising a disclosed polymer as disclosed herein. In some
embodiments, the
second total extracellular water level is lower than the baseline total
extracellular water
level. Any suitable method for determining a total extracellular water level
associated with
a subject may be used, for example, by bioimpedance measurement, or through
invasive
procedures, such as central vein catheters for measurement of pulmonary wedge
pressure.
[00609] In some embodiments, methods according to the present
disclosure may
further comprise determining a baseline total intracellular water level
associated with a
subject before administering a polymer, the composition comprising a disclosed
polymer,
and/or the dosage form comprising a disclosed polymer as disclosed herein, and
determining a second total intracellular water level associated with the
subject after
administering a polymer, the composition comprising a disclosed polymer,
and/or the
dosage form comprising a disclosed polymer as disclosed herein. In some
embodiments,
the second total intracellular water level is lower than the baseline total
intracellular water
level. Any suitable method for determining a total intracellular water level
associated with
a subject may be used, for example, by bioimpedance measurement, or through
invasive
procedures, such as central vein catheters for measurement of pulmonary wedge
pressure.
[00610] In some embodiments, methods according to the present
disclosure may
further comprise determining a pH level associated with a subject. Any method
known in
the art for determining a pH level may be employed. For example and without
limitation, a
pH level associated with a subject may be determined by determining the
subject's pCO2,
serum carbonate, urinary phosphorous level, etc. In some embodiments, methods
according
to the present disclosure comprise determining a pH level associated with a
subject after
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administering a polymer, composition comprising a polymer, and/or dosage form
according
to the present disclosure. In related embodiments, the pH level is within a
normal range for
the subject, and/or within a clinically acceptable range for the subject. In
some
embodiments, a pH level associated with a subject after administering a
polymer,
composition comprising a polymer, and/or dosage form comprising a polymer
according to
the present disclosure is closer to a normal level for the subject, closer to
a clinically
acceptable level, etc., than compared to a baseline pH level associated with
the subject
before administration of the composition. In some embodiments, a pH level
associated with
the subject does not significantly change within about 1 day, within about 18
hours, within
about 12 hours, within about 6 hours, within about 4 hours, or within about 2
hours of
administration of the composition.
[00611] In some embodiments, methods according to the present
disclosure may
further comprise determining an acid/base status (e.g., acid/base balance)
associated with a
subject. Any method known in the art for determining an acid/base status
(e.g., acid/base
balance) may be employed. In some embodiments, methods according to the
present
disclosure comprise determining an acid/base status (e.g., acid/base balance)
associated with
a subject after administering a composition according to the present
disclosure.
[00612] For example, an acid/base status (e.g., acid/base balance)
may be measured by
serum total bicarbonate, arterial blood pH, urine pH, urine phosphorus, urine
ammonium,
and/or anion gap. In an exemplary method, anion gap may be calculated by
subtracting the
serum concentrations of chloride and bicarbonate (anions) from the
concentrations of
sodium and potassium (cations) as follows:
Anion gap = ([Na] + [K+]) ¨ ([C[] + [HCO3 ])
[00613] Alternatively, in another exemplary method, anion gap may be
calculated by
ignoring potassium concentration as follows:
Anion gap = [Na] ¨ ([C1-] + [HCO3 1)
[00614] In related embodiments, the acid/base status (e.g.,
acid/base balance) is within
a normal range as set by a clinical laboratory.
[00615] In related embodiments, the acid/base status (e.g.,
acid/base balance) is within
a normal range for the subject, and/or within a clinically acceptable range
for the subject.
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[00616] In some embodiments, an acid/base status (e.g., acid/base
balance) associated
with a subject after administering a disclosed polymer, composition comprising
a disclosed
polymer, formulation comprising a disclosed polymer, and/or dosage form
comprising a
disclosed polymer, according to the present disclosure, is closer to a normal
level for the
subject, closer to a clinically acceptable level, etc., than compared to a
baseline acid/base
status (e.g., acid/base balance) associated with the subject before
administration of the
polymer, composition, formulation, and/or dosage form.
[00617] In some embodiments, an acid/base status (e.g., acid/base
balance) associated
with the subject does not change or does not significantly change, for
example, at the end of
io a time interval, or about 1 day, within about 18 hours, within about 12
hours, 10 hours,
within about 9 hours, within about 8 hours, within about 7 hours, within about
6 hours,
within about 5 hours, within about 4 hours, within about 3 hours, within about
2 hours, or
within about 1 hour of administration of the composition. An acid/base status
that does not
change includes one that does not change outside the normal range or outside
the normal
range for the subject. In some embodiments, an acid/base status (e.g.,
acid/base balance)
associated with the subject does not change, for example, as measured by serum
total
bicarbonate, serum total CO2, arterial blood pH, urine pH, urine phosphorus,
urine
ammonium, and/or anion gap. An acid/base status that does not change includes
one that
does not change outside the normal range or outside the normal range for the
subject.
[00618] Methods for determining an ion level in a subject are known to
those skilled in
the art. Any suitable method for determining an ion level may be used.
However,
determination of serum sodium levels should be avoided as such levels tend not
to fluctuate,
even in hypernatremic subjects. If sodium ion levels are desired, another
suitable method
for determining such levels should preferably be used, such as determining a
subject's total
body sodium level.
[00619] In some embodiments, methods according to the present
disclosure may
further comprise determining a blood pressure level before, after, or both
before and after
administration of a composition according to the present disclosure. A
subject's blood
pressure level may be determined using any suitable method known in the art.
For example
and without limitation, a subject's blood pressure level may be determined by
measuring the
subject's systolic blood pressure, the subject's diastolic blood pressure,
and/or the subject's
mean arterial pressure ("MAP"). In some embodiments, the subject's blood
pressure is
lower after treatment than before treatment.
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[00620] In some embodiments, the compositions according to the
present disclosure
are administered as needed to reduce an ion level in a subject, or to maintain
an acceptable
level of one or more ions in a subject, or to reduce a fluid overload state or
fluid
maldistribution state in a subject. In some embodiments, compositions
according to the
present disclosure are administered at a frequency from 1 time per every 3
days to about 4
times per day. Preferably, the compositions according to the present
disclosure are
administered from about 1 time per day to about 4 times per day; even more
preferably once
or twice per day.
EXAMPLES
[00621] The following examples are for illustrative purposes only
and are not to be
construed as limiting in any manner.
Example 1
[00622] This example demonstrates the preparation of an exemplary cross-
linked
polyelectrolyte polymer, such as crosslinked polyacrylic acid partially
neutralized with
sodium.
[00623] An inverse suspension process may be used with the following
components: a
monomer (e.g., acrylic acid), solvent for the monomer (e.g., hydrophilic, for
example,
water), base for neutralization of monomer (e.g., NaOH), lipophilic (e.g.,
hydrophobic)
solvent (e.g., IsoparTM L), suspending agent (e.g., fumed silica such as
Aerosil R972),
chelating agent (e.g., VersenexTm-80), polymerization initiator (e.g., sodium
persulfate), and
cross-linking agent (e.g., TMPTA).
[00624] A monomer solution is prepared in a vessel as the aqueous
phase by
dissolving an unsaturated carboxylic acid monomer (e.g., acrylic acid) in
water and
neutralizing with an aqueous alkali (e.g., NaOH) to a desired percentage
neutralization (e.g.,
70% to 95% neutralized). Just before addition of this aqueous, partially
neutralized,
monomer solution to the reactor, one or more polymerization initiators (e.g.,
sodium
persulfate alone or a redox-couple, such as t-butylhydroperoxide paired with
thiosulfate) are
added under conditions that do not favor polymerization. Optionally, a
chelating agent
(e.g., VersenexTm-80) can be added to the aqueous mixture ensure control of
transition
metal ions. An organic phase (e.g., IsoparTM L or toluene or n-heptane or
cyclohexane) is
placed into the main reactor (not the vessel with the aqueous monomer
solution). A
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hydrophobic suspending agent (e.g., Aerosil R972) is dissolved or dispersed in
the organic
phase. A crosslinking agent is added. If the crosslinking agent is soluble in
the organic
phase (e.g., divinylbenzene or 1,1,1-trimethylolpropane triacrylate¨also
called TMPTA), it
is added to the reactor with the organic phase. If the crosslinking agent is
water soluble
(e.g., highly-ethoxylated trimethylolpropane triacrylate¨also called HE-
TMPTA¨or
diacryl glycerol), the crosslinking agent is added to the aqueous phase. The
aqueous phase
is then added to the organic phase in the reactor, e.g., with mixing, and the
reaction mixture
is agitated to produce aqueous droplets of the appropriate size in the organic
solvent.
Simultaneously, oxygen is removed from the reaction mixture by bubbling an
inert gas (e.g.,
nitrogen) through the reaction mixture. After adequate deoxygenation, the
reaction will
either begin (e.g., in the case of redox couples) or be started by increasing
the temperature
(e.g., in the case of sodium persulfate). A second addition of hydrophobic
suspending agent
may be added as the polymerization proceeds, i.e., to further stabilize the
particles.
Reaction is completed by maintaining an elevated temperature (e.g., 65 C) for
a time
adequate to allow removal, i.e., reaction of substantially all of the monomer
(e.g., 2 to 4
hours). Water may then be removed by azeotropic distillation and the
crosslinked cation-
binding polymeric material may be isolated by filtration or centrifugation to
remove the
remaining organic solvent. The polymeric material may be rinsed with fresh
organic
solvent and dried to the desired moisture and/or organic solvent content as
measured by loss
on further drying. In some embodiments, less than 500 ppm of the monomer
remains after
polymerization. The polymer may be rinsed to remove this residual monomer.
[00625] In an exemplary method, acrylic acid (140 g) was added
dropwise to a
solution of 124.35 g of 50% NaOH and 140 g of deionized water while keeping
the
temperature below 40 C to prevent initiation of polymerization. 3.5 g of
VersenexTM 80
and 0.70 g of a 10% solution of sodium persulfate were added. Meanwhile, 1200
g of
IsoparTM L were charged into the main reactor. 0.80 g Aerosil R972 dissolved
in 40 g of
IsoparTM L and 0.50 g of TMPTA were added to the main reactor. The aqueous
monomer
solution was added to the reactor, which was then closed. Agitation was
started at 330
RPM and argon was bubbled through the reaction mixture. After 70 minutes of
bubbling
argon, the reaction was heated rapidly at 4 C increase per minute. When the
temperature
reached 50 C, another 0.80 g of Aerosil R972 in 40 g of IsoparTM L (that had
been
separately bubbled with argon) was added to the reaction mixture. The reaction
exotherm
heated the mixture to 80 C over the next 15 minutes while the constant
temperature bath
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was removing heat to keep the reaction mixture at 65 C. The reaction mixture
cooled to
70 C at approximately 60 minutes from the start of heating. The reaction
mixture was kept
at 65 C to 70 C for 4 hours. The reaction mixture was allowed to cool. The
resulting
crosslinked cation-binding polymer was isolated by filtration and dried in
vacuum at 105 C.
Example 2
[00626] This example illustrates the preparation of an exemplary
crosslinked
polyelectrolyte polymer by an aqueous phase reaction of a partially
neutralized carboxylic
acid monomer.
[00627] A monomer solution is prepared in a reactor by dissolving an
unsaturated
carboxylic acid monomer (e.g., acrylic acid) in water and neutralizing with an
aqueous
alkali (e.g., NaOH) to a desired percentage neutralization (e.g., 70 to 95
percent
neutralized). Optionally, a chelating agent (e.g., VersenexTM 80) may be added
to control
metal ions. A suitable crosslinking agent (e.g., 1,1,1-trimethylolpropane
triacrylate or
diacryl glycerol) is added to the reactor. A polymerization initiator is added
to the reactor.
The reactor is then closed and the reaction mixture is bubbled with an inert
gas (e.g.,
nitrogen) and agitated until adequate removal of oxygen is achieved. The
reaction is then
initiated either by reaching an oxygen concentration where a redox couple
produces radicals
or by adding heat to cause a temperature dependent initiator (e.g., persulfate
salts) to
produce radicals. The reaction is allowed to proceed through the exothermic
heating that
occurs during reaction. After 2 to 6 hours, the reaction is completed and the
gel-like mass
of reaction product can be removed from the reactor and cut into appropriately
sized pieces.
After drying, the particles can be separated by size or milled to produce the
desired size or
size distribution.
[00628] Thus, in an exemplary method, 140 g of acrylic acid were added
dropwise to a
solution of 124.35 g of 50% NaOH and 140 g of deionized water while keeping
the
temperature below 40 C to prevent initiation of polymerization. Then, 3.5 g of
VersenexTM
80 and 0.70 g of a 10% solution of sodium persulfate were added. The final
addition was
0.50 g of TMPTA. The reactor was closed and the reaction mixture agitated at
200 RPM
while argon was bubbled through the mixture. After 70 minutes of bubbling
argon, the
reaction was initiated by heating at a rate of a 4 C temperature rise per
minute. After 7
minutes, the reaction reached 55 C and the entire reaction mixture became a
gel. The
agitation was stopped, allowing the gel to slowly settle to the bottom of the
reactor. The
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temperature of the heating bath was maintained at 65 C for another 4 hours.
The gel was
then cooled, cut into pieces, and dried in a vacuum at 105 C.
[00629] In an alternative exemplary large scale continuous
production method, a
monomer feed mix of approximately 6.0 g TMPTA, 2.2 kg water, 0.4 kg sodium
hydroxide,
and 3.0 g sodium persulfate per kg of acrylic acid was deoxygenated and
polymerization
initiated with 0.6 g sodium ascorbate per kg of acrylic acid. The solution was
then charged
to a curing conveyor belt, where the sodium acrylate solution polymerized to a
gel as it
traveled on the conveyor belt. The polymer gel was then mechanically cut and
granulated
to reduce the polymer gel particle size and then the polymer was dried. The
dried polymer
was then milled and sieved to a desired particle size.
Example 3
[00630] This example illustrates the conversion of a partially
sodium-substituted
crosslinked polycarboxylic polymer prepared, for example, according to Example
1 or 2, to
a crosslinked polycarboxylic acid polymer with a reduced degree of sodium
substitution
(e.g., an acidified polymer).
[00631] The polymer is weighed and the relative content of different
cations (either
from knowledge of the preparation or, more preferably, from elemental analysis
of a
sample) is used to determine the number of moles of carboxylate present. The
polymer is
then washed with an excess (e.g., twice the number of moles of carboxylates,
or more) of 1
N acid (preferably HC1), either in batches or by column elution. The resulting
acidified
polymer is rinsed with water to remove any excess of the 1 N acid, and dried
in a vacuum at
60 C.
[00632] For example, 89.65 g of a polymer produced by the technique
of Example 1
were placed into a beaker and stirred with 667 mL of 1 N HC1 for 2 hours. The
liquid was
drained and the polymeric particles were returned to the vessel. A second
aliquot of 667
mL of 1 N HC1 was added and the mixture was stirred for 1 hour. The liquid was
drained
and a third rinse with 667 mL of 1 N HC1 was performed for 1 hour. The liquid
was drained
and the polymeric material was placed into 667 mL of deionized water and
stirred for 1
hour. The liquid was drained and another 667 mL of deionized water was added.
The
polymeric material was then stirred for 1 hour before draining the liquid.
This water
washing was continued until the pH of the rinse water was above 3. The
crosslinked cation-
binding polymer was then dried in a vacuum at 60 C.
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[00633] Alternatively, one-hundred grams of a cross-linked
polyelectrolyte polymer,
such as a partially neutralized cross-linked polyacrylate polymer (e.g.,
prepared as described
in Example 1 above) was placed into a vessel. Next, about 2,250 milliliters of
pure (e.g.,
trace metal or otherwise certified low metal) 1 M HC1 was added to the vessel
and then the
polymer and the acid were stirred gently for two hours. The liquid was removed
by
decanting or filtration. If desired due to vessel size or for improved mass
balance, the 2,250
milliliters of 1M HC1 is divided into multiple batches and used sequentially.
For instance,
750 milliliters were added, stirred with the polymer, and removed followed by
two or more
separate additions of 750 milliliters. The polymer was then rinsed with 2,250
milliliters of
low metal content water to remove excess acid surrounding the polyelectrolyte
such as a
polyacrylate. The crosslinked cation-binding polymer was then dried.
[00634] Further alternatively, one-hundred grams of a cross-linked
polyelectrolyte
polymer, such as a cross-linked polyacrylate polymer were placed into a
filtration funnel or
a column equipped with a bottom filter. The polymer was then rinsed with about
2,250
milliliters of pure (e.g., trace metal or otherwise certified low metal) 1 M
HC1 for about an
hour or more. Next, the polymer was rinsed with 2,250 milliliters of low metal
content
water. The crosslinked cation-binding polymer was then dried.
[00635] Exemplary acidified polymers useful as crosslinked cation-
binding polymers
prepared according to this Example generally have a saline holding capacity of
greater than
about 40 g/g (see, e.g., Examples 8 and 9); and contain less than about 5,000
ppm of
sodium, less than about 20 ppm of heavy metals, less than about 500 ppm of
residual
monomer, less than about 2,000 ppm of residual chloride, and less than about
20 wt.% of
soluble polymer. Preferably, acidified polymers useful as crosslinked cation-
binding
polymers prepared according to this Example have a saline holding capacity of
greater than
about 80 g/g (see, e.g., Examples 6-8); and contain less than about 500 ppm of
sodium, less
than about 20 ppm of heavy metals, less than about 50 ppm of residual monomer,
less than
about 1,500 ppm of residual chloride, and less than about 10 wt.% of soluble
polymer.
Crosslinked cation-binding polymers prepared according to the method of
Example 1 (using
acrylic acid monomers) and acidified to prepare the exemplary acidified
polymers of the
present Example may be referred to as "H-CLP" or "HCLP".
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Example 4
[00636] This example demonstrates the preparation of substantially
metal free (e.g.,
acid form) cross-linked polyelectrolyte polymers, such as cross-linked
polyacrylic acid
polymer.
[00637] In an exemplary method, substantially metal free (e.g., acid form)
cross-linked
polyacrylic acid polymer was prepared by placing 140 g of glacial acrylic acid
(e.g., not
neutralized as in Example 1) into a three to five liter reactor with 2,200 to
2,500 milliliters
of dilute acid, such as 1 M HC1. A water soluble cross linking agent, such as
1,3-
diglycerate diacrylate, in a ratio chosen to produce the desired saline
holding capacity (e.g.,
20-fold, 30-fold, 40-fold or more) and an initiator were added to the monomer
solution.
After sparging the reactor with an inert gas, (e.g., nitrogen) and agitating
the reaction
mixture, the reaction was started and allowed to proceed for two to four hours
until
substantially all of the monomer had reacted. The resultant mass of wet
polymer was then
cut into smaller pieces (e.g., 1-2 cm per side), dried in a vacuum or in an
inert atmosphere,
and then disrupted (e.g., by milling) to produce particles or powder.
[00638] 140 g of acrylic acid was placed into a reactor and diluted
with 326 g of
deionized water followed by addition of 0.50 g of TMPTA and 0.70 g of a 10%
solution of
sodium persulfate. The reactor was closed and the reaction mixture was
agitated at 250
RPM while argon was bubbled through the reaction mixture. After 70 minutes of
bubbling
argon, the reaction mixture was heated to produce an approximately 4 C
increase in
temperature per minute. After 7 minutes, the temperature reached approximately
50 C and
the entire reaction mixture became a gel that quickly settled to the bottom of
the reactor
when the agitation was stopped. Heating at 65 C was continued for 2 hours and
the gel was
allowed to cool overnight. The gel was then cut into pieces and dried in a
vacuum oven at
60 C.
[00639] 150 g of acrylic acid was placed into a reactor and diluted
with 444 g of
deionized water containing 0.5 g of iron sulfate heptahydrate, followed by
addition of 0.17
mol% TMPTA. The solution is cooled to 20 C with a N2 purge. Then 0.091 mol%
sodium
persulfate (mol% is moles per mole of acrylic acid) is added. The solution was
stirred and
inertized with nitrogen. Sodium ascorbate at 0.022 mol% was then added and
nitrogen
purge continued. The reactor was heated to 65 C and the reaction was allowed
to proceed
for more than two hours. The gel was then cut into pieces and dried in an oven
at 80-
100 C.
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[00640]
150 g of acrylic acid was placed into a reactor and diluted with 444 g of
deionized water containing 0.5 g of iron sulfate heptahydrate, followed by
addition of 0.34
mol% TMPTA. The solution is cooled to 20 C with a N2 purge. Then 0.091 mol%
sodium
persulfate (mol% is moles per mole of acrylic acid) is added. The solution was
stirred and
inertized with nitrogen. Sodium ascorbate at 0.022 mol% was then added and
nitrogen
purge continued. The reactor was heated to 80 C and the reaction was allowed
to proceed
for more than two hours. The gel was then cut into pieces and dried in an oven
at 80-
100 C.
[00641]
A crosslinked polyacrylic acid polymer was prepared as follows: 0.14g of
TMPTA was placed in a reactor with 140g acrylic acid with stirring. Once the
TMPTA is
dissolved 0.17g of Versenex 80 and 420 g of water are added and the solution
deoxygenated
with argon sparging. Then 4.2g of a 10 wt% solution of sodium persulfate and
2.1 g of a 1
wt% solution of tert-butylhydroperoxide were added. After stirring for 2
minutes 1.05g of a
10 wt% solution of sodium thiosulfate pentahydrate and 0.84g of a 10 wt%
solution of
sodium erythorbate were added to initiate the polymerization. After the
temperature rose to
41 C the reactor was heated at 65 C for 2 hours. The polymer gel was then
removed from
the reactor, torn and cut into pieces and dried in a vacuum oven.
[00642]
Free-acid forms of crosslinked cation-binding polymers prepared according to
the present example represent alternative forms of H-CLP.
[00643] In
another exemplary method, the content of certain cations (e.g., calcium,
sodium, magnesium, potassium or other cations) on a polymer may be determined
by ICP-
OES using microwave digestion of the sample in a nitric acid, hydrochloric
acid, hydrogen
peroxide digestion medium. For example, the sodium content of a polymer
prepared
according to any of Examples 1 to 4 can be determined by placing 50 mg of
polymer with
0.800 mL trace metal grade nitric acid, 0.450 mL concentrated trace metal
grade
hydrochloric acid and 0.200 mL of 30 wt% hydrogen peroxide in a digestion
vessel. The
vessel is then placed in a MARS 5 (CEM Corp) microwave at 100% power for 10
minutes
(to a temperature of 185 C) followed by 5 minutes at 100% power (to a
temperature of
195 C) and then holding the sample at 195 C for 15 minutes to digest the
sample.
[00644] The
digested polymer sample is then diluted to a final volume of 50 mL with
purified water to bring the concentration of the cation within the range of
the standard
curve. Standard solutions for construction of the standard curve were prepared
at 0 (blank),
0.10, 0.50 and 1.00 ug/mL Na in 4% (v/v) nitric acid.
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[00645]
An internal standard solution was prepared containing 20 mcg/mL yttrium and
100 mcg/mL germanium in 4% trace metal grade nitric acid. The internal
standard was
used in all analyses to normalize results and correct for matrix effects.
[00646]
Samples were analyzed on a Thermo Electron iCAP 6000 ICP-OES. Ca
concentrations in mcg/g were determined from the standard curve with
correction for
dilution, and converted to weight percent as described above.
[00647]
Likewise, sodium content in the same sample was analyzed by placing 50 mg
of polymer with 0.800 mL trace metal grade nitric acid, 0.450 mL concentrated
trace metal
grade hydrochloric acid and 0.200 mL of 30% (w/w) hydrogen peroxide in a
digestion
vessel. The vessel is then placed in a MARS 5 (CEM Corp) microwave at 100%
power for
10 minutes (to a temperature of 185 C) followed by 5 minutes at 100% power (to
a
temperature of 195 C) and then holding the sample at 195 C for 15 minutes to
digest the
sample.
[00648]
The digested polymer sample is then diluted to a final volume of 50 mL with
purified water to bring the concentration of the cation within the range of
the standard
curve. Standard solutions for construction of the standard curve were prepared
at 0 (blank),
0.1, 0.5 and 1.0 mcg/mL Na in 4% (v/v) nitric acid.
Example 5
[00649] The
content (e.g., percentage; %) of certain cations including, for example,
calcium, sodium, magnesium, and/or potassium, on a polymer may be determined
by ICP-
OES, ICP-AES and/or ICP-MS, for example, with a ThermoElectron Finnegan
Element 2
or a Perkin Elmer Elan 6000 instrument. The percentage of cations that are
counterions to
the carboxylate groups in the polymer determined in different ICP measurements
may vary
by 20% or less. For example, the determination of 5% to 30% or 15% to 35%
calcium
and/or magnesium cations as counterions to carboxylate groups in the polymer
may vary in
different measurements by ICP (e.g., 5% 20% to 30% 20% or 15% 20% to 35%
20%).
[00650]
For example, the calcium and/or sodium content of a polymer prepared
according to Examples 1-4 can be determined by diluting a 250 mg sample of the
polymer
with 5% nitric acid solution to a total volume of 100 mL. After shaking
overnight to extract
the calcium and sodium cations from the polymer, an aliquot of the mixture can
be diluted
with a 1% nitric acid solution as necessary to bring the concentration of the
cation within
the range of a suitable calibration curve (e.g., a standard curve with a
linear range). An
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appropriate internal standard (e.g., scandium, yttrium, germanium) is used to
correct for
matrix effects. Samples are diluted to within the range of the linear standard
curve for
analysis. Preferably the polymer is completely digested. To ensure complete
digestion of
the sample, an exemplary method is to fully digest the sample in nitric acid
(e.g., until the
solution becomes clear and colorless), for example by application of heat;
using microwave
digestion; using other acids or mixture of acids, hydrogen peroxide, or other
reagents; or by
other methods known in the art. For example, the polymer may be placed in a
nitric acid,
hydrochloric acid, and hydrogen peroxide medium and microwave digesting the
sample
using any method known to one of skill in the art. For example, when using ICP-
AES with
a sample size (e.g., 250 mg), such as with a ThermoElectron Finnegan Element 2
instrument, a 10-fold dilution is used for sodium determinations and a 100-
fold dilution is
used for calcium determinations. For example, when using ICP-MS, such as with
a Perkin
Elmer Elan 6000 or a ThemoElement2 instrument, a 10-fold dilution is used for
sodium
determinations and a 10,000-fold dilution is used for calcium determinations.
The final
dilution volume should be 10.0 mL to fall within a standard curve generated
using standards
at 0, 100, 250, 500, 2500, and 5000 ug/L. In order to normalize the results of
multiple runs,
an internal standard such as scandium or germanium (e.g., about 100 ILIL of a
10,000 ig/mL
solution of 99.999% scandium oxide in 5% nitric acid) was added to the 10-mL
diluted
samples before analysis.
[00651] In an exemplary method, a 250.08 mg sample of a polymer prepared
according to Examples 1-4 (e.g., Ca-CLP and/or Mg-CLP) was placed in a 100-mL
polypropylene tube and a 5% nitric acid solution was added until the total
volume of the
sample was 100 mL. The tube was then shaken overnight to produce "Mixed Sample
A."
A 250.11 mg sample of the same polymer used to prepare Mixed Sample A was
placed in a
100-mL polypropylene tube and a 5% nitric acid solution was added until the
total volume
of the sample was 100 mL. The tube is then shaken overnight to produce "Mixed
Sample
B." Next, three 0.100-mL aliquots Mixed Sample A were diluted with a 1% nitric
acid
solution to final volumes of 10.0 mL. As an internal standard, 102 L, 101 L,
and 100 ILIL
of a 10,000 ig/mL standard solution of 99.999% scandium oxide in 5% nitric
acid was
added to the three aliquots, respectively. Separately, three 0.100-mL aliquots
of Mixed
Sample B were similarly diluted with 1% nitric acid to final volumes of 10.0
mL and doped
with 100 L, 99.0 L, and 100 ILIL of the standard scandium solution,
respectively.
Analysis of calcium content proceeded using a ThermoElectron Finnigan Element
2 ICP-
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AES instrument (equipped with software version 2.42) according to the
manufacturer's
specifications. Standards at 0, 100, 250, 500, 2500, and 5000 ug/L were
analyzed to
generate a standard curve. The six raw calcium concentration measurements
(e.g., 55,449,
55,318, 54,761, 56,079, 56,375, and 55,949 g/g, respectively) were determined
(e.g., from
the standard curve) by normalizing the intensity of the raw calcium
measurement to the
measurement of the internal scandium standard. These six raw calcium
concentration
measurements were then converted into weight percent values (e.g., 5.54, 5.53,
5.48, 5.61,
5.64, and 5.59 wt.% Ca, respectively) and averaged to provide an overall
calcium content of
5.6 wt.%. The percentage of carboxylate groups to which calcium serves as a
counterion on
a polymer (e.g., the "[x]% Ca-CLP" nomenclature) can be determined from the
weight
percent calcium measurement (wt.% Ca) by the following equation:
[x]%Ca-CLP = (72.06)(wt.% Ca)/(20.05 ¨(0.19)(wt.% Ca))
[00652] For this example analysis, therefore, the polymer would be
termed "21% Ca-
CLP."
[00653] For example, polymers of the present disclosure such as crosslinked
polyacrylate polymers may have calcium concentration measurements (e.g.,
average
calcium concentration measurements as determined by ICP-AES analysis) of about
13,700
1..tg of calcium to about 77,300 [tg of calcium per gram of the polymer. This
range
approximately corresponds to a polymer in which calcium serves as a counterion
to about
5% to about 30% of the carboxylate groups, as shown in Table 3 below.
Alternatively, for
example, polymers of the present disclosure such as crosslinked polyacrylate
polymers may
have calcium concentration measurements (e.g., average calcium concentration
measurements as determined by ICP-AES analysis) of about 40,100 [tg of calcium
to about
89,100 [tg of calcium per gram of the polymer. This range approximately
corresponds to a
polymer in which calcium serves as a counterion to about 15% to about 35% of
the
carboxylate groups, as shown in Table 3 below.
Table 3: Calcium Content for Various Exemplary Polyacrylate Polymers.
% of Carboxylates
with Ca MW Wt% Ca ug/g Ca
0 72.06 0.00 0
5 73.01 1.37
13723
10 73.97 2.71
27092
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% of Carboxylates
with Ca MW Wt% Ca ug/g Ca
15 74.92 4.01 40122
20 75.87 5.28 52825
25 76.82 6.52 65214
30 77.77 7.73 77299
35 78.72 8.91 89092
40 79.68 10.06 100603
45 80.63 11.18 111843
50 81.58 12.28 122821
55 82.53 13.35 133545
60 83.48 14.40 144025
62 83.86 14.82 148150
65 84.43 15.43 154269
70 85.38 16.43 164284
72 85.77 16.82 168228
75 86.34 17.41 174078
80 87.29 18.37 183660
85 88.24 19.30 193034
90 89.19 20.22 202208
95 90.14 21.12 211189
100 91.09 22.00 219982
[00747] Additionally, for example, polymers of the present disclosure such as
crosslinked polyacrylate polymers may have magnesium concentration
measurements (e.g.,
average magnesium concentration measurements as determined by ICP-AES
analysis) of
about 8,400 [ig of magnesium to about 48,300 [ig of magnesium per gram of the
polymer.
This range approximately corresponds to a polymer in which magnesium serves as
a
counterion to about 5% to about 30% of the carboxylate groups, as shown in
Table 4 below.
Alternatively, for example, polymers of the present disclosure such as
crosslinked
polyacrylate polymers may have magnesium concentration measurements (e.g.,
average
io magnesium concentration measurements as determined by ICP-AES analysis)
of about
24,700 [ig of magnesium to about 56,000 [ig of magnesium per gram of the
polymer. This
range approximately corresponds to a polymer in which magnesium serves as a
counterion
to about 15% to about 35% of the carboxylate groups, as shown in Table 4
below.
Table 4:Magnesium Content for Various Exemplary Polyacrylate Polymers.
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% of Carboxylates
with Mg MW Wt% Mg ug/g Mg
0 72.06 0.00 0
72.62 0.84 8365
73.18 1.66 16603
73.73 2.47 24717
74.29 3.27 32709
74.85 4.06 40581
75.41 4.83 48338
75.96 5.60 55980
76.52 6.35 63511
77.08 7.09 70934
77.64 7.82 78249
78.19 8.55 85461
78.75 9.26 92570
62 78.97 9.54 95386
79.31 9.96 99580
79.87 10.65 106491
72 80.09 10.92 109229
80.42 11.33 113307
80.98 12.00 120029
81.54 12.67 126659
82.10 13.32 133199
82.65 13.97 139651
100 83.21 14.60 146016
[00748] Using Mixed Sample A and Mixed Sample B described in the previous
paragraph, sodium content was determined by ICP-AES as follows. Three 1.0-mL
aliquots
of Mixed Sample A were each diluted to a final volume of 10.0 mL using a 1%
nitric acid
5 solution. To each was added 113 ILIL of a 10,000 ig/mL standard solution
of 99.999%
scandium oxide in 5% nitric acid. Similarly, three 1.00-mL aliquots of Mixed
Sample B
were diluted to final volumes of 10.0 mL and were doped with 115 L, 115 L,
and 116 ILIL
of the standard scandium solution. Analysis of sodium content proceeded using
a
ThermoElectron Finnigan Element 2 ICP-AES instrument (equipped with software
version
10 2.42) according to the manufacturer's specifications. The six raw sodium
concentration
measurements (e.g., 327, 328, 328, 381, 381, and 381 iLig/g, respectively)
were determined
by normalizing the intensity of the raw sodium measurement to the measurement
of the
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internal scandium standard. These six raw sodium concentration measurements
were then
averaged (354 ug/g) wherein:
354 iug/g is equivalent to 0.035 wt% sodium
[00749] The percentage of carboxylate groups to which sodium serves as a
counterion
(e.g., the "[x]% Na-CLP" nomenclature) on a polyacrylate polymer can be
determined from
the weight percent sodium measurement (wt.% Na) by the following equation:
[x]%Na-CLP = (72.06)(wt.% Na)/(23.0 ¨ (0.23)(wt.% Na))
[00750] For this example analysis, with an average sodium concentration of 354
ug of
sodium per gram of polyacrylate polymer, or 0.035 wt.% sodium, sodium cations
are
counterions to about 0.11% of the carboxylate groups in the polymer.
[00751] Polymers of the present disclosure may have sodium concentration
measurements
(e.g., average sodium concentration measurements as determined by ICP-AES
analysis) of
about Oi_tg of sodium to about 16,100 [tg of sodium per gram of polyacrylate
polymer. This
range approximately corresponds to a polymer in which sodium serves as a
counterion to
about 0% to about 5% of the carboxylate groups.
[00752] The percentage of carboxylate groups to which magnesium serves as a
counterion
on a polymer (e.g., the "[x]% Mg-CLP" nomenclature) can be determined from the
weight
percent measurement (wt.% Mg) by the following equation:
[x]%Mg-CLP = (72.06)(wt.% Mg)/(12.15 ¨ (0.11(wt.% Mg))
[00753] In another exemplary method, the content of certain cations (e.g.,
calcium,
sodium, magnesium, potassium or other cations) on a polyacrylate polymer may
be
determined by ICP-OES. For example, the calcium content of a polymer prepared
according
to Examples 1-4 can be determined by diluting a measured mass of polyacrylate
polymer
with a known volume of a 5% aqueous solution of trace metal grade nitric acid.
The sample
is then digested by first heating the polyacrylate polymer mixture until
gaseous NO2 is
apparent. While continuing to heat, a small measured aliquot of 30-40%
hydrogen peroxide
is added to the solution. The solution foams and may turn brown. Once the
foaming
subsides an additional aliquot of hydrogen peroxide is added and repeated
until the foaming
after hydrogen peroxide addition is minimal, no particulate is visible, and a
clear and
colorless solution including, for example, a fully digested sample, has been
prepared. The
total volume of hydrogen peroxide is recorded. Additional measured volumes of
5% nitric
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acid may be added during the digestion process to maintain an adequate volume
of liquid.
An appropriate volume of the digested polyacrylate polymer sample is diluted
to a final
volume of 10 mL with the 5% nitric acid solution to bring the concentration of
the cation
within the range of a suitable calibration curve; serial dilutions in 5%
nitric acid can be
made with the total dilution recorded. An internal scandium/cesium
standard/ionization
buffer was prepared from CsNO3 and a scandium standard and was used in all
analyses to
normalize results and correct for matrix effects. The internal standard was
prepared by
adding 50 mg scandium standard (1000 g/mL) and 1.48 g anhydrous CsNO3 to 1 L
of 5%
trace metal grade nitric acid. The internal was mixed with the sample online
prior to
injection into the ICP instrument. Standard solutions for construction of the
standard curve
were prepared at 0.2, 1, 5 and 25 [ig/g Ca in 5% nitric acid. Samples were
analyzed by ICP-
OES on a Perkin Elmer Optima 5300 DV. Ca concentrations in iLig/g were
determined from
the standard curve with correction for dilution, and converted to weight
percent as described
above.
[00754] In another exemplary method, the content of certain cations (e.g.,
calcium,
sodium, magnesium, potassium or other cations) on a polymer may be determined
by ICP-
OES using microwave digestion of the sample in a nitric acid, hydrochloric
acid, and
hydrogen peroxide digestion medium. For example, the calcium content of a
polymer
prepared according to Example 5 can be determined by placing 50 mg of polymer
with
0.800 mL trace metal grade nitric acid, 0.450 mL concentrated trace metal
grade
hydrochloric acid and 0.200 mL of 30% (w/w) hydrogen peroxide in a digestion
vessel. The
vessel is then placed in a MARS 5 (CEM Corp) microwave at 100% power for 2
minutes (to
a temperature of 165 C) followed by 3 minutes at 100% power (to a temperature
of 175 C)
and then holding the sample at 175 C for 10 minutes to digest the sample
including, for
example, to completely digest the sample. The digested polymer sample is then
diluted to a
final volume of 50 mL with purified water to bring the concentration of the
cation within
the range of the standard curve. Standard solutions for construction of the
standard curve
were prepared at 0 (blank), 100, 500 and 1000 ug/mL Ca in 4% (v/v) nitric
acid. An internal
standard solution was prepared containing 20 ig/mL yttrium and 100 ig/mL
germanium in
4% trace metal grade nitric acid. The internal standard was used in all
analyses to
normalize results and correct for matrix effects. Samples were analyzed on a
Thermo
Electron iCAP 6000 ICP-OES. Ca concentrations in iLig/g were determined from
the
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standard curve with correction for dilution, and converted to weight percent
as described
above.
[00755] Likewise, sodium content in the same sample was analyzed by placing 50
mg of
polymer with 0.800 mL trace metal grade nitric acid, 0.450 mL concentrated
trace metal
grade hydrochloric acid and 0.200 mL of 30% (w/w) hydrogen peroxide in a
digestion
vessel. The vessel is then placed in a MARS 5 (CEM Corp) microwave at 100%
power for
minutes (to a temperature of 185 C) followed by 5 minutes at 100% power (to a
temperature of 195 C) and then holding the sample at 195 C for 15 minutes to
digest the
sample. The digested polymer sample is then diluted to a final volume of 50 mL
with
10 purified water to bring the concentration of the cation within the range
of the standard
curve. Standard solutions for construction of the standard curve were prepared
at 0 (blank),
0.1, 0.5 and 1.0 ug/mL Na in 4% (v/v) nitric acid.
Example 6
[00699] The saline holding capacity of a cross-linked polyelectrolyte
polymer, such as
a cross-linked polyacrylate polymer, may be determined by known methods in the
art.
[00700] In an exemplary method, saline holding capacity was
determined with a 0.15
M sodium solution as follows. A pH seven buffer of sodium phosphate tribasic
(Na3PO4=12H20; MW 380.124) was prepared by dissolving 19.0062 grams in about
950
milliliters pure water and adjusting the pH to a final pH of 7 0.1 with 1N
HC1 before final
dilution to one liter resulting in a solution with a sodium concentration of
0.15 M. Next, an
amount of cross-linked cation-binding polyelectrolyte, for example, cross-
linked
polyacrylate beads (e.g., HCLP prepared according to Examples 1-4) (e.g., 0.1
+ 0.025
grams), were transferred to a tared filter tube and the mass of the polymer
was recorded as
in W1. Next, the tube was returned to the balance to record the weight of the
tube plus the
sample as W2. An excess (e.g., more than seventy times the mass of polymer)
amount of
the pH 7.0 buffer (e.g., ten milliliters) was then transferred to the tube
containing the CLP
sample. The tube was then placed on a flat bed shaker with shaking for two,
four or six
hours. After shaking, all excess fluid was removed from the tube (e.g., no
visible fluid in
the tube). Last, the tube and sample were weighed and recorded as W3. The
saline holding
capacity (SHC) was calculated by dividing the mass of the fluid absorbed by
the mass of the
dry crosslinked polyacrylate polymer, for example, SHC (g/g) = (W3-W2)/ (W1).
According to the present disclosure, cross-linked cation-binding polymers,
including
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polyacrylate beads prepared according to the methods disclosed herein, had a
saline holding
capacity of 20 g/g, 30 g/g, 40 g/g, or more. Alternatively stated, such cross-
linked cation-
binding polymers, including where the polyelectrolyte is polyacrylate, can
absorb 20-fold,
30-fold, 40-fold, or more of their mass in a saline solution.
Example 7
[00701] The saline holding capacity of a cross-linked
polyelectrolyte polymer, such as
a cross-linked polyacrylate polymer, may be determined by known methods in the
art.
[00702] In an exemplary method, saline holding capacity is
determined with a 0.15 M
sodium phosphate solution buffered to pH 7 containing 0.05 wt.% sodium dodecyl
sulfate
(or other similar anionic surfactant) as follows. A sealable pouch, for
example, a 2.5-inch
by 3-inch rectangular pouch, is made by folding heat sealable tea bag
material, for example,
a 5-inch by 3-inch piece of heat sealable tea bag material (available from
www.organzabagg.com) in half and heat-sealing two edges of the formed pouch.
The
empty tea bag is weighed (MI). An amount of HCLP, for example, 200 mg of the
cross-
linked polyacrylate polymer, is added to the tea bag, which is then heat-
sealed along the
remaining edge. The mass of the polymer-containing tea bag is then recorded
(M2).
[00703] A second tea bag is prepared in the same manner, except no
polymer is added.
[00704] The sealed bags are then placed between two pieces of
fiberglass screen (e.g.,
Teflon coated fiberglass screens having 0.635 cm opening, Taconic Plastics
Inc.,
Petersburg, NY). The tea bags and fiberglass screens are then submerged in the
saline
solution and allowed to soak for the desired time, typically 30 minutes.
[00705] The wet tea bags are removed from the saline solution and
placed into a
centrifuge with water collection basket, digital speed gauge and drainage
basket. The tea
bags are spun in the centrifuge, for example, for 3 minutes at 350 G.
[00706] The mass of the wet polymer-containing tea bag is recorded
(M3). The mass
of the wet, empty tea bag is recorded (M4). The absorbent capacity of the
polymer per gram
of polymer, S, is calculated according to equation (1):
S = (M3 ¨ M2 ¨ (M4 ¨ Mr)) / (M2 ¨ Mr)
Example 8
[00756] The saline holding capacity of a cross-linked polyelectrolyte polymer,
such as a
cross-linked polyacrylate polymer, may be determined by known methods in the
art.
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[00757] In an exemplary method, a saline absorption capacity (e.g., saline
holding
capacity) of crosslinked cation-binding polymers comprising monomers
containing
carboxylate groups, wherein the polymers further comprise calcium and/or
magnesium
cations (e.g., calcium cations or magnesium cations or a mixture thereof),
wherein the
calcium and/or magnesium cations are counterions to the carboxylate groups in
the polymer
is measured using a centrifugal method. According to this method, the
centrifuge retention
capacity (CRC) of the polymer (e.g., HCLP or HCLP) is determined without first
treating
the polymer with acid.
[00758] For example the saline holding capacity of HCLP particles may be
determined. A
pH 7 phosphate buffered saline uptake buffer is prepared with 10.65 g of
sodium phosphate
dibasic (anhydrous) in 1 L purified water, with pH adjustment to pH 7.0 with
1N HC1. The
weight of a centrifuge tube is determined (Wtube). 100 10 mg of the HCLP
particles are
weighed and added to centrifuge tube and the tube reweighed (Wtube+sample). 25
mL of
uptake buffer is then added to centrifuge tube and the tube capped and shaken
vigorously.
The tube is then shaken on a wrist-action shaker for at least 8 hours. The
tube is then
centrifuged for 10 minutes at 3500 rpm and the supernatant decanted. The tube
with the
swollen gel particles is reweighed (Wtube+swollen gel) and the saline holding
capacity
determined as:
Saline holding capacity (w/w) = (Wt(tube+swollen gel) - W(tube) ) /
(W(tube+sample) -
W(tube)).
Example 9
[00707] Mixtures of H-CLP with basic salts of calcium were tested in
rats to determine
the effect of administered calcium on the fecal removal of Na, K, and/or P
ions, and/or fluid
(e.g., increase in fecal mass), and to evaluate the effect of added base on
acid/base
parameter (as urinary phosphate). The amount (mEq) of base administered was
equivalent
to the mEq of acid administered as polyacrylic acid. Multiple sets of 3 or 6
rats per set were
placed into metabolic cages to allow assessment of food and water intake,
measurement of
fecal and urinary excretion, and collection of feces and urine for chemical
analysis. Rats
were fed diets with crosslinked polyacrylate polymer (H-CLP) made as described
in
Example 3), at 5% of the weight of their diets daily. Each rat was co-
administered various
amounts of calcium oxide, calcium carbonate, or calcium citrate mixed into the
diet. After
stabilization on the diets, feces and urine were collected for three
consecutive days. These
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daily fecal and urinary samples were digested and analyzed by ICP/AES
(inductively
coupled plasma/atomic emission spectroscopy) for fecal sodium, fecal
potassium, and
urinary phosphate.
Table 5. Change in Daily Fecal Sodium, Fecal Potassium, and Urinary
Phosphorous in
Rats Co-Administered H-CLP and a Calcium Base
A Urinary
Equivalents A Fecal Sodium A Fecal Potassium Phosphorous
of Base (mg/day) (mg/day) (mg/day)
0 35.1 99.9 25.6
0.5 36.7 46.2 2.6
0.625 37.4 46.8 -1.4
0.75 33.2 36.2 -4.1
0.875 28.7 26.2 -10.5
1 18.1 18.7 -7.4
[00708] As shown in Table 5, co-administration of H-CLP and base
increased fecal
excretion of both sodium and potassium. However, increasing amounts of co-
administered
base decreased the net effect on fecal changes in sodium and potassium, and
decreased
urinary phosphorous levels (decreasing phosphorous levels indicates less
acidosis). When
H-CLP was administered without base, or with small amounts of base, acidosis
was
observed as indicated by increased levels (positive values of urinary
phosphorous).
Surprisingly, however, co-administration of a moderate amount of base (e.g.,
0.5 to 0.625
equivalents) largely prevented acidosis. When more than about 0.8 equivalents
of base
were co-administered, rats became slightly alkalotic.
[00709] Changes in fecal fluid excretion are shown in Table 6, in
comparison to
baseline values.
Table 6. Net Change from Baseline in Daily Fecal Mass in Rats Co-Administered
H-
CLP and a Calcium Base
Equivalents A Fecal
of Base Mass
(g/day)
0 7.44
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0.5 4.15
0.625 3.46
0.75 3.75
0.875 2.74
1 4.56
[00710] In an additional rat experiment with H-CLP made as described
in Example 4,
the H-CLP was similarly able to remove fecal sodium and potassium ions, as
well as to
increase fecal mass.
Example 10
[00711] Mixtures of H-CLP with a basic salt of magnesium were tested
in rats to
determrine whether the addition of Mg improves removal of Na, K, and/or fluid.
All
mixtures supplied enough base to potentially neutralize the acid groups on the
H-CLP.
Multiple sets of 3 or 6 rats per set were placed into metabolic cages to allow
assessment of
food and water intake, measurement of fecal and urinary excretion, and
collection of feces
and urine for chemical analysis. Rats were fed diets with crosslinked
polyacrylate polymer
(H-CLP, made as described in Example 4), at 5% of the weight of their diets
daily. Various
amounts of magnesium oxide were co-administered with the polymer. After
stabilization on
the diets, feces and urine were collected for three consecutive days. These
daily fecal and
urinary samples were digested and analyzed by ICP/AES for fecal sodium, fecal
potassium,
and urinary phosphorous.
Table 7. Net Change in Daily Fecal Sodium, Fecal Potassium, and Urinary
Phosphorous in Rats Co-Administered H-CLP and a Magnesium Base
A Fecal A Urinary
Equivalents A Fecal sodium potassium phosphorous
of Base (mg/day) (mg/day) (mg/day)
0 35.1 99.9 25.6
0.25 50.2 72.2 27.1
0.4 21.0 58.3 2.7
0.5 36.8 48.1 7.1
[00712] As shown in Table 7, co-administration of H-CLP and up to
about 0.5
equivalents of magnesium base increased both fecal sodium excretion and fecal
potassium
excretion. As shown by the dramatic and unexpected changes in urinary
phosphorous
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levels, co-administration of 0.4 or 0.5 equivalents of magnesium base largely
prevented
acidosis.
Example 11
[00713] A study was conducted in rats to evaluate an additional crosslinked
polyacrylic acid polymer and its ability to remove fluid and impact on fecal
and urinary
levels of cations. For this study, polycarbophil was purchased from Lubrizol
Advanced
Materials, Inc. (Noveon AA-1). Polycarbophil is a polymer of acrylic acid,
crosslinked
with divinyl glycol. Polycarbophil used for this study contains carboxylic
acid groups in
acidic form. Noveon AA-1 polycarbophil is provided as a flocculated powder of
particles
averaging about 0.2 micron in diameter. The individual colloidal 0.2 micron
polymer
particles are formed by precipitation polymerization in an organic solvent
such as benzene
and/or ethyl acetate. The flocculated powders average 2 to 7 microns as
determined by
Coulter Counter. These agglomerates cannot be broken down into the primary
particles once
produced. In this study, the ability of polycarbophil to remove Na and K ions
and fluid was
examined.
[00714] To prepare the diet for the study, Noveon AA-1
polycarbophil was first
granulated by spraying deionized water lightly on a non-stick sheet followed
by spreading a
thin layer of the flocculated polycarbophil powder on the wet surface.
Deionized water was
sprayed again onto the polycarbophil layer and the material was allowed to dry
at room
temperature. All the dried material was collected and further dried at 80 C.
The dried
material was placed into a vessel and mixed with pulverized Purina Rat Chow
LabDiet
5012. This mixture was then milled in a blender until a powder with uniform
distribution
was obtained. Six male Sprague Dawley rats were fed with a diet of the
milledpolycarbophil
at 5% of the weight of their diets daily. An additional six male Sprague
Dawley rats were
fed diets with crosslinked polyacrylate polymer (H-CLP may as described in
Examples 1
and 3) at 5% of the weight of their diets daily.
[00715] Daily measurements of rat weight, food intake, water intake,
urine output, and
fecal output were recorded. This was a 9-day study with the first 3 days of
the study
providing a baseline period, followed by a 6-day treatment period. Daily
measurements of
rat weight, food intake, water intake, urine output, and fecal output were
recorded. The first
three days of the treatment period were regarded as days of equilibration and
after
stabilization on the diets; feces and urine were collected for three
consecutive days. Days 7,
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8, and 9 of the study period (Days 4, 5, and 6 of the treatment period) were
used for
collection of the urine and feces for digestion and ICP-AES analysis. These
daily fecal and
urinary samples were digested by placing each sample into a flask, adding
trace metal grade
concentrated nitric acid, heating to boiling. This was followed by adding 30%
hydrogen
peroxide in small aliquots until the solutions were clear and the vigorous
foaming after
additions of hydrogen peroxide had ceased. The digested samples were analyzed
by
ICP/AES (Inductively coupled plasma atomic emission spectroscopy) for fecal
sodium,
fecal potassium, and urinary phosphate. Changes in fecal sodium and potassium
excretion
levels and urinary phosphorus values over control (rats on rat chow and no
polymer) were
calculated and are shown in Table 6 (i.e., control fecal sodium and potassium
and control
urinary phosphorus excretion levels were subtracted from fecal sodium and
potassium and
urinary phosphorus levels in treatment groups). Changes in fecal weights over
control (rats
on rat chow and no polymer) as a measure of fecal fluid were also calculated
and are shown
in Table 8 (control fecal mass was subtracted from fecal mass in treatment
groups).
Table 8. Net Change in Daily Fecal Sodium, Fecal Potassium, Urinary
Phosphorous,
and Fecal Mass in Rats Administered HCLP or Polycarbophil
A Fecal A Fecal A Urinary A Fecal
Sodium Potassium Phosphorous Mass(g/day)
(mg/day) (mg/day) (mg/day)
H-CLP 29.9 90.3 25.6
7.89
Polycarbophil 24.1 79.7 34.1
8.72
[00716] As shown in Table 8, these results show that polycarbophil
has the ability to
remove sodium and potassium in the feces.
Example 12
[00717] An open-label, multiple-dose escalation clinical trial was
performed in
twenty-five healthy human subjects divided into five groups (Table 9). One
control group
received no treatment, one group received 7.5 g H-CLP/day with meals, one
group received
15 g H-CLP/day with meals, one received 15 g H-CLP/day one hour before meals,
and one
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group received 25 g H-CLP/day with meals. Subjects remained in the clinical
research unit
for the duration of the study.
[00718] H-CLP was prepared according to Examples 1 and 3, for
example, a cross-
linked polyacrylic acid polymer with less than 5000 ppm sodium (e.g., 153 ppm
sodium),
less than 20 ppm heavy metals, less than 1000 ppm residual monomer (e.g., 40
ppm residual
monomer), less than 20% insoluble polymer (e.g., 3% insoluble polymer), and
with loss on
drying of less than 5% of its weight (e.g., loss on drying of 1% of its
weight). The H-CLP
polymer was milled to break up the bead structure and reduce the particle
size. The milled
H-CLP was then filled into capsules with 0.7 g per capsule.
[00719] The objectives of the clinical trial included (1) determination of
the safety,
tolerability and efficacy of H-CLP to remove, i.e., altered fecal excretion
of, sodium,
calcium, magnesium, potassium, iron, copper, zinc and/or phosphorous; (2) to
determine
whether administration of H-CLP altered the amount of fluid absorbed, i.e.,
altered fecal
weight, per gram of H-CLP administered; (3) to determine whether
administration of H-
CLP altered measures of acidosis, including serum total bicarbonate, urine pH,
and urine
phosphorous; and (4) to determine whether administration of H-CLP altered
serum
potassium levels. For all outcomes, treated groups were compared to the
control group.
[00720] The primary endpoints included net sodium balance compared
among treated
and control groups. Secondary endpoints included change in stool weight
compared among
treated and control groups; net balance of calcium, magnesium, potassium,
iron, copper,
zinc and phosphorous compared among treated and control groups; fluid consumed
and
excreted in the treated groups compared with the control group; and safety and
tolerability
based upon review of vital signs, clinical safety labs and adverse events.
[00721] H-CLP was administered with water, 4 times a day for a total
of 9 days (a total
of 36 consecutive doses). For each dose group of five subjects, H-CLP was
administered
one hour before or just after each of 4 standardized meals or snacks as shown
in Table 9.
Doses were given at the scheduled time (+/- 10 minutes) for each subject.
Table 9: Dose Groups and Feeding Status at Dose Administration
Group Number of Dose H-CLP Timing of Duration
of
Subjects (g/day) Dosing Dosing
(d)
Control 5 0 9
A 5 7.5 Just after each 9
meal or snack
B 5 15 Just after each 9
meal or snack
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C 5 15 One hour before 9
each meal or
snack
D 5 25 Just after each 9
meal or snack
[00722] Diet was controlled with all participants having identical
meals. Each day all
meals and snacks representing one subject were homogenized and the sodium,
potassium,
calcium, phosphorus, iron, copper, zinc and magnesium content determined. All
meals
provided to the subjects were controlled for the number of calories, level of
sodium (5000
mg per day +/- 100 mg), fiber content (10-15 g per day), fat content and
approximate
recommended Dietary Reference Intakes. Subjects were requested to consume all
of their
meals. Meals that were not fully consumed were collected for an entire twenty-
four hour
period, weighed and frozen for possible metal analysis.
[00723] Subjects fasted for at least eight hours at screening and four
hours at
admission prior to the collection of blood and urine samples for clinical
laboratory tests.
Fasting was not required prior to urine and blood samples taken during the
study. Water ad
libitum was allowed during the periods of fasting.
[00724] Stool weight, fecal electrolytes and fluid balance were
determined daily.
Serum samples were collected daily and the concentration of sodium, potassium,
magnesium, calcium, phosphorus and carbon dioxide determined. All urine
specimens were
collected and volume recorded. An aliquot of a daily afternoon urine sample
was analyzed
for pH and osmolality. Urine samples were pooled for each 24-hour period and
an aliquot
sampled for sodium, potassium, calcium, phosphorous and magnesium analysis.
[00725] All feces eliminated after consumption of the first controlled meal
were
collected as individual samples in tared collection containers. The color and
consistency of
the stool were noted, the sample weighed, then frozen and stored at or below -
20 C. All
fecal collections were analyzed for sodium, potassium, magnesium, calcium,
phosphorous,
iron, zinc and copper content. Fecal weights for all samples eliminated in
each 24-hour
period were added together to determine the total fecal weight per subject per
day.
[00726] Daily fecal and urine weight, urine osmolality and pH, and
daily fecal and
urine content and concentrations of sodium, calcium, magnesium, potassium and
phosphorus (plus copper, iron and zinc only in the stool) were determined for
each subject
and each treatment group. Daily fluid balance (fluid intake - output) and
daily net balance of
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sodium, magnesium, calcium, potassium and phosphorus were calculated based on
the
analysis of diet, urine and stool samples for each patient and each group.
[00727] Daily parameters were compared for each H-CLP dose group and
the control
group. A steady state effect of dosing with H-CLP administered 4 times daily
was reached
after 4 days of dosing. Daily parameters were also averaged for days 5-9 for
each group
and treatment groups compared to the control group.
[00728] Fecal metal excretion (e.g., sodium, potassium, magnesium
and calcium) for
doses of H-CLP between 0 and 25 g are shown in Tables 10 to 13 below. Daily
excretion of
sodium, potassium, magnesium and calcium for the control group are shown in
Table 10.
io The average daily value of metal cation excretion on days 1 to 9 for the
treatment groups are
compared to the average value for the control group and are shown for 7.5 g of
H-CLP daily
(Group A, Table 11), for 15 g of H-CLP daily taken immediately after meal
(Group B,
Table 12), and for 25 g of H-CLP daily (Group D, Table 13). Fasting before
administration
of H-CLP did not significantly affect ion excretion.
Table 10: Fecal Metal Excretion (mg/day)-0 grams H-CLP (Control Group)
Day Sodium Potassium
Magnesium Calcium
Excretion Excretion Excretion
Excretion
(mg/day) (mg/day) (mg/day)
(mg/day)
1 33.5 906.5 141.2
554.9
2 70.5 239.6 342.1
1663.4
3 12.1 728.7 112.1
691.2
4 114.8 394.4 292.6
2005.6
5 21.5 453.3 149.1
1134.1
6 32.8 680.2 182.2
1351.7
7 151.5 289.4 289.2
2003.1
8 44.9 259.0 120.2
1059.0
9 45.5 0 109.0
866.0
Sodium Potassium Magnesium
Calcium
Day Excretion Excretion Excretion
Excretion
(mg/day) (mg/day) (mg/day)
(mg/day)
1 33.5 280.1 141.2
554.9
2 70.5 906.5 342.1
1663.4
3 12.1 239.6 112.1
691.2
4 114.8 728.7 292.6
2005.6
5 21.5 394.4 149.1
1134.1
6 32.8 453.3 182.2
1351.7
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Day Sodium Potassium
Magnesium Calcium
Excretion Excretion
Excretion Excretion
(mg/day) (mg/day) (mg/day)
(mg/day)
7 151.5 680.2 289.2 2003.1
8 44.9 289.4 120.2
1059.0
9 45.5 259.0 109.0 866.0
Table 11: Changes in Fecal Metal Excretion Over Control (mg/day) for Subjects
Administered 7.5 grams of H-CLP Daily (Group A)
Day A Sodium A Potassium A Magnesium A
Calcium
Excretion Excretion
Excretion Excretion
(mg/day) (mg/day) (mg/day)
(mg/day)
1 22.5 313.6 130.3 742.7
2 62.7 147.1 -17.5 147.2
3 348.6 1188.1 127.1 758.0
4 473.0 1554.0 -17.7 -130.4
362.1 981.7 2.2 -71.2
6 365.3 1182.3 27.3 105.2
7 531.6 1223.3 -22.4 -445.6
8 524.5 1763.4 159.6 728.3
9 298.0 1104.9 72.6 247.9
5 Table 12: Changes in Fecal Metal Excretion Over Control (mg/day) for
Subjects
Administered 15 grams of H-CLP Daily (Group B)
Day A Sodium A Potassium A Magnesium A
Calcium
Excretion Excretion
Excretion Excretion
(mg/day) (mg/day)
(mg/day) (mg/day)
1 -16.2 254.2 78.2 390.3
2 70.4 222.2 -102.2 -541.3
3 338.5 1442.6 66.9 240.5
4 565.9 1195.0 -96.9 -829.6
5 1032.2 2531.8 78.3 167.6
6 1158.3 1744.8 49.9 -29.0
7 1003.5 1422.0 -26.5 -519.2
8 1103.0 1555.7 103.5 342.3
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9 808.2 1888.7 108.3 350.8
Table 13: Changes in Fecal Metal Excretion Over Control (mg/day) for Subjects
Administered 25 grams of H-CLP Daily (Group D)
Day A Sodium A Potassium A Magnesium
A Calcium
Excretion Excretion Excretion
Excretion
(mg/day) (mg/day) (mg/day)
(mg/day)
1 86.9 302.9 80.3 470.6
2 779.8 347.7 -142.0 -693.1
3 723.5 1314.9 13.6 46.8
4 1947.1 2956.3 -38.3 -593.6
1763.2 3644.0 43.7 -63.5
6 1905.8 4872.7 130.0 617.3
7 2489.5 4631.2 34.0 -248.4
8 2529.0 3631.2 191.9 598.6
9 1641.6 2248.8 84.5 189.6
5 [00729] For each treatment group the amount of Na and K excreted in
the feces
increased between days 1 to 4 and then became fairly constant on days 5 to 9.
The net
change from the control group in the average daily fecal sodium and potassium
content for
days 5-9 was determined for each treatment group and shown in Table 14.
Table 14. Change in Daily Average of Fecal Sodium and Potassium Excretion and
Serum Potassium Compared to Control for Days 5-9
Na K Serum K
Dose (g) Dose Administration (mg/day) (mg/day)
(mmol/L)
7.5 With meals 417 1228 -0.5
With meals 981 1825 -0.5
15 One hour prior to meals 1034 1749 -0.8
With meals 2046 3668 -1.5
[00730] The administration of HCLP results in a dose dependent
increase in the fecal
excretion of sodium and potassium.
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[00731] Serum potassium levels were also evaluated daily. The change
in average
serum potassium for the treatment groups from the average for the control
group on Days 5
to 9 values are shown in Table 15. Serum potassium decreased from control
values in all
treatment groups.
[00732] Measures of acidosis included total serum bicarbonate and urine
phosphate.
The average change from control in these parameters for Days 5-9 are shown in
Table 15.
Table 15. Average Change from Control in Acidosis Parameters for Days 5-9
Time of Urine pH Urine Fecal
Administration Total serum CO2 Phosphate
Phosphate
Dose (g) (mmol/L) (mg/day) (mg/day)
7.5 With meal -1.3 -2.3 255 -181
(fed) With meal -1.21 -4.4 341 -365
15 One hour prior -0.78 -363
(fasted) to meal -4.4 389
With meal -0.79 -8.8 341 -305
[00733] For all doses of HCLP there was an apparent acidosis as
measured by these
1 o parameters. The decrease from control in total serum bicarbonate and
serum phosphate
were dose dependent.
[00734] Administration of HCLP led to an increase in fecal weight in
a dose dependent
manner as shown in Table 16. This increase in fecal weight was not associated
with
diarrhea but is expected to be due to water entrapped in the superabsorbent
polymer.
15 Table 16. Average Change from Control in Fecal Weight for Days 5-9
Dose (g) Time of Administration Fecal Wt (g)
7.5 With meal 121
15 With meal 173
15 One hr prior to meal 162
25 With meal 360
[00735] Administration of HCLP led to a decrease in serum phosphate,
a dose
dependent increase in fecal excretion of sodium and potassium and a dose
dependent
increase in fecal weight.
20 [00736] Administration of HCLP also caused acidosis.
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Example 13
[00737] An open-label, multiple-dose clinical trial was conducted in
34 human end-
stage renal disease (ESRD) patients. The study evaluated the effect of
administration of H-
CLP, for example, a cross-linked polyacrylic acid polymer with less than 5000
ppm sodium
(e.g., 153 ppm sodium), less than 20 ppm heavy metals, less than 1000 ppm
residual
monomer (e.g., 40 ppm residual monomer), less than 20% insoluble polymer
(e.g., 3%
insoluble polymer), and with loss on drying of less than 5% of its weight
(e.g., loss on
drying of 1% of its weight) with or without varying doses of CaCO3 (as CaCO3
or Tums )
on (1) fecal excretion of sodium, calcium, magnesium, potassium, iron, copper,
zinc, and
phosphorous; (2) measures of acidosis including [total] serum bicarbonate,
urine pH and
urine phosphorous excretion; (3) serum potassium levels; and (4) fecal weight.
For all
outcomes, treated groups were compared to baseline or to a control group.
[00738] This was a three-stage study. The primary endpoint for Stage
1 was sodium
and potassium removal in the stool compared between the baseline and treatment
periods.
The primary endpoint for Stage 2 was to demonstrate the ability of CaCO3
and/or other
alkali, such as magnesium oxide, to maintain serum bicarbonate levels in a
range between
18 and 27 mEq/dL. Secondary endpoints included: change in stool weight
compared
between baseline and treatment periods (Stage 1) or trends in stool weight
(Stage 2);
changes in fecal levels of calcium, magnesium, iron, copper, zinc and
phosphorous
compared between baseline and treatment periods (Stage 1) or trends in these
parameters
(Stage 2); fluid consumed and excreted between baseline and treatment periods
(Stage 1) or
trends in these parameters (Stage 2); net sodium, magnesium, calcium,
potassium, iron and
phosphorus balance (Stage 2); safety and tolerability based upon review of
vital signs,
clinical safety labs and adverse events and change in intradialytic weight
gain, intradialytic
hypotension, and blood pressure compared between baseline and treatments
periods
(Stage 1) or trends in these parameters (Stage 2). In Stage 3, the daily fecal
levels of
sodium and potassium were determined for one control and two treatment groups.
Total
serum bicarbonate and urine phosphorus were evaluated for all stages.
[00739] This study included six treatment groups and one control
group. The six
groups were treated with H-CLP and varying amount of CaCO3 (administered as
TUMS
or CaCO3) as an acid neutralizing base. The 8g or 15 g doses of H-CLP were
divided into
four parts (qid) in Stages 1 and 2 and administered one hour before each of
four meals. In
Stage 3, th 8 g doses of H-CLP were divided into two parts and administered
one hour
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before morning and evening meals. TUMS was either given with the H-CLP or
immediately after the meal. The doses of H-CLP and CaCO3 ( as CaCO3 or TUMS )
are
shown in Table 15. In groups 1 to 3, there was a baseline period of 3 days
prior to the
planned dosing period of 9 days. For treatment groups 2 and 3, the average
change from
baseline on days 7-12 were determined and compared to baseline parameters
(average days
1 to 3). For group 1, dosing was terminated after 5 days of dosing because the
subjects
developed serum acidosis. For this group the average parameters for days 7-8
were
compared to the baseline period of days 1-3, . In Stage 2, the same patients
as in group 2
were dosed a second time as group 4, administering H-CLP for 14 days. The
baseline
period from group 2 was used for the comparison of the average parameters for
Group 4
days 4 to 14 compared to baseline. Groups 5 to 7 were dosed for 14 days with
no baseline
period. Group 7 was a control group in which no H-CLP was administered. For
groups 5
and 6, the change from control (group 7) for the average of days 4 to 14 was
determined.In
groups 2 to 4, the patients were dosed with H-CLP and TUMS (the base CaCO3
active
ingredient), which was given to maintain serum bicarbonate levels by
neutralizing the acid
(protons) released from H-CLP. These patients were administered H-CLP and TUMS
as
follows: Group 2 was administered 7.5 g H-CLP one hour before meals and
varying
amounts of TUMS after meals as needed to maintain serum bicarbonate levels
within
clinically acceptable levels; Group 3 was administered 15 g H-CLP one hour
before meals
and and TUMS after each meal at doses that would neutralize up to 50% of the
acid
administered as H-CLP if H-CLP released all its carboxylate protons (0.5
equivalents); and
Group 4 was administered 15 g H-CLP and 1.1 equivalent TUMS one hour before
each
meal (Table 17). Thus, the amount of CaCO3 administered varied from zero to
that which
would theoretically neutralize 100% of protons shed by the dose of H-CLP
administered to
the subject (0 to 100% of the mEq of carboxyl groups administered with the H-
CLP).
Groups 5 and 6 received 8g H-CLP and 0.72 equivalents of TUMS either one hour
beforethe meal (Group 5) or one hour after the meal (Group 6). Group 7 was a
control
group that was not administered H-CLP or TUMS . The seven dose groups are
shown in
Table 17. Subjects remained in a clinical research unit for the duration of
the study.
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Table 17: H-CLP and CaCO3 Dosing Details
Stage Group Number H-CLP Administration of Baseline Duration
of Dose CaCO3 ( as CaCO (days) of
Dosing
Subjects (g/day) or TUMS )1' 2
(days)
1 1 5 15 None 3 5
(3.75g
qid)
2 4 8 After meals as 3 9
(2g qid) needed to maintain
serum bicarbonate
within clically
acceptable limits.
Average of 0.25
eq., (range 0.12 to
0.44 eq) a
3 6 15 Up to 0.5 3 9
(3.75g equivalentes, taken
qid) after meals as
needed to maintain
serum bicarbonate
levels within
clinically
acceptable limits.
Average of 0.5 eq
after meals
2 4 4 8 1.1 eq, one hour 0 14
(2g qid) before meals
3 5 5 8 0.7 eq, one hour 0 14
(2g qid) before meals
6 5 8 0.7 eq, after meals 0 14
(2g qid)
7 5 0 None 0 14
'After each of four meals
20ne equivalent = mEq of CaCO3 base equal to the total equivalents of carboxyl
groups in the administered H-
CLP
[00740] H-CLP was prepared according to Examples 1 and 3. The H-CLP
polymer
was milled to break up the bead structure and reduce the particle size. The
milled H-CLP
was then filled into capsules. In Stage 3, H-CLP and CaCO3 were filled into
capsules.
Capsules were administered with water 2 to 4 times a day for a total of 5 to
14 days,
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depending upon the dose group. Doses were given within ten minutes of the
scheduled time
for each subject. For Groups 1-3, the patients were dosed starting on Day 4,
after a 3-day
baseline period. Subjects in Groups 4-8 did not undergo a baseline period, and
dosing
started on Day 1.
[00741] Diet was controlled with all subjects having identical meals and
the same
meals served in a repeating three day schedule. All meals and snacks from each
of these 3
days, representing one subject's diet, were homogenized and the sodium,
potassium,
calcium, phosphorus, iron, copper, zinc and magnesium content determined. All
meals
provided to the subjects were arranged by the dietician in consultation with
the subjects'
1 o nephrologists. The subjects were requested to consume all of their
meals. The total daily
weight of uneaten food was recorded. Uneaten food in excess of 10% was
analyzed for
electrolyte content.
[00742] Subjects fasted for at least eight hours at screening and
four hours at
admission prior to the collection of blood and urine samples for clinical
laboratory tests.
Fasting was not required prior to urine and blood samples taken during the
study. Water ad
libitum was allowed during the periods of fasting. Clinic staff monitored and
recorded
ingestion of the meals served during the study and any beverages (including
water
consumed).
[00743] Stool weight, fecal electrolytes and fluid balance were
determined throughout
the in-patient period. Serum samples were collected daily for serum chemistry
and the
concentration of sodium, potassium, magnesium, calcium, and phosphorus
determined. All
urine specimens were collected and volume measured. An aliquot of an afternoon
sample
was analyzed for pH. Urine samples were pooled for each 24-hour period and an
aliquot of
the pooled sample was sent for sodium, potassium, calcium, magnesium and
phosphorus
analysis.
[00744] All feces eliminated after consumption of the first
controlled meal were
collected as individual samples in tared collection containers. The color and
consistency of
the stool were noted. The stool samples were weighed, then frozen and stored
at or below -
20 C. All fecal collections were submitted for analysis of sodium, calcium,
magnesium,
potassium, phosphorous, iron, zinc and copper levels by ICP. Fecal weights for
all samples
eliminated in each 24-hour period were added together to determine the total
fecal weight
per day.
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[00745] Weight and fluid removal were recorded during each of the 3
weekly dialysis
sessions.
[00746] Daily fecal and urine weight, urine pH, and daily fecal and
urine content and
concentrations of sodium, calcium, magnesium, potassium and phosphorus (plus
copper,
iron and zinc only in the stool) were determined. Serum concentrations of
sodium,
potassium, magnesium, calcium, phosphorus, and carbon dioxide were determined
for each
subject and each treatment group. Daily fluid balance (fluid intake ¨ output)
was calculated
for each patient and each group. Daily net balance of sodium, magnesium,
calcium,
potassium and phosphorus were calculated for each subject based on the
analysis of diet,
urine and stool samples.
[00747] Daily parameters were compared for each H-CLP dose group and
the control
group or baseline.
[00748] Intradialytic weight loss (pre-dialysis body weight minus
post-dialysis body
weight), intradialytic weight gain (IWG) from one dialysis session to the next
and fluid
removal during each dialysis session were determined for each subject and
group.
Table 18: Change from Baseline (or Control for Groups 5 and 6) in Metal
Excretion
and Acidosis Parameters per Gram of H-CLP in Humans with ESRD
Fecal Na Fecal K Total serum
Eq of Base Timing of CaCO3 mg/day/ mg/day bicarbonate
Urine P
Group Administeredl administrationl g /g mmol/L/g mg/day/g
1 Immediately after
0 meal 107 86 -0.54
10
2 Average of Immediately after
0.24 meal 71 112 -0.40
21
3 Average of Immediately after
0.51 meal 94 116 -0.39
14
5 Immediately after
0.7 meal 59 57 -0.38 -
0.39
4 1hr before meal
1.1 with H-CLP 22 61 0.15 -
16
1
CaCO3 administered as CaCO3 or Tums
[00749] As shown in Table 18, administration of H-CLP without base
increased fecal
excretion of sodium and potassium over baseline levels. However, acidosis was
also
observed as shown by the decrease in serum bicarbonate levels. Co-
administration of base
eliminated acidosis at approximately 0.75 equivalents of base as shown by the
total serum
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bicarbonate going from negative to positive and urinary phosphorus excretion
going from
positive to negative at this level of base administration. At all levels of
base administration,
a clinically relevant fecal excretion of potassium was maintained. Above 0.75
equivalents
of base, the amount of sodium excreted dropped substantially. Co-
administration of less
than about one equivalent of base (e.g., from about 0.7 to about 0.8
equivalents, for
example, about 0.75 equivalents) was approximately acid-neutral, while still
promoting
excretion of substantial amounts of both sodium and potassium over baseline
levels.
Example 14
[00750] The study was conducted with twelve rats housed in
individual Techniplast
Metabolic Cage Systems, allowing daily collection of urine and feces with
daily
measurement of food and water intake. Doses of the Renvela , a phosphate
binder, in
humans were mimicked. Thus, based on Nephrol Dial Transplant 1998; 13:2303-
2310 by
Goldberg, et al, for the Renvela diet, 800 g of LabDiet 5012 were blended
with thirty 800
mg tablets of Renvela , at an approximate dose of 1g/rat/day. This diet was
fed during the
first 6 day period of the study. For the second period of the study, diets
were made in the
same fashion except that 40 g of HCLP (5% of the diet) was substituted for 40
g of the
LabDiet 5012. For the third period of the study, the phosphate binder was
removed and all
rats were fed a diet of 760 g LabDiet 5012 blended with 40 g HCLP (5% of the
diet).
[00751] Daily urine and feces collections were weighed and samples
were digested by
placing the fecal or urine samples into trace metal grade concentrated
sulfuric acid and
heating to boiling. Trace metal grade concentrated nitric acid was then added
in small
aliquots until the organic matter was completely oxidized and the solutions
were clear. Na,
K, Mg, Ca, and P content were measured by ICP-AES. This allowed following the
changes
in fecal and urinary levels of these ions. The first three days on diet with
HCLP alone were
were used for equilibration and statistical comparisons were only performed on
samples
collected on the fourth day or later on that diet.
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Table 19. Net Change in Daily Fecal Sodium, Fecal Potassium, Urinary
Phosphorous
and Fecal Fluid in Rats Co-Administered HCLP and Renvela
Groups A Fecal A Fecal A
Urinary A Fecal
Sodium Potassium Phosphorus Mass(g/day)
(mg/day) (mg/day) (mg/day)
HCLP 35.7 90.2 28.5
3.4
Renvela 2.2 9.3 -15.5
12.1
Renvela + H-CLP 42.8 100.5 4.0
10.1
[00752] Changes in fecal sodium and potassium excretion levels and
urinary
phosphorus values over control (rats on rat chow and no polymer) were
calculated and are
shown in Table 19 (i.e., control fecal sodium and potassium and control
urinary
phosphorus excretion levels were subtracted from fecal sodium and potassium
and urinary
1 o phosphorus levels in treatment groups). Changes in fecal mass over
control (rats on rat
chow and no polymer) were calculated and are shown in Table 19 (e.g., control
fecal mass
was subtracted from fecal mass in treatment groups). Simultaneous
administration of HCLP
with the phosphate binder, Renvela did not alter the ability of HCLP to
increase fecal mass
and to increase sodium and potassium in the feces.
Example 15
[00753] This clinical trial, an open-label, non-randomized, multiple-
dose study, was
conducted in a single cohort of 5 human ESRD patients all currently taking
Renvela and
on dialysis. A 5-day baseline period was followed by 7 days of dosing. All
patients were
dosed with a total of 15 g crosslinked polyacrylate polymer (H-CLP) per day.
The dose was
administered (following a 5-day baseline period) as 3.75 g given four times
daily for a total
of 7 days. Patients remained in the clinical research unit for the duration of
the study.
[00754] The objectives of this clinical trial included determination
of: the safety and
tolerability of CLP; the effects of CLP on sodium, calcium, magnesium,
potassium and
phosphorus excretion in stool; the effects of CLP on fecal weight; the ability
of calcium
carbonate to control serum bicarbonate levels when co-administered with CLP;
and the
effects of CLP on blood pressure, symptomatic intradialytic hypotension, 6
minutes walk
test and subjective thirst levels.
[00755] The primary endpoint was the change in fecal sodium content.
The secondary
endpoints included changes in: fecal sodium, potassium, calcium, magnesium,
and
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phosphorus content; stool weight; vital signs and clinical safety labs;
incidence and severity
of adverse events; intradialytic weight gain; blood pressure before, during
and after dialysis
(including 24h and 44h ambulatory blood pressure and manual measurements);
serum
bicarbonate levels; and 6 minutes walk test.
Table 20: H-CLP and CaCO3 Dosing Details
Cohort Number H-CLP CaCO3 Timing Baseline Duration
of Dose Dose of Dosing (days) of
Dosing
Patients (g/day) (days)
1 5 15 8 grams One hour 5 7
(3.75g (0.75 before
qid) equivalents, breakfast,
administered lunch and
with H- dinner,
CLP) and
evening
snack
[00756] H-CLP was administered with water for a total of 7 days.
Doses were given
within 10 minutes of the scheduled time.
[00757] The H-CLP polymer, prepared as described in Examples 1 and
3, was milled
to break up the bead structure and reduce the particle size. The milled H-CLP
was then
filled into capsules with calcium carbonate; 0.7 g CLP and 0.27 g calcium
carbonate per
capsule (0.75 equivalents).
[00758] A standardized diet was served. The menu for Days 2-6 were
identical to that
on Days 9-13. The subjects were requested to consume all of their meals.
Estimated weight
and content of any uneaten food was recorded.
[00759] Subjects were required to fast for at least eight hours at
screening and four
hours at admission prior to the collection of blood and urine samples for
clinical laboratory
tests. Fasting was not required prior to urine and blood samples taken during
the study.
Water ad libitum was allowed during the periods of fasting. Clinic staff
monitored and
recorded ingestion of the meals served during the study and any beverages,
including water
consumed.
[00760] Stool weight, fecal and urinary metal balance, serum
chemistries and fluid
balance were determined throughout the study.
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[00761]
Serum samples were collected daily for serum chemistries and for
determination of the concentration of sodium, potassium, magnesium, calcium,
phosphorus.
Hematology and urinalysis were done on Days 1,7, and 14 (discharge).
[00762]
All urine was collected, the volume measured, and then specimens pooled for
each 24 hour period. Each 24 hours sample was then analyzed for sodium,
potassium,
calcium, magnesium and phosphorus. The morning urine specimen was checked
daily for
pH within 5 minute of micturition.
[00763]
All feces eliminated were collected as individual samples in tared
collection
containers. The color and consistency of the stool were noted, the sample
weighed, then
frozen and stored at or below -20 C. All fecal collections were submitted for
analysis of
sodium, calcium, magnesium, potassium, and phosphorous levels. Fecal weights
for all
samples eliminated in each 24-hour period were added together to determine the
total fecal
weight per day.
[00764]
Daily fecal and urine weight, urine pH, and daily fecal and urine content
and
concentrations of sodium, calcium, magnesium, potassium and phosphorus and
serum
concentrations of sodium, potassium, magnesium, calcium, phosphorus, and
carbon dioxide
were determined for each subject and each treatment group. Daily fluid balance
(fluid intake
- output) was calculated for each patient and each group. For each parameter
the daily
average for the treatment period was compared to the baseline period.
Table 21: Increased Metal Excretion (mg/day) and Serum Total CO2 Content in
Humans with ESRD on Renvela Therapy and Co-Administered 15 g H-CLP and 8 g
CaCO3 (0.75 equivalents) Daily
A Serum Total
Renvela A Fecal Sodium A Fecal Potassium CO2 Content
(g/day) (mg/day) (mg/day) (mmol/L)
0 107.1 76.0 -5.7
1.6 120.5 64.1 -6.0
2.4 75.3 82.9 -2.8
4.8 31.6 42.4 -3.4
Example 16
[00765]
The objectives of this open-label, randomized, multiple-dose clinical trial
of
24 normal, healthy human volunteer subjects included determination of the
effects of four
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different dosing regimens on the safety and tolerability of H-CLP; the effects
of H-CLP on
fecal and urinary excretion of sodium, calcium, magnesium, potassium, and
phosphorous,
and the effects of H-CLP on stool weight.
[00766] The primary endpoint was the change in fecal sodium content.
The secondary
endpoints included changes in fecal and urine sodium, potassium, calcium,
magnesium, and
phosphorus content; changes in stool weight; change in vital signs and
clinical safety labs;
incidence and severity of adverse events; and serum bicarbonate levels.
[00767] Six subjects were randomly assigned to one of four cohorts
(Table 22). A 5-
day baseline period was followed by 7 days of dosing. All subjects were dosed
with a total
of 15 g crosslinked polyacrylate polymer (H-CLP) and 7.8 g of CaCO3 per day.
Subjects in
Cohort 1 were given H-CLP once daily (QD), those in Cohort 2 were given H-CLP
twice
daily (BID), subjects in Cohort 3 were given H-CLP three times daily (TID),
and subjects in
Cohort 4 were given H-CLP four times daily (QID). Subjects remained in the
clinical
research unit for the duration of the study.
[00768] H-CLP was prepared according to Examples 1 and 3, for example, a
cross-
linked polyacrylic acid polymer with less than 5000 ppm sodium (e.g., 16- ppm
sodium),
less than 20 ppm heavy metals, less than 1000 ppm residual monomer (e.g., 4
ppm residual
monomer), less than 20% insoluble polymer (e.g., 4% insoluble polymer), and
with loss on
drying of less than 5% of its weight (e.g., loss on drying of 3% of its
weight) The H-CLP
polymer was milled to break up the bead structure and reduce the particle
size. The milled
H-CLP was mixed with the CaCO3 and then filled into capsules with 0.7 g of
polymer per
capsule. H-CLP was administered with water for a total of 7 days. Doses were
given to
subjects within 10 minutes of the scheduled time.
[00769] A standardized diet was served. The menu for Days 2-6 were
identical to that
on Days 9-13. The subjects were requested to consume all of their meals.
Estimated weight
and content of any uneaten food was recorded.
[00770] Subjects fasted for at least eight hours at screening and
four hours at
admission prior to the collection of blood and urine samples for clinical
laboratory tests.
Fasting was not required prior to urine and blood samples taken during the
study. Water ad
libitum was allowed during the periods of fasting. Clinic staff monitored and
recorded
ingestion of the meals served during the study and any beverages, including
water
consumed.
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[00771] Stool weight, fecal and urinary electrolyte balance, serum
chemistries and
fluid balance were determined throughout the study.
[00772] Serum samples were collected daily for serum chemistries and
for the
concentration of sodium, potassium, magnesium, calcium, phosphorus and
bicarbonate
determined. Hematology and urinalysis were performed on samples from Days 1, 7
and 14.
[00773] Each subject's urine was collected and pooled for each 24-
hour period. The
total volume was measured and a sample analyzed for sodium, potassium,
calcium,
magnesium and phosphorus. The morning urine specimen was checked daily for pH
within
5 minutes of micturition.
[00774] Feces eliminated on Days 2 (start of baseline period) through 14
was collected
as individual samples in tared collection containers. The color and
consistency of the stool
samples were noted, the sample weighed, then frozen and stored at or below -20
C. All
fecal collections were submitted for analysis of sodium, calcium, magnesium,
potassium,
and phosphorous levels. Fecal weights for all samples eliminated in each 24-
hour period
were added together to determine the total fecal weight per subject per day.
[00775] Daily fecal and urine weight, urine pH, and daily fecal and
urine content and
concentrations of sodium, calcium, magnesium, potassium and phosphorus and
serum
concentrations of sodium, potassium, magnesium, calcium, phosphorus, and
carbon dioxide
were determined for each subject and each treatment group (see Table 23).
Daily fluid
balance (fluid intake ¨ output) was calculated for each subject and each
group.
[00776] Average daily parameters for each H-CLP dose group for days
10-13 were
compared for the baseline period and treatment period (days 3-6).
Table 22: H-CLP and CaCO3 Dosing Details
Cohort Number H-CLP H-CLP CaCO3 Timing of
Duration
of Dose Dose Dose Dosing of
Dosing
Subjects (g/day) Regimen
(days)
1 6 15 15g QD 8g Immediately 7
before
bedtime
2 6 15 7.5g BID 8g One hour 7
before
breakfast
and dinner
3 6 15 5g TID 8g One hour 7
before
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Cohort Number H-CLP H-CLP CaCO3 Timing of
Duration
of Dose Dose Dose Dosing of
Dosing
Subjects (g/day) Regimen (days)
breakfast,
lunch and
dinner
4 6 15 3.75g QID 8g One
hour 7
before
breakfast,
lunch and
dinner, and
immediately
before
bedtime
Table 23: Change from Baseline in Fecal Excretion of Sodium and Potassium and
Urinary pH in Normal Humans Co-Administered 15 g H-CLP and 0.75 Equivalents of
CaCO3 Base
Number of A Serum
Divided Potassium
Doses per A Fecal Sodium A Fecal
Potassium (mmol/L) A
Day (mg/day/g H-CLP) (mg/day/g H-CLP)
in Urinary pH
1 36.0 117.6 -0.2 -0.4
2 39.3 119.0 -0.3 -0.8
3 44.6 147.5 -0.7 -0.3
4 43.0 93.4 -0.4 -0.4
[00777] There is no significant difference in the change from
baseline average daily
fecal excretion of sodium or potassium or the average daily change from
baseline in serum
potassium due to administration of the daily dose of H-CLP and CaCO3 as one to
four
divided doses. There is also no significant difference in acidosis parameters
due to dividing
the daily dose.
Example 17
[00778] This example demonstrates the treatment of heart failure
patients with a
cross-linked polyelectrolyte polymer such as a crosslinked cation-binding
polymer
comprising hormones that comprise carboxylic acid groups (e.g., crosslinked
polyacrylic
acid polymer such as H-CLP).
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A. Overview of Study and Results
[00779] A double-blind, randomized, parallel group, placebo
controlled clinical study
was conducted in 111 heart failure patients (NYHA Classification III or IV)
with chronic
kidney disease (estimated glomerular filtration rate < 60 mUmin/1.73 m2) and
serum
potassium value between 4.3-5.1 mEq/L at screening (see also, e.g., section B
below). The
study evaluated the effect of H-CLP with 0.75 equivalents of CaCO3 versus
placebo in
preventing clinically significant hyperkalemia and improving symptoms of fluid
overload in
patients with heart failure and renal insufficiency impairment (e.g., renal
impairment with
glomerular filtration rate (GFR) < 60 mUmin/1.73 m2) who are on recommended
heart
failure therapies (e.g., ACE inhibitor or Angiotensin Receptor Blocker and a
Beta Blocker)
and had a clinical indication for addition of spironolactone. The study
incorporated a
Screening Period, Baseline Visit, and an 8-week fixed dose Treatment Period of
15 g of H-
CLP with 0.75 Eq CaCO3 or Placebo. Patients were enrolled in a 1:1 allocation
to H-CLP
(Cohort 1) or Placebo (Cohort 2) treatment groups. Patients received 15 g/day
of H-CLP
with 0.75 equivalents of CaCO3 (n=59) or placebo (n=52) in capsules given as
twice daily
dosing of 15 capsules for eight weeks. H-CLP was prepared as described in
Examples 1 and
3, for example, a cross-linked polyacrylic acid polymer with less than 5000
ppm sodium
(e.g., 335 ppm sodium), less than 20 ppm heavy metals, less than 1000 ppm
residual
monomer (e.g., 36 ppm residual monomer), less than 20% insoluble polymer
(e.g., 4%
insoluble polymer), and with loss on drying of less than 5% of its weight
(e.g., loss on
drying of 2% of its weight), or for example, a cross-linked polyacrylic acid
polymer with
less than 5000 ppm sodium (e.g., 300 ppm sodium), less than 20 ppm heavy
metals, less
than 1000 ppm residual monomer (e.g., 14 ppm residual monomer), less than 20%
insoluble
polymer (e.g., 7% insoluble polymer), and with loss on drying of less than 5%
of its weight
(e.g., loss on drying of 2% of its weight). If a patient was unable to comply
with taking 15
capsules BID, the investigator was permitted to alter the dosing regimen to
allow the patient
to take fewer capsules more frequently throughout the day to maintain the
total dose of 30
capsules per day. Patients were clinically indicated to receive spironolactone
treatment and
were placed on spironolactone (25 mg/day) at the Baseline Visit (see also,
e.g., section B
below). An evaluation of spironolactone dosing occurred at the end of week 4
where the
dose was increased for some patients, if clinically indicated, from 25 to 50
mg/day. Serum
chemistry, clinical signs and symptoms of heart failure, urinary electrolytes,
thirst
evaluation and other assessments were evaluated throughout the study.
Assessments which
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evaluated signs and symptoms of heart failure included the New York Heart
Association
Class, changes in dyspnea as assessed by the patient's response to a single
question using
responses on a Likert scale ranging from "much worse" to "much better," the
six minute
walk test and a patient reported outcome (Kansas City Cardiomyopathy
Questionnaire).
Signs and symptoms of heart failure are directly associated with fluid
overload status (see,
e.g., www.nhlbi.nih.gov/health/health-topics/topics/hf/signs.html). Clinical
signs of fluid
overload may be measured, for example, by chest x-ray, jugular vein preseure,
dyspnea
scale, and/or edema. Fluid status was also evaluated by total body weight and
extremity
edema.
[00780] The New York Heart Association Classification is shown in Table 24.
Table 24: New York Heart Association Classification of Heart Failure Patients
Class I No limitation of physical activity. Ordinary physical
activity does not cause undue fatigue,
palpitation, dyspnea (shortness of breath), or angina pain.
(mild)
Class II Slight limitation of physical activity. Comfortable at
rest, but ordinary physical
activity results in fatigue, palpitation, dyspnea, or angina pain.
(mild)
Class III Marked limitation of physical activity. Comfortable at
rest, but less than ordinary activity causes
fatigue, palpitation, dyspnea, or angina pain.
(moderate)
Class IV Unable to carry out any physical activity without
discomfort. Symptoms of cardiac insufficiency
at rest. If any physical activity is undertaken, discomfort is increased.
(severe)
[00781] The change New York Heart Associate Class for each of the
patients was
evaluated at baseline and after 8 weeks of treatment (see also, e.g., section
F below). The
percent of patients in each class is shown in Table 25. Also shown are the
percent of
patients who improved at least one class from baseline.
Table 25: New York Heart Associate Class at Baseline and After 8 Weeks of
Treatment
Baseline
After 8 Weeks of Treatment
NYHA H-CLP+0.75 Eq H-CLP+0.75 Eq
Placebo Placebo
Class CaCO3 CaCO3
Patients with at least one class improvement
48.8% 17.4%
from baseline
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[00782] Dyspnea was evaluated using a quantitate patient self-
assessment of
breathing status compared to baseline with answers on a 7-point Likert scale
ranging from
"much worse" to "much better" (see also, e.g., section F below). The percent
of patients
who reported moderately or markedly better breathing status on H-CLP or
placebo is shown
in Table 26. Also shown in Table 26 is the performance of patients in the 6-
minute walk
test. Patients reported greater improvements in dyspnea and were able to walk
farther when
on H-CLP compared to placebo.
[00783] The six-minute walk test is a well-accepted measure of
heart failure status,
with patients able to walk shorter and shorter distances as heart failure
progresses. The
distance walked in six minute time period is measured in meters.
Table 26: Change from Baseline in Dyspnea at Exertion and Distance Walked in
the 6-
Minute Walk Test at Study Week 8
H-CLP Placebo
CaCO3
Dyspnea at Exertion: % of Patients Moderately or 36.6 21.7
Markedly Better Compared to Baseline
6 Minute Walk Test 39.3 19.7
(change from baseline, meters)
[00784] The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a
disease-
specific instrument for measuring health related quality of life in patients
with congestive
heart failure (see also, e.g., section F below). KCCQ is a valid, reliable and
responsive
health status measure for patients with congestive heart failure and may serve
as a clinically
meaningful outcome in cardiovascular research, patient management and quality
assessment.
(see, e.g., Green et al., 2000, J Am Coll Cardiol 35:1245-1255). The scale for
each of the
quality of life parameters is 0 to 100, with 100 being the best quality of
life. The KCCQ
results from this study are shown in Table 27.
Table 27. KCCQ Parameters at 8 Weeks Compared to Baseline (Mean Change from
Baseline)
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KCCP H-
Parameter CLP Placebo
Physical
Limitation 17.1 10.6
Symptom
Frequency 22.1 16.9
Quality of Life 15.0 8.5
Social
Limitations 20.1 14.7
Overall
Summary 18.3 12.5
Clinical
Summary 18.8 13.6
[00785] Fluid status was directly evaluated by measuring changes in
body weight and
absence of extremity edema (see also, e.g., section F below). Changes in body
weight and
absence of extremity edema throughout the 8 week study are shown in Table 28.
Body
weights decreased for the H-CLP treated group while they increased for the
placebo group
at all time points. More patients in the H-CLP group than placebo group had an
absence of
extremity edema at 2 to 8 weeks of treatment.
Table 28. Change from Baseline in Body Weight and Percent of Patients with
Absence
of Extremity Edema
Absence of Extremity
Body Weight (kg) Edema (%)
Week H-CLP Placebo H-CLP Placebo
1 -0.71 0.11 32.1 38.5
2 -0.83 0.29 40.4 35.3
4 -0.68 0.11 55.3 47.9
8 -0.73 0.14 70.7 58.7
[00786] Mean serum CO2 was measured throughout the study as a
measure of
acid/base status (e.g., acid/base balance). As shown in Table 29, there was no
significant
change from baseline, or significant difference between the H-CLP and placebo
groups, in
total serum CO2, showing that the addition of 0.75 equivalents of base as
CaCO3 to the H-
CLP prevented a change in acid/base status (see also, e.g., section G below).
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Table 29. Total Serum CO2 over the 8 Week Study
Week H-CLP Placebo
0 25.7 26.5
1 23.9 26.1
2 23.4 26.2
4 25.0 25.2
25.2 25.1
8 24.8 26.2
[00787] Multiple endpoints of patient signs and symptoms of heart
failure (e.g., fluid
retention, dypsnea (shortness of breath), NYHA class) and fluid status (e.g.,
body weight)
5 exhibited improvement with administration of H-CLP with 0.75 equivalents
of base for
eight weeks without a change in acid/base status.
[00788] In summary, treatment with H-CLP with 0.75 equivalents of
base for eight
weeks resulted in significant and clinically meaningful improvement of signs
and symptoms
in NYHA class III/IV heart failure patients. The data shows reduction of body
weight,
improvement in subjective symptoms (dyspnea) and quality of life (Kansas City
Cardiomyopathy Questionnaire scores), and improvements in objective measures
of
physical function (6 Minute Walk Test) and clinical signs and symptoms (NYHA
Classification; extremity edema). The concordance of these positive effects
across multiple
endpoints suggests the usefulness of H-CLP with 0.75 equivalents of base for
the treatment
of symptoms of heart failure while preserving a neutral acid/base status.
[00789] Further in summary, use of H-CLP with base is an effective
treatement of
heart failure, including for the removal of sodium and fluid (e.g., water) in
patients with
heart failure. Such patients include those concurrently treated with guideline
therapy
including with diuretics. Such treatment results in clinical meaningful
improvement in
function and symptoms as measured by body weight reduction, NYHA class
improvement,
dypsnea improvement, six minute walk test improvement, and/or improvements in
KCCQ
in patients with heart failure. Use of H-CLP with base as described herein may
provide
sodium and fluid removal independent of the kidneys, and accordingly, is
useful alone or in
combination with other agents (e.g., ACE inhibitors, angiotensin II blockers,
diuretics, beta
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blockers, aldosterone antagonists such as spironolactone, and/or digoxin) for
treating
patients with heart failure.
B. Additional Description of Study Design
[00790] A double-blind, randomized, parallel, placebo controlled
Phase 2 study
examined the effect of H-CLP versus placebo in preventing clinically
significant
hyperkalemia and improving symptoms of fluid overload in patients with HF and
renal
insufficiency. The study was conducted in accordance with the principles
described in the
Declaration of Helsinki (1964) up to and including the Seoul revision (2008).
A common
clinical protocol was approved for each investigational site (located in
Armenia, Georgia,
and Moldova) by the appropriate Ethics Committee and all subjects provided
written
informed consent prior to participation.
[00791] Major inclusion criteria included age over 18 years with
NYHA Class III or
IV HF and chronic kidney disease (CKD) Stage 3 or 4 [estimated glomerular
filtration rate
(eGFR) < 60 mUmin/1.73 m2]; not receiving indicated spironolactone therapy
based on
degree of HF; a recent hospitalization for HF (within 1-6 months); at least
two signs of
current fluid overload [jugular venous pressure (JVP) > 8 cm; peripheral edema
or ascites;
pulmonary congestion on chest X-ray; pulmonary rales on auscultation]; ongoing
stable
treatment with a beta-blocker in addition to an angiotensin converting enzyme
inhibitor
(ACEI) or an angiotensin receptor blocker (ARB); a screening serum K+ value of
4.3 -
5.1 mEq/L, and a serum NT-proBNP level > 1000 pg/mL. Exclusion criteria
included
concomitant use of sodium bicarbonate, antacids containing magnesium or
calcium,
polystyrene sulfonate; any cardiovascular, renal, hepatic, endocrine,
neurological or other
disease or condition that made the patients study participation unsafe;
history of clinically
significant GI pathology; severe, uncontrolled hypertension; use of
aldosterone antagonist in
the last 30 days or of K+ sparing medications or K+ supplements; liver
transaminases > 3
times ULN; serum creatinine value of > 3 mg/dL; uncorrected primary severe
valvular
disease, known obstructive or restrictive cardiomyopathy, or uncontrolled
arrhythmias;
coronary-artery bypass graft or percutaneous cardiac interventions within 3
months; heart
transplant recipient; myocardial infarction, transient ischemic attack,
stroke, or acute
coronary syndrome within 1 month; current dialysis patient or kidney
transplant recipient or
need for such during the study.
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[00792] The study incorporated a screening period, baseline visit,
and an 8-week
fixed dose treatment period during which patients were randomized at the
baseline visit to
15 g/day of H-CLP (with 7-8 g of CaCO3) or identical placebo capsules
containing
microcrystalline methyl cellulose, a white powder similar in appearance to H-
CLP.
Spironolactone was initiated at 25 mg/day and if the serum K+ was < 5.1 mEq/L,
the dose
was increased to 50 mg/day at the Week 4 visit. Doses of ACEI and ARB were not
to be
changed during the study. A central laboratory was utilized for laboratory
assessments.
Serum chemistry, clinical status, and HF assessments were monitored throughout
the study
a mean of every 1-2 weeks. Single 6 minute walk tests (6MWT) were performed
using
standard techniques at baseline, and Weeks 4 and 8 (see, e.g., Bittner et al.,
1993, JAMA
270:1702-7). Evaluation of subjective dyspnea level using a 7-point Likert
Scale, and the
Kansas City Cardiomyopathy Questionnaire (KCCQ) were evaluated at baseline,
and
Weeks 4, and 8 (see, e.g., Teerlink, 2003, Am Heart J 145:S26-33; Spertus et
al., 2005, Am
Heart J150:707-15).
C. Additional Description of Study Endpoints
[00793] A primary endpoint in the study was the change in serum K+
from baseline
to end of study (or last observation). Several secondary endpoints focused on
measures of
congestion and functional capacity including changes in 6MWT, NYHA functional
class,
KCCQ, physician assessment of exertional dyspnea and patient-reported dyspnea
level
(7-point Likert Scale) (see, section A above). Additional exploratory
endpoints included
incidence of serum K+ elevation > 5.5 mEq/L; achieving the target 50 mg
spironolactone
dose; HF-related hospitalization; systolic and diastolic blood pressure (BP);
body weight;
and NT-proBNP levels.
D. Additional Description of Statistical Analysis
[00794] An analysis plan was prepared prior to study unblinding or
performance of
statistical analyses. Formal power/sample size calculations were not performed
for a Phase
2 study and 100 patients were targeted for enrollment. Primary analyses were
performed on
the intent to treat (ITT) population, and end of study results for non-
completers were
excluded. Sensitivity analyses were performed for primary and secondary
endpoints using a
last observation carried forward approach which included Week 8/End of Study
results for
non-completers. Categorical data were evaluated using the chi-square test for
homogeneity
of proportions. Continuous or ordinal data were analyzed with repeated
measures analysis
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of covariance (RM-ANCOVA) using change from baseline values to compare the H-
CLP
and placebo treatments. Using this model, a restricted maximum likelihood
approach was
used to estimate and compare mean profiles among the two treatment groups,
assuming an
unstructured covariance matrix. Corrections for multiplicity were not
performed for a Phase
2 study and a p-value < 0.05 was considered statistically significant.
Statistical testing was
not performed for a Phase 2 study for any of the non-efficacy variables. No
clinically
important differences in baseline characteristics were observed between
treatment groups
with the exception of a gender imbalance as shown in Table 30.
Table 30. Baseline Characteristics
Characteristic H-CLP Placebo
CaCO3 (N=52)
(N=59)
Age (yrs) Mean SD (Range) 68 8 (51-84) 70 10 (49-86)
Male gender, n (%) 71 (71.2) 40 (55.8)
Comorbidities, (%)
Hypertension 78.0 92.3
Coronary artery disease 67.8 75.0
Chronic obstructive pulmonary 11.9 7.7
disease 23.7 30.8
Diabetes mellitus 20.3 25.0
Atrial fibrillation
NYHA Functional Class, n (%)
II 0(0.0) 2(3.8)
III 52 (88.1) 45 (86.5)
IV 7(11.9) 5(9.6)
KCCQ Overall Summary Score
Mean SD (Range) 37.3 16.1 38.1 17.1
(6.3-84.9) (3.9-78.6)
Vital Signs [Mean SD (Range)]
Weight (kg) 75.6 13.6 75.0 16.6
(45.4-109.6) (40.9-
119.1)
Systolic blood pressure (mmHg) 129.1 14.1 132.6
15.7
(100-160) (100-165)
Diastolic blood pressure (mmHg) 79.4 8.5 (60-100) 80.7 8.5
(70-100)
Heart rate (beats/min) 74.9 10.1 77.0 14.0
(53-102) (58-139)
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Laboratory Measurements
[Mean SD (Range)]
Blood urea nitrogen (mg/di) 25.2 12.8 (13-
72) 25.5 10.4 (12-56)
Serum creatinine (mg/di) 1.7 0.6 (0.7-
3.2) 1.6 0.6 (0.9-3.3)
eGFR (ml/min/1.73 m2) 45.0 14.2 44.9 17.3
(19.2-75.3) (11.3-95.9)
Serum sodium (mg/di) 140.2 2.8 141.4 2.5
(132-144) (137-149)
Serum potassium (mg/di) 4.73 0.4 (3.3-
5.7) 4.9 0.3 (4.3-5.6)
Serum bicarbonate (mmol/L) 25.7 4.4 26.5 2.9
(11.7-38.5) (17.5-34.6)
NT-proBNP (mg/di) 5169.8 6181.3
4868.3 6603.7
(1085-29753) (924-35382)
Hematocrit (mg/di) 39.4 4.7 40.3 5.6
(28.9-50.2) (29.4-53.7)
Medication, n (%)
ACE inhibitor/ARB 56 (95) 49 (94)
13-B1ocker 56 (95) 46 (89)
Aldosterone antagonists 59 (100) 52 (100)
Diuretics 49 (83) 48 (92)
E. Results: Additional Description of Baseline Characteristics
[00795] Of 223 subjects screened at 24 sites, 113 were randomized
to either H-CLP
(59) or placebo (54). The most frequent reasons for screen failures were eGFR
above the
60 mL/min/1.73 m2 inclusion threshold, serum creatinine > 3 mg/dL, serum K+
outside the
4.3 - 5.1 mEq/L range, or low NT-proBNP <1,000 pg/ml. Demographic
characteristics
were similar between groups except that a larger percentage of males were
randomized to
H-CLP than to placebo (71.2% vs. 55.8%) as shown in Table 30. Clinical and
laboratory
variables were similar between groups. By design, all patients had advanced HF
(?1 HF
hospitalizations in the 6 months preceding randomization, baseline NYHA
functional class
3.1 0.4, presence of signs and symptoms of congestion and baseline mean NT-
proBNP
values of 5028 6355 pg/mL) and CKD (average eGFR 44.9 15.7 mUmin/1.73 m2).
At
study onset all patients received optimal medical HF therapy. From baseline to
the end of
Week 8, compliance with the study drug was excellent, as indicated by the fact
that the H-
CLP and placebo patients took, respectively, 96.3% and 97.2% of the prescribed
capsules.
F. Additional Description of Results: Efficacy Evaluation
[00796] Serum K+ was similar in the H-CLP and placebo groups at
baseline and
throughout the 8-week study period. The two groups were similar in terms of
incidence of
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hyperkalemia (K+> 5.5 mEq/L), 13 (22.4%) vs. 11 (21.2%), and hyperkalemia
prompting
discontinuation of study drug, 6 (10.2%) vs. 5 (9.3%). At the End of Week 4,
the
percentages of patients eligible to increase their daily spironolactone dose
to 50 mg because
their serum K+ level was < 5.1 mEq/L were similar in the H-CLP and placebo
groups
(64.4% vs. 73.1%; p=0.327).
[00797]
Weight loss was significantly greater in the H-CLP than in the placebo group
at Week 1 (-0.71 1.5 kg vs. -0.11 2.0 kg; p=0.014) and at Week 2 (-0.83
1.8 kg vs.
-0.29 2.3 kg; p=0.004) and a trend toward greater weight loss in the CLP
group continued
at Weeks 4 (p=0.066) and 8 (p=0.212).
[00798] The
frequency of marked or disabling exertional dyspnea by physician
assessment decreased over time for the entire study population. However, fewer
patients in
the H-CLP group than the placebo group had this degree of dyspnea at Week 4
[10 (21.3%)
vs. 5 (12.2%)] and Week 8 [14 (29.2%) vs. 12 (26.1%)]. The percentage of
patients
reporting "moderately or markedly better" breathing (by the 7-point Likert
scale), was
21.3% in the H-CLP group and 16.7% in the placebo group (p=0.5665) at Week 4
and
36.6% and 21.7%, respectively (p=0.1266), at Week 8.
[00799]
The two groups were similar throughout the study in NT-proBNP levels.
However, at Weeks 4 and 8, fewer patients in the H-CLP group than the placebo
group had
NT-proBNP levels higher than 1000 pg/mL [Week 4: 43 (91.5%) vs. 48 (100 %);
p=0.039
and Week 8: 36 (87.8%) vs. 45 (97.8%); p=0.0656, respectively].
[00800]
Changes in diuretic doses during the study period were modest and similar in
the two groups. During the study two H-CLP patients and one placebo subject
had a HF-
related hospitalization.
[00801]
The proportion of patients improving by at least one NYHA functional class
from baseline to Week 8 was substantially higher in the H-CLP than in the
placebo group
[20 (48.8%) vs. 8 (17.4 %); p=0.0002]. At Week 4, the 6MWT distance increased
from
baseline by approximately 20 meters in both groups. However, the 6MWT distance
from
baseline to Week 8 tended to increase more in the H-CLP than in the placebo
group (39.3
53.39 m vs. 19.7 39.17 m; p=0.072).
[00802] Quality
of life improvement by the KCCQ Overall Score was greater in the
H-CLP than in the placebo group at the end of Weeks 4 (13.53 12.23 vs. 6.40
12.3;
p=0.0050) and 8 (18.3 17.4 vs. 12.5 13.6; p=0.0624). Similar directional
differences
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occurred in all of the individual components of the KCCQ, including social
limitations,
physical limitations, symptom frequency and clinical summary scores.
[00803]
For the entire cohort there were no differences in BP between groups
throughout the course of the study. However among the 47 individuals with
baseline
systolic BP > 130 mmHg (not a pre-specified categorization), both systolic and
diastolic BP
were significantly lower at Week 8 in the H-CLP than in the placebo group [-
12.6 vs. -6.7
mmHg (p= 0.0186) for systolic BP and -5.8 vs. -1.2 mmHg (p=0.0121) for
diastolic BP].
G. Additional Description of Results: Safety Evaluation
[00804]
Adverse events reported for the H-CLP and Placebo groups are shown in
Table 31.
Table 31. Summary of Total, Cardiac, and Gastrointestinal Adverse Events
MeDRA SOC 15 g H-
CLP Placebo
Preferred Term CaCO3 (N=52)
(N=59)
Total Number of Patients with Adverse Events 21 (35.6%) 16 (30.8%)
Cardiac disorders
Total 3 (5.1%) 3 (5.8%)
Atrial fibrillation 1 (1.7%) 1 (1.9%)
Cardiac failure 1 (1.7%) 0 (0/0%)
Cardiac failure acute 1 (1.7%) 1 (1.9%)
Cardiac failure congestive 0 (0.0%) 1 (1.9%)
Gastrointestinal disorders
Total 14(23.7%) 7(13.5%)
Abdominal discomfort 7 (11.9%) 2 (3.8%)
Abdominal distention 3 (5.1%) 1 (1.9%)
Abdominal pain 1 (1.7%) 0 (0.0%)
Abdominal pain (upper) 0 (0.0%) 1 (1.9%)
Constipation 1 (1.7%) 0 (0.0%)
Diarrhea 0 (0.0%) 1 (1.9%)
Nausea 3 (5.1%) 0 (0.0%)
Vomiting 1 (1.7%) 3 (5.8%)
[00805]
Most gastrointestinal disturbances were transient and mild to moderate.
Only four patients, all in the H-CLP group, experienced adverse events leading
to study
discontinuation (constipation; nausea and vomiting; nausea, bloating and loss
of appetite;
generalized weakness, bloating and loss of appetite). There were no clinically
relevant
changes in serum Na+, calcium, magnesium or phosphorus. In the H-CLP group,
mean
serum bicarbonate level decreased about 2-3 mmol/L from baseline to the end of
Week 2
but mean values remained in the normal range and returned to pre-treatment
levels by the
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end of Week 4. Measures of renal function [blood urea nitrogen (BUN), serum
creatinine
and eGFR] did not change significantly from baseline to the end of Week 8 in
either the
CLP or Placebo group.
[00806] Four deaths, all in the H-CLP group, occurred during the
study. Each death
was judged by the investigator to be definitely unrelated to the study drug.
The first death
occurred suddenly at Week 3 in a 70 year old NYHA class IV male with ischemic
HF,
LVEF = 20%, atrial fibrillation and eGFR= 46 mUmin/1.73 m2. He was seen by the
investigator two weeks before the event and was clinically stable with no ECG
or laboratory
changes.
[00807] The second death occurred at Week 4 in a 60 year old NYHA class III
diabetic male with ischemic HF, LVEF = 20%, previous pulmonary embolism, and
eGFR =
48 mUmin/1.73 m2. The patient was seen by the investigator two days before he
developed
an acute HF decompensation complicated by impaired consciousness and hypoxia.
[00808] The third death occurred at Week 6 in a 63 year old NYHA
class III male
with ischemic HF. Two weeks before death the patient had refused
hospitalization
recommended on the basis of worsening fluid overload and progressive renal
impairment, as
indicated by a drop in eGFR from 48 to 20 mL/min/1.73 m2.
[00809] The fourth death occurred at Week 6 in a 67 year old NYHA
class IV male
with non-ischemic HF, atrial fibrillation and eGFR = 36 mUmin/1.73 m2 who
complained
of abdominal distension and loss of appetite associated with a metabolic
acidosis in the
absence of renal function changes three days before the patient stopped taking
study drug.
The patient was hospitalized three days after study drug discontinuation due
to worsening
dyspnea, hydrothorax, ascites, and marked acidosis and died three days later.
H. Additional Description: Discussion Summary
[00810] An exemplary study treating subjects by administering a cross-
linked
polyelectrolyte polymer, such as a cross-linked polyacrylate polymer (e.g., H-
CLP and base
such as 0.75 equivalents of base) was conducted. A Phase 2, double-blind,
randomized,
parallel group, placebo controlled study was designed to explore, for example,
the effects of
H-CLP and base versus placebo on serum K+ concentration and fluid overload in
HF
patients with renal impairment who are on the guideline recommended
combination of an
ACE inhibitor or ARB, a Beta Blocker and diuretics and have a clinical
indication for the
addition of spironolactone (for a description of such drugs and their effects,
see, e.g., Pitt et
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