U.S. patent application number 14/943507 was filed with the patent office on 2016-07-21 for delivery and controlled release of encapsulated lipophilic nutrients.
The applicant listed for this patent is PepsiCo, Inc.. Invention is credited to Peter GIVEN, Daniel S. KOHANE, Robert S. LANGER, Yoon YEO.
Application Number | 20160206561 14/943507 |
Document ID | / |
Family ID | 39769513 |
Filed Date | 2016-07-21 |
United States Patent
Application |
20160206561 |
Kind Code |
A1 |
KOHANE; Daniel S. ; et
al. |
July 21, 2016 |
Delivery and Controlled Release of Encapsulated Lipophilic
Nutrients
Abstract
A complex coacervate delivery system is provided which
encapsulates lipophilic nutrients such as, for example, fish oils
high in omega-3 fatty acids. The complex coacervate delivery system
protects the lipophilic nutrient from degradation, e.g., oxidation
and hydrolysis, and also reduces or eliminates the unpleasant taste
and odor of the lipophilic nutrient. The complex coacervate
delivery system upon ingestion is operative to substantially
release the lipophilic nutrient in the lower gastrointestinal tract
in a pH-controlled manner. The complex coacervate delivery system
may be included in a food or beverage product having a pH value
within the range of about 1.5 to about 5.0.
Inventors: |
KOHANE; Daniel S.; (Newton,
MA) ; YEO; Yoon; (West Lafayette, IN) ; GIVEN;
Peter; (Ridgefield, CT) ; LANGER; Robert S.;
(Newton, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
PepsiCo, Inc. |
Purchase |
NY |
US |
|
|
Family ID: |
39769513 |
Appl. No.: |
14/943507 |
Filed: |
November 17, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11846212 |
Aug 28, 2007 |
9186640 |
|
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14943507 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 9/1075 20130101;
A23L 29/25 20160801; B01J 13/10 20130101; A23V 2002/00 20130101;
A23V 2002/00 20130101; A23V 2250/54252 20130101; A23V 2200/224
20130101; A23L 2/52 20130101; A61K 31/202 20130101; A61K 35/60
20130101; A23L 33/12 20160801; A23V 2002/00 20130101; A23P 10/30
20160801; A61P 43/00 20180101; A23L 29/219 20160801; A61K 9/0053
20130101; A23V 2002/00 20130101; A61K 9/0095 20130101; A23V 2002/00
20130101; A23V 2200/224 20130101; A23L 29/281 20160801; A23V
2250/1868 20130101; A23V 2250/187 20130101; A23V 2250/1868
20130101; A23V 2250/1868 20130101; A23V 2250/5432 20130101; A23V
2200/254 20130101; A23V 2250/187 20130101; A23V 2250/1868 20130101;
A23V 2200/224 20130101; A23V 2200/224 20130101; A23V 2250/51
20130101; A23V 2200/254 20130101; A23V 2250/187 20130101; A23V
2250/5432 20130101; A23V 2200/254 20130101; A23V 2250/511 20130101;
A23V 2250/187 20130101; A23V 2250/51 20130101; A23V 2250/5022
20130101; A23V 2200/254 20130101; A23V 2250/51 20130101 |
International
Class: |
A61K 9/107 20060101
A61K009/107; A23L 2/52 20060101 A23L002/52; A61K 9/00 20060101
A61K009/00; A61K 35/60 20060101 A61K035/60; A61K 31/202 20060101
A61K031/202 |
Claims
1-36. (canceled)
37. A complex coacervate delivery system comprising an aqueous
dispersion of complex coacervates; wherein the complex coacervates
comprise: a single shell comprising at least one food-grade
cationic polymer and at least one food-grade anionic polymer; and a
core comprising at least one lipophilic nutrient; wherein complex
coacervates in the complex coacervate delivery system release the
lipophilic nutrient in the gastrointestinal tract below the stomach
where the pH. is substantially neutral or alkaline.
38. The complex coacervate delivery system of claim 37, which is
stable at at least one pH value within the range of 1.5 to 5.0.
39. The complex coacervate delivery system of claim 37, wherein the
lipophilic nutrient comprises at least one of fatty acids, fat
soluble vitamins, vitamin. A, vitamin D, vitamin E, vitamin K,
tocotrienols, carotenoids, xanthophylls, lycopene, lutein,
astaxanthin, zeazanthin, fat soluble nutraceuticals, phytosterols,
stanols and esters thereof, Coenzyme Q10, ubiquinol, hydrophobic
amino acids and peptides, essential oils and extracts.
40. The complex coacervate delivery system of claim 39, wherein the
fatty acid comprises at least one of conjugated linolenic acid
(CLA), one or more omega-3 fatty acid and one or more omega-6 fatty
acids.
41. The complex coacervate delivery system of claim 40, wherein the
omega-3 fatty acid comprises at least one of eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA).
42. The complex coacervate delivery system of claim 40, wherein the
omega-3 fatty acid comprises 55-65% EPA and 45-35% DHA.
43. The complex coacervate delivery system of claim 37, wherein the
core farther comprises at least one weighting agent.
44. The complex coacervate delivery system of claim 43, wherein the
weighting agent comprises at least one of ester gum, sucrose
acetate isobutyrate, and brominated vegetable oil.
45. The complex coacervate delivery system of claim 37, wherein at
least a majority of the complex coacervates have a particle size
within the range of 0.1 .mu.m to 5.0 .mu.m.
46. The complex coacervate delivery system of claim 37, wherein the
cationic polymer comprises at least one of dairy proteins, whey
proteins, caseins and fractions thereof, gelatin, corn zein
protein, bovine serum albumin, egg albumin, grain protein extracts,
vegetable proteins, microbial proteins, legume proteins, proteins
from tree nuts, proteins from ground nuts, and chitosan.
47. The complex coacervate delivery system of claim 37, wherein the
anionic polymer comprises at least one of pectin, carrageenan,
alginate, xanthan gum, modified celluloses, carboxymethylcellulose,
gum acacia, gum ghatti, gum karaya, gum tragacanth, locust bean
gum, guar gum, psyllium seed gum, quince seed gum, larch gum
(arabinogalactans), stractan gum, agar, furcellaran, modified
starches, gel Ian gum, and fucoidan.
48. The complex coacervate delivery system of claim 37, wherein the
cationic polymer comprises gelatin and the anionic polymer
comprises gum acacia.
49. The complex coacervate delivery system of claim 37, wherein the
weight to weight ratio of cationic polymer to anionic polymer is
from 10:1 to 1:10.
50. The complex coacervate delivery system of claim 37, wherein the
single shell is substantially non-crosslinked.
51. The complex coacervate delivery system of claim 37, wherein the
single shell is substantially non-gelled.
52. The complex coacervate delivery system of claim 37, wherein the
complex coacervates are substantially non-agglomerated.
53. An aqueous dispersion of complex coacervates, wherein the
complex coacervates comprise: a single shell comprising at least
one food-grade cationic polymer and at least one food-grade anionic
polymer; and a core comprising at least one lipophilic nutrient;
wherein complex coacervates release the lipophilic nutrient in the
gastrointestinal tract below the stomach where the pH is
substantially neutral or alkaline.
54. A beverage product comprising a complex coacervate delivery
system comprising an aqueous dispersion of complex coacervates,
wherein the complex coacervates comprise: a single shell comprising
at least one food-grade cationic polymer and at least one
food-grade anionic polymer, and a core comprising at least one
lipophilic nutrient; wherein the beverage product has a pH value
within the range of 1.5 to 5.0; and wherein complex coacervates in
the complex coacervate delivery system release the lipophilic
nutrient in the gastrointestinal tract below the stomach where the
pH is substantially neutral or alkaline.
55. The beverage product of claim 54, wherein the beverage product
comprises a ready-to-drink beverage.
56. The beverage product of claim 54, wherein the beverage product
is selected from the group consisting of carbonated beverages,
non-carbonated beverages, fountain beverages, liquid concentrates,
fruit juices, fruit juice-flavored drinks, sports drinks, energy
drinks, fortified/enhanced water drinks, soy drinks, vegetable
drinks, grain-based drinks, malt beverages, fermented drinks,
yogurt drinks, kefir, coffee beverages, tea beverages, dairy
beverages, and mixtures thereof.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to the field of delivering
lipophilic nutrients in an acidic aqueous system for controlled
release to a consumer, more particularly encapsulated lipophilic
nutrients in acidic aqueous systems such as food and beverage
products.
BACKGROUND
[0002] Certain functional nutrients have been discovered to have
beneficial health effects. Lipophilic nutrients, such as, for
example, omega-3 and omega-6 fatty acids, form an important part of
the human diet. These are referred to generally as "essential fatty
acids," at least some of which are understood in many cases to
constitute important components of cell membranes, regulate the
body's use of cholesterol, and control the production of substances
that affect many other bodily processes. For example,
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
long-chain forms of omega-3 fatty acids, are understood in many
cases to support brain and cardiovascular health and functions,
amongst other health benefits. To increase or optimize health
benefits from essential fatty acids, it has been suggested that
consumption of omega-3 fatty acids should be increased.
[0003] Previously, water-insoluble lipophilic nutrients were
incorporated directly into an aqueous system in one of four
physical forms: a solution (with a compatible solvent), an extract,
an emulsion, or a micellular dispersion (a so-called
microemulsion). While all of these approaches serve to disperse the
lipophilic nutrient in an aqueous system, they do not provide any
additional benefits like controlled (triggered) release or extended
protection against hydrolysis and oxidation. Commercially available
fish oils can be high in omega-3 fatty acids, and in some cases are
"encapsulated," but these commercially available fish oils have not
proven physically or taste-stable in acidic food and beverage
products. This results in negative hedonistic changes to the food
or beverage product, such as unpleasant fishy flavors and aromas
after ingestion, particularly a fishy aftertaste caused by belching
fish oil from the stomach. Additionally, omega-3 fatty acids are
unstable to degradation, e.g., by oxidation or hydrolysis, when
exposed to air, water and/or light.
[0004] It would be desirable to provide a composition containing
lipophilic nutrients which can reduce or eliminate the unpleasant
taste and odor of the lipophilic nutrients, and which can be
incorporated into a beverage product, food product, or other
aqueous system suitable for consumption by a human or animal. It
would also be desirable to provide lipophilic nutrients in a stable
form for use in aqueous systems such as food and beverage products,
so that the lipophilic nutrient is stable to oxidation and
hydrolysis during the shelf life of the food or beverage product.
It would also be desirable to provide a composition which releases
lipophilic nutrients in the lower gastroinstestinal tract rather
than the stomach.
BRIEF SUMMARY OF THE INVENTION
[0005] Aspects of the invention are directed to delivery systems
for lipophilc nutrients which may be incorporated into food and
beverage products such as, for example, a ready-to-drink acidic
beverage. By encapsulating the lipophilic nutrient, any negative
effects (e.g., oxidation, off flavor, unpleasant aroma, etc.) can
be reduced. Controlled release of the encapsulated lipophilic
nutrient in the lower gastrointestinal tract reduces aftertaste,
and also enhances bioavailability and overall physiological
efficacy of the lipophilic nutrient.
[0006] One aspect of the invention is directed to complex
coacervate delivery systems comprising an aqueous dispersion of
complex coacervates. The complex coacervates have a shell
comprising at least one food-grade cationic polymer and at least
one food-grade anionic polymer, and a core comprising at least one
lipophilic nutrient. The complex coacervate delivery system upon
ingestion is operative to substantially release the lipophilic
nutrient in the lower gastrointestinal tract.
[0007] Other aspects of the invention are directed to complex
coacervate delivery systems comprising an aqueous dispersion of
complex coacervates. The complex coacervates have a shell
comprising at least one food-grade cationic polymer and at least
one food-grade anionic polymer, and a core comprising at least one
lipophilic nutrient. The complex coacervate delivery system is
operative to substantially release the lipophilic nutrient in a
pH-controlled manner.
[0008] In certain exemplary embodiments, the complex coacervate
delivery systems comprise an aqueous dispersion of substantially
non-agglomerated complex coacervates. The complex coacervates have
a substantially non-crosslinked, substantially non-gelled shell
comprising gelatin and gum acacia in a weight to weight ratio of
about 4:1, and a core comprising an omega-3 fatty acid. In certain
exemplary embodiments, all or at least a majority of the complex
coacervates have a particle size within the range of 0.1 .mu.m to
5.0 .mu.m, e.g., at least a majority of the complex coacervates
have a particle size within the range of 0.1 .mu.m to 2.0 .mu.m, or
within the range of 0.3 .mu.m to 0.5 .mu.m. The complex coacervate
delivery system is stable at pH values within the range of 2.8 to
4.0. The complex coacervate delivery system upon ingestion is
operative to substantially release the omega-3 fatty acid in the
lower gastrointestinal tract at a pH value within the range of
about pH 6.0 and above.
[0009] Other aspects of the invention are directed to aqueous
dispersions of complex coacervates. The complex coacervates have a
shell comprising at least one food-grade cationic polymer and at
least one food-grade anionic polymer, and a core comprising at
least one lipophilic nutrient. The aqueous dispersion of complex
coacervates is operative to substantially release the lipophilic
nutrient in a pH-controlled manner.
[0010] Other aspects of the invention are directed to beverage
products that deliver lipophilic nutrients beneficial for general
health and well-being, without compromising to any significant
extent the taste characteristics of the beverage product. The
lipophilic nutrients can be added to beverage products having
associated health benefits, as well as other beverage products that
may not typically be perceived as having nutritional and health
benefits, to promote healthy lifestyles. In certain exemplary
embodiments, a beverage product is provided which includes a
complex coacervate delivery system comprising an aqueous dispersion
of complex coacervates. The complex coacervates have a shell
comprising at least one food-grade cationic polymer and at least
one food-grade anionic polymer, and a core comprising at least one
lipophilic nutrient. The beverage product can have a pH of about
1.5 to about 5.0. Upon ingestion of the beverage product, complex
coacervate delivery system is operative to substantially release
the lipophilic nutrient in the lower gastrointestinal tract in a
pH-controlled manner.
[0011] Other aspects of the invention are directed to food products
which include a complex coacervate delivery system comprising an
aqueous dispersion of complex coacervates. The complex coacervates
have a shell comprising at least one food-grade cationic polymer
and at least one food-grade anionic polymer, and a core comprising
at least one lipophilic nutrient. The food product can have a pH of
about 1.5 to about 5.0. Upon ingestion of the food product, the
complex coacervate delivery system is operative to substantially
release the lipophilic nutrient in the lower gastrointestinal tract
in a pH-controlled manner.
[0012] Other aspects of the invention are directed to complex
coacervate delivery systems comprising an aqueous dispersion of
complex coacervates. The complex coacervates have a shell
comprising at least one cationic polymer and at least one anionic
polymer, and a core comprising at least one lipophilic nutrient.
The complex coacervate delivery system is operative to
substantially release the lipophilic nutrient in a pH-controlled
manner. In certain exemplary embodiments, the cationic polymer
comprises at least one of Eudragit E, Eudragit E 100, and Eudragit
E PO.
[0013] These and other aspects, along with advantages and features
of the present invention herein disclosed, will become apparent
through reference to the following detailed description.
Furthermore, it is to be understood that the features of the
various embodiments described herein are not mutually exclusive and
can exist in various combinations and permutations.
DETAILED DESCRIPTION
[0014] Aspects of the invention relate to complex coacervate
delivery systems disclosed herein for lipophilic nutrients, which
provide a stable composition suitable for inclusion in food and
beverage products, that is, the complex coacervates are stable for
shelf-storage, for use in making foods and beverages, and for
shelf-storage when included in acidic food and beverages, etc. The
complex coacervate delivery systems also provide pH-controlled
release of the one or more lipophilic nutrients in the neutral to
basic conditions of the lower gastrointestinal tract. That is, the
complex coacervates in the complex coacervate delivery systems
dissociate upon entering the part of the gastrointestinal tract
below the stomach where the pH becomes substantially neutral or
alkaline. As used herein, "pH-controlled release" (optionally
referred to as release in a pH-controlled manner, or pH-dependent
release, or pH-triggered release, or the like) means that the
complex coacervates release at least the majority of the
encapsulated lipophilic nutrient when the pH of the complex
coacervate delivery system or the environment in which it is placed
reaches or goes beyond a certain pH value, e.g., at any pH value
within a specified range, or at one or more pH values within a
specified range. The complex coacervate delivery system reduces or
eliminates the unpleasant taste and odor of many lipophilic
nutrients such as fish oil, reduces degradation, e.g. by oxidation
or hydrolysis, of unstable lipophilic nutrients, and delays release
of the lipophilic nutrient until the lower gastrointestinal tract,
where good absorption and bioavailability occurs. The complex
coacervate delivery system may be incorporated into a food or
beverage product associated with health benefits, for example
orange juice, to provide enhanced nutritional value. Additionally,
the complex coacervate delivery system may be incorporated into
food and beverage products, for example carbonated soft drinks. By
encapsulating such lipophilic nutrients in a complex coacervate
delivery system, possible negative hedonic, visual and physical
changes to the food or beverage product may be reduced or avoided.
The resulting food and beverage product is appealing to the
consumer, as well as being stable and having an adequate shelf
life.
[0015] In certain exemplary embodiments, a complex coacervate
delivery system is provided comprising an aqueous dispersion of
complex coacervates. As used herein, a "delivery system" is a
composition or a mixture of components which can be used to carry
the complex coacervates encapsulating the lipophilic nutrient and
to provide or deliver them into a system or environment or the
like, e.g. into a food or beverage intended for consumption by
humans or animals. As used herein, an "aqueous dispersion" is
defined as particles distributed throughout a medium of liquid
water, e.g., as a suspension, a colloid, an emulsion, a sol, etc.
The medium of liquid water may be pure water, or may be a mixture
of water with at least one water-miscible solvent, such as, for
example, ethanol or other alcohols, propylene glycol, glycerin,
dimethylsulfoxide, dimethylformamide, etc. In certain exemplary
embodiments, there may be a substantial concentration of
water-miscible solvent in the aqueous dispersion of the complex
coacervate delivery system, such as, between about 1% and about 20%
by volume, for example 5%, 10%, or 15%. In other exemplary
embodiments, the complex coacervate delivery system is diluted into
a beverage or food product and the concentration of water-miscible
solvent is negligible. As used herein, a "complex coacervate" is a
particle having a shell comprising at least two oppositely charged
polymers (that is, cationic polymers of at least one type and
anionic polymers of at least one type) which substantially
encapsulates a core material. As used herein, polymers include not
only traditional polymers, but also oligomers and the like. At
least a majority of the complex coacervates have a particle size
within the range of about 0.1 .mu.m to about 5.0 .mu.m, preferably
within the range of about 0.1 .mu.m to about 2.0 .mu.m, most
preferably within the range of about 0.3 .mu.m to about 0.5 .mu.m.
The particle sizes disclosed here include any or at least one value
within the disclosed ranges as well as the endpoints of the ranges.
Preferably, the complex coacervates are substantially
non-agglomerated, but comprise a single shell encapsulating a
single core. The core includes at least one water-insoluble,
lipophilic nutrient, for example a liquid such as an oil. As used
herein, a "lipophilic nutrient" is a substance that provides
nourishment needed for life or growth or good health, which has an
affinity for or is capable of dissolving in lipids, fats, oils, or
non-polar solvents (e.g., a non-polar, hydrophobic substance). The
shell includes a net positive charged (cationic) polymer and a net
negative charged (anionic) polymer. It is believed that the net
charge of each polymer is dependent on the pH of the environment
and the isoelectric point of each polymer, which is in turn
dependent on the density of ionizable groups in each polymer and
the pKa values of those groups. Thus, disclosure here of complex
coacervates comprising cationic and anionic polymers refers to the
charge of the polymers in the environment or reaction conditions
used for formation of the complex coacervates. Complex coacervates
of the type used here are presently understood to be stabilized at
least in part by the electrostatic attraction between the
oppositely charged polymers, and thus are selected or designed to
release upon a particular physiological trigger, specifically a pH
change. In certain exemplary embodiments, the complex coacervates
are not substantially additionally stabilized, for example by
substantial gelling, substantial crosslinking, or substantial
hardening of the complex coacervate shell. Gelling, crosslinking,
and hardening are believed to hinder pH-controlled dissociation of
the complex coacervates and the resulting release of lipophilic
nutrients.
[0016] Exemplary polymers for use in the complex coacervates
delivery systems disclosed here include oppositely charged polymers
that form complex coacervates at an acidic pH, e.g., a pH value
below about pH 6.0, in certain exemplary embodiments, a pH value
within the range of about 1.5 to about 5.0, in certain exemplary
embodiments, a pH value within the range of about 2.8 to about 4.0.
The complex coacervates disclosed here are stable at an acidic pH,
e.g., a pH value within the range below about pH 6.0, in certain
exemplary embodiments, a pH value within the range of about 1.5 to
about 5.0, in certain exemplary embodiments, a pH value within the
range of about 2.8 to about 4.0. In certain exemplary embodiments,
the complex coacervates are stable at a pH within such recited
ranges in the sense that they are stable at any pH value within the
recited range, including the endpoints. In other exemplary
embodiments, the complex coacervates are stable at one or more pH
values within the recited range, including the endpoints, but are
not stable at every pH value within the recited range. As used
herein, "stable" means that at least a majority of the complex
coacervates do not dissociate and release the lipophilic nutrients.
In certain exemplary embodiments, the oppositely charged cationic
and anionic polymers are food-grade biopolymers. As used herein,
"food-grade" is defined as any material that is deemed by the
United States Food and Drug Administration to be safe for use in
food and beverage products. Exemplary food-grade cationic polymers
include but are not limited to proteins such as dairy proteins,
including whey proteins, caseins and fractions thereof, gelatin,
corn zein protein, bovine serum albumin, egg albumin, grain protein
extracts, e.g. protein from wheat, barley, rye, oats, etc.,
vegetable proteins, microbial proteins, legume proteins, proteins
from tree nuts, proteins from ground nuts, and polysaccharides such
as chitosan. Other exemplary cationic polymers include but are not
limited to Eudragit E, Eudragit E 100, and Eudragit E PO. Eudragit
E 100 has an average molecular weight of approximately 150,000,
with repeating units having the following structure:
##STR00001##
[0017] Exemplary food-grade anionic polymers include but are not
limited to polysaccharides such as pectin, carrageenan, alginate,
xanthan gum, modified celluloses, e.g., carboxymethylcellulose, gum
acacia, gum ghatti, gum karaya, gum tragacanth, locust bean gum,
guar gum, psyllium seed gum, quince seed gum, larch gum
(arabinogalactans), stractan gum, agar, furcellaran, modified
starches, gellan gum, fucoidan, and the like. An exemplary complex
coacervate shell comprises gelatin and gum acacia. There are many
possible combinations of oppositely charged polymers that are
useful for forming the complex coacervates disclosed here. The
weight to weight ratio of cationic polymer to anionic polymer can
be from about 10:1 to about 1:10, and is preferably about 4:1.
[0018] When included in an acidic food or beverage product, e.g. a
food or beverage product having a pH value within the range below
about pH 6.0, in certain exemplary embodiments, a pH value within
the range of about 1.5 to about 5.0, in certain exemplary
embodiments, a pH value within the range of about 2.8 to about 4.0,
the complex coacervate delivery systems disclosed here provide a
stable dispersion of encapsulated lipophilic nutrient. Upon
ingestion of the food or beverage product, that is, upon being
consumed by a human or animal, the complex coacervate delivery
systems are also stable and the complex coacervates do not
substantially dissociate in the acidic environment of the stomach,
where the pH is typically about pH 1-4. Since the lipophilic
nutrient remains substantially encapsulated in the stomach,
unpleasant aftertaste and bad breath from belching of free
lipophilic nutrient is greatly reduced. The complex coacervate
delivery system substantially releases the lipophilic nutrient in a
pH-controlled manner in the lower gastrointestional tract, e.g. the
small intestine, thus enhancing bioavailability and overall
physiological efficacy of the encapsulated lipophilic nutrient. It
is believed that neutral to basic conditions of the lower
gastrointestinal tract, e.g. typically having a pH value within the
range of about pH 6.0 and above, and in certain exemplary
embodiments having a pH value within the range of about pH 7.0 and
above, trigger dissociation of the complex coacervates and release
of the encapsulated lipophilic nutrient due to weakening of the
electrostatic forces that stabilize the complex coacervate shell.
It should be understood that in at least certain exemplary
embodiments, the complex coacervates can release the encapsulated
lipophilic nutrient in a pH-controlled manner in almost any system,
for example, under in vitro conditions such as a simple aqueous
dispersion at any or one or more selected pH values about 6.0 and
above, or about 7.0 and above. In certain exemplary embodiments,
the complex coacervates may not release the encapsulated lipophilic
nutrient in a pH-controlled manner under in vitro conditions, but
can undergo pH-controlled release in vivo in a human or animal
lower gastrointestinal tract at any or at least one pH value about
6.0 and above or about 7.0 and above, where additional biological,
chemical and/or mechanical factors act upon the complex coacervate.
In addition, it is contemplated that complex coacervate delivery
systems according to aspects of the present invention will exhibit
additional desired physical properties. For example, it is
contemplated that complex coacervate delivery systems will have an
acceptable mouthfeel, taste, aroma, and appearance.
[0019] In certain exemplary embodiments, the lipophilic nutrients
include fat soluble vitamins, (e.g., vitamins A, D, E, and K),
tocotrienols, carotenoids, xanthophylls, (e.g., lycopene, lutein,
astaxanthin, and zeazanthin), fat-soluble nutraceuticals including
phytosterols, stanols and esters thereof, Coenzyme Q10 and
ubiquinol, hydrophobic amino acids and peptides, essential oils and
extracts, and fatty acids. Fatty acids may include, for example,
conjugated linolenic acid (CLA), omega-6 fatty acids, and omega-3
fatty acids. Suitable omega-3 fatty acids include, e.g.,
short-chain omega-3 fatty acids such as alpha-linolenic acid (ALA),
which are derived from plant sources, for example flaxseed, and
long-chain omega-3 fatty acids such as eicosapentaenoic acid (EPA)
and docosahexaenoic acid (DHA). The long-chain omega-3 fatty acids
can be derived from, for example, marine or fish oils. Such oils
can be extracted from various types of fish or marine animals, such
as anchovies, capelin, cod, herring, mackerel, menhaden, salmon,
sardines, shark and tuna, or from marine vegetation, such as
micro-algae, or a combination thereof. Other sources of omega-3
fatty acids include liver and brain tissue and eggs.
[0020] In at least certain exemplary embodiments, at least one of
EPA and DHA is included in the complex coacervate delivery system.
When included as a mixture, the ratio of EPA to DHA may vary
depending on the source of the omega-3 fatty acids (e.g., fish
oils), the manner in which the omega-3 fatty acids are mixed, and
the food or beverage product to be produced. The EPA:DHA ratio will
vary to suit a particular application and can include, for example,
0:100, 100:0, 2:1, or 3:2. In certain exemplary embodiments, the
mixture of omega-3 fatty acids comprises about 55-65% EPA and about
45-35% DHA. In a particular application the EPA:DHA ratio is about
60:40; however, other ratios are contemplated and within the scope
of the invention.
[0021] In certain exemplary embodiments, a desired amount of a
lipophilic nutrient in the above-described complex coacervate
delivery system is included in a food or beverage product. The
complex coacervate delivery system may be added to the food or
beverage product in any number of ways, as will be appreciated by
those of ordinary skill in the art given the benefit of this
disclosure. In certain exemplary embodiments, the complex
coacervate delivery system is sufficiently mixed in the food or
beverage product to provide a substantially uniform distribution,
for example a stable dispersion. Mixing should be accomplished such
that the complex coacervates are not destroyed. If the complex
coacervates are destroyed, oxidation of the lipophilic nutrient may
result. The mixer(s) can be selected for a specific application
based, at least in part, on the type and amount of ingredients
used, the viscosity of the ingredients used, the amount of product
to be produced, the flow rate, and the sensitivity of ingredients,
such as the complex coacervate delivery system, to shear forces or
shear stress.
[0022] The amount of lipophilic nutrient included in a food or
beverage product may vary depending on the application and
nutritional content desired. In one embodiment, the food or
beverage product comprises orange juice including about 5-5000 mg
of omega-3 fatty acids per 8 fluid ounces (0.24 liters) (serving
size). The amount to be added will vary to suit a particular
application and can be based, at least in part, on nutritional
value, taste, shelf-life, efficacy levels approved, qualified
health claims, and combinations thereof. Other amounts are also
contemplated and within the scope of the invention. For example, it
may be desired to provide at least 32 mg of omega-3 fatty acids
(combined EPA and DHA) per 8 fluid ounces of the food or beverage
product to meet the United States Food and Drug Administration
(FDA) excellent source nutrient content claim requirements, or 16
mg per 8 fluid ounces to meet the FDA good source nutrient content
claim requirements.
[0023] Encapsulation of lipophilic nutrients using the
above-described complex coacervate delivery system stabilizes the
lipophilic nutrient, protecting it from degradation by, for
example, oxidation and hydrolysis. When included in an acidic food
or beverage product, the complex coacervate delivery system can
provide a stable dispersion of lipophilic nutrient over a suitable
shelf-life for the food or beverage product. In certain exemplary
embodiments, the finished food or beverage product including
complex coacervate delivery systems disclosed here have a
shelf-life greater than one week, e.g., about 1-12 months and
possibly up to 24 months or longer under ambient conditions (e.g.,
room temperature of between 70.degree. F. and 80.degree. F. and
controlled light exposure), depending on the level of processing
the product undergoes, the type of packaging, and the materials
used for packaging the product. In other embodiments, the finished
product with the complex coacervate delivery system may have a
shelf-life of about 12 weeks up to about 20 weeks under
refrigerated conditions. In other embodiments, the finished product
may be stored indefinitely under frozen conditions. Additional
factors that may affect the shelf-life of the product include, for
example, the nature of the base formula (e.g., an acidic beverage
sweetened with sugar has a longer shelf-life than an acidic
beverage sweetened with aspartame) and environmental conditions
(e.g., exposure to high temperatures and sunlight is deleterious to
ready-to-drink beverages).
[0024] Certain exemplary embodiments of the beverage products
disclosed here include ready-to-drink beverages, beverage
concentrates, syrups, shelf-stable beverages, refrigerated
beverages, frozen beverages, and the like. Preferably, the beverage
product is acidic, e.g. having a pH value within the range below
about pH 6.0, in certain exemplary embodiments, a pH value within
the range of about 1.5 to about 5.0, or in certain exemplary
embodiments, a pH value within the range of about 2.8 to about 4.0.
Beverage products include but are not limited to, e.g., carbonated
and non-carbonated soft drinks, fountain beverages, liquid
concentrates, fruit juice and fruit juice-flavored drinks, sports
drinks, energy drinks, fortified/enhanced water drinks, soy drinks,
vegetable drinks, grain-based drinks (e.g. malt beverages),
fermented drinks (e.g., yogurt and kefir) coffee beverages, tea
beverages, dairy beverages, and mixtures thereof. Exemplary fruit
juice sources include citrus fruit, e.g. orange, grapefruit, lemon
and lime, berry, e.g. cranberry, raspberry, blueberry and
strawberry, apple, grape, pineapple, prune, pear, peach, cherry,
mango, and pomegranate. Beverage products include bottle, can, and
carton products and fountain syrup applications.
[0025] Certain exemplary embodiments of the food products disclosed
here include fermented food products, yogurt, sour cream, cheese,
salsa, ranch dip, fruit sauces, fruit jellies, fruit jams, fruit
preserves, and the like. Preferably, the food product is acidic,
e.g. having a pH value within the range below about pH 6.0, in
certain exemplary embodiments, a pH value within the range of about
1.5 to about 5.0, or in certain exemplary embodiments, a pH value
within the range of about 2.8 to about 4.0. All variations,
alternatives, options, etc., discussed elsewhere in this disclosure
apply to food embodiments of the invention, for example, any
disclosed complex coacervate comprising any cationic or anionic
polymer in any ratio, any lipophilic nutrients, and any particle
size can be used in food embodiments in any combination suitable
for application to food products.
[0026] The food or beverage product may optionally include other
additional ingredients. Optional additional ingredients include,
for example, vitamins, minerals, sweeteners, flavorings, colorings,
edible particulates, thickeners, emulsifiers, acidulants,
electrolytes, antifoaming agents, proteins, carbohydrates,
preservatives, and mixtures thereof. Other ingredients are also
contemplated. The ingredients can be added at various points during
processing, including before or after pasteurization, and before or
after addition of the complex coacervate delivery system.
[0027] In at least certain exemplary embodiments, food and beverage
products disclosed here may be pasteurized. The pasteurization
process may include, for example, ultra high temperature (UHT)
treatment and/or high temperature-short time (HTST) treatment. The
UHT treatment includes subjecting the food or beverage product to
high temperatures, such as by direct steam injection or steam
infusion, or by indirect heating in a heat exchanger. Generally,
after the product is pasteurized, the product can be cooled as
required by the particular product composition/configuration and/or
the package filling application. For example, in one embodiment,
the food or beverage product is subjected to heating to about
185.degree. F. (85.degree. C.) to about 250.degree. F. (121.degree.
C.) for a short period of time, for example, about 1 to 60 seconds,
then cooled quickly to about 36.degree. F. (2.2.degree. C.)
+/10.degree. F. (5.degree. C.) for refrigerated products, to
ambient temperature for shelf stable or refrigerated products, and
to about 185.degree. F. (85.degree. C.) +/-10.degree. F. (5.degree.
C.) for hot-fill applications for shelf-stable products. The
pasteurization process is typically conducted in a closed system,
so as not to expose the food or beverage product to atmosphere or
other possible sources of contamination. Other pasteurization or
sterilization techniques may also be useful, such as, for example,
aseptic or retort processing. In addition, multiple pasteurization
processes may be carried out in series or parallel, as necessitated
by the food or beverage product or ingredients.
[0028] Food and beverage products may, in addition, be post
processed. Post processing is typically carried out following
addition of the complex coacervate delivery system. Post processing
can include, for example, cooling the product and filling it into
container for packaging and shipping. Post processing may also
include deaeration of the product to less than 4.0 ppm oxygen,
preferably less than 2.0 ppm and more preferably less than 1.0 ppm
oxygen. Deaeration, however, and other post processing tasks may be
carried out prior to processing, prior to pasteurization, prior to
mixing with the complex coacervate delivery system and/or at the
same time as adding the complex coacervate delivery system. In
addition, an inert gas (e.g., nitrogen or argon) headspace may be
maintained during the intermediary processing of the product and
final packaging. Additionally/alternatively, an oxygen or UV
barrier and/or oxygen scavengers could be used in the final
packaging.
[0029] The following examples are specific embodiments of the
present invention but are not intended to limit it.
EXAMPLE 1
[0030] A complex coacervate delivery system was prepared using the
following methods. A 25 mL aqueous solution of 2% by weight gum
acacia was prepared. Fish oil high in omega-3 fatty acid (1.3 mL)
was added to the 25 mL gum acacia solution. The mixture was
sonicated for two minutes, alternating pulsing on for 1 second and
off for 1 second, to form an oil-in-water emulsion. Then, a 100 mL
aqueous solution of 2% by weight gelatin type A pre-heated to
50.degree. C. was added slowly to the emulsion while stirring the
mixture at 500 rpm. Maintaining the temperature at 50.degree. C.,
the pH was lowered to between 4.8 and 5.0 using 0.1 M phosphoric
acid. Then the mixture was cooled in an ice bath. Once the
temperature reached 5-10.degree. C., the pH was lowered to between
4.0 to 4.5 using another portion of 0.1 M phosphoric acid to allow
formation of coacervate complexes of cationic gelatin and anionic
gum acacia encapsulating droplets of fish oil. Particle size of the
complex coacervates was about 2.0 to about 3.0 .mu.m.
[0031] It should be noted that the sonication in Example 1 could be
replaced or supplemented with high-speed homogenization.
EXAMPLE 2
[0032] Fish oil high in omega-3 fatty acid (1.3 mL) was added to 25
mL aqueous solution of 0.4% by weight modified starch containing
0.83% polyvinyl alcohol, of which pH was pre-adjusted to 2.6 using
citrate buffer. The mixture was sonicated for two minutes in the
same manner as described in Example 1. Then, a 5 mL aqueous
solution of 0.5% by weight whey protein (pH 2.6 in 10 mM citrate
buffer) was added to the mixture and further sonicated for another
30 seconds. Particle size of thus formed complex coacervates was
about 0.5-1 .mu.m.
[0033] It should be noted that the modified starch in Example 2
could be replaced wholly or partly with gum acacia and/or other
anionic polymers. The whey protein in Example 2 could be replaced
wholly or in part with chitosan, gelatin, and/or other cationic
polymers. The polyvinyl alcohol in Example 2 could be replaced
wholly or partly with modified starch, polyethylene glycol,
maltodextrin DE5, guar gum, and/or hydroxypropylmethylcellulose
(HPMC). Also, it should be noted that the concentration of modified
starch in Example 2 could be increased up to 4% by weight or
more.
[0034] Also, it should be noted that the acid in Examples 1 and 2
could be selected from other organic and inorganic acids, such as,
for example, phosphoric acid, ascorbic acid, citric acid, acetic
acid, malic acid, tartaric acid, glucono delta-lactone, succinic
acid, and any combination thereof.
EXAMPLE 3
[0035] The amount of encapsulated oil produced in Example 2 was
estimated by subtracting unencapsulated oil from total oil in the
system. For extracting unencapsulated free oil, the particle
suspension was mixed with hexane at 1:1 ratio and spun at 14,000
rpm for 15 minutes. The hexane layer was then collected and
analyzed as described in Examples 4 and 5. Total oil in the system
(encapsulated oil and unencapsulated free oil) was extracted as
follows. Particle suspension was brought to pH 6.7-6.8 using 1N
NaOH solution and heated to 50.degree. C. to dissolve the
coacervate coats surrounding oil droplets. The suspension was mixed
with hexane at 1:1 ratio and spun at 14,000 rpm for 15 minutes. The
hexane layer was then collected and analyzed as described in
Examples 4 and 5.
EXAMPLE 4
[0036] Five ml of methylating reagent (BCl.sub.3-methanol) was
added to 2 ml of hexane layer collected as described in Example 3,
mixed well by shaking, and then placed in a heat block and heated
at 60.degree. C. for 10 min. The methylated solution was allowed to
return to room temperature, mixed for 1 min. using a vortex mixer,
and left until two layers (hexane and water) separated. The top
layer was transferred into a glass vial, to which an equal volume
of internal standard (0.01 mg/ml methyl laurate in hexane) was
added prior to GC/MS analysis.
EXAMPLE 5
[0037] Methylated omega-3 fatty acids were analyzed using the
Agilent 5973N GC/MS. One .mu.l of each sample was injected onto the
column (Restek Rtx-1, Crossbond 100% dimethylypolysiloxane, 30
m.times.250 .mu.m.times.1.00 .mu.m) that was programmed for a 5
min. solvent delay at 100.degree. C., followed by heating to
250.degree. C. at a rate of 20.degree. C./min., holding at
250.degree. C. for 5 min., and then heating to 320.degree. C. at a
rate of 20.degree. C./min. Helium was used as a carrier gas and
flowed at 1 ml/min.
EXAMPLE 6
[0038] A complex coacervate delivery system was prepared in the
same way as in Example 1, by replacing the gum acacia solution with
a 5% by weight aqueous solution of modified starch, and replacing
the gelatin solution with a 0.5% by weight aqueous solution of whey
protein. No apparent difference was observed whether starting with
modified starch or whey protein.
EXAMPLE 7
[0039] A complex coacervate delivery system was prepared in the
same way as Example 1 with weighting agents added to the fish oil
to increase its density. Exemplary weighting agents include ester
gum, sucrose acetate isobutyrate, and brominated vegetable oil,
among others.
EXAMPLE 8
[0040] A complex coacervate delivery system was prepared in the
same way as Example 1 with a 5% by weight aqueous solution of
polyvinylalcohol added.
EXAMPLE 9
[0041] A complex coacervate delivery system was prepared in the
same way as in Example 1, replacing the gelatin and gum acacia
solutions with a 0.083% by weight aqueous solution of chitosan, a
0.33% by weight aqueous solution of modified starch, and a 0.67% by
weight aqueous solution of polyvinylalcohol.
EXAMPLE 10
[0042] Eudragit E polymers can be used as the cationic polymer in
Examples 1 and 2. In this case, the Eudragit E polymer is first
dissolved in ethanol, then the ethanolic solution is added to the
coacervation system, of which the pH is pre-adjusted to less than
pH 5.0. Once the complex coacervates form, 90-95% of ethanol in the
system is removed by ultrafiltration. Alternatively, Eudragit E
polymers can be dissolved in any other water-miscible organic
solvents, such as, for example, other alcohols, propylene glycol,
glycerin, dimethylsulfoxide, or dimethylformamide. Alternatively,
Eudragit E polymers can be dissolved in acidic aqueous solutions
with a pH less than pH 5.0. The acidic aqueous solution can be
prepared with various organic and inorganic acids, such as, for
example, phosphoric acid, ascorbic acid, citric acid, acetic acid,
malic acid, tartaric acid, glucono delta-lactone, succinic acid,
and any combination thereof.
[0043] To prepare 2.0-3.0 gm complex coacervates, a 25 mL aqueous
solution of 2% by weight gum acacia is prepared. Fish oil high in
omega-3 fatty acid (1.3 mL) is added to the 25 mL gum acacia
solution. The mixture is sonicated for two minutes, alternating
pulsing on for 1 second and off for 1 second, to form an
oil-in-water emulsion. The pH is lowered to between pH 4.0 to 4.5
using 0.1 M phosphoric acid. Then, a 5 mL ethanolic solution of 5%
by weight Eudragit E 100 is added slowly to the emulsion while
stirring the mixture at 500 rpm. Ethanol and polymers that have not
participated in the complex coacervation are then removed by
ultrafiltration.
EXAMPLE 11
[0044] To prepare 0.5-1 .mu.m complex coacervates, fish oil high in
omega-3 fatty acid (1.3 mL) is added to a 25 mL aqueous solution of
0.4% by weight modified starch containing 0.83% polyvinyl alcohol,
of which pH is pre-adjusted to pH 2.6 using citrate buffer. The
mixture is sonicated for two minutes, alternating pulsing on for 1
second and off for 1 second, to form an oil-in-water emulsion.
Then, a 5 mL ethanolic solution of 0.5% by weight Eudragit E 100 is
added and the mixture is further sonicated for another 30 seconds.
Ethanol and polymers that have not participated in the complex
coacervation are then removed by ultrafiltration.
[0045] The invention has been described with reference to the
preferred embodiments. Obviously, modifications and alterations
will occur to others upon reading and understanding the preceding
detailed description. It is intended that the invention be
construed as including all such modifications and alterations
insofar as they come within the scope of the appended claims or the
equivalents thereof.
* * * * *