Note: Descriptions are shown in the official language in which they were submitted.
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FORMULATIONS AND METHODS FOR SOLID CHITOSAN-CONTAINING
BLENDS
CROSS-REFERENCE TO RELATED APPLICATION
This application claims the benefit of U.S. Provisional Application
No. 61/187,516, filed June 18, 2009, which is incorporated herein by reference
in its
entirety.
FIELD OF THE INVENTION
The present invention relates to a formulation of solid chitosan and a solid
acid or
a solid agent that generates a proton in situ in the presence of water blend
having
improved solubilization properties. The invention further relates to a process
for
solubilizing the solid chitosan contained in the blend. The invention further
relates to a
process for using the method of solubilization to achieve flocculation in an
aqueous
medium, such as a stream, containing matter, such as suspended sediment,
insoluble
organic matter, or soluble organic matter. The invention further relates to
kits for use in
flocculation in aqueous systems or streams containing such matter.
BACKGROUND
Chitin is a linear polysaccharide composed of (3-(1-4)-linked
2-acetoamido-2-deoxy-D-glucose units that occur naturally in the exoskeleton
of
invertebrates, in particular, the carapace of marine crustaceans. Chemical
deacetylation
of chitin yields chitosan, which is a copolymer of 2-amino-2-deoxy-D-glucose
and
2-acetoamido-2-deoxy-D-glucose units.
Soluble chitosan is useful as a coagulant and flocculant in removing
impurities
such as suspended sediment, proteins, fats, tannins, and metals from aqueous
mediums.
Soluble chitosan is more commonly used to remove contaminants such as
suspended
sediment and particulate matter from stormwater running off of construction
sites.
Chitosan is insoluble in water, alkali solutions, and most organic solvents.
Its
effectiveness as a flocculant and coagulant requires it to be dissolved and
delivered in
soluble form to the aqueous medium containing the material to be coagulated or
flocculated. The concentration of soluble chitosan delivered to the aqueous
medium
containing the material to be coagulated or flocculated affects its
effectiveness as a
flocculant or coagulant.
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Chitosan is soluble in certain solutions of acids at defined acid and chitosan
concentrations and slightly soluble to insoluble in other acid solutions. The
type of the
acid can influence the consistency of the chitosan rendering it paste-like,
gelatinous, or
more like a pseudo-plastic. In soluble form, chitosan is most commonly found,
in
commercial applications, to be dissolved in dilute acetic or lactic acid.
Because of the
high viscosity that chitosan exhibits in dissolved form, commercial chitosan
solutions
typical exhibit concentrations ranging from 1% (wt./wt.) to 3% (wt./wt.). In
flocculation/coagulation applications, the dissolved chitosan in the 1%-3%
solutions is
metered into the aqueous medium containing the impurity, such as stormwater or
industrial water using a metering pump. Higher concentrations (>3%) of
dissolved
chitosan exhibit such high viscosities that delivery using a metering pump
becomes
difficult and not practical. Therefore, this limits the commercial
applications of liquid
chitosan solutions due to the cost of shipping, which is based on weight. For
example, a
3% chitosan solution is essentially -97% water and the shipping cost is
primarily
attributed to water.
An alternative to liquid formulations has been to prepare dry solid chitosan
salts
that are water soluble. This involves reacting chitosan, dispersed in an
organic medium,
with an organic acid. The reaction product is then dried, resulting in a dry
solid
protonated chitosonium salt derivative that is water soluble. Although the
production of a
dry solid water soluble chitosonium salt mitigates the cost limitations of
shipping a 1-3%
-chitosan solution, there is the production cost to produce the chitosonium
salt that still
limits the number of potential commercial applications.
SUMMARY
This summary is provided to introduce a selection of concepts in a simplified
form that are further described below in the Detailed Description. This
summary is not
intended to identify key features of the claimed subject matter, nor is it
intended to be
used as an aid in determining the scope of the claimed subject matter.
An alternative to chitosan dissolved in acidic solutions or solid water
soluble
chitosonium salts is to prepare a blend of (a) solid chitosan and (b) a solid
acid or a solid
agent that generates a proton in situ in the presence of water (also referred
to herein as a
"solid agent") such that the blend, when added to a relatively low volume of
water, results
in the solubilization of the chitosan. This solution of solubilized chitosan
may then be
diluted with water to a desired chitosan concentration, such as a 3% chitosan
solution.
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Thus, some embodiments of the present invention contemplate a method of
solubilizing chitosan comprising: (1) selecting a desired final chitosan
concentration
having a total volume of water, VF; (2) obtaining a blend comprising: a solid
chitosan
that may be partially protonated but is greater than 80% insoluble when added
to water
and in a dry, free-flowing, particulate form, and a solid acid or a solid
agent that
generates a proton in situ in the presence of water, wherein the solid acid or
the solid
agent that generates a proton in situ in the presence of water is in a dry,
free-flowing,
particulate form, wherein the solid chitosan and the solid acid or the solid
agent that
generates a proton in situ in the presence of water are not reacted together
or otherwise
chemically bound, and wherein the solid chitosan in the blend is not soluble
when added
to the total volume of water, VF; (3) adding one or more volumes of water, V1,
to the
blend, wherein V 1 is less than VF and V 1 is effective to swell and dissolve
the solid
chitosan within a predetermined time period, and optionally adding subsequent
volumes
of water V 1 or fractions thereof, when after an addition of VI, the solid
chitosan does not
swell and dissolve after the predetermined time period; and (4) after the
solid chitosan has
swelled and dissolved, adding water to bring the total volume of added water
to VF,
thereby producing solubilized chitosan of a desired concentration.
Also contemplated is a method of solubilizing chitosan comprising: (1)
selecting a
desired final chitosan concentration having a total volume of water, VF; (2)
obtaining a
blend consisting of. a solid chitosan that may be partially protonated but is
greater than
80% insoluble when added to water and in a dry, free-flowing, particulate
form, a solid
acid defined as solid malic acid, solid citric acid, or solid tartaric acid,
wherein each solid
acid is in a dry, free-flowing, particulate form, wherein the solid chitosan
and the solid
acid are not reacted together or otherwise chemically bound, and wherein the
solid
chitosan in the blend is not soluble when added to the total volume of water,
VF; and
optionally a component selected from the group consisting of solid sodium
acetate,
glycerin, a solid salt of the solid acid or a solid salt of a different solid
acid, a solid
preservative acid, a solid salt of a preservative acid, a solid antimicrobial
agent, a solid
metal salt, a solid neutral aqueous-soluble polysaccharide, a solid cationic
aqueous-
soluble polysaccharide, a solid anionic aqueous-soluble polysaccharide, a
solid organic
amine, or a solid inorganic amine, or a combination thereof, wherein each
component
aside from glycerin is in a dry, free-flowing, particulate form; (3) adding
one or more
volumes of water, V 1, to the blend, wherein V 1 is less than VF and V 1 is
effective to
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swell and dissolve the solid chitosan within a predetermined time period, and
optionally
adding subsequent volumes of water V 1 or fractions thereof, when after an
addition of
V 1, the solid chitosan does not swell and dissolve after the predetermined
time period;
and (4) after the solid chitosan has swelled and dissolved, adding water to
bring the total
volume of added water to VF, thereby producing solubilized chitosan of a
desired
concentration.
Compositions of blends are also provided. In some embodiments, a composition
comprises a blend of. a solid chitosan that may be partially protonated but is
greater than
80% insoluble when added to water and in a dry, free-flowing, particulate
form, and solid
sodium diacetate or solid potassium diacetate, or a combination thereof, that
is in a dry,
free-flowing, particulate form, wherein the solid chitosan and the solid
sodium diacetate
or solid potassium diacetate, or combination thereof, are not reacted together
or otherwise
chemically bound. Methods of solubilizing blends or compositions comprising
blends are
also provided. In some embodiments, a method of solubilizing a composition
comprising
a blend of a solid chitosan that may be partially protonated but is greater
than 80%
insoluble when added to water and in a dry, free-flowing, particulate form,
and solid
sodium diacetate or solid potassium diacetate, or a combination thereof, that
is in a dry,
free-flowing, particulate form, wherein the solid chitosan and the solid
sodium diacetate
or solid potassium diacetate, or combination thereof, are not reacted together
or otherwise
chemically bound, the method comprising: (1) selecting a desired final
chitosan
concentration having a total volume of water, VF; (2) obtaining the blend; (3)
adding one
or more volumes of water, V1, to the blend, wherein V 1 is less than VF and V
1 is
effective to swell and dissolve the solid chitosan within a predetermined time
period, and
optionally adding subsequent volumes of water V1 or fractions thereof, when
after an
addition of V1, the solid chitosan does not swell and dissolve after the
predetermined time
period; and (4) after the solid chitosan has swelled and dissolved, adding
water to bring
the total volume of added water to VF, thereby producing solubilized chitosan
of a
desired concentration.
Further, any blend described herein may be solubilized by adding a volume of
water that results in a chitosan concentration of greater or equal to about
1.0%.
DESCRIPTION OF THE DRAWINGS
The foregoing aspects and many of the attendant advantages of this invention
will
become more readily appreciated as the same become better understood by
reference to
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the following detailed description, when taken in conjunction with the
accompanying
drawings, wherein:
FIGURE 1 shows a representative embodiment of a device of the present
invention comprising a segmented body (partially cut away); and
FIGURE 2 shows a cross-sectional view of the device shown in FIGURE X which
more clearly shows the blend disposed within the device.
DETAILED DESCRIPTION
It has been discovered that the addition of a relatively low volume of water,
optionally in increments, to a blend comprising a solid chitosan and a solid
acid or solid
agent that generates a proton in situ in the presence of water solubilizes the
solid chitosan,
whereas the solid chitosan is insoluble when the blend is mixed in a
relatively large
volume of water all at once. In some embodiments, the method comprises adding
the
blend to a relatively small volume of water, as compared to the total amount
of water
added to achieve a desired chitosan concentration, and stirring to dissolve
the chitosan to
produce a highly viscous paste or gel followed by slowly adding increasing
amounts of
water to achieve the desired chitosan concentration.
Use of solids herein that are in a dry, free-flowing, particulate form refer
to solids
that behave much like sand flowing from one portion of an hourglass to
another. Use of
the word "solid" is intended to exclude other states of matter such as liquids
and gases.
Provided herein is a method of solubilizing chitosan comprising: (1) selecting
a
desired final chitosan concentration having a total volume of water, VF; (2)
obtaining a
blend comprising: a solid chitosan that may be partially protonated but is
greater than
80% insoluble when added to water and in a dry, free-flowing, particulate
form, and a
solid acid or a solid agent that generates a proton in situ in the presence of
water, wherein
the solid acid or the solid agent that generates a proton in situ in the
presence of water is
in a dry, free-flowing, particulate form, wherein the solid chitosan and the
solid acid or
the solid agent that generates a proton in situ in the presence of water are
not reacted
together or otherwise chemically bound, and wherein the solid chitosan in the
blend is not
soluble when added to the total volume of water, VF; (3) adding one or more
volumes of
water, V 1, to the blend, wherein V 1 is less than VF and V 1 is effective to
swell and
dissolve the solid chitosan within a predetermined time period, and optionally
adding
subsequent volumes of water V 1 or fractions thereof, when after an addition
of V1, the
solid chitosan does not swell and dissolve after the predetermined time
period; and (4)
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after the solid chitosan has swelled and dissolved, adding water to bring the
total volume
of added water to VF, thereby producing solubilized chitosan of a desired
concentration.
The predetermined time may be about, at most about, or at least about 5, 10,
25,
20, 25, or 30 minutes, or any range derivable therein. The volume V1 is
greater than
zero. The volume V 1 may be up to about 10% by volume of VF. The volume V 1
may be
up to about 5% by volume of VF. The volume V 1 may be up to about 1% by volume
of
VF. The volume may range from about, at least about, or at most about 0.1%,
0.5%, 1%,
1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%,
9%,
9.5%, or 10%, or any range derivable therein.
In some embodiments, the method of step (4) described above comprises adding a
plurality of incremental volumes of water, such as 2, 3, 4, 5, 6, 7, 8, 9, or
10 increments,
or any range derivable therein, wherein each incremental volume may be the
same or
different, with mixing after each addition, until VF is achieved, thereby
providing
solubilized chitosan of a desired concentration.
The solid chitosan may have an average molecular weight of between about
20,000 Da and about 2,000,000 Da. In some embodiments, the average molecular
weight
is about, at most about, or at least about 20,000, 50,000, 100,000, 150,000,
200,000,
250,000, 500,000, 750,000, 1,000,000, 1,250,000, 1,500,000, 1,750,000, or
2,000,000, or
any range derivable therein. The solid chitosan may have a percent
deacetylation of
greater than about 50%. In some embodiments, the solid chitosan may have a
percent
deacetylation of about, at least about, or at most about 50%, 60%, 70%, or
80%, or more,
or any range derivable therein.
In some embodiments, the particle size or the average particle size of the
solid
chitosan ranges from about 125 microns to about 850 microns. In some
embodiments,
about 90% of the particles of solid chitosan in a blend range from about 125
microns to
about 850 microns, or have an average particle size that ranges from about 125
microns to
about 850 microns. In some embodiments, the particle size or the average
particle size of
the solid chitosan is greater than 850 microns. In some embodiments, the
particle size or
average particle size of the solid chitosan ranges from about 850 microns up
to about 1
cm. In some embodiments, the particle size or average particle size ranges
from about
0.5 cm to about 1 cm.
In some embodiments, the particle size or the average particle size of the
solid
acid or solid agent ranges from about 125 microns to about 850 microns. In
some
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embodiments, about 90% of the particles of solid acid or solid agent in a
blend range
from about 125 microns to about 850 microns, or have an average particle size
that ranges
from about 125 microns to about 850 microns. In some embodiments, the particle
size or
the average particle size of the solid acid or solid agent is greater than 850
microns. In
some embodiments, the particle size or average particle size of the solid acid
or agent
ranges from about 850 microns up to about 1 cm. In some embodiments, the
particle size
or average particle size of the solid acid or solid agent is less than the
solid chitosan
particle size or average particle size. In some embodiments, the particle size
or average
particle size of the solid acid or solid agent is greater than the solid
chitosan particle size
or average particle size.
In some embodiments, the particle size of the solid chitosan is within about
20%
of the particle size of the solid acid or the solid agent that generates a
proton in situ in the
presence of water. In some embodiments, the particle size of the solid
chitosan is within
about, at most about, or at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%,
10%,
11%, 12%,13%,14%,15%,16%,17%,18%,19%,20%,21%,22%,23%,24%, or 25%,
or any range derivable therein, of the particle size of the solid acid or the
solid agent.
In some embodiments, the solid acid is a protic acid. The solid acid may be
malic
acid, citric acid, tartaric acid, sodium diacetate, or potassium diacetate,
for example. The
solid acid may be sodium diacetate or potassium diacetate.
In some embodiments, the solid agent that generates a proton in situ in the
presence of water is selected from the group consisting of a solid sulfite
salt, a solid
organic acid lactone, and a solid organic acid anhydride.
The ratio of a solid chitosan to a solid acid or solid agent that generates a
proton
in situ in the presence of water may vary. In some embodiments, the ratio of
the solid
chitosan to the solid acid or the solid agent that generates a proton in situ
in the presence
of water ranges from about 1:10 to about 10:1 (wt./wt.). In other embodiments,
the ratio
of solid chitosan to the solid acid or the solid agent that generates a proton
in situ in the
presence of water is about 1:1 (wt./wt.). In yet other embodiments, the ratio
of solid
chitosan to the solid acid or the solid agent that generates a proton in situ
in the presence
of water is about 1:2 (wt./wt.).
A blend may comprise additional components. In some embodiments, the blend
further comprises glycerin. Addition of glycerin may aid in the solubility of
chitosan. A
blend may comprise a solid salt of the solid acid or a salt of a different
solid acid, wherein
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the salt is in a dry, free-flowing, particulate form. A blend may comprise a
solid
preservative acid, a solid salt of a preservative acid, or a solid
antimicrobial agent,
wherein the solid preservative acid, the solid salt of a preservative acid, or
the solid
antimicrobial agent is in a dry, free-flowing, particulate form. In some
embodiments, a
blend may comprise a solid metal salt that is in a dry, free-flowing,
particulate form. A
blend may comprise a solid, neutral polysaccharide that is in a dry, free-
flowing,
particulate form. A blend may comprise a solid cationic or solid anionic
polysaccharide,
wherein the solid cationic or solid anionic polysaccharide is in a dry, free-
flowing,
particulate form. A blend may comprise a solid organic amine that is in a dry,
free-
flowing, particulate form. In some embodiments, a blend further comprises a
solid
inorganic amine that is in a dry, free-flowing, particulate form.
In some embodiments, a blend is further defined as a blend of a solid
chitosan, a
solid protic acid, and a solid organic acid anhydride, wherein the solid
chitosan, the solid
protic acid, and the solid organic acid anhydride are each in a dry, free-
flowing,
particulate form.
Any blend described herein may further comprise sodium acetate. The acetate
ion
may aid in chitosan solubility.
The chitosan-containing blends described herein may be used to prepare a
desired
final chitosan concentration, such as a desired final chitosan concentration
that ranges
from about 1% to about 5% (wt./wt.). In some embodiments, the desired final
chitosan
concentration ranges from about 1% to about 3% (wt./wt.).
In some embodiments, a solid acid or the solid agent that generates a proton
in
situ in the presence of water is selected by a method comprising: (A)
preparing a test
blend of a test solid chitosan and a test solid acid or a test solid agent
that generates a
proton in situ in the presence of water, wherein the ratio of test solid
chitosan to test solid
acid or test solid agent that generates a proton in situ in the presence of
water is about
1:1:1 (gram: gram: liter); wherein the test solid chitosan and the test solid
acid or the test
solid agent that generates a proton in situ in the presence of water are each
in a dry, free-
flowing, particulate form, and wherein the test solid chitosan and the test
solid acid or the
test solid agent that generates a proton in situ in the presence of water are
not reacted
together or otherwise chemically bound; (B) adding a test volume of water (VT)
to the
test blend and mixing; (C) determining if the test solid chitosan swells and
if the test
blend dissolves, and then doing one of two things: (a) if the test solid
chitosan swells and
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the test blend dissolves, then establishing that the test solid acid or test
solid agent that
generates a proton in situ in the presence of water solubilizes the test solid
chitosan in
water under these conditions; or (b) if the test solid chitosan does not swell
and the test
blend does not dissolve, then employing the test blend in step (2) of the
method described
above.
Also contemplated is a method of solubilizing chitosan comprising: (1)
selecting
a desired final chitosan concentration having a total volume of water, VF; (2)
obtaining a
blend consisting of. a solid chitosan that may be partially protonated but is
greater than
80% insoluble when added to water and in a dry, free-flowing, particulate
form, a solid
acid defined as solid malic acid, solid citric acid, or solid tartaric acid,
wherein each solid
acid is in a dry, free-flowing, particulate form, wherein the solid chitosan
and the solid
acid are not reacted together or otherwise chemically bound, and wherein the
solid
chitosan in the blend is not soluble when added to the total volume of water,
VF; and
optionally a component selected from the group consisting of solid sodium
acetate,
glycerin, a solid salt of the solid acid or a. solid salt of a different solid
acid, a solid
preservative acid, a solid salt of a preservative acid, a solid antimicrobial
agent, a solid
metal salt, a solid neutral aqueous-soluble polysaccharide, a solid cationic
aqueous-
soluble polysaccharide, a solid anionic aqueous-soluble polysaccharide, a
solid organic
amine, or a solid inorganic amine, or a combination thereof, wherein each
component
aside from glycerin is in a dry, free-flowing, particulate form; (3) adding
one or more
volumes of water, V1, to the blend, wherein V 1 is less than VF and V 1 is
effective to
swell and dissolve the solid chitosan within a predetermined time period, and
optionally
adding subsequent volumes of water V 1 or fractions thereof, when after an
addition of
V 1, the solid chitosan does not swell and dissolve after the predetermined
time period;
and (4) after the solid chitosan has swelled and dissolved, adding water to
bring the total
volume of added water to VF, thereby producing solubilized chitosan of a
desired
concentration. In this or any other method, the predetermined time period may
be about
15 to about 30 minutes. The predetermined time may be about, at most about, or
at least
about 5, 10, 25, 20, 25, or 30 minutes, or any range derivable therein. The
volume V1 is
greater than zero. The volume V1 may be up to about 10% by volume of VF. The
volume V 1 may be up to about 5% by volume of VF. The volume V 1 may be up to
about
1% by volume of VF. The volume may range from about, at least about, or at
most about
0.1%, 0.5%,1%,1.5%,2%,2.5%,3%,3.5%,4%,4.5%,5%,5.5%,6%,6.5%,7%,7.5%,
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8%, 8.5%, 9%, 9.5%, or 10%, or any range derivable therein. The method of step
(4)
may comprise adding a plurality of incremental volumes of water, such as 2, 3,
4, 5, 6, 7,
8, 9, or 10 increments, or any range derivable therein, wherein each
incremental volume
may be the same or different, with mixing after each addition, until VF is
achieved,
thereby providing solubilized chitosan of a desired concentration.
Compositions comprising blends are also provided. In some embodiments, a
composition comprises a blend of: a solid chitosan that may be partially
protonated but is
greater than 80% insoluble when added to water and in a dry, free-flowing,
particulate
form, and solid sodium diacetate or solid potassium diacetate, or a
combination thereof,
that is in a dry, free-flowing, particulate form, wherein the solid chitosan
and the solid
sodium diacetate or solid potassium diacetate, or combination thereof, are not
reacted
together or otherwise chemically bound. The ratio of solid chitosan to solid
sodium
diacetate or sodium potassium diacetate may range from about 1:1 to about 1:5
(wt./wt.).
In some embodiments, the ratio ranges from about 1:2 to about 1:3 (wt./wt.).
In
compositions comprising a blend of a solid chitosan and solid sodium diacetate
or solid
potassium diacetate, the particle size of each may be any particle size or
average particle
size described herein. In some embodiments, the particle size or the average
particle size
of the solid chitosan and solid sodium diacetate or solid potassium diacetate
are each
about 125 microns to about 850 microns. In some embodiments, about 90% of the
solid
chitosan or the solid sodium diacetate or solid potassium diacetate ranges
from about 125
microns to about 850 microns.
Also disclosed is a method of solubilizing a blend of solid chitosan and solid
sodium acetate or solid potassium acetate, or a combination thereof, as
described above,
comprising: (1) selecting a desired final chitosan concentration having a
total volume of
water, VF; (2) obtaining such a blend; (3) adding one or more volumes of
water, V1, to
the blend, wherein V 1 is less than VF and V 1 is effective to swell and
dissolve the solid
chitosan within a predetermined time period, and optionally adding subsequent
volumes
of water V 1 or fractions thereof, such as 2, 3, 4, 5, 6, 7, 8, 9, or 10
fractions, or any range
derivable therein, when after an addition of V1, the solid chitosan does not
swell and
dissolve after the predetermined time period; and (4) after the solid chitosan
has swelled
and dissolved, adding water to bring the total volume of added water to VF,
thereby
producing solubilized chitosan of a desired concentration.
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To blends described herein, a volume of water (i.e., a non-incremental volume
of
water) may be added to result in a chitosan concentration of greater than or
equal to about
0.1%. For example, to a blend comprising a solid chitosan and solid sodium
acetate or
solid potassium acetate as described above, a volume of water may be added to
result in a
chitosan concentration of greater than or equal to about 0.1%. The chitosan
concentration
may be from about 1% to about 5%, for example. The chitosan concentration may,
in
some embodiments, range from about 1% to about 3%. The ratio of chitosan to
sodium
diacetate or potassium diacetate may be about 1:2 or greater.
Chitosan. As noted above, chitosan is a copolymer of
2-amino-2-deoxy-D-glucose and 2-acetoamido-2-deoxy-D-glucose units. Chitosan
is
commercially available from a variety of sources, and the average molecular
weight
range and percent deacetylation may vary. For example, solid chitosan may have
an
average molecular weight of between about 20,000 Da and 2,000,000 Da and may
have a
percent deacetylation of greater than about 50%. A solid chitosan may be
partially
protonated but is typically greater than about, at least about, or at most
about 65%, 70%,
75%, 80%, 85%, 90%, 95%, or 99% insoluble, or any range derivable therein,
when
added to water and in a dry, free-flowing, particulate form. In other words,
greater than a
particular percentage of the solid chitosan does not dissolve. Solid chitosan
employed in
blends described herein is in dry, free-flowing, particulate form that
excludes any solvent,
such as water or an organic solvent. Solid chitosan in blends also excludes
chitosan
complexes. In some embodiments, chitosan may be further defined as excluding a
metal,
such as chelated metal.
Solid Acids. Solid acids employed in blends described herein are in dry, free-
flowing, particulate form. Solid acids are typically protic acids which, on
dissociation,
provide at least one proton (H+). Both mono and polyprotic (e.g., diprotic)
acids may be
used. The term "monoprotic" is intended to refer to an acid having one
displaceable
hydrogen atom per molecule. The term "polyprotic" should be construed
accordingly.
Non-limiting examples of protic acids include lactic acid, adipic acid,
pyruvic
acid, phenyl. pyruvic acid, p-hydroxyphenylpyruvic acid, p-hydroxypyruvic
acid,
2-keto-glutaric acid, glyoxylic acid, a-ketoisocaproic acid, oxalacetic acid,
levulinic acid,
acetoacetic acid, malonaldehydric acid, glutaraldehydic acid, malonaldehydic
acid,
glutaraldehydic acid, p-(3-formylpropyl)benzoic acid, 3 -oxovaleric acid,
2-keto-3-hydroxybutyric acid, 3-benzoylpropionic acid, 4-benzoylbenzoic acid,
caprylic
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acid, citraconic acid, citamalic acid, citrazinic acid, hexanoic acid, n-
capric acid, glutamic
acid, citric acid, tartaric acid, malic acid, maleic acid, malonic acid,
propionic acid,
succinic acid, fumaric acid, glycolic acid, D-glucuronic acid, benzoic acid,
sorbic acid,
salicylic acid, galacturonic acid, ascorbic acid, glucaric acid, (meso)-
galactaric acid,
D-arabinaric acid, oxalic acid, benzoic acid, sulphanilic acid, gluconic acid,
palmitic acid,
stearic acid, ethylene diamine tetraacetic acid, glucoheptonic acid, nicotinic
acid, oleic
acid, phytic acid, polygalacturonic acid, sulfamic acid, uric acid, carminic
acid,
L-pyroglutamic acid, D-pyroglutamic acid, amino benzoic acid, 6-amino caproic
acid,
glutaric acid, dodecylbenzene sulfonic acid, octanoic acid, glyoxylic acid,
isovaleric acid,
boric acid, mercaptoacetic acid, aspartic acid, alanine, arginine, asparagine,
cysteine,
glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine,
phenylalanine,
proline, serine, threonine, tryptophan, tyrosine, valine, sodium diacetate and
potassium
diacetate. In some embodiments, the solid acid is malic acid, citric acid;
tartaric acid,
sodium diacetate (a combination of acetic acid and sodium acetate), or
potassium
diacetate (a combination of acetic acid and potassium acetate). It is
understood that
liquid acids can be made into solid forms, i.e., solid lactic acid is
commercially available
in a solid form.
The corresponding solid salts of solid acids listed above may also be
incorporated
into the blends in combination with their respective solid acids or different
solid acids.
Solid Agents. Solid agents that generate a proton in situ in the presence of
water
may also be employed (e.g., the solid agent provides at least one proton when
dissolved
in water). With regard to solid agents that generate a proton in situ in the
presence of
water, sulfite salts, organic acid lactones, organic acid anhydrides are
contemplated.
Sulfite salts may be used because they form sulfurous acid when dissolved in
water.
Organic acid lactones can also be used to formulate blends of solid chitosan.
The
lactones undergo hydrolysis in water and produce the corresponding organic
acid in situ.
The hydrolysis rate of organic acid lactones into the corresponding acid can
vary between
different organic acid lactones. The in situ generation of the acid in an
aqueous medium
can likely influence the solubility profile of chitosan and may be very
different compared
to the solubility profile of the chitosan contained in the solid corresponding
solid
acid-solid chitosan blend. This is one way to control the solubilization rate
of the
chitosan. Examples of organic acid lactones include glucuronic acid lactone,
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D-glucono-1,4-lactone, gluconic acid lactone, galacturonic acid lactone,
mannuronic
acid lactone, glyconic acid lactone, D-glucofuranurono-6,3-lactone, and D-
galactopyranurono-6,3 -lactone.
Solid organic acid anhydrides can also be used in the blends of solid
chitosan.
The solid organic acid anhydrides undergo hydrolysis in water and produce the
corresponding organic acid in situ. The hydrolysis rate of solid organic acid
anhydrides
into the corresponding acids can vary between different organic acid lactones.
The in situ
generation of the acid in an aqueous medium can likely influence the
solubility profile of
chitosan and may be very different compared to the solubility profile of the
chitosan
contained in the solid corresponding acid-solid chitosan blend. This is one
way to control
the solubilization rate of the chitosan. Non-limiting examples include
succinic anhydride,
maleic anhydride, malic anhydride, and citraconic anhydride.
It has also been demonstrated that derivatization of chitosan by the reaction
of the
anhydride in an aqueous medium such as water is possible. The resulting
chitosan
derivative is no longer cationic, but exhibits anionic properties due to
covalent attachment
of carboxyl functional groups derived from the anhydride, such as from
succinylation
with succinic anhydride. It is envisioned that a solid acid-solid chitosan
blend containing
the corresponding or different organic acid anhydride can result in formation
of chitosan
derivatives in situ that contain both cationic and anionic properties
attributed to
covalently bound carboxyl functions and protonated primary amines. The nature
and
properties of the chitosan derivative can be influenced and controlled by
the'ratio of solid
acid to chitosan and the ratio of solid organic acid anhydride. It also
envisioned that by
controlling the ratio of organic acid anhydride added to solid chitosan in an
organic acid
anhydride blend without the addition of an added solid organic acid, the
normal cationic
chitosan could be converted into an anionic chitosan in situ. The solid
organic acid
anhydride-solid chitosan blend or solid organic acid-solid organic acid
anhydride-solid
chitosan blend could also be contained within a porous containment device
capable of
releasing the derivatized chitosan, as described below. The released
derivatized chitosan
would have desirable properties useful for flocculation, coagulation,
precipitation
(dissolved substances), coatings, etc.
In some embodiments, the solid acid is not hyaluronic acid, nicotinic acid
(see
U.S. Patent No. 5,736,532), a fatty acid, a nucleic acid, lactic acid (see
U.S. Publ. Appl.
No. 2005/0239657), or succinic acid (see U.S. Publ. Appl. No. 2005/0239657).
In some
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embodiments, the solid acid is not a non-phytotoxic acid, such as arginine,
histidine,
isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan,
valine,
alanine, aspartic acid, citrulline, cystine, glutamic acid, glycine,
hydroxyglutamic acid,
norleucine, proline, serine, and tyrosine, adipic acid, hydrochloric acid,
tartaric acid,
nitric acid, formic acid, or citric acid (see U.S. Patent No. 4,964,894).
In some embodiments, the solid acid or solid agent that generates a proton in
situ
in the presence of water is not a polymer (see WO 2010/023463). In some
embodiments,
the solid acid is not glyoxylic acid (see WO 2008/087845). In some
embodiments, the
solid acid is not ascorbic acid (see WO 00/024785).
Blends. The present invention further contemplates blends. Blends refer to any
combination of a solid chitosan and one or more of the solid acids or agents
discussed
herein, and may optionally comprise additional components, as explained
herein. Blends
of a solid chitosan and a solid acid or a solid agent that generates an acid
in situ in the
presence of water refer to mixtures or formulations of dry, free-flowing,
particulates of
each component. The solid chitosan and the solid acid or the solid agent are
not reacted
together or otherwise chemically bound while in the blended condition. That
is, the solid
chitosan and the solid acid or the solid agent are chemically separate from
each other.
For example, the solid chitosan and the solid acid or the solid agent are not
covalently
bound together, do not form a complex, and are not cross-linked together, nor
does one
component "cage" the other component.
Blends may comprise, consist essentially of, or consist of a solid chitosan
and a
solid acid or a solid agent that generates an acid in situ in the presence of
water. In some
embodiments, the only two components of the blend are a solid chitosan and a
solid acid
or a solid agent. In blends consisting essentially of a solid chitosan and a
solid acid or a
solid agent, the blend excludes components that do not materially affect the
novel and
basic characteristics of the solid chitosan and the solid acid or the solid
agent. For
example, a blend consisting essentially of a solid chitosan and a solid acid
or a solid agent
may exclude water and organic solvents. It is specifically contemplated that a
blend may
comprise, consist essentially of, or consist of a solid chitosan, a solid
acid, and a solid
agent. Trace amount of impurities may be present in blends. Impurities may
include, for
example, digested proteinaceous material from the processing of chitin into
chitosan, or
mineral salts such as potassium or calcium carbonate or potassium or calcium
phosphate.
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Blends comprising a solid chitosan and a solid acid or a solid agent may, in
some
embodiments, be further defined as not comprised in a film, coating, or
tablet. In some
embodiments, the blend is not in layer form. In some embodiments, the blend is
not
comprised in a hydrogel. In some embodiments, a blend does not comprise, nor
is
comprised in, a slurry, a liquid, or a solution. In some embodiments,
carbonates or
bicarbonates are excluded from a blend (see U.S. Publ. Appl. No.
2008/0190861). In
some embodiments, drugs are excluded from a blend (see U.S. Publ. Appl. No.
2006/0115525).
Different ratios of solid chitosan to solid acid or solid agent are possible
on a
weight or molar equivalent basis. This ratio would depend on the type of solid
acid or
solid agent used and the molecular weight and the degree of deacetylation of
the solid
chitosan. In some embodiments, the ratio of solid chitosan to solid acid or
solid agent
ranges from about 1:10 to about 10:1. In some embodiments, the ratio is about,
at least
about, or at most about 1:10, 1:5, 3:10, 2:5, 1:2, 3:5, 7:10, 4:5, 9:10, 1:1,
10:9, 5:4, 10:7,
5:3, 2:1, 5:2, 10:3, 5:1, or 10:1, or any range derivable therein.
The particle size range of the solid chitosan and the particle size range of
the solid
acid or solid agent in a blend may vary. It is expected that there would be an
optimum
particle size range for both the solid chitosan and the solid acid or solid
agent. Existing
data presented in the examples demonstrate that particles of solid chitosan
that are less
than 850 microns, such as ranging from about 125 to about 850 microns, can be
effectively blended with solid acids exhibiting particle sizes that range in
size from table
salt and granulated refined sugar to powders. Larger particle sizes of solid
acids and solid
agents may also be used. In some embodiments, about 90% of the solid chitosan
in a
blend has a particle size of about 125 microns to about 850 microns. It is
expected that
particle sizes of chitosan greater than about 850 microns would also be
effectively
blended with solid acids or solid agents of a similar size range, or larger or
smaller size
range. In some embodiments, the particle size of the solid chitosan is within
about, at
most about, or at least about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 70%, 80%, or
90%
of the particle size of the solid acid or the solid agent, or any range
derivable therein.
When particle sizes are comparable in size, the chance of settlement of larger
particles is
minimized. It is typically easier to alter the particle size of the solid
chitosan, which is
typically in particle or flake form, to approach the size of the solid acid or
solid agent,
rather than vice versa. For example, coarse-ground chitosan, which is
typically between
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about 0.25 cm to about 0.5 cm, may be further ground to approach the particle
size of a
solid acid or solid agent, which may be more of a powder.
Additional Components. In some embodiments, a blend containing solid chitosan
and a solid acid or solid agent may comprise one or more additional
components.
Combinations of the following components are also contemplated. Typically, an
additional component will be in a solid, dry, free-flowing, particulate form.
However,
embodiments contemplate blends containing glycerin to enhance the solubility
of the
solid chitosan.
Other embodiments include solid chitosan blended with combinations of solid
acids together with solid salts of organic acids, wherein each salt is in a
dry, free-flowing,
particulate form. Examples include solid chitosan blended with lactic acid and
calcium
lactate; chitosan blended with lactic acid, calcium lactate in combination
with sodium
acetate; chitosan blended with adipic acid in combination with sodium or
potassium
acetate; chitosan blended with adipic acid in combination with sodium or
potassium
hexanoate; chitosan blended with glutamic acid in combination with sodium or
potassium
acetate; chitosan blended with glutamic acid in combination with sodium or
potassium
hexanoate; chitosan blended with solid adipic acid in combination with solid
benzoic
acid. These examples are not meant to be exhaustive but merely to provide
examples of
the types and possible varieties of combinations that are possible. These
blends may act
to influence chitosan's solubility properties and provide benefits in certain
applications.
Another embodiment contemplates blends containing solid preservative acids or
solid salts of preservative acids or solid antimicrobial agents that retard or
prevent the
growth of microorganisms such as molds, yeasts, fungi, and bacteria in the
wetted blend.
Such components are in a dry, free-flowing, particulate form. Non-limiting
examples of
solid preservative acids include benzoic acid, propionic acid, sorbic acid, or
solid salts of
these acids blended with solid acids such as glutamic acid, citric acid,
adipic acid, tartaric
acid, etc. Non-limiting examples of solid antimicrobial agents include
parabens and
methylparabens, sulfite salts, sodium and potassium sulfite, sodium or
potassium
metabisulfite, zinc salts, pyrithiones, essential oils, etc.
Another embodiment contemplates blends containing a solid metal salt that is
in a
dry, free-flowing, particulate form. Non-limiting examples of solid metal
salts include
lanthanum chloride, lanthanum oxide, lanthanum acetate, zirconium acetate,
zirconium
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oxychloride, aluminum sulfate, aluminum chloride, ferric chloride, ferric
sulfate, sodium
aluminate, copperas (FeS04.7H20), and iron salts.
Another embodiment contemplates blends containing solid, neutral (non-ionic)
polysaccharides in a dry, free-flowing, particulate form that are typically
water-soluble.
Non-limiting examples include guar, starch, glucomannans, glucans,
methylcellulose,
hydroxypropylcellulose, hydroxypropylmethylcellulose, galactomannans, mannans,
xyloglucans. These blends can also contain solid metal salts to aid in
coagulation or
flocculation and removal of impurities in water.
Another embodiment contemplates blends containing solid anionic
polysaccharides in a dry, free-flowing, particulate form that are typically
water-soluble.
Non-limiting examples include agars, carrageenans, xanthans,
polygalacturonates,
pectins, alginates, gellans, and carboxymethylcellulose.
Blends may also comprise solid cationic polysaccharides in a dry, free-
flowing,
particulate form that are typically water-soluble. Non-limiting examples
include cationic
guars or cationic starches.
Blends may comprise solid organic or inorganic amines in a dry, free-flowing,
particulate form. Non-limiting examples include diallyl-dimethyl ammonium
chloride,
dimethylamine, dimethylaminoethyl-methacrylate, ethanolamine, methylamine, and
triethylamine.
It is envisioned that solid metal salts or solid organic amines can be used in
various combinations with solid cationic polysaccharides alone, solid neutral
polysaccharides alone, or solid anionic polysaccharides alone. For example, a
solid
cationic polysaccharide may be combined in a blend with a solid metal salt or
a solid
organic amine, wherein each component is in a dry, free-flowing, particulate
form.
Alternatively, a solid, anionic polysaccharide may be combined in a blend with
solid
chitosan, a solid acid, and a solid metal salt, wherein each component is in a
dry, free-
flowing, particulate form. As another alternative, a solid neutral
polysaccharide may be
combined in a blend with a solid metal salt or a solid organic amine, a solid
chitosan, and
a solid metal acid, wherein each component is in a dry, free-flowing,
particulate form.
Devices. Devices may be employed that contain blends described herein such
that
solubilized chitosan is released into water surrounding part or all of the
device. For
example, a permeable soluble chitosan delivery device may contain any blend of
a solid
chitosan and a solid acid or a solid agent that generates a proton in situ in
the presence of
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water as described herein. Such devices are porous, wherein the pores allow
water to
enter and hydrate the blend, dissolving the solid chitosan and releasing
soluble chitosan
through the pores into the aqueous medium outside of the device. The pore size
and
quantity or configuration of the device can be made in a way to influence the
release of
the soluble chitosan. A delivery device may be a porous fabric (e.g., a porous
"sock") or
metal or plastic container. The delivery device may be a woven or non-woven
porous
material.
Another embodiment contemplates blends contained within a device for
controlling the rate of release or dose of chitosan. The rate of
solubilization and release
of soluble chitosan can be controlled by, for example, the solubility of the
acid chosen.
For example, a solid chitosan/solid malic acid blend versus a solid
chitosan/solid lactic
acid-solid calcium lactate blend contained in a textile sachet were compared
with respect
to their release rates of solubilized chitosan into water at pH 8. The solid
chitosan/solid
lactic acid-solid calcium lactate blend dissolved faster and exhibited a
faster release rate
from the sachet into the water compared to the solid chitosan/solid malic acid
blend in
conditions as set forth in Example 5. It is envisioned that a fast dissolving
blend
containing a solid chitosan and a solid acid or solid agent would be
advantageous for
certain waters containing impurities that need to be removed more rapidly.
This could be
due to a higher amount of impurities in the water requiring a higher dose rate
of dissolved
chitosan. The containment of solid organic acid lactones together with solid
chitosan in
porous permeable devices represents another embodiment. The hydrolysis rate of
the
lactone into the corresponding acid can influence the solubility rate and
release of the
dissolved chitosan and can be influenced by the size and quantity of pores of
the
containment device. It is also understood that solid organic acid lactones and
solid
chitosan can be blended together with solid organic acids in various ratios to
influence the
rate of solubilization of the chitosan.
In some embodiments, a permeable soluble chitosan delivery device is
contemplated comprising a blend of a solid chitosan that may be partially
protonated but
is greater than 80% insoluble when added to water and in a dry, free-flowing,
particulate
form, a solid acid or a solid agent that generates a proton in situ in the
presence of water,
wherein the solid acid or the solid agent that generates a proton in situ in
the presence of
water is in a dry, free-flowing, particulate form, wherein the solid chitosan
and the solid
acid or the solid agent that generates a proton in situ in the presence of
water are not
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reacted together or otherwise chemically bound as described herein, and a
porous
container that holds the blend. The porous container may be, for example, a
segmented
fabric sock. The sock may be exposed to running water, wherein a blend
comprised in
the sock dissolves. Non-limiting examples of devices are set forth in U.S.
Patent Nos.
6,749,748 and 6,821,427, each of which is incorporated herein by reference.
In one aspect, the present invention provides a device for reducing the amount
of
contaminants in water, each device comprising a blend as described herein
disposed
within a body defining a multiplicity of pores, wherein the pores may have an
average
diameter in the range of from 1 m to 2000 m. U.S. Patent No. 6,749,748,
incorporated
herein by reference, discloses a suitable device.
For example, FIGURE 1 shows one embodiment of a device 10 of the present
invention, which includes a body 12 that has a first end 14 and a second end
16, and a
handle 18 attached to body first end 14. As shown more clearly in the cross-
section of
device 10 shown in FIGURE 2, body 12 includes a body wall 20 defining an inner
surface 22 and an outer surface 24. Again with reference to FIGURE 1, body
wall 20
includes stitching 26, perpendicular to the long axis of body 12, at regularly
spaced
intervals along its length that divide body wall 20 into segments 28. Each
segment 28
defines a lumen 30. Body wall 20 is penetrated by a multiplicity of pores 32
(shown
more clearly in FIGURE 2) that connect body inner surface 22 and body outer
surface 24.
A blend 34 is disposed within lumen 30 of each segment 28. In the embodiment
shown in FIGURE 1, lumen 30 closest to first end 14 is only partially filled
with blend 34
in order to more clearly show lumen 30. Each segment 28 can include the same
or
different blend 34 as one or more of the other segments 28. The embodiment of
device
10 shown in FIGURE 1 is flexible. Flexibility is facilitated by the
segmentation of body
12. Device body 12 includes a first half 36, extending from body first end 14
to body
midpoint 38, and a second half 40, extending from body midpoint 38 to body
second end
16.
In operation, device 10 is at least partially immersed in moving water that
contains one or more contaminants. The water penetrates pores 32 and contacts
blend 34
which begins to dissolve. Dissolved blend 34 leaves lumen 30 through pores 32
and
forms insoluble complexes with contaminants in the water (although the
formation of
insoluble complexes can begin at the moment that blend 34 is dissolved by the
water).
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Although the embodiment of device 10 shown in FIGURE 1 has a generally
cylindrical (although segmented) shape when filled with blend 34, device 10
can be any
shape that is adapted for use in a particular application. Device body 12 can
be made
from any material that is sufficiently strong to retain blend 34 and to resist
the forces
exerted by water moving over device 10, and which is sufficiently porous to
allow water
to penetrate device 10 to contact blend 34 within lumen 30, although pores 32
should not
be so large that they permit rapid escape and dissolution of blend 34. Some
embodiments
of device body 12 are stretchable. Device 10 can optionally include an
attachment
means, such as handle 18, that is attached to device body 12 and which is used
to attach
device 10 to a support, such as to a metal or plastic pipe when device 10 is
disposed
therein.
Methods. Disclosed herein are methods for solubilizing solid chitosan. As
discussed in the background above, dilute solutions of chitosan are costly to
ship.
Accordingly, blends of solid dry chitosan and solid dry acids or solid dry
agents provide
an alternative to supplying chitosan in solution form, provided the chitosan
blend can
dissolve. It has been found that blending solid dry, solid chitosan that may
be partially
protonated but is greater than 80% insoluble when added to water and in a dry,
free-
flowing, particulate form, with a solid dry acid or a solid dry agent will not
result in a
blend that dissolves when added to a high volume of water such as the total
amount of
water used to prepare a 1-5% chitosan solution (wt./wt.), but will dissolve
when low
volumes of water are added. After addition of a low volume of water that
causes the solid
chitosan in the blend to swell and dissolve within a predetermined period of
time, the
remainder of the water can be added to bring the final chitosan concentration
to that
which is desired, such as 1-5% (wt./wt.) or 1-3% (wt./wt.). The predetermined
time may
be about, at least about, or at most about 5, 10, 15, 20, 25, or 30 minutes,
or any range
derivable therein.
Other blends will dissolve in high volumes of water. Therefore, methods for
solubilizing blends that are capable of dissolving when added to high volumes
of water
such that the chitosan concentration is at least 0.1 % are also contemplated.
Also contemplated is a method of releasing soluble chitosan into water
comprising contacting the permeable soluble chitosan delivery device with
water to
release soluble chitosan into the water. In some embodiments, flocculation or
precipitation of matter in the water is induced after soluble chitosan is
released into the
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water. As used herein, "flocculation" refers to a process of contact and
adhesion whereby
particles of a dispersion form larger-size clusters. Flocculation is
synonymous with
coagulation. As used herein, "precipitation" refers to the sedimentation of a
solid
material from a liquid solution. The matter may be organic matter. The matter
may be
selected from the group consisting of particles, sediment, suspended matter,
and dissolved
substances. The water may be moving water, stream water, or stormwater.
Methods of determining solubility of chitosan are well-known in the art. One
may
determine solubility by, for example, weighing a sample of solid chitosan and
correcting
for moisture, form a solution with dilute acid, filter the solution through
tared filter paper
and collect insoluble material on the tared filter paper, dry and weigh the
paper, and then
calculate the percent of material that did not dissolve.
Methods may comprise steps described herein, or may consist of only of such
steps, to the exclusion of any other steps. Methods may alternatively consist
essentially
of steps described herein. Methods consisting essentially of steps are methods
that
exclude components or steps that do not materially affect the novel and basic
characteristics of the method or its effects. For example, methods consisting
essentially
of solubilizing chitosan in a chitosan-containing blend described herein to
achieve a
desired final chitosan concentration may exclude addition of a volume of a
dilute acid
solution.
It is contemplated that any embodiment discussed herein can be implemented
with
respect to any method, composition, or blend of the invention, and vice versa.
Furthermore, blends and compositions described herein can be used to achieve
methods
of the invention.
The use of the term "or" in the claims is used to mean "and/or" unless
explicitly
indicated to refer to alternatives only or the alternatives are mutually
exclusive, although
the disclosure supports a definition that refers to only alternatives and
"and/or."
Throughout this application, the term "about" is used to indicate that a value
includes the standard deviation of error for the device or method being
employed to
determine the value. In any embodiment discussed in the context of a numerical
value
used in conjunction with the term "about," it is specifically contemplated
that the term
"about" can be omitted.
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Following long-standing patent law, the words "a" and "an," when used in
conjunction with the word "comprising" in the claims or specification, denotes
one or
more, unless specifically noted.
Publications cited herein and the material for which they are cited are hereby
specifically incorporated by reference in their entireties.
The following examples are provided for the purpose of illustrating, not
limiting,
the material disclosed herein.
EXAMPLES
In each Example below, solid chitosan was ground and passed through a 20 mesh
screen. The solid particles that passed through the screen were then employed.
About
90% of the particles that passed through the screen ranged from about 125
microns to
about 850 microns. The water employed in each Example was deionized water.
EXAMPLE 1. HIGH VOLUME WATER DISSOLUTION OF BLENDS
Test 1. Mix 1 gm of solid acid and 1 gm of solid chitosan. Then slowly pour
this
blend into 1 L of stirring deionized water. Determine if chitosan is soluble.
See Table 1
below.
Table 1
Sample Acid Solubility Time Results (Visual) Comments
1 Adipic Good Fast Only a few particles left
2 Glutamic Fair-Good Medium -100 particles left Added 1 gm more acid to
solution,
better solubility resulted.
3 Glycine Poor Slow -1000s particles left
4 Tartaric Poor Slow -1000s particles left Starting with 2 gm acid did not
improve solubility.
5 Malic Poor Slow -1000s particles left Added 1 gm more acid to solution, no
solubility change.
6 Maleic Good Fast-Med Only a few particles left
7 Malonic Poor-Fair Slow '-1000s particles left Added 1 gm more acid to
solution,
better solubility resulted.
8 Succinic Poor Slow -1000s particles left Added 1 gm more acid to solution,
no
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Sample Acid Solubility Time Results (Visual) Comments
solubility change.
9 Fumaric Poor Slow -1 000s particles left
13 Glycolic Good Fast Only a few particles left
11 Glucuronic Fair Medium -100 particles left
12 Citric Poor Slow -1000s particles left Added 1 gm more acid to solution, no
solubility change. Starting with 2 gm
acid did not improve solubility.
13 Benzoic Good Fast Only a few particles left
14 Sorbic Poor-Fair Slow-Med -500 particles left Added 1 gm more acid to
solution, no
solubility change.
15 Salicylic Poor Slow-Med -1000s particles left Added 1 gm more acid to
solution, no
solubility change.
16 Galactu- Fair Medium -100s particles left Added 1 gm more acid to solution,
ronic slightly better solubility.
17 Lactic (dry) Fair Medium -100s particles left
18 Gluconic Fair Medium -100s particles left
acid
lactone
19 Ascorbic Fair Medium -100s particles left Added 1 gm more acid to solution,
no
solubility change.
Some solid acids solubilized chitosan well using the above method; others
needed
more acid to dissolve the chitosan; and still other acids did not solubilize
the chitosan
under the above scenario even with additional acid added.
EXAMPLE 2. LOW VOLUME WATER DISSOLUTION OF BLENDS
(LOW VOLUME SOLUBILITY (LVS) TEST)
Test 2. The acids used for this experiment were chosen from the acids that did
not
solubilize chitosan from Test 1. See Table 1 above.
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Mix 1 gm of solid acid and 1 gm of solid chitosan. Then slowly add water
(2.5-5.0 ml) to this admixture and mix. Allow time (up to 5 minutes) for the
chitosan to
swell, then slowly add more water, about 2.5-5.0 ml at a time. Allow time for
the
chitosan to swell and dissolve. Determine if chitosan is soluble. If chitosan
is not
swelling and dissolving after 10 ml of water, the acid will not work under
these
conditions. One may then try 2 gm acid per 1 gm chitosan or add sodium
acetate, as the
acetate counter ion may improve solubility. If after about 30 minutes or 20 ml
of water
the chitosan is swelling and dissolving, then add 10 ml of water at a time
with quick
mixing. Once 50 ml of water has been added, add 50 ml more water with quick
mixing.
When 100 ml of water has been added, add additional 100 ml increments of water
with
mixing until 500 ml of water has been added. Then add 500 ml more water for a
total of
1000 ml water added. Let the solution mix. See Table 2 below for results.
Table 2
Sample Acid Solubility Results Comments
A Malic Good -100 particles left
B Glycine Poor
Glycine Poor 1 gm acid, 1 gm chitosan, 1.6 gm sodium acetate
trihydrate
C Citric Poor-Fair -500 particles left
Citric Fair -100 particles left 2 gm acid, 1 gm chitosan
D Tartaric Poor-Fair 1000 swollen particles
Good Only a few particles left 2 gm acid, 1 gm chitosan
Some solid acids solubilized chitosan well using the slow addition of water.
Others needed more solid acid to dissolve the chitosan. And still other solid
acids did not
completely solubilize the chitosan using the slow water addition method even
with
additional acid.
Not all solid acids performed in a similar manner in solubilizing chitosan
using
the methods described above. The solid chitosan in some blends would not
dissolve
when added to a large volume of water (such as in Test 1). Surprisingly, the
chitosan in
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these blends would dissolve when a small amount of water was slowly added to
the
blend. Some solid acids would not solubilize chitosan under any of the
conditions tested.
EXAMPLE 3. DISSOLUTION OF DIFFERENT TYPES OF CHITOSAN
Test 3. A different type and lot of solid chitosan was used to determine if it
was
soluble at 0.1 % as in Test 1 above. The solid chitosan used in Examples 1 and
2 was
derived from crab shell. A different solid chitosan was then prepared from
Icelandic
shrimp shell, ground to a particle size where about 90% of the particles
ranged from
about 125 microns to about 850 microns, as before. As the chitosan was sourced
from
different starting materials, the molecular weights and the percent
deacetylation differed
between the two chitosans. The solid acid used was adipic acid. The results
were very
comparable to the results with the previous lot and type of solid chitosan:
the solid
chitosan dissolved fast and only a few particles were left.
EXAMPLE 4. VERY HIGH VOLUME WATER DISSOLUTION OF BLENDS
CONTAINING LOW CHITOSAN CONCENTRATION
Test 4. Table 3 below shows the results from an experiment in which a very
high
volume of water was used to attempt to dissolve the chitosan acid blends, very
much like
Test 1 above. But unlike Test 1 above, the concentration of both solid
chitosan and solid
acid was 10 times less: the concentration of solid chitosan was 0.01 % vs. 0.1
% in Test 1
above and the concentration of solid acid was 0.01% vs. 0.1% in Test 1. The
experiment
entailed mixing 0.1 gm of solid chitosan with 0.1 gm of solid acid, then
slowly adding it
to 1 L of mixing water.
The solubility of the chitosan was very poor at this concentration of acid.
There
seems to be a limit to how low the acid chitosan concentration can go when
attempting to
solubilize chitosan using this method of batch solubilization using large
amounts of
water.
Table 3. Very high volume (water); 0.01% chitosan;
0.1 gm chitosan in 1 L water blended with solid acids.
Sample Acid Solubility Time Results Comments
1 Adipic Poor Slow -1000s particles left Some slight dissolving
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Sample Acid Solubility Time Results Comments
2 Glutamic Poor Slow -1000 particles left No solubility.
3 Maleic Poor Slow -1000s particles left Ve `little solubility observed
4 Solid Poor Slow -1000s particles left Possibly some dissolving
Lactic
EXAMPLE 5. PERMEABLE SOLUBLE CHITOSAN DELIVERY DEVICE
Test 5. In the next experiment, the blends were put into fabric bags or
sachets
made from the same material as what is used for the StormKlear Gel FIocTM
contactor.
The fabric has small holes or pores to allow the release of the solubilized
chitosan. The
size of the sachet was about 2-1/4" x 2-1/4" and contained 2.25 gm of solid
acid mixed
with 2.25 gm of solid chitosan. The particle size of the solid acid was
typically smaller
than the particle size of the chitosan, e.g., the solid acid was more of a
powder, such as
smaller than about 125 microns. The sachets were then placed into flowing tap
water to
determine if soluble chitosan would be released. Three sachets were made of
dry
blends-one with solid adipic acid, one with solid lactic acid, and the last
made with
solid malic acid. The solid adipic and solid lactic acid chitosan admixtures
worked both
in Test 1 (0.1 % chitosan concentration solubilization) and Test 2 (low volume
solubility
addition), and poorly in Test 4 (very high water solubility, 0.01% chitosan).
Solid malic
acid, on the other hand, did not work well in Test 1: it only worked well in
Test 2.
All three sachets had soluble chitosan coming out of them within 15 minutes of
being introduced to the flowing tap water. After about an hour, the sachets
were placed
in separate beakers containing 3.5 L of mixing water and allowed to stir for
at least
overnight. When viewed after at least overnight mixing, much of the chitosan
had been
solubilized and the sachets only had small amounts of solubilized gel left in
them. Even
though large amounts of water were passed over the sachets, the blend was
still able to be
solubilized.
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EXAMPLE 6. HIGH pH DISSOLUTION OF BLENDS CONTAINED IN A
PERMEABLE SOLUBLE CHITOSAN DELIVERY DEVICE
Test 6. Experiment using the sachets (porous fabric bags) of Example 5 in
high pH (8.5) water. This experiment was used to determine if the blends
remained
soluble in higher pH water.
Two sachets were placed in 4 gallons of recirculating water at first, then
placed
into 20 gallons later in the day. A pH controller and 0.1 N NaOH was used to
keep
the pH at approximately 8.4-8.8. One sachet used solid malic acid and the
other used
solid lactic acid. The 20 gallons of water was changed twice a day, once in
the morning
and once in the afternoon. The reason the water was changed was to remove any
solubilized chitosan building up, so that the solubility limit of chitosan at
that pH was not
reached, which would retard the release of additional chitosan. The test was
run over the
course of 3 days and the sachets were examined periodically. The sachets
released
chitosan immediately upon placement in the high pH water, and solubilized
chitosan gel
could be seen on the outside of the sachets. By the second day, the sachet had
swelled
and, when pressed, chitosan gel came out. On the third day the sachet with the
lactic acid
was less swollen but the sachet with the malic acid was about the same. Both
seem to
have solubilized chitosan gel in them. It seems under these conditions the
high pH of 8.5
does not seem to prevent the solubilization of the chitosan. The size and
weight of the
sachets were different, demonstrating that the release rate of the chitosan
between the two
blends was different. The water containing the released chitosan was able to
flocculate
sediment suspended in water.
EXAMPLE 7. BLENDS HAVING LARGER SOLID CHITOSAN PARTICLE SIZES
The table below shows the results of using larger chitosan particle size
(about
1700 microns or less and flake about 0.5 to about 1 cm) compared to previous
Examples
and the effect on solubility. With a solid acid that solubilizes chitosan well
such as adipic
acid, the 0.1% concentration method and low volume solubility (LVS) method
have good
solubility results. Complete solubility takes longer because of the larger
particle size.
Solid malic acid, which has a good LVS with the standard particles (that is,
wherein
about 90% of the particles range in size from about 125 microns to about 850
microns, as
described above), did not have as good solubility with the larger particles
(even allowing
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hours to dissolve) unless 2 times the normal amount of acid was used. See the
table
below.
Table 4
Sample Acid Solubility Results Comments
< 1700 microns Adipic good Only few particles left 0.1 % Conc
Flake Adipic good Only a few particles left 0.1 % Conc
< 1700 microns Adipic og od Only a few particles left Low volume solubility
(LVS)
Flake Adipic good Only a few particles left Low volume solubility (LVS)
< 1700 microns Malic poor -100s particles left Low volume solubility (LVS)
Flake Malic poor -100s particles left Low volume solubility (LVS)
< 1700 microns Malic good Onl rya few particles left LVS, 2X acid
Flake Malic good Only a few particles left LVS, 2X acid
As another part of this experiment, the blends with the larger particle size
were
placed inside sachets as used in Example 5 to determine solubility
performance. The
sachets were placed in running tap water for 30 minutes then placed into 20
gallons of pH
7 controlled water until the end of the experiment. The sachets with solid
adipic acid
released chitosan well and no particles were left in the sachet at the end of
the
experiment. See the table below. The sachet with 2 times the normal amount of
solid
adipic acid seemed to release the chitosan faster. The sachets with 2 times
the normal
amount of solid malic acid released chitosan to some extent but some particles
were left
behind at the end of the experiment. More particles were left behind in the
sachet with
flake in it. Possibly more solid acid would work better.
Table 5
Sample Acid Solubili Results Comments
-10 Adipic good Soluble gel is released Sachet, all gone
i
Flake Adipic good Soluble gel is released Sachet, all gone
Flake Adipic good Soluble gel is released Sachet 2X acid, all gone
-10 Malic fair-poor Soluble gel is released Sachet 2X acid, Particles left
Flake Malic fair-poor --Soluble gel is released Sachet 2X acid, Particles left
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EXAMPLE 8. SOLID CHITOSAN/SOLID SODIUM DIACETATE BLENDS
Test 1: Mix 2 gm of sodium diacetate and 1 gm of chitosan. Then slowly pour
this admixture into 1 L of stirring deionized water. Solubility, fair; Time,
medium.
Test 2: Mix 3 gm of sodium diacetate and 1 gm of chitosan. Then slowly pour
this admixture into 1 L of stirring deionized water. Solubility, good; Time,
medium.
Test 3: Low water volume solubility (LVS) method: Mix 1 gm of sodium
diacetate and 1 gm of chitosan. Then slowly add water (2.5-5.0 ml) to this
admixture and
mix. Allow time (up to 5 minutes) for the chitosan to swell, then slowly add
more water,
about 2.5-5.0 ml at a time. Allow time for the chitosan to swell and dissolve.
Chitosan
was mostly soluble under this method.
While illustrative embodiments have been illustrated and described, it will be
appreciated that various changes can be made therein without departing from
the spirit
and scope of the invention.
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