Note: Descriptions are shown in the official language in which they were submitted.
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KAPPA-2 CARRAGEENAN COMPOSITION AND
PRODUCTS MADE THEREFROM
FIELD OF THE INVENTION
The present invention is directed to a kappa-2 carrageenan composition
comprising: (i) kappa-2 carrageenan, (ii) at least 70 % sodium by weight of
all cations
in the composition; and (iii) free salt present in an amount of 0-25% by
weight of the
composition; wherein the composition has a viscosity of 20 cps to 40 cps. The
present invention is also directed to products made from such kappa-2
carrageenan
composition, as well as to processes of manufacture and use thereof.
BACKGROUND OF THE INVENTION
Gelatin has long been used to form films useful in the preparation of soft
capsules. It is a hydrolyzed protein from collagen usually obtained by boiling
animal
bones and cartilage under pressure with water. However, the use of gelatin
suffers
from several commercial drawbacks; e.g., its animal origins often preclude its
availability to those who cannot or will not take animal derived capsules and
recent
concerns over bovine spongiform encephalopathy, BSE, or "Mad Cow Disease."
As a result, academia and industry have been trying for many years to develop
alternatives to gelatin that can desirably use many of the machines and
processes,
such as rotary dies, that are already in place to make soft capsules from
gelatin
alternatives.
For example, Japanese Patent Application Kokai Publication No. 61-10508A
discloses capsules made from the composition of polysaccharides including at
least
carrageenan and polyhydric alcohols. Carrageenan can be used wholly or partly
with
other polysaccharides such as tamarind gum, pectin, gelatin, alginates, agar,
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furcellaran, cellulose derivatives, locust bean gum, and guar gum. Polyhydric
alcohols include sorbitol, glucose, sucrose, ethylene glycol, diethylene
glycol,
triethylene glycol, polyethylene glycol, propylene glycol, polypropylene
glycol,
butane diol and glycerin. The soft capsules are made from concave stamping
dies.
Japanese Patent Application Kokai Publication No. 63-164858 discloses
mixtures of polysaccharides and polyhydric alcohols with/without alkaline
substances. The broad list of polysaccharides purported to be useful in the
application
include natural polysaccharides such as carrageenan, alginic acid, alginate
derivatives,
agar, locust bean gum, guar gum, tamarind seed polysaccharides, pectin,
xanthan
gum, glucomannan, chitin, pullulan and cyclodextrine. The polysaccharides are
stated
to be combined with a concentrated water solution of at least one of a
polyhydric
alcohol, sugar alcohol, monosaccharide, disaccharide and oligosaccharide. The
mixtures are stated to be useful in forming hulls of soft capsules. The three
examples
are directed to making hulls of soft capsules having double layers of the
mixture with
gelatin and a single layer consisting of the mixture of the invention with
gelatin. No
specific carrageenans are mentioned.
U.S. Patent No. 5,089,307 discloses heat-sealable edible films comprising at
least a film layer containing a water-soluble polysaccharide as the principal
component, a polyhydric alcohol and water. The films are stated to be useful
for
sealing and packaging materials for dried foods, oily foods and the like. The
polysaccharides purported to be useful include alginic acid and its salts
(such as
sodium salt); furcellaran; carrageenan such as kappa-, iota- and lambda-
carrageenans;
agar; pectin such as high-methoxy and low-methoxy pectins; gums such as
tamarind
seed gum, xanthan gum, guar gum, tara seed gum, locust bean gum; pullulan;
chitin
derivatives such as chitosan; starch such as wheat, corn and potato starches;
dextrin;
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edible water-soluble cellulose derivatives such as carboxymethylcellulose; and
mixtures of the foregoing. The weight ratio of the polyhydric alcohol to
polysaccharide is preferably used in an amount of 1:5 to 1:1, and the
polysaccharide is
present in an amount of not less than 50% of the total amount of active
components.
There is no disclosure that such films can be used in the manufacture of soft
or hard
capsules.
U.S. Patent No. 6,331,205 discloses aqueous viscous compositions for making
soft or hard capsules containing carrageenan, preferably, iota carrageenan as
the
single gelling agent. Iota-, lambda-, mu-, and nu-carrageenans are disclosed
as the
types of carrageenans that can be used in the invention, and such are stated
to be
extracted from a variety of different seaweed sources depending on the
extraction
method utilized. Plasticizers are disclosed such as those belonging to the
polyoxyls
class; e.g., glycerol, sorbitol, maltodextrins, dextrose, mannitol, xylitol,
polyoxyethylene glycol 400 to 6000, natural glycerides and hemisynthetics and
their
derivatives, etc. Soft capsules are said to be obtained by an adaptation of
the
"Scherer" method. Films made from kappa carrageenans are said to have
syneresis
causing problems in the manufacturing of hard and soft capsules. There is no
description of any specific iota carrageenans, kappa carrageenans, kappa-2
carrageenans, etc.
U.S. Patent No. 6,214,376 discloses gelatin-free capsules made from
compositions comprising water-soluble hydrophilic colloidal layers comprising
gel
films of kappa-carrageenan and a plasticizer. The gelatin free soft capsules
are said to
be made from kappa-carrageenan as the main gel-forming polymer (at least 50%
by
weight of gums that form thermoreversible gels or contribute to the formation
of
thermoreversible gels). Hydrolyzed starches such as maltodextrin may be added
to
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increase solids concentration, aid heat scaling and prevent hazing induced by
gelling
salts. Other types of gums, such as iota carrageenan, are taught to be
minimized, most
preferably, to an amount less than 0.5% of the total film composition.
U.S. Patent No. 6,340,473 requires the use of a modified starch 'having a
hydration temperature below about 90 C and iota carrageenan for the
manufacture of
soft capsules using rotary die encapsulation apparatus. The weight ratio of
the
modified starch to the iota carrageenan is stated to be crucial to forming a
satisfactory
film. That is, the weight ratio of the modified starch to the iota carrageenan
is said to
be 1.5:1. The inventors purportedly found that iota-carrageenan alone does not
produce an acceptable film and that modified starch alone does not produce an
acceptable film useable for encapsulation. The stated theory is that the iota
carrageenan functions as an elasticizing agent rendering an otherwise
inelastic,
modified starch film, elastic. Carrageenans are stated to be complex with
hundreds of
different products on the market having different functionalities. Eucheuma
spinosum
is stated to be the seaweed source for iota carrageenan, and not all
carrageenans are
stated to be useable in the invention, e.g., kappa carrageenan is stated not
to be a
substitute for iota carrageenan therein.
It is known that certain high solids, low moisture film forming compositions
containing, for example, hydrocolloids, form highly viscous solutions that
make
formation of hydrated films difficult to obtain.
In addition, many attempts have been made to make soft capsules from high
solids, low moisture films such as hydrocolloids. However, such attempts to
make
soft capsules have suffered from the drawback mentioned above. That is,
hydrocolloids are known to form highly viscous solutions that are difficult to
sufficiently hydrate and form a film in conventional soft capsule making
processes.
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US 2005/0019374 and US 20050014852 disclose the use of kappa-2
carrageenans in general as well as very low molecular weight carrageenans,
including
kappa-2 carrageenans, in making gel films and soft capsules
SUMMARY OF THE INVENTION
The present invention is directed to a kappa-2 carrageenan composition
comprising: (i) kappa-2 carrageenan, (ii) at least 70 % sodium by weight of
all cations
in the composition; and (iii) free salt present in an amount of 0-25% by
weight of the
composition; wherein the composition has a viscosity of 20 cps to 40 cps. The
present invention is also directed to products made from such kappa-2
carrageenan
composition, as well as to processes of manufacture and use thereof.
DETAILED DESCRIPTION OF THE INVENTION
Kappa-2 carrageenan is generally contained in a composition containing
cations complexed therewith, as well as other cations and/or anions that are
free salts
not complexed with the kappa-2 carrageenan. The kappa-2 carrageenan
composition
of the present invention comprises kappa-2 carrageenan and at least 70% sodium
cation by weight of the cations in the composition (free or complexed with the
kappa-
2 carrageenan), more particularly, at least 75%, at least 80%, at least 85%,
at least
90%, at least 92%, at least 95%, at least 98% sodium cation, all based on the
total
weight of the cations in the composition. The composition further contains
free salts
in an amount of 0% to 25% based on the total weight of the composition, more
particularly, 0 to 20%, 0 to 15%, 0 to 10%, 0 to 8%, 0 to 5%, and 0 to 2%, all
based
on the total weight of the composition. In other embodiments of the invention,
the
composition contains free salts in the amount of 0.001% to 20%, 0.001% to 15%,
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0.001% to 10%, 0.001% to 8%, 0.001% to 5%, or 0.001% to 2%, all based on the
total weight of the composition.
The amount of free salt in the composition is determined by washing the
kappa-2 carrageenan composition in a mixture of isopropanol and water (60%
isopropanol) for two hours, separating the kappa-2 carrageenan from the water
and
alcohol mixture by filtration, separately drying the kappa-2 carrageenan and
the water
and alcohol mixture (filtrate), and calculating the per cent recovered
carrageenan and
free salt (from the dried filtrate), correcting for the moisture content in
the kappa-2
carrageenan. The kappa-2 carrageenan composition of the present invention also
has
a viscosity of 20 cps to 40 cps, more particularly, from 20 cps to 36 cps,
when
measured using a Brookfield LV viscometer with appropriate spindles and speeds
in a
1.5% solids in water solution at 75 C. The tested solution does not contain
any added
salts.
Further, kappa-2 carrageenan compositions consisting of, or consisting
essentially of, (i) kappa-2 carrageenan, (ii) at least 70 % sodium by weight
of all
cations in the composition; and (iii) free salt present in an amount of 0-25
'o by weight
of the composition; wherein the composition has a viscosity of 20 cps to 40
cps, more
particularly, from 20 cps to 36 cps, are also included within the scope of the
present
invention.
Without being bound by any theory, it is believed that the kappa-2
carrageenan compositions of the present invention (containing the amount of
sodium
and free salt as well as having the viscosity of 20 cps to 40 cps)
surprisingly enable
the manufacture of gel films having a high solids system that are strong and
elastic.
Carrageenan is a commercially significant galactan polysaccharide found in
red seaweed. All carrageenans contain repeating galactose units joined by
altemating
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a1->3 and P1---*4 glycosidic linkages and are sulfated to widely varying
degrees. The
types of carrageenan may be distinguished, in part, by their degree and
position of
sulphation, as well as the seaweed from which they are obtained. For example,
iota
carrageenan has a repeating unit of D-galactose-4-sulfate-3,6-anhydro-D-
galactose-2-
sulfate providing a sulfate ester content of about 25 to 34%. Iota carrageenan
can be
obtained, for example, from Eucheuma denticulatum ("also referred to as
"Spinosum'). Kappa carrageenan has a repeating unit of D-galactose-4-sulfate-
3,6-
anhydro-D-galactose and is obtained, for example, from Kappaphycus alvarezii
(also
known as "Eucheuma cottonii'). In contrast, kappa-2 carrageenan is reported by
R.
Falshaw, H.J. Bixler and K. Johndro, Structure and Performance of Commercial
Kappa-2 Carrageenan Extracts, Food Hydrocolloids 15 (2001) 441-452, and by H.
Bixler, K Johndro and R Faishaw, Kappa-2 carrageenan: structure and
performance
of commercial extracts II, Food Hydrocolloids 15 (2001) 619-630 to be
copolymers
containing a certain amount of kappa repeating units (3:6-anydroglactose (3:6-
AG))
and iota repeating units (3:6-anhydrogalactose-2-sulfate (3:6-AG-2-S))
covalently
bound in the copolymer backbone and obtained from certain Gigartinaceae algae.
The foregoing references state that such kappa-2 carrageenans have distinctly
different properties as compared to simple mixtures of kappa and iota
carrageenans.
Other references discussing kappa-2 carrageenan are discussed in these
publications.
Kappa-2 carrageenan extracted from Gigartina atropurpurea is reported by R.
Falshaw, H Bixler and K Johndro, Structure and Performance of Commercial Kappa-
2 Carrageenan extracts III, Food Hydrocolloids 17 (2003) 129-139. While there
has
been considerable confusion historically about the physical nature of kappa-2
carrageenans, recent studies, such as those mentioned immediately above, have
confirmed that kappa-2 carrageenans are copolymers containing kappa and iota
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repeating units covalently bound (in certain ratios of kappa to iota moieties)
in clear
distinction to physical mixtures of kappa and iota polymers.
As used herein, kappa-2 carrageenan has a molar ratio of 3:6AG-2S to 3:6AG
content of 25 to 50%, iota carrageenan has a molar ratio of 3:6AG-2S to 3:6AG
content of 80 to 100% and kappa carrageenan has a molar ratio of 3:6AG-2S to
3:6AG content less than that for kappa-2 carrageenan. For example, kappa
carrageenan from Euclzeuma cottonii, a commonly known and used seaweed source
for kappa carrageenan, has a molar ratio of 3:6AG2S to 3:6AG content of less
than
about 10%; and iota carrageenan from SpinQsum, a commonly known and used
seaweed source for iota carrageenan, has a molar ratio of 3:6AG2S to 3:6AG
content
greater than about 85%. This means that kappa-2 carrageenan comprises a ratio
of
kappa (3:6-AG) repeating units to iota (3:6-AG-2-S) repeating units between
1.0 to
3.0:1, more particularly, 1.5 to 3.0:1 (more particularly depending on the
desired
application). The molar ratio of 3:6AG-2S to 3:6AG content of 25 to 50% holds
in
kappa-2 carrageenans regardless of its degree of modification and precursor
content
(e.g, mu and nu repeating units). Thus, any kappa-2 carrageenan meeting the
molar
ratio of 3:6AG-2S to 3:6AG content of 25 to 50%, regardless of its degree of
modification, is within the scope of this invention.
The kappa-2 carrageenan to be used in the present invention may be contained
within or purified or separated from a number of seaweed species within the
class of,
for example, Gigartinaceae algae such as Gigartina radula, Gigartina
coryinbifera,
Gigartina skottsbergii, Iridaea cordata, Sarcothalia crispata, and Mazzaella
laminarioides. The seaweed source of the kappa-2 carrageenan to be used in
this
invention is any that produces kappa-2 carrageenan having the molar content of
3:6AG-2S to 3:6AG described herein. The kappa-2 carrageenan used in the
present
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invention can be obtained from a single seaweed source, or from a mixture of
two or
more different seaweed sources. The kappa-2 carrageenan that can be used in
the
present invention may occur naturally in the seaweeds above or may be modified
from the above seaweeds to increase the amount of 3:6AG-2S and 3:6AG moieties
in
the kappa-2 carrageenan from their precursors (e.g., 3:6AG-2S moiety within
the
kappa-2 carrageenan modified from its precursor nu upon alkali treatment, and
3:6AG
moiety within the kappa-2 carrageenan modified from its precursor mu upon
alkali
treatment). The recovery and modification techniques are well known in the art
including the cited publications by Falshavci, Bixler and Johndro. For
example,
modification of the kappa-2 carrageenan can occur during its recovery from
certain
Gigartinacean algae as a result of alkali treatment at elevated temperatures.
Recovery
methods include the optional full or partial filtration of insolubles from the
starting
material or the use of unfiltered material. When the nu and mu precursors in
the
kappa-2 carrageenan are modified to 3:6AG-2S to 3:6AG, respectively, such
modification may be complete (i.e., 100% of the nu and mu precursors in the
kappa-2
carrageenan are modified to 3:6AG-2S and 3:6AG moieties, respectively) or less
than
fully complete (i.e., less than 100% of the nu and mu precursors in the kappa-
2
carrageenan are modified to 3:6AG-2S and 3:6AG moieties, respectively). It is
understood that during the recovery process of the kappa-2 carrageenan from
the
above seaweeds small or trace amounts of other carrageenans may be present
(e.g.,
lambda carrageenans) and such can be used with the kappa-2 carrageenans in the
present invention.
The kappa-2 carrageenan of the present invention can be prepared using any
conventional process, for example, processes involving: washing the seaweed to
remove extraneous material, separating the lambda fraction of the seaweed
(e.g.,
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manually), bleaching to reduce color, washing in KCl or KCl and combinations
of
sodium chloride to remove excess bleach, color bodies, etc., modifying the
seaweed in
alkali and KCl or combinations of KCl and NaCl, washing in KCI or combinations
of
KCl and NaCI to remove excess alkali and non-carrageenan seaweeds,
neutralizing in
KCl or combinations of KCI and NaCI to approximately neutral pH, a second
bleaching step, viscosity adjustment, additional washing steps in NaCI,
drying,
grinding, solubilizing in hot water and NaCl to further ion exchange the
carrageenan,
viscosity adjustment with H202, filtration, concentration, precipitation with
isopropyl
alcohol, dewatering, washing in isopropyl alcohol, drying and grinding.
Conventional
ion exchange processes can be utilized to make the kappa-2 carrageenan
compositions
of the present invention, e.g., such conventional processes as dialysis;
washing with
salt, water and alcohol; and diafiltration (using a membrane).
The products that can be made from the kappa-2 carrageenan composition of
the present invention include homogeneous gel films, delivery systems,
barriers,
controlled release systems, oral dose forms such as hard capsules, soft
capsules,
enrobed solid materials (such as powders, aggregates), food products,
agricultural
products, industrial products such as paintballs, etc. The kappa-2 carrageenan
can
also be used in coatings for a variety of substrates and such coatings can be
applied in
multiple layers to any such substrate.
The kappa-2 carrageenan composition can be used to make gel films by using
the kappa-2 carrageenan in a film forming amount (i.e., an amount that adds
film
strength to the gel film) which is distinguished from trace amounts of kappa-2
carrageenan that do not add film properties to the film. Thus, for exainple,
in a gel
film of the present invention containing the second film formers discussed
below, a
film forming amount of kappa-2 carrageenan is an amount that adds film
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the overall film. Such film forming amounts are generally at least 0.5% by
weight of
the gel film, particularly, 0.5% to 90%, more particularly, 0.5% to 50%, more
particularly, 0.5% to 25%, more particularly, 1.5% by weight of the dry gel
film
depending on the application.
As used herein, "homogeneous film" defines films that, to the naked eye, are
visually uniform and free of defects such as lumps, cracks, particles of the
primary
structure forming components that are undissolved that should be dissolved,
non-
uniform distribution of insoluble particles, etc. "Fish eyes" (mixed liquid
and solid
states) or "gel balls" (non-uniform gel structure) would not meet the
definition of
"homogeneous" as used herein.
The gel films of the present invention are homogeneous, thermoreversible gel
films. They can be cast and used in a wide variety of applications as cast
films or in
subsequent processing.
As used herein, "thermoreversible film" defines a film that has a melting
temperature. As used herein, the melting temperature is the temperature or
temperature range over which the gel film softens or flows due to
gravitational or
induced forces to move the molten mass.
As used herein, the phrase "gel films" refer to a thin membrane or three-
dimensional network (sponge-like), formed from structured kappa-2 carrageenan.
The gel-forming composition is characterized by a gel temperature, the
temperature
below which the molten mass of the gel composition must be cooled to form a
self-
supporting structure. Optionally, a molten mass can be cast hot and allowed to
cool,
as well as dry to further concentrate the solids (controlled moisture removal)
until a
gel film is formed by the gel composition. The melt temperature of a
thermoreversible
gel film is higher than its gel temperature.
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The homogeneous, thermoreversible gel film of the present invention can
optionally contain at least one of a plasticizer, a second film former, a
bulking agent
and a pH controlling agent. The components to be added to the gel film and
their
amounts can vary depending on the desired use of the kappa-2 gel film.
Examples of such a plasticizer include polyols such as glycerin, sorbitol,
maltitol, lactitol, corn starch, fructose, polydextrose and polyalkylene
glycols such as
propylene glycol and polyethylene glycol. The amount of the plasticizer can
vary
depending on the use of the gel film and its desired elasticity. For example,
such
plasticizers can generally be used in an amount of at least 5%, more
preferably, at
least 10%, more preferably, at least 20%, more preferably, at least 30% by
weight of
all the components including water in the dry film if a gel film having more
elasticity
is desired; e.g., films to be used to make soft capsules.. For other
applications, such
as hard capsules, where less elastic films are desired, the plasticizer can be
present in
an arnount of 0% to 20% by weight of all the components in the dry film. It is
possible that the gel film of the invention contains no plasticizer at all.
Examples of the second film former that can be used in the present invention
include at least one of a starch, starch hydrozylate, starch derivative,
digestion
resistant maltodextrins, cellulose gum, hydrocolloid, an alkylcellulose ether
or a
modified alkyl cellulose ether. Examples of the hydrocolloid include at least
one of
kappa carrageenan; iota carrageenan; kappa and iota carrageenans having a
reduced
molecular weight (e.g., having an extract viscosity of 20 cps or less at 75 C
in a 1.5%
aqueous sodium chloride solution); alginates including potassium alginate,
sodium
alginate, ammonium alginate and propylene glycol alginate; polymannan gums
(e.g.,
generally less than about 1000 mPs viscosity as measured at 1 wt % in water at
25 C)
such as low viscosity guar gum; pullulan, gellan (including high and low-acyl
gellan);
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pectin and less than fully modified versions thereof and combinations thereof.
An
example of an alkylcellulose ether that can be used in the present invention
is
hydroxyethylcellulose. Examples of modified alkylcellulose ethers that can be
used
in the present invention include hydroxypropylcellulose and
hydroxypropylmethylcellulose. The kappa-2 carrageenan can be the only film
former
in the gel film. When the gel films of the present invention contain second
film
formers, the kappa-2 carrageenan can be present in an amount of at least 10%,
at least
20%, at least 50% or at least 80% by weight of the total amount of film
formers in the
dry gel film. A dried film is the controlled residual form of a cast film, as
described
within this application. Combinations of ingredients, such as: kappa-2
carrageenan,
and, optionally, a starch, a polyol and water for processing, are dispersed,
hydrated,
solubilized and, optionally, de-aerated within the process options described
within.
The resulting homogeneous mass is cast or formed at the desired solids level
(necessary to achieve the intended end-product). The cast system is formed,
via
gravitational or controlled forces, and subsequently either immediately
further
processed (such as soft gel capsule production) or the cast mass is
additionally
processed by utilizing various methods for uniform and controlled water
removal until
the desired moisture level is reached. Controlled water removal from the cast
system
allows a further strengthening/alignment of the homogeneous film ingredients
into a
denser structure, which can further strengthen film characteristics. Moisture
removal
is limited to that moisture not bound to the molecular surface of the various
hydrocolloid and carbohydrate components. The dried film is achieved when the
originally cast film does not lose additional weight while subject to the
various drying
methods employed in the dewatering/dehydration process. A reduction in
moisture
content to constant levels also imparts stability to the film and, optionally,
its contents
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(if embedded or enrobed or entrapped, etc.) as water activity is also reduced
by the
process. It is understood that the resulting cast film can be fully dried or
to an
intermediate, retained moisture level between the cast film moisture level and
the
maximum dried moisture level, depending upon the final product use and
functions.
Examples of the bulking agent include non-colloidal (vegetal sourced)
cellulose, microcrystalline (vegetal sourced) cellulose, microcrystalline
starch,
modified and unmodified starch, starch derivatives and fractions, inulin,
digestion
resistant maltodextrins, starch hydrozylates, sugar, corn syrup and
polydextrose. As
used herein and in the claims, the tenn "modified starch" includes such
starches as
hydroxypropylated starches, acid-thinned starches, and the like. Examples of
modified starches that can be used in the present invention include Pure
CoteTM B760,
B790, B793, B795, M250 and M180, Pure-DentTM B890 and Pure-SetTM B965, all
available from Grain Processing Corporation of Muscatine, Iowa, and C AraTexTM
75701, available from Cerestar, Inc. Examples of starch hydrozylates include
maltodextrin also known as dextrin. An example of a digestion resistant
maltodextrin
that can be used in this invention includes Fibersol-2 available from Archer
Daniels
Midland/Mitsutani America. Unmodified starches such as potato starch can also
contribute to the film strength when combined with the hydrocolloids within
the scope
of the invention. In general, modified starches are products prepared by the
chemical
treatment of starches, for example, acid treatment starches, enzyme treatment
starches, oxidized starches, cross-bonding starches, and other starch
derivatives. It is
preferred that the modified starches be derivatized wherein side chains are
modified
with hydrophilic or hydrophobic groups to thereby form a more complicated
structure
with a strong interaction between side chains.
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The amount of the bulking agent to be used in the present invention is
generally in the amount of 0 to 20% by weight of the dry film, but more can be
used,
if desired, for example, at least 20%, more preferably, at least 30% by weight
of the
dry film.
Note that starch, starch derivatives, digestion resistant maltodextrin and
starch
hydrozylates can be multifunctional. That is, in addition to being used as
bulking
agents, they can be used as second film formers. When such are used as bulking
agents and second film formers, they are generally used in an amount of at
least 10%,
preferably, at least 20%, more preferably, at least 30% by weight of the dry
ge1 film
depending on the application; e.g., soft capsules.
Examples of the pH controlling agent that can optionally be used in the
present invention include bases such as hydroxides, carbonates, citrates and
phosphates, mixtures thereof and their salts (e.g., sodium citrate). The pH
controlling
agent can be chosen as the source of added beneficial cations such as
potassium or
sodium. For some compositions, the pH controlling agent can be used to improve
the
stability of the gel film. The amount of the pH controlling agent is generally
in the
amount of 0 to 4%, preferably, 0 to 2%.
The gel films of the invention can also contain colorants and/or flavorants
such as sugar, corn syrup, fructose, sucrose, etc, and/or antioxidants, such -
as
anthocyanins, whether or not other components, such as plasticizers, bulking
agents,
second film formers, etc. are present. One embodiment of a gel film of the
invention
comprises kappa-2 carrageenan, flavorant and water in a high solids system;
e.g.,
greater than 50%, 60%, 65%, 75%, 80%, 85%, 90% solids.
The dry gel films (e.g., 80% solids or higher) of the present invention have
been found to have, for example, a break force of at least 2,500 grams, at
least 4,000
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grams, at least 5,000 grams and at least 6,000 grams, as determined using a
Texture
Analyzer TA-108S Mini Film Test Rig. At lower solids, the gel films have been
found to have a break force of at least 50 grams, at least 100 grams, at least
200
grams, at least 500 grams, at least 1000 grams, as determined in a similar
manner.
The films of the present invention have been found to have a solids content of
at least 50%, at least 60%, at least 70%, at least 80% and at least 90% of all
components in the gel film. It is understood that 15%, 10 % or 5% water may
remain
strongly associated with the solids in the gel film.
Dry film thicknesses generally used for soft capsules are in the range of 0.5
to
3.0 mm, more preferably, 0.8 to 1.2 mm.
It is possible that the gel films of the present invention can contain
nonthermoreversible gums. However, so as not to adversely impact the
homogeneous
and thermoreversible nature of the gel films of the present invention, such
nonthermoreversible gums should be present in an amount of less than 50% by
weight
of the kappa-2 carrageenan, preferably, less than 40%, more preferably, less
than
30%. Examples of such nonthermoreversible gums include crosslinked (and
partially
crosslinked) gums such as calcium set (e.g., crosslinked) pectins and/or
alginates.
Calcium reactive alginates and pectins, as well as their less refined forms,
are
considered as thermoreversible gums in the absence of divalent cations. Other
non-
thermoreversible gums such as tragacanth gum contribute to the
therrnoreversability
of the kappa-2 carrageenan by absorption of water within its structure thereby
causing
the kappa-2 carrageenan to form a denser, three-dimensional structare, as it
is
solubilized in less water, providing the same effect as increasing the kappa-2
carrageenan amount without the secondary film formers. Additional film
formers,
such as polymannans can form continuous networks, either by themselves or
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synergistically with other components during the activation and casting
process.
These polymannans can be optionally used in various molecular weights (related
to
their chain length/size) which allow their use without substantially affecting
the
process of the molten mass and film formation.
The kappa-2 carrageenan gel films of the present invention are generally made
from a process utilizing an apparatus that enables sufficiently high shear,
temperature
(above the gelling temperature) vacuum control and residence time so as to
provide a
homogeneous molten mass of the composition and fortnation of the gel upon
cooling.
Such apparatus include but are not limited to Ross mixers, Stephan processors,
conventional jet cookers and extruders. Ross mixers, Stephan processors,
extruders
and conventional jet cookers are readily available commercially. Prior to
cooling, the
molten mass can also be fed to at least one of a pump, mixer or devolatilizer.
An
example of a device that performs any one of such functions is an extruder. An
extruded molten mass can also be directed to a film forming or shaping device
(e.g.
open or closed spreader box or die, as used in a capsule forming machine) that
aids in
the uniform casting of a continuous film, or, through a die that allows a
direct
formation of a film from the molten mass delivery equipment. Care must be
taken to
maintain the molten mass above the initiation of restricted flow/gel structure
formation. Insulated and pre-heated (to maintain proper temperatures) transfer
hoses
may be used to insure molten mass flow until desired gel film formation is
initiated on
the casting rolls or at other film formation points, such as an extruder
(restrictive flow,
film forming device) or die. Additional processing methods (such as pre-
heating the
discharge/plunger-like head as seen in a Ross process system) can force (by
pressure)
the molten mass through the transfer hoses mentioned above. Additional
insulation
can help maintain molten mass temperatures, for example, through the use of a
Teflon
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disk initially placed upon the molten mass surface immediately after removing
the
mixing device. In addition, the feeder hoses can be introduced to the heat
controlled
molten mass feeder (casting) boxes located on a capsule machine either
directly to the
boxes or through an optional modification of the feeder boxes which introduces
a top
half enclosure/cover that helps maintain molten mass temperatures within the
feeder
box, reduces moisture loss, and maintains uniform (center) filling of the box
during
the extended process of forming films for capsules. It is understood that
other
methods of maintaining molten mass temperatures can be used to form films for
capsules. This includes, but is not limited to: extrusion of the molten mass
through
dies/orifrices into films that: can be immediately fed into the capsule
forming
apparatus, stored at temperatures that maintain proper film conditions (to
form
capsules) until needed, or dried to desired moisture, solids and texture
levels, until
needed. Such dried films have the property of re-absorbing water (water is
introduced
by any means) throughout its gel film matrix. Moisture is introduced to the
film until
a desired moisture content and strength/texture is reached that will allow the
film's
introduction into a capsule machine to make soft capsules. It is also
understood that
the homogeneous molten mass can be transferred to a heated reservoir or
holding tank
until the mass is further transferred (at a sufficient temperature to all its
redirection by
the use of pumps through heated hoses to the area where the molten mass is
cast,
formed, cooled to gel, and further utilized or processed for the cited
applications).
The process for making soft capsules from the kappa-2 carrageenan gel films
of the invention includes the use of any conventional encapsulating apparatus,
e.g., a
conventional rotary die apparatus or concave stamping die. For example, once
the
molten mass of the present invention has been made, it can be cast onto drums,
cooled
and then fed between rotary encapsulation dies where the films are heated
again,
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filled, sealed and cut. For a good description of this conventional process,
see WO
98/42294. Alternatively, and as benefit of the present invention over
conventional
soft capsule processes, the use of the high shear apparatus disclosed above
allows the
molten mass to be sufficiently hydrated, applied to drums as they are cooling
and then
fed into conventional encapsulating apparatus for filling, sealing, and
cutting. This
continuous type process can be used to eliminate the step of having to reheat
fully
gelled and cooled films. The above rotary die process can be used to make soft
capsules of the invention having any desired shape.
The fill materials for the soft capsules can be any materials widely used in
the
above rotary die process, including pharmaceutical ingredients, agricultural
ingredients, nutraceutical ingredients, veterinary ingredients, foods,
cosmetics,
personal care, industrial, etc. and can be a liquid, solid, suspension,
dispersion, etc.
The present invention is also directed to a solid form comprising a fill
material
encapsulated by the homogeneous, thermoreversible gel film of the present
invention.
One type of such solid form is a hard capsule. Hard capsules, as used herein,
refer to
those solid forms that are conventionally used, e.g., in the pharmaceutical
industry
whereby two half shells are formed, a fill material, usually a powder, is
placed in the
shells and the two halves are placed together to form the hard capsule. One
process
for making such hard capsules would typically involve dipping metal pins or
bars into
the molten composition of the present invention and allowing the gel film to
form
around the pins. The gel films are dried and then removed from the pins. These
processes are well known in the industry as methods of making hard capsules.
The
fill materials for the hard capsules can be any fill materials commonly used
in such
dosage forms. Generally, the fill materials can be liquids (including
emulsions) or
solids such as powders. The fill materials can be a pharmaceutical ingredient,
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agricultural ingredient, nutraceutical ingredient, veterinary ingredient,
food, cosmetic
ingredient, etc.
The solid form may also encapsulate a powder, tablet, caplet, microcapsule or
capsule in accordance with known techniques. For example, encapsulating a hard
capsule with the gel film of the invention would allow for safety seal/tamper
resistant
capabilities.
The gel film can also be used to modify the dissolution profile of the dosage
forms. For example, gel films of the invention can contain added components
that
can create solid dosage forms having immediate release, controlled, enteric or
delayed
release capabilities or can be released upon activation by a known event,
condition or
process. Definitions of "immediate release", "delayed release" and "enteric"
can be
found in the U.S. Pharmacopeia and are incorporated herein by reference.
The present invention is now described in more detail by reference to the
following examples, but it should be understood that the invention is not
construed as
being limited thereto. Unless otherwise indicated herein, all parts, percents,
ratios and
the like are by weight.
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Examples
The following are prepared examples of the kappa-2 carrageenan
compositions of the present invention.
Table
Sample A B C D
wt%of wt%of wt%of wt%of
composition composition composition com osition
Chemical
Analysis
Cl- 0.11 0.14 0.10 0.14
K+ 1.09 0.94 1.05. 1.09
Na+ 5.38 5.16 5.26 5.41
Ca++ 0.17 0.19 0.20 0.24
M++ 0.01 0.01 0.01 0.01
Gum
Content 88.76 88.3 91.3 91.0
Physical
Analysis
Moisture
Content 12.1 13 10.3 9_5
Viscosity
(cp s 33 36 33 32
pH 8.8 9.5 9.5 9.4
Properties were determined for the samples and are reported in the Table. The
gum
recovered as the gum content is kappa-2 carrageenan. The gum content is
determined
by the following process: mixing a 1 gram sample of the kappa-2 carrageenan
composition with 200 ml of an alcohol/EDTA solution containing 5 grams of
Na4EDTA (ethylene-diamine tretraacetic acid) in 1,000 ml of 60% isopropanol (a
mixture of 60% isopropanol and 40% water by weight), and stirring for two
hours;
filtering the sample, and washing the sample with successive additions (two
washes of
about 50 ml each) of 65% isopropanol (a mixture of 65% ispropanol and 35%
water
by weight) to remove Na4EDTA. The gum remaining after washing the sample is
dried in an oven at 60 C for at least thirty minutes, and then in a vacuum
oven at 70 C
overnight, and cooled to room temperature in a desiccator. The recovered gum
is
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weighed and the gum content is calculated as the percent recovered. The weight
%
provided in the table above is the weight percent based on the total weight of
all
components in the kappa-2 composition. Cation concentration was determined by
atomic absorption (AA) spectroscopy. Chloride concentration was determined by
titration. Moisture content was determined by drying overnight at 70 C in a
vacuum
oven. Viscosity of the kappa-2 carrageenan compositions was determined at 75 C
for
a 1.5% aqueous solution using a Brookfield LVF viscometer with spindle #1 at
30
rpm.
While the invention has been described in detail and with reference to
specific
embodiments thereof, it will be apparent to one skilled in the art that
various changes
and modifications can be made therein without departing from the spirit and
scope
thereof.
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