U.S. patent application number 10/203178 was filed with the patent office on 2003-01-30 for homogenous solid matrix cotaining vegetable proteins.
Invention is credited to Friedman, Doron I..
Application Number | 20030021881 10/203178 |
Document ID | / |
Family ID | 11073864 |
Filed Date | 2003-01-30 |
United States Patent
Application |
20030021881 |
Kind Code |
A1 |
Friedman, Doron I. |
January 30, 2003 |
Homogenous solid matrix cotaining vegetable proteins
Abstract
The invention provides a homogenous solid matrix composition,
enabling an improved dispersion of and bitter taste masking of
hydrophobic, bioactive ingestibles, of at least low water
solubility comprising: (a) at least 10 % w/w vegetable proteins;
(b) lecithin; and (c) at leaset one ingestible bioactive compound
of at least low water solubility.
Inventors: |
Friedman, Doron I.;
(Karme-Yosef, IL) |
Correspondence
Address: |
TOWNSEND AND TOWNSEND AND CREW, LLP
TWO EMBARCADERO CENTER
EIGHTH FLOOR
SAN FRANCISCO
CA
94111-3834
US
|
Family ID: |
11073864 |
Appl. No.: |
10/203178 |
Filed: |
August 5, 2002 |
PCT Filed: |
February 8, 2001 |
PCT NO: |
PCT/IL01/00128 |
Current U.S.
Class: |
426/634 |
Current CPC
Class: |
A61K 9/1658 20130101;
A61K 9/1617 20130101 |
Class at
Publication: |
426/634 |
International
Class: |
A23L 001/20 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 23, 2000 |
IL |
134,701 |
Claims
What is claimed is:
1. A homogeneous solid matrix composition, enabling an improved
dispersion of and bitter taste masking of hydrophobic, bioactive
ingestibles, of at least low water solubility comprising: (a) at
least 10% w/w vegetable proteins; (b) lecithin; and (c) at least
one ingestible bioactive compound of at least low water
solubility.
2. A composition of claim 1, comprising lecithin and said
ingestible bloactive compound in relative amounts of 1:3 to
3:1,
3. A composition of claim 1, comprising lecithin and said
ingestible bioactive compound in relative amounts of 1:1.
4. A composition of claim 2, wherein the ratio of vegetable protein
to the combined amounts of lecithin and ingestible bioactive
compound is between 20:1 to 1:2.
5. A composition of claim 2, wherein the ratio of vegetable protein
to the combined amounts of lecithin and ingestible bioactive
compound is between 4:1 to 1:1.
6. A composition of claim 1, wherein said ingestible bioactive
compound has a water solubility of less then 0.5 mg/ml at
25.degree. C.
7. The composition of claim 1, wherein said vegetable proteins are
selected from isolated and concentrated soybean proteins,
containing at least 50% protein wherein the average MW of said
proteins is larger then 25K Dalton.
8. The composition of claim 1, wherein said vegetable proteins are
selected from isolated and concentrated soybean proteins,
containing at least 60% proteins and said proteins are
non-denatured.
9. The composition of claim 1, wherein said vegetable proteins are
soybean proteins, containing at least 60% proteins and having a
nitrogen solubility index (NSI) of at least 20%.
10. composition of claim 1, wherein said vegetable proteins are
soybean proteins, containing at least 70% proteins and wherein the
average MW of said proteins is larger then 25K Dalton and the NSI
thereof is higher then 20%.
11. The composition of claim 1, wherein said vegetable proteins are
selected from the group consisting of concentrated and isolated
proteins of: corm potatoes, wheat, peanuts, beans, rice, sesame,
barley, sunflower, canola and rapeseed.
12. The composition of claim 1, wherein ingestible bioactive
compound is selected from the group consisting of a drug, a
nutrient, a vitamin, a food supplement and mixtures thereof.
13. A composition of claim 1, wherein said ingestible bioactive
compound is an herbal extract containing low water soluble
ingredients.
14. A method for preparing the composition of claim 1, wherein
lecithin is swollen in water in a ratio of between about 1:2 to
1:10 and said ingestible bioactive compound is added until complete
solubilization, vegetable protein is then added with additional
water to produce granulation dough, whereafter, the wet mass is
granulated and dried.
15. A method of claim 14, wherein said wet mass is further diluted
with water and spray dried.
16. A method according to claim 14, wherein the wet granulation is
extruded through a screen having openings of 0.5 mm to 2.5 mm and
spheronized in a spheronizer.
17. A method according to claim 14, wherein said ingestible
bioactive compound is a bitter tasting compound and homogeneous
particles and taste masking are obtained.
18. A method according to claim 14, in which the wet granulation is
prepared and formed into spheres, utilizing a high shear granulator
to form taste-masked spheres.
19. The composition of claim 1, wherein the limiting step for the
ingestible bioactive compound release is the proteins
gasto-intestinal digestion and decomposition of the matrix.
20. The composition of claim 1, wherein ingestible bioactive
compound is released over period of one to three hours in the
gastrointestinal tract.
21. A composition of claim 1, which is further coated or
encapsulated.
22. A core compound encapsulated with the homogenous matrix of
claim 1, in fluidized bad or spray drying process.
Description
[0001] The present invention relates to a homogeneous solid matrix
composition containing vegetable proteins, lecithin and an
ingestible bioactive compound of at least low water solubility. The
term, at least low-water solubility, as used herein, is 5 intended
to denote a compound having low or poor water solubility as well as
compounds which are water insoluble due to the presence of at least
a hydrophobic moiety in the compound or, the hydrophobicity of the
compound as a whole.
[0002] The bioactive compound is homogeneously embedded in an
amorphous, non-crystalline form in the matrix for achieving the
advantages of enhanced 10 dissolution and biological availability
of said ingestible, bioactive compound to be administered to
mammals, as well as taste masking of bitter ingestable
substances.
[0003] This invention has been developed to provide an answer for
an unmet therapeutic or nutraceutic need of low biological
availability of: drugs, phytomedicines, phytonutrients, vitamins
and nutraceutical or food supplements, 15 especially herbal
extracts comprising variable levels of assembly of hydrophobic
constituents, which do not mix or disperse well enough in the
gastrointestinal physiological fluids. These have a low
dissolution, low oral bioavailability and large inter-individual
availability variation, which is an obstacle for their full
exploitation.
[0004] Since most bitter tasting compounds are poorly water soluble
or at least have a hydrophobic moiety, this invention has been
developed to give an answer for an unmet therapeutic or nutraceutic
need of rejected and undesired bitter tasting drugs or
nutrients.
DESCRIPTION OF THE PRIOR ART
[0005] A variety of solid matrix compositions and production
techniques have been used for years by the pharmaceutical and food
industry in order to:
[0006] a) convert liquids to free-flowing powder,
[0007] b) improve the dissolution rates and bioavailabilities of
drugs, specifically of insoluble or of low solubility,
[0008] c) protect the compounds from decomposition, and
[0009] d) mask unfavorable odor or taste.
[0010] Such methods and matrices include particular solids in the
form of: microencapsules, microspheres, granules, pellets,
nano-particles, etc.
[0011] Microparticles are spherical polymeric particles ranging in
size from greater than one micron, up to 2000 microns.
Microparticles include microcapsules in which the biological agent
is uniformly confined within a cavity, and microspheres in which
the agent is dispersed throughout the microparticle. The agent may
be dispersed in the microparticle matrix as discrete crystals or in
an amorphous homogeneous form. Many processes can be used for the
preparation of microparticles including solvent evaporation,
organic phase separation, interfacial polymerization, emulsion
polymerization, and spray drying.
[0012] Numerous polymers have been used as matrices for
microparticles including polysaccharides, polyesters, and
nonbiodegradable synthetic polymers. Polyesters, especially,
poly(D,L-lactide-co-glycolide) are desirable for microencapsulation
of peptides because aside from being biodegradable or bioerodible,
they are also readily available, easily processed and
non-toxic.
[0013] Matrices and microparticles are also prepared from
bio-compatible materials such as starch, cross linked starch,
starch derivatives and modified starches including: amylodextrin,
gelatin, albumin, collagen, dextrin and dextrin derivatives,
polyvinyl alcohol, polylactide-co-glycolide, hyaluronic acid and
derivatives thereof, such as benzyl and ethyl esters, gellan gum
and derivatives, cellulosic polymers, specifically lower alkyl
ethers of cellulose in addition to protein polymers such as
albumin, sephadex, or DEAE-sephadex.
[0014] Other known materials used in manufacturing microparticles
include alginates, xanthan gum, and gellan gum. All three
substances are effective as enteric coatings. Alginates are known
to produce uniform films and are applied in industries as diverse
as paper coatings, textile printing, and foods. The alginate film
is particularly effectual as an enteric coating because it normally
is applied as the soluble sodium form, which then is converted to
the insoluble alginic acid form by gastric fluids. Improvements
have been made by combining sodium alginate with sodium calcium
alginate in tablet: containing high drug loading.
[0015] U.S. Pat. No. 5,972,387 discloses a "modified vegetable
protein" to produce microspheres for oral delivery of
pharmaceutical agents. The "vegetable protein" is modified with
benzene sulfonyl chloride and benzoyl chloride. The present
invention makes it possible to produce microspheres with
non-modified vegetable proteins.
[0016] U.S. Pat. Nos. 5,558,880 and 5,684,093 "relate to methods
for preparing products by removal of a solid frozen solvent from a
frozen matrix mixture". A fast dissolving porous solid matrix is
formed, containing small amounts of gelatin, pectin and/or soy
fiber protein as an anti cracking and anti meltback.
[0017] U.S. Pat. No. 5,725,899 "relates to a novel composition of
lipoprotein material having emulsification and gel-forming
properties and more particularly to such a composition prepared
from edible soy flour". This patent discloses the use of a defatted
oil-seed protein material, in contrast to the present invention
which makes use of concentrated or isolated vegetable proteins.
This patent also aims to produce emulsifying and gelling agents and
not a solid lipid matrix.
[0018] Synthetic proteins are used for microencapsulation. For
example, U.S. Pat. No. 5,840,340, uses small proteins, 25 to 2400
daltons or 2 to 20 amino acids, to form "protenoid carriers" with
solubility within selected pH ranges, for oral delivery of
pharmaceutical agents. U.S. Pat. No. 5,904,936 applies synthetic
polyamino acids of specific type in the range of 4,000 daltons. The
present invention utilizes all natural, non-synthetic, vegetable
proteins of 25,000 daltons and higher.
[0019] Co-precipitation is a common method for obtaining
homogeneous, non-crystalline dispersions of an agent in a specific
matter. Preparing such solid particles including microparticles,
microspheres, microcapsules, nanoparticies, pellets or granules,
and the incorporation of ingestible bioactive compounds, involves
the use of synthetic polymers and organic solvents. For example,
U.S. Pat. No. 6,004,973 uses organic solvent, ethanol/acetone, to
produce nanparticles made of synthetic polymers containing
Rafamycin in a non-crystalline amorphous dispersion. U.S. Pat. No.
5,776,495 utilizes a range of organic solvents, such as methylene
chloride, alkanols, chlorinated and oxygenated solvents, in order
to produce solid co-precipitates U.S. Pat. No. 5,491,154 employs
acetone to co-precipitate dihydropyridines with PVP. U.S. Pat. No.
4,880,623 uses acetone;
[0020] methylene chloride to co-precipitate Nifedipine with
polyethylene glygol and hydroxypropylmethylcellulose;
methylcellulose; hydroxypropylcellulose; carboxyvinyl polymers; and
xanthan gum. U.S. Pat. No. 4,758,427 teaches solid molecular
dispersion of 2-aryl-pyrazolo quinolines with PVP, co-precipitated
by the use of methanol. U.S. Pat. No. 4,610,875 makes enhanced
dissolution of dipyridamole in amorphous form in PVP, using organic
solvents and an agent inhibiting the formation of crystals. The
present invention does not make use of organic solvents or
synthetic polymers, although it does enable co-precipitation of
ingestible bioactive compounds in a homogeneous solid matrix made
of vegetable ingredients.
[0021] U.S. Pat. No. 4,404,228 relates to a lipid and protein
containing material in particulate form. Such materials are widely
used in the human and animal foodstuff industries, including calf
milk substitutes and coffee whiteners.
[0022] Bitter tasting agents are generally administered orally in
gelatin capsules or coated tablets, however, other methods for
taste masking of bitter compounds are available, including mixing
the substance with taste modifying agents, granulating or
microencapsulation. U.S. Pat. No. 5,904,937 discloses use of
microcrystaline cellulose for wet granulation of bitter drugs. U.S.
Pat. No. 5,728,403 discloses coating technology for taste masking
orally administered bitter drugs. U.S. Pat. No. 5,382,535 discloses
"chewable drug-delivery compositions" for oral delivery of
unpalatable drugs. The drug is intimately dispersed or dissolved in
a pharmaceutically acceptable lipid that is solid at room
temperature. U.S. Pat. No. 5,785,984 discloses a "protein-lipid
complex which modifies the taste of a food, pharmaceutical or
cosmetic". The "protein-lipid complex" agent, acts with the sensory
taste to block out and reduce the sensation of bitterness. This
patent also teaches the use of organic solvents for incorporating
hydrophobic ingestibles. This patent does not teach the use of a
homogeneous solid matrix where ingestible bioactive compounds are
embedded in a non-crystaline amorphous manner. U.S. Pat. No.
5,972,373 discloses compositions for taste masking and
bioavailability with synthetic stomach soluble polymers and
monoglyceride in a beta-crystal form. The disclosed polymers are:
polyvinylacetal diethylaminoacetate, aminoalkylmethacrylate
copolymer E or a mixture thereof.
SUMMARY OF THE INVENTION
[0023] According to the present invention there is provided a novel
composition of a homogeneous solid matrix of various shapes, that
absorb water, swell and form suspended gel or hydrated particles,
for administration of ingestible, bioactive compounds of at least
low water solubility as hereinbefore defined, and which
compositions improve gastrointestinal dissolution and consequent
oral availability or bio-compatibility, in addition to taste
masking of bitter drugs, nutrients, food additives, vitamins,
minerals or phytomedicines.
[0024] Thus, according to the present invention, there is now
provided a homogeneous solid matrix composition, enabling an
improved dispersion of and bitter taste masking of hydrophobic,
bioactive ingestibles, of at least low water solubility
comprising:
[0025] (a) at least 10% w/w functional vegetable proteins;
[0026] (b) lecithin; and
[0027] (c) at least one ingestible bioactive compound of at least
low water solubility.
[0028] In preferred embodiments of the present invention said
composition comprises at least 20% w/w vegetable proteins and in
especially preferred embodiments of the present invention said
composition comprises at least 40% w/w vegetable proteins.
[0029] The composition of the present invention includes:
[0030] (a) the required amount of ingestable bioactive drugs,
nutrients or phytomedicines to achieve the desired physiological
benefit;
[0031] (b) functional vegetable proteins of the type and in an
amount sufficient to produce and support solid dry matrix; and
[0032] (c) lecithin, in sufficient amounts, to enable solvent free
water solubilization of various hydrophobic bioactives, having
limited solubility in water.
[0033] According to a preferred embodiment of the present
invention, the hydrophobic bioactive and ingestible ingredients are
solubilized and/or co-melted with required amounts of
lecithin-water mixture, until homogeneity is achieved. Homogeneity
is defined as absence of crystalline form of the ingestible
bioactiveWO compound. The homogeneous wet mixture is further mixed
with vegetable proteins to homogeneity, sufficient water is added
to produce a desired consistency appropriate for screen
granulation, sieving and shaping. Said mixture is finally molded
and dried for the desired shape. The final mixing with vegetable
proteins and the drying step may also be accomplished
simultaneously in case such as spray drying.
[0034] According to a preferred embodiment of the present
invention, the solubilization is a solvent free process whereby the
hydrophobic, low or poor water soluble compounds, are solubilized
within the hydrated lecithin aggregates's hydrophobic and
amphiphilic micro-environments.
[0035] In preferred embodiments of the present invention, there is
provided a composition comprising lecithin and said ingestible
bioactive compound in relative amounts of 1:4 to 4:1, preferably
1:2 to 2:1 and most preferred in relative amounts of 1:1.
[0036] In especially preferred embodiments of the present
invention, the ratio of vegetable protein to the combined amounts
of lecithin and ingestible bioactive compound is between 20:1 to
1:4, preferably 10:1 to 1:2 and most preferably the ratio is
between 3:1 and 1:1.
[0037] Various vegetable proteins possessing diversity of
functionality levels which 20 directly influence the matrix
formation, its density and the required amount of protein to obtain
the matrix. More functional vegetable proteins are forming denser
three dimensions network, enabling formation of the matrix at lower
protein concentration or forming much tighter condensed matrix.
[0038] The active compounds are released from the homogeneous solid
matrix in a non-immediate manner. By selecting proteins with
different functionality and at different concentration, the
magnitude of delaying the release is controlled. For purposes of
masking bitter taste, there is a need for short delay of release,
while the granules are passing the oral cavity. A hydrophobic
compound will be released from a very tight matrix in a slow
release manner. The current invention enable control and design of
the release pattern from very short release delay for purpose of
taste masking to prolonged delay of as long as couple of hours for
effective absorption and lowering number of daily
administrations.
[0039] Water soluble, hydrophylic, compound will be very fast
released from the matrix whereas hydrophobic compounds will be
released mostly at the small intestine as the proteins are digested
and the matrix decomposes.
[0040] Thus, in preferred embodiments of the present invention said
matrix provides for the release of said ingestible bioactive
compound over a period of one to three hours in the
gastrointestinal tract.
[0041] In especially preferred embodiments of the present invention
the limiting step for the ingestible bioactive compound release is
the gastrointestinal digestion of said proteins and decomposition
of the matrix.
[0042] The release rate is also influenced from the amount of
lecithin in the matrix. High lecithin concentration enhance the
release profile due to better hydration, swelling and decomposing
of the matrix.
[0043] As defined hereinbefore, the compounds of the present
invention, have at least low water solubility and especially
preferred are ingestible bioactive compounds having a water
soubility of less then 0.5 mg/ml at 25.degree. C. Also compositions
or mixtures, such as plant extracts, comprising such at least low
water soluble fractions.
[0044] In a further preferred embodiment of the present invention,
the drying process may be performed by heat, circulating hot air,
microwave, a combination of heat and vacuum, lyophilization or
sprat dry.
[0045] According to a further preferred embodiment of the present
invention, the ingestible bioactive compound or mixture is
homogeneously embedded in the final matrix in a way that the
original crystals or powder or amorphous solid does not exist, and
the dispersability in the matrix is uniform, so that the matrix is
a monolithic entity, made up of an even homogeneous distribution of
the various ingredients; actives and excipients.
[0046] According to a preferred embodiment of the present
invention, additives, such as fumed silica may be added before or
after drying, in order to advance flowing properties of resulting
powder
[0047] According to a preferred embodiment of the present
invention, additives such as pharmaceutical or food grade
emulsifiers, or gliding agents, may be added before or after drying
in order to advance the free flowing properties of resulting
powder.
[0048] According to a preferred embodiment of the present
invention, the composition may include additives such as colorants,
ant-oxidants, preservatives, etc. known in the art for
nutraceuticals, food or medicines.
[0049] According to a preferred embodiment of the present
invention, the composition may include within the primary
composition or added to the post drying product taste and flavoring
agents known in the art for nutraceuticals, food or medicines, such
as fruits flavors or instant fruits powders for reconstitution as
beverage.
[0050] According to a preferred embodiment of the present
invention, the resulting dry solid matrix may be shaped as
granules, pellets, microspheres, nanoparticles, in addition to
irregular shapes of various sizes and quantities.
[0051] The ratio of the amount of hydrophobic bicactive mixture or
bitter compound, and the lecithin and vegetable proteins, is
adjustable according to the nature of the bioactive compound, and
is adequately designed by those skilled in the art.
[0052] The compositions are well suited for pharmaceutical use,
complementary medicine, nutraceutical and veterinary use, as well
as for oral consumption in the shape of bars, nuggets, tablets,
capsules, coated tablets or capsules, dissolve-in-the-mouth
tablets, effervescent tablets or powder, concentrated powders for
in situ, instant, juice or beverage preparations and confectionery,
etc.
[0053] According to another embodiment of the present invention,
there is provided a method of releasing the ingestible bioactive
from the homogeneous solid matrix.
[0054] Hereinafter, the term "subject" is the human or mammal to
which the homogeneous matrix of the present invention is
administered.
[0055] In another aspect of the present invention, there is
provided a method for preparing the composition of claim 1, wherein
lecithin is swollen in water in a ratio of between about 1:3 to
1:10 more preferable 1:5 to 1:8 and said ingestible bioactive
compound is added until complete solubilization, functional
vegetable proteins is then added with additional water, if
necessary and in quantum sufficient, to produce granulation dough,
whereafter, the wet mass is granulated and dried.
[0056] In another embodiment, the resulting granules are spread
evenly on large pieces of paper in shallow trays and dried in
dedicated regulated heat oven, hot circulating oven, or microwave
oven or under reduced pressure and temperature or fluid bed
drier.
[0057] In preferred embodiments of this method said wet mass is
further diluted with water and spray dried.
[0058] In further preferred embodiments of the method, the wet
granulation is extruded through a screen having openings of 0.5 mm
to 2.5 mm and spheronized in a spheronizer.
[0059] In yet further preferred embodiments, of said method the wet
granulation is prepared and formed into spheres, utilizing a high
shear granulator to form taste-masked spheres.
[0060] Preferably, said method is applied to an ingestible
bioactive compound, which is a bitter tasting compound, and
homogeneous particles and taste masking are obtained.
[0061] Functional vegetable proteins that are suitable for solid
matrix forming have the following physico-chemical
characteristics:
[0062] A) high molecular weight of 50,000 daltons and higher
[0063] B) NSI (nitrogen solubility index) of at least 10% and
preferably higher then 20%, and
[0064] C) non-denaturated or only partially denaturated
proteins.
[0065] Therefore, said vegetable proteins are non or minimally
denturated, having at least 10% NSI with a preferred NSI of 20% and
an even more preferred, higher NSI and MW of not less then 50 kD
with a range of 100,000 to 300,000 MW, non or minimally
hydrolyzed.
[0066] Vegetable proteins may be protein concentrates or protein
isolates of: soy (soybeans), wheat and wheat germ, barley, sesame,
pea, rice, beans, peanuts, potatoes, legume, corn, sunflower,
canola or rapeseed.
[0067] Said functional vegetable proteins should contain at least
65% Protein (N.times.6.25) mfb and.
[0068] The soybean, Glycine max, is a leguminous crop grown in many
parts of the world. Soybeans are of great economic importance as a
source of edible oil, high-protein foods, food ingredients, and
stockfeed, as well as many industrial products. Native to Eastern
Asia, the soybean has been used as the chief source of protein for
millions of people in the Orient, for centuries. It was not until
the late 19th century, however, that soybeans began to attract
serious attention from Western scientists.
[0069] The term "soy proteins" typically refers to processed,
edible dry soybean products other than soybean meals for
animals.
[0070] Soy protein products, for human consumption, fall into three
major groups:
[0071] (a) Soy flours and grits having 52 to 54% Protein
(N.times.6.25) on a moisture-free basis (mfb),
[0072] (b) soy protein concentrates containing at least 65% Protein
(N.times.6.25) mfb, and
[0073] (c) soy protein isolates (or soy proteinates) having a
minimum of 90% Protein (N.times.6.25) mfb.
[0074] The term "% Protein (N.times.6.25)" is often used to express
the percentage of protein in soy protein products in order to
reflect that only part of the nitrogen in soy proteins is of
protein origin. The American Oil Chemists' Society (AOCS)
conversion factor for soybean protein is N.times.5.71; however,
industry practice is to label protein in soybeans as "Protein
(N.times.6.25)."
[0075] Soy flours and grits are the least refined forms of soy
protein products used for human consumption and may vary in fat
content, particle size, and degree of heat treatment. These
products also still contain about five (5) to six (6)% of the
oligosaccharides and most of the original lipoxygenase, as well as
about 4.3% fiber. As a result, they can only be used in small
amounts in various products; otherwise intestinal discomfort. and
poor flavor become the overriding consideration. Soy flours and
grits are considered to be "poorly" functional and typically have
an NSI less than about 60%.
[0076] Soy protein concentrates have much of the indigestible
oligosaccharides removed and therefore the raffinose content is
less than about 0.5% and the stachyose content is less than about
three (3)%. However. depending on the process used, soy protein
concentrates have only poor to adequate flavor, and low to adequate
functionality, having NSI's in the range of 15-70%. Additionally,
the various processes for producing soy protein concentrates result
in a recovery of only about 50% to 95% of the protein. In every
instance, the high cost of such processes limit the use of these
products in many areas such as aquacultural diets, poultry diets,
and so forth. Furthermore, the presence of approximately four (4)%
fiber in soy protein concentrates makes them unsuitable for use in
certain products such as beverages, milk and infant formulas. The
current processes also remove important vitamins, minerals,
isoflavones and phytoestrogens along with the low molecular-weight
sugars, ash, and minor components.
[0077] Soy protein isolates are the most highly refined soy protein
products commercially available, as well as the most expensive. As
with the soy protein concentrates, soy protein isolates are also
low in oligosaccharides, having negligible amounts of raffinose and
less than two 2(%) stachyose in the final product. Additionally,
the isolates have a satisfactory flavor and are highly functional,
having a NSI in the range greater than about 85%. Isolates also
improve dispersibility and reduce dusting. Both gelling and
non-gelling varieties are available in addition to various
viscosity grades. They possess a low fiber content of less than
about 0.3%. As discussed above, it is desirable to remove the fiber
in certain products because fiber is non-functional and dilutes
protein content,
[0078] Soy Protein Concentrates: Concentrates produced by the
aqueous alcohol and heat treatment/water extraction processes have
low nitrogen solubility because of protein denaturation. In
contrast, the products made by aqueous acid leaching or by steam
injection/jet cooking, and subsequent high shear treatment, have
higher solubility if neutralized prior to drying. These
concentrates vary in particle size, water and fat absorption
properties and flavor. They all have improved flavor
characteristics compared to commercially available soy flours. They
provide several functional characteristics in forming fat emulsions
in food systems such as fat-micelle stabilization, water and fat
absorption, viscosity control and textural control. Many of these
characteristics are inter-related in a stable food system. Both pH
and temperature affect the emulsifying properties of soy
concentrates. Soy concentrates contain polysaccharides, which
absorb a significant amount of water Processing conditions can vary
the amount of water that can be absorbed. In fact, these conditions
can be varied to influence how tightly the water is bound by the
protein in the finished food product.
[0079] Since the acid leach and steam injection/jet cooking
processes can result in a product with higher dispersibility, these
concentrates are more desirable for functional properties in
emulsion-type applications. Nevertheless, all soy protein
concentrates, regardless of the process used, do have certain fat
and water-retaining characteristics.
[0080] Soy Protein Isolates: Isolates have specific functional
properties that enable them to modify the physical properties of
food products. Soy isolates are characterized by certain functional
properties i.e., solubility, gelation, emulsification,
dispersibility, viscosity and retort stability.
[0081] Solubility ranges from 5 NSI (Nitrogen Solubility Index) to
95 NSI. The emulsion capacity of soy protein isolates can vary from
10 to about 35 milliliters of oil per 100 milligrams of protein.
Isolates have water absorption values of up to 400% (3).
[0082] Neutralized isolates are usually highly soluble; certain
types will gel under appropriate aqueous conditions. They possess
both emulsifying and emulsion-stabilizing properties, are excellent
binders of fat and water, and are good adhesive agents. They vary
mainly in their dispersibility, gelling and viscosity
characteristics.
[0083] Soy protein isolate aids in forming a gel which acts as a
matrix for holding moisture, fat and solids. This results in
textural properties resembling those of meat proteins, which is
especially important for use in comminuted meats and non-meat items
such as tofu. Its ability to form a gel (from fragile to firm)
depends on concentration, functionality and the presence or absence
of salt. Some isolates are designed not to form a gel even at a 14%
solids content.
[0084] Gelation is the formation of three dimensional,
intermolecular networks through hydrogen, hydrophobic, and
disulfide bonds that entrap water solvent and other ingredients.
This is another aspect of hydration and of textural and rheological
properties of protein; further defined as the formation of three
dimensional intermolecular networks through hydrogen, hydrophobic,
and disulfide bonds that entrap water and other ingredients. This
entrapment contributes to the texture and chewiness of the food
products. The important initial step in heat-induced gelation of
globula proteins, is heating of the protein solution above the
denaturation temperature to expose the functional groups, so that
the intermolecular network can be produced. Additionally, high
numbers of intermolecular disulfide bonds increase water holding
capacity, and, as a result, increases gel hardness.
[0085] Wang and Damodaran (1990) studied the thermal gelation of
globular protein of bovine serum albumin (BSA), soy isolate, 7S,
11S, and phaseolin. They reported that gel hardness or strength of
globular protein gels is fundamentally related to the size and
shape of the polypeptide in the gel network, rather than to their
chemical nature such as amino acid composition and distribution.
Globular protein with MW<23 kD canrot form a self-supporting gel
network in any reasonable concentration.
[0086] The homogeneous solid matrix is formed during the drying
process, whereby the vegetable proteins form the solid matrix by
constituting molecular connections between the proteins in a
similar or equal process to denaturation.
[0087] Example of commercially available isolated soy proteins are
the Supro.sup.R types 810, 760 and EX 34K and others from Protein
Technologies International, St Louis, Mo., USA and Soyarich R from
Central Soy Protein, USA. Examples of concentrated soy proteins are
Solcon HV, and other brands from ADM and Cargill both of USA.
[0088] Lecithin is a mixture of phospholipids from vegetable or
animal origin; e.g. these may be obtained from soybean, wheat, corn
or eggs. More preferably, the lecithin concentration is equal to
the amount of the bioactive compound- and is present in an amount
of not less then 1 percent and up to 50 percent.
[0089] Phospholipids are the main building blocks of all cell
membranes--in human beings, animals, plants and micro-organisms. As
such they have two important physico-chemical properties which are
being put to increasing use in pharmaceutical technolog.
[0090] 1) amphiphilic molecules which contain excellent emulsifying
properties; and
[0091] 2) under certain conditions, especially with respect to
concentration and temperature, phospholipids spontaneously form
membrane structures (lamella, liposomal, micellar).
[0092] Products include vegetable (mainly soybean) and animal
phospholipid mixtures (egg) with greatly differing compositions and
properties, and also hydrogenated products that are especially
useful for their resistance to oxidation.
[0093] Lecithin may also be obtained from various vegetable
origins, for example: oatmeal, wheat germ or peanuts.
[0094] Historically, the term lecithin originated from the Greek
word `lekithos`, which was used for the phosphorus containing
lipids from egg yolk. Later, this term was only used for one
defined phospholipid, phosphatidylcholine. This is still the common
usage in scientific literature, where lecithin stands for
1,2-diacyl-sn-glycero-3-phosphatidy- lcholine. On the contrary, the
industrial and commercial understanding of the term lecithin is
used for the complex mixture of neutral lipids (predominantly
triglycerides, a small amount of free fatty acids and sterols),
polar lipids (phospho- and glycolipids) and carbohydrates.
[0095] The technological and physiological properties of lecithins
are primarily determined by the kind and portion of the various
polar lipids, especially the phospholipids. It is evident that
these compositions may vary considerably, depending on the origin
of the soybeans. Climate, soil conditions, harvest time and, last
but not least, processing conditions, greatly influence the
composition and properties of lecithin too.
[0096] The molecular structure of phospholipids is derived from the
structure of triglycerides by replacement of one fatty acid by a
phosphoric acid ester Depending upon the molecule (predominantly an
aminoalcohol) linked to the phosphate group, the various
phospholipids are nominated.
[0097] Choline=Phosphatdylcholine (PC)
[0098] Ethanolamine=Phosphatdylethanolamine (PE)
[0099] Inositol=Phosphatdylinositol (PI)
[0100] Hydrogen=Phosphatidic acid (PA)
[0101] By virtue of their ampiphilic molecular structure with the
hydrophilic phosphoric acid ester and the lipophilic fatty acids,
phospholipids in oil and water systems always concentrate at the
interphase. This typical emulsifying property is the reason for
their successful use in a variety of foodstuffs, dietetic, cosmetic
and pharmaceutical preparations.
[0102] Lecithin is described as a generally permitted food additive
in Europe under E 322 and in the US in the Code of Federal
Regulations (GRAS status) referring to the Food Chemical Codex.
Both descriptions differ to a minor extent in their specification
details, but not in principle.
[0103] Example of commercially available lecithins are,
Phospholipons from Natterman, Epikurons from Lucas Meyer, Pure
lecithin powder de-oiled from Stern, all from Germany, and
others.
[0104] Insoluble or low water soluble ingestible bioactive
compounds may be any chemical, drug, molecule, substance, extract,
herbal, vitamin, synthetic or semisynthetic or biotechnology
product, hormone, peptide, protein, or mixture comprising such
ingredient, that has a desired and or required bio-activity, and
its biological activity is reduced, limited or is practically
erratic, due to low or poor water solubility and low dissolution or
wetting and insufficient concentratiori at the absorption or
administration or biological target site. Most preferably, the
bioactive compound is present in an amount of from about 0.1
percent to 50 percent weight of the final product, more preferably
in the range of 1.0 to 30%, and is practically dictated by its
bio-active dose relevant for the specific use, purpose, expected
results and physico-chemical formulation properties.
[0105] Hydrophobic, water insoluble or lipophilic agents and low or
poor water solubility compounds, as used herein, refer to
ingestable agents, having a water solubility of <1 mg/ml and,
more preferably, <0.5 mg/ml in water, at room temperature
(25.degree. C.).
[0106] Most phytomedicinal extracts are mixtures or assemblies of
many types of molecules, usually comprising a fraction that is
water insoluble or has low water solubility. With regard to proper
and effective herbal extracts, solvents such as alcohol or
propylene glycols or glycerin, and hexane or cyclohexane, are
frequently and abundantly employed in phytomedicinal extract
production. Another method for herbal extraction of water insoluble
precious bloactive compound, is lipid extraction, hot or cold
compression and super fluid extraction. All these methods are
employed in order to obtain herbal fraction with poor water
solubility. The non-aqueous extracts are important constituents of
the majority of herbal bioactive products. A part from few
exceptions, most top marketed herbal extracts contain some
hydrophobic active molecules of poor water solubility. Many of the
herbal extracts, especially those extracted from lower underground
root parts of the herbs, are also typically bitter.
[0107] Examples of herbal, poorly water-soluble or mixtures
comprising hydrophobic phytomedicines are: Gingko biloba, Hypericum
perforatum, Echinacea purpurea or angustifolia, Ginseng, Piper
methisticum (Kava), Tanacetum parthenium, Allium sativum
(Garlic).
[0108] Examples of lipophilic vitamins include. Carotenoids and
lycopene, Tocopherols (Vit E), Riboflavin (Vit B2), Retinol (Vit
A), Calciferol (Vit D2), Cholecalciferol (Vit D3), Menadion (Vit
K), Folic acid and ubiquinones.
[0109] Absorption of lipophilic vitamins is much more limited in
comparison to water-soluble vitamins. Fortunately, only very minute
quantities of vitamins are required for normal living, however,.
elderly people who need them more, less effectively assimilate
vitamins and essential nutrients. Another population in great need
of a sufficient supply of vitamins is the cancer chemotherapy and
radiation patients who suffer from mal-absorption syndrome and
would benefit from an improved delivery of vitamins and essential
nutrients.
[0110] A bitter taste compound is any drug, nutrient, vitamin or
food supplement or phytomedicine of herbal origin compound, which
exerts a rejecting unpleasant bitter bad taste. Bitter taste is
associated to hydrophobic compounds or the like, having hydrophobic
moiety. Most bitter compounds are lipophilic (fat loving). Examples
of bitter taste forming substances that exhibit unpleasant oral
taste are: Aloe barbadensis extracts, barbeloins. Artemisia species
and various absinthes, gingko biloba extracts, gentian, artichoke
leaves centaury, aloe species, barberry, dandelion, wormwood or
mugwort (or other Artemesias) and blessed thistle. Some of the
common bitter herbs are dandelion (Taraxacum officinale) and
chicory (Cichorium intybus), whose roots have been used in coffee
drinks. Beer is made from the bitter hops (Humulus lupulus). Other
bitters include: alfalfa, endive, arugula, spinach. unripe apples.
citrus peel, scallion, rye, turnip, white pepper, and celery. The
bitterest herb in the medicinal herb garden is wormwood. Some less
bitter common nutrients are: hesperidine, limonene, and
anthocyanines derived from fruits or vegetables.
[0111] Production methods
[0112] A) Hydrating and swelling the lecithin in water.
[0113] B) Solubilizing the bioactive components in (A) until
complete solubilization and visual homogeneity is obtained.
[0114] C) Mixing the vegetable proteins with (B) to obtain an
appropriate required consistency, adding water if required.
[0115] D) Molding, shaping, sieving or granulating.
[0116] E) Drying; evaporating the excess water by heat or heat and
vacuum combination, by spray dry, or fluidized bed, to obtain a dry
homogeneous matrix.
[0117] Lecithin is hydrated and swelled in a minimal amount of
water (a preferred ratio of lecithin to water is 1:3 to 1:10. The
preferred amounts of lecithin, bioactive compounds and hydrophobic
ingestibles, are ratios of 2:1 to 1:2 and more favourably, 1:1 on a
dry weight basis. The ratio amount of obtained solubilized
bioactive compound in lecithin to vegetable protein is 10:1 to 1:2,
and more preferably 3:1 to 1:1 on a dry weight basis.
[0118] Applied heat and water evaporation converts the vegetable
proteins to a state that favours intermolecular interactions.
[0119] The composition may be used for oral delivery, taste
masking, further enterocoating or coating or immediate release in
the mouth. It can also be incorporated in bars, nuggets, solid
foods and powders for in situ beverage reconstitutions and the
like. The composition may be mixed with flavoring agents such as
fruits flavors, natural or artificial, to denote appealing product
to the user.
[0120] Various delivery systems and dosage forms are possible,
including oral capsule tablets or dry suspensions for dilution
before use. Instant beverage, instant soup and also incorporation
into solid bars or nuggets.
[0121] It should be noted that the above descriptions are intended
only to serve as examples, and that many other embodiments are
possible, within the spirit and the scope of the present
invention.
[0122] Examples of lipophilic substances that exhibit poor oral
bioavailability include: lipophilic drugs, vitamins, NSDA steroids,
anti-fungal agents, antibacterial agents, antiviral agents,
anticancer agents, anti-hypertensive agents, anti-oxidants,
anti-depressants and phyto-chemicals combining herbal extracts.
[0123] Low, or poor water soluble compounds, include: fatty sterols
of saw palmetto, carotenes and lycopenes, non aqueous soluble
fractions of echinacea, ginseng and gingko biloba, in addition to
many minerals, such as iron and complex vitamin coenzymes, such as
ubiquinones.
[0124] After mixing with body fluids, the homogeneous solid matrix
composition absorbs water and swells. Following hydration and
swelling, the release of the bioactive ingestable takes place in
the gastrointestine. The unique matrix and its ingredients as well
as the homogeneous dispersion of the bioactive ingestible within
the matrix, promotes the solubilization, miclization and
emulsification of the insoluble bioactive ingestible, thus
enhancing dissolution and bio-availability.
[0125] While the invention will now be described in connection with
certain preferred embodiments in the following examples so that
aspects thereof may be more fully understood and appreciated, it is
not intended to limit the invention to these particular
embodiments. On the contrary, it is intended to cover all
alternatives, modifications and equivalents as may be included
within the scope of the invention as defined by the appended
claims. Thus, the following examples which include preferred
embodiments will serve to illustrate the practice of this
invention, it being understood that the particulars shown are by
way of example and for purposes of illustrative discussion of
preferred embodiments of the present invention only and are
presented in the cause of providing what is believed to be the most
useful and readily understood description of formulation procedures
as well as of the principles and conceptual aspects of the
invention.
EXAMPLES
Example 1. Aloe Vera S.D and concentrated soy proteins.
[0126] Barbeloin and its derivatives are some of the bitterest
extracts. Aloe Vera S.D (frutarom meer) is a very bitter powder--a
non diluted, concentrated extract characterised by a large fraction
of many water insoluble ingredients.
[0127] A) One gram of soybean lecithin, (Pure lecithin powder,
de-oiled, Stern, Hamburg, Germany) was mixed and swelled in 5 ml of
water at room temperature.
[0128] B) Half a gram of Aloe Vera S.D. dry extract (Frutarom Meer)
was added and well mixed to obtain a homogeneous fluid paste.
[0129] C) Two grams of functional soy proteins concentrate (Solcon
HV, Solbar, Ashdod, Israel), were added and mixed well with QS of
water to produce a homogeneous mass in the appropriate consistency
for passing through a granulating net.
[0130] D) An obtained wet mass was mesh granulated and dried in
ovens or microwave ovens.
[0131] Three aliquots, equivalent to 10 mg of Aloe Veras S. D.
powder in 10 ml of water, were prepared and their bitterness
evaluated:
[0132] 1) Non-treated, Aloe Vera S. D. powder in water was so
bitter that it was almost impossible to keep in the mouth,
requiring many mouthwashes afterwards, and still leaving a
long-lasting bitter taste.
[0133] 2) Aloe Vera S. D. in water with added lecithin and solcon
HV was equally as bitter.
[0134] 3) Aloe Vera S. D. granules, prepared according to the
present example, equivalent to 10 mg Aloe Vera S. D. suspended in
10 ml water was devoid of the original bitter unpleasant taste, and
contained no after taste at all.
Example 2. Aloe Vera S.D and isolated soy proteins.
[0135] A) 0.5 gram of soybean lecithin, (Phospholipon 90,
Natterman, Germany) was mixed and swelled in 4 ml of water at room
temperature.
[0136] B) 0.5 gram of Aloe Vera S. D. dry extract (Frutarom Meer)
was added and well mixed to obtain a homogeneous fluid paste.
[0137] C) 1.0 gram of functional soy proteins isolate (Supro EX34K,
Protein Technologies International, USA), and 0.5 gram
microcrystaline cellulose (Avicel HP101, FMC, USA) were added and
mixed well with QS of water to produce a homogeneous mass in the
appropriate consistency for passing through a granulating net.
[0138] D) An obtained wet mass was mesh granulated and dried in
ovens or microwave ovens.
[0139] Aloe Vera S. D. soy protein granules, prepared according to
the present example, suspended in water was devoid of the original
bitter unpleasant taste and after taste.
Example 3, Artemisia abrotantum.
[0140] Artemisin and derivatives are also extremely bitter.
Artemisia abrotantum (in house hot maceration, commorly called
"Shiba") is a very bitter concentrated extract of Artemisia
abrotantum, characterised by large fraction of many water insoluble
ingredients.
[0141] A) One gram of soybean lecithin, de-oiled, powdered
(Epikuron 100, Lucas Meyer, Germany) was mixed and swelled in 2 ml
of Artemisia abrotantum extract.
[0142] B) Two grams of functional soy proteins (Solcon HV, Solbar
Ashdod, Israel), was added and well mixed with QS of water to
produce a homogeneous mass in an appropriate consistency for
passing through a granulating net.
[0143] C) Obtained wet mass was granulated and dried in an oven or
microwave oven.
[0144] Three aliquots equivalent to one ml of Artemisia abrotantum
extract in 10 ml of water were prepared and their bitterness
evaluated:
[0145] 1) Artemisia abrotantum extract in water was so bitter that
it was almost impossible to hold in the mouth and required many
mouthwashes afterwards and left a long-lasting bitter taste.
[0146] 2) Artemisia abrotantum extract in water with lecithin and
solcon HV and slight vortex was equally as bitter.
[0147] 3) Artemisia abrotantum granules, prepared according to the
present example, which were devoid of the original bitter taste,
contained no after taste at all.
Example 4. Artemisia abrotantum.
[0148] a) 1.0 gram of soybean lecithin, de-oiled, powdered (Pure
lecithin powder, de-oiled. Stern, Hamburg, Germany) was mixed and
swelled in 10 ml of Artemisia abrotantum extract.
[0149] b) 2.0 gram of concentrated soy proteins (Solcon HV, Solbar
Ashdod, Israel), and 0.5 gram of soy proteins isolate (Supro EX34K,
Protein Technologies International, USA), and 0.5 gram
microcrystaline cellulose (Avicel HP101, FMC, USA) were added and
well mixed to produce a homogeneous mass in an appropriate
consistency for passing through a granulating net.
[0150] c) Obtained wet mass was granulated and dried in an oven or
microwave oven. Artemisia abrotantum granules, prepared according
to the present example, were devoid of the original bitter taste
and after taste.
[0151] Resulting granules of Artemisia abrotantum are useful
against digestive parasites and are appropriate for use in
gastrointestinal disorders that are traditionally treated with
Artemisia abrotantum.
Example 5 Gingko biloba and concentrated soy proteins.
[0152] Gingko biloba pure concentrated extracts are typical
bitters. Gingko biloba (Frutarom Meer, Haifa, Israel) is
standardized concentrated 24% gingkolides bitter powder,
characterised by the large fraction of many water insoluble
ingredients.
[0153] a) 0.1 of soybean lecithin was mixed and swelled in 1 ml of
water at room temperature.
[0154] b) 0.5 a gram of Gingko biloba was added and well mixed to
obtain a homogeneous liquid paste.
[0155] c) Five grams of functional soy proteins (Solcon HV, Solbar
Ashdod, Israel) were added and well mixed with QS of water to
produce a homogeneous mass in an appropriate consistency ready for
passing through a granulating net.
[0156] d) The Obtained wet mass was granulated and dried in an oven
or microwave oven.
[0157] Three aliquots of equivalent to ten mg of Gingko biloba
powder in 10 ml water were prepared and their bitterness
evaluated:
[0158] 1) Gingko biloba powder in water was typically bitter and
very unpleasant in the mouth.
[0159] 2) Gingko biloba in water, mixed with lecithin and solcon
HV, was equally as bitter and
[0160] 3) Gingko biloba granules, prepared according to the present
example, was devoid of the original bitter taste and contained no
after taste at all for couple of hours.
Example 6, Gingko biloba and isolated soy proteins.
[0161] a) 1 gram of soybean lecithin was mixed and swelled in 8 ml
of water at room temperature.
[0162] b) 1 gram of Gingko biloba, standardized 24% Gingcolides,
(Frutarom Meer, Haifa, Israel) was added and well mixed to obtain a
homogeneous liquid paste.
[0163] c) 2.5 grams of functional isolated soy proteins (Supro 810,
Protein Technology International, St Louis, Mo., USA) were added
and well mixed to produce a homogeneous mass or dough, in an
appropriate consistency ready for passing through a granulating
net.
[0164] d) The Obtained wet mass was granulated and dried in a
microwave oven. Three aliquots of equivalent to ten mg of Gingko
biloba powder in 10 ml water were prepared and their bitterness
evaluated:
[0165] 1) Gingko biloba powder in water was typically bitter and
very unpleasant in the mouth.
[0166] 2) Gingko biloba in water, mixed with lecithin and solcon
HV, was equally as bitter and
[0167] 3) Gingko biloba granules, prepared according to the present
example, was devoid of the original bitter taste and contained no
after taste at all for couple of hours.
Example 7, Gingko biloba instant powder.
[0168] The obtained granules of example 6 were ground to
homogeneity with instant fruit flavored powders. The resulting
powder is reconstituted with tap water to produce in-situ a
tasteful beverage. Desired dose of Gingko Biloba extract is
delivered in a glass of beverage preferred by those who experience
difficulties upon swallowing tablets or capsule.
Example 8. Ginqko biloba bars.
[0169] Resulting granules of example 6 were mixed with granola and
honey or isomaltose premix to produce regular or low calorie and
diabetic bar delivering doses of Gingko biloba extracts without the
unwanted bitter taste associated with Gingko biloba extracts.
Example 9, Saw palmetto.
[0170] Saw palmetto 90% fatty sterol and lipid (Frutarom Meer,
haifa, Israel) is a water insoluble, oily substance that does not
mix with water.
[0171] a) 0.5 grams of soybean lecithin was mixed and swelled in 3
ml of water at room temperature.
[0172] b) 0.5 grams of Saw palmetto fatty sterols (90%) was added
and well mixed to obtain a homogeneous liquid paste.
[0173] c) 1.0 gram of concentrated soy protein (Solcon HV, Solbar,
Ashdod, Israel) was added and well mixed with QS of water to
produce homogeneous mass in an appropriate consistency ready for
passing through a granulating net.
[0174] d) The obtained wet mass was granulated and dried in an oven
or microwave oven.
[0175] Saw palmetto fatty sterols (90%) were mixed in water with
lecithin or with functional soybean protein, or both, to yield a
non homogogenios dispersion which, after the high energy
emulsification step, could be further homogenized to yeald emulsion
or related dispersion systems. Saw palmetto, dry powder 25% fatty
sterols, (Frutarom Meer) obtained by spray drying Saw palmetto
fatty sterols (90%) with filler excipients such as dextrins, were
mixed in water and released a separation of the lipids which
floated on top of the water within a short period of time.
[0176] Obtained granules, whilst dispersed in water, did not
release Saw palmetto fatty sterols (90%) and no lipid was floating
after many weeks.
Example 10, Ubiguinone. Coenzyme Q10 and concentrated soy
proteins.
[0177] Ubiquinone is a very hydrophobic water insoluble and lipid
soluble solid substance. Ubiquinone was obtained as a solid
crystals powder.
[0178] a) 0.5 grams of soybean lecithin was mixed and swelled in 3
ml of water at room temperature.
[0179] b) 0.5 grams of Ubiquinone was added and mixed well, to
obtain a homogeneous liquid paste.
[0180] c) 1.0 gram of concentrated soy proteins (Solcon HV, Solbar,
Ashdod, Israel) was added and mixed well with QS of water to
produce a homogeneous mass in consistency ready for passing through
a granulating net.
[0181] d) An obtained wet mass was granulated and dried in an oven
or microwave oven.
[0182] Ubiquinone was mixed in water with lecithin, functional
soybean protein or both, with very limited yield of
non-homogogenios dispersion. A large part of the Ubiquinone was
still in crystal particles.
[0183] The Ubiquinone was dispersed uniformly in the homogeneous
amorphous matrix. The granules dispersed well in water and did not
release the Ubiquinone, and no lipid was floating after many
weeks.
Example 11, Ubiguinone, Coenzyme Q10 and isolated soy proteins.
[0184] a) 0.5 grams of soybean lecithin was mixed and swelled in 3
ml of water at room temperature.
[0185] b) 0.5 grams of Ubiquinone was added and mixed well, to
obtain a homogeneous liquid paste.
[0186] c) 1.0 gram of isolated soy proteins (Supro 810, Protein
Technologies International, USA) was added and mixed well with QS
of water to produce a homogeneous mass in consistency ready for
passing through a granulating net.
[0187] d) An obtained wet mass was granulated and dried in a
microwave oven.
[0188] The Ubiquinone was dispersed uniformly in the homogeneous
amorphous, matrix.
Example 12. Ubiguinone, Coenzyme Q10 and isolated soy proteins.
[0189] a) 0.5 grams of soybean lecithin was mixed and swelled in 3
ml of water at room temperature.
[0190] b) 0.5 grams of Ubiquinone was added and mixed well, to
obtain a homogeneous liquid paste.
[0191] c) 10 gram of isolated soy proteins (Supro 810, Protein
Technologies International, USA) and 1.0 gram of microcrystaline
cellulose (Avicel PH101, FMC, USA) were added and mixed well with
QS of water to produce a homogeneous mass in consistency ready for
passing through a granulating net.
[0192] d) An obtained wet mass was granulated and dried in a
microwave oven. The Ubiquinone was dispersed uniformly in the
homogeneous amorphous matrix.
Example 13, Ubiguinone, Coenzyme 010 and isolated soy proteins.
[0193] a) 0.5 grams of soybean lecithin was mixed and swelled in 3
ml of water at room temperature.
[0194] b) 0.5 grams of Ubiquinone was added and mixed well, to
obtain a homogeneous liquid paste.
[0195] c) 1.0 gram of isolated soy proteins (Supro 810, Protein
Technologies International, USA) and 0.5 gram of microcrystaline
cellulose (Avicel PH101, FMC, USA) and 0.5 gram of fumed silica
(Tixosil, Rhone-Poulenc, France) were added and mixed well with QS
of water to produce a homogeneous mass in consistency ready for
passing through a granulating net.
[0196] d) An obtained wet mass was granulated and dried in a
microwave oven. The Ubiquinone was dispersed uniformly in the
homogeneous amorphous matrix.
Example 14, Vitamin E.
[0197] Vitamin E, Tocopherol acetate is a water-insoluble, oily
substance that does not dissolve in water.
[0198] a) 0.5 grams of soybean lecithin was mixed and swelled in 5
ml of water at room temperature.
[0199] b) 0.5 grams of Vit E was added and mixed well to obtain a
homogeneous liquid paste.
[0200] c) 1.0 gram of functional soy protein (Supro 810, Protein
Technologies International, USA), was added and equally mixed with
QS of water to produce a homogeneous mass in a desired consistency
ready for passing through a granulating net.
[0201] d) An obtained wet mass was granulated and dried in an oven
or microwave oven.
[0202] Vit E was mixed in water with lecithin, functional soybean
protein or both, to yield a non-homogogenios dispersion that after
the high energy emulsification step, could be further homogenized
to yeald an emulsion or related dispersion system. Homogeneous
dispersion of Vit E was obtained in the granule matrix. Obtained
granules dispersed in water did not release the Vit E and,
consequently, no Vit E was floating after many weeks.
Example 15, Lycopene.
[0203] Lycopene is a water-insoluble, oily substance that does not
mix dissolve in water.
[0204] A) 0.5 grams of soybean lecithin was mixed and swelled in 1
ml of water at room temperature.
[0205] B) 0.5 grams of 10% Lycopene in tomato oleoresins,
(Lycomato, (Lycored, Beer-Sheva, Israel), was added and equally
mixed to obtain a, homogeneous liquid paste.
[0206] C) One gram of functional soy proteins (Solcon HV) solbar
hatsor, was added and mixed with QS of water to produce a
homogeneous mass in a desired consistency for passing through a
granulating net.
[0207] D)An obtained wet mass was granulated and dried in an oven
or microwave oven.
[0208] Vit E was mixed in water with lecithin; functional soybean
protein or both to yield non homogogenios dispersion that, after
the high energy emulsification step, could be further homogenized
to yeald emulsion or related dispersion systems. Homogeneous
dispersion of Vit E was obtained in the granule matrix. Obtained
granules dispersed in water did not release Vit E, and no Vit E was
floating after many weeks.
Example 16, Ubiguinone, Coenzyme Q10 and isolated soy proteins.
[0209] 0.5 grams of soybean lecithin was mixed and swelled in 3 ml
of water at room temperature.
[0210] 0.5 grams of Ubiquinone was added and mixed well, to obtain
a homogeneous liquid paste.
[0211] 4.0 gram of isolated soy proteins (Supro 810, Protein
Technologies International, USA) was added and mixed well with QS
of water to produce a homogeneous mass in consistency ready for
passing through a granulating net An obtained wet mass was
granulated and dried in a microwave oven.
[0212] The Ubiquinone was found to be uniformly dispersed in the
homogeneous amorphous matrix.
Example 17. Aloe Vera S. D. and isolated soy proteins.
[0213] 0.5 gram of soybean lecithin, (Phospholipon 90, Natterman,
Germany) was mixed and swelled in 4 ml of water at room
temperature.
[0214] 0.5 gram of Aloe Vera S. D. dry extract (Frutarom Meer) was
added and well mixed to obtain a homogeneous fluid paste.
[0215] 5.0 gram of functional soy proteins isolate (Supro EX34K,
Protein Technologies International, USA, were added and mixed well
with QS of water to produce a homogeneous mass in the appropriate
consistency for passing through a granulating net.
[0216] An obtained wet mass was mesh granulated and dried in ovens
or microwave ovens.
[0217] Aloe Vera S. D. soy protein granules, suspended in water was
devoid of the original bitter unpleasant taste and after taste.
Example 18, Gingko biloba and isolated soy proteins.
[0218] 1 gram of soybean lecithin was mixed and swelled in 10 ml of
water at room temperature.
[0219] 1 gram of Gingko biloba, standardized 24% Gingcolides,
(Flacksman, Swiss) was added and well mixed to obtain a homogeneous
liquid paste. 10 grams of functional isolated soy proteins (Supro
810, Protein Technology International, St Louis, Mo., USA) were
added and well mixed to produce a homogeneous mass or dough, in an
appropriate consistency ready for passing through a granulating
net.
[0220] The Obtained wet mass was granulated and dried in a
microwave oven.
[0221] Three aliquots of equivalent to a dose of fifty mg of Gingko
biloba powder in 100 ml tomato juice were prepared and their
bitterness evaluated: Gingko biloba powder in tomato juice was
typically bitter and very unpleasant in the mouth.
[0222] Gingko biloba mixed with lecithin and solcon HV, was equally
as bitter.
[0223] Gingko biloba granules, prepared according to the invention,
was devoid of the original bitter taste and contained no after
taste at all for several hours.
Example 19, Fish oil and isolated soy proteins.
[0224] 0.5 gram of soybean lecithin was mixed and swelled in 4 ml
of water at room temperature.
[0225] 2.5 gram of Fish oil, (Denofa, Norway) was added and well
mixed to obtain a homogeneous liquid paste.
[0226] 5.5 grams of functional isolated soy proteins (Supro 810,
Protein Technology International, St Louis, Mo., USA) and 1.5 grams
fumed silica (Aerosil 200) were added and wall mixed to produce a
homogeneous mass or dough, in an appropriate consistency ready for
passing through a granulating net.
[0227] The Obtained wet mass was granulated and dried.
[0228] Unpleasant typical fish oil mouth feel taste and smell were
masked.
Example 20, Ferrous sulfate and isolated soy proteins.
[0229] 1 gram of soybean lecithin was mixed and swelled in 8-10 ml
of water at room temperature.
[0230] 1 gram of Ferrous sulfate was added and well mixed. grams of
functional isolated soy proteins (Supro 810, Protein Technology
International, St Louis, Mo., USA) were added and well mixed to
produce a homogeneous mass or dough, in an appropriate consistency
ready for passing through a granulating net.
[0231] The Obtained wet mass was granulated and dried.
[0232] Three aliquots of equivalent to a dose of 10 mg of Ferrous
sulfate in 100 ml tomato juice were prepared and their bitterness
evaluated:
[0233] Ferrous sulfate was typically bitter and very unpleasant in
the mouth. Ferrous sulfate mixed with lecithin and solcon HV, was
equally as bitter while Ferrous sulfate granules, prepared
according to the invention, was devoid of the original bitter taste
and contained no after taste at all for several hours.
Example 21. Ferrous chelate and isolated soy proteins.
[0234] 1 gram of soybean lecithin was mixed and swelled in 8-10 ml
of water at room temperature.
[0235] 1 gram of Ferrous chelate (ferrous glycinate or ferrous
protein hydrolysate) was added and well mixed.
[0236] 20 grams of functional isolated soy proteins (Supro 810,
Protein Technology International, St Louis, Mo., USA) were added
and well mixed to produce a homogeneous mass or dough, in an
appropriate consistency ready for passing through a granulating
net.
[0237] The Obtained wet mass was granulated and dried.
[0238] Three aliquots of equivalent to a dose of 10 mg of Ferrous
sulfate in 100 ml tomato juice were prepared and their bitterness
evaluated:
[0239] Ferrous sulfate was typically bitter and very unpleasant in
the mouth.
[0240] Ferrous sulfate mixed with lecithin and solcon HV, was
equally as bitter while Ferrous chelate grarules, prepared
according to the invention, was devoid of the original bitter taste
and contained no after taste at all for several hours.
Example 22, Melatonin and isolated soy proteins.
[0241] 1 gram of soybean lecithin was mixed and swelled in 10 ml of
water at room temperature.
[0242] 1 gram of Melatonin was added and well mixed to obtain a
homogeneous liquid paste.
[0243] 10 grams of functional isolated soy proteins (Supro 810,
Protein Technology International, St Louis, Mo., USA) were added
and well mixed to produce a homogeneous mass or dough, in an
appropriate consistency ready for passing through a granulating
net.
[0244] The Obtained wet mass was granulated and dried.
[0245] Melatonine typical unpleasant taste was well masked in the
granules.
Example 23, Isoflavones and isolated soy proteins.
[0246] 1 gram of soybean lecithin was mixed and swelled in 10 ml of
water at room temperature.
[0247] 1 gram of Isoflavones (Solgen 10 or Solgen 40. Solbar plant
extracts, Ashdod, Israel) was added and well mixed to obtain a
homogeneous liquid paste.
[0248] 8 grams of functional Isolated soy proteins (Supro 810,
Protein Technology International, St Louis, Mo., USA) were added
and well mixed to produce a homogeneous mass or dough, in an
appropriate consistency ready for passing through a granulating
net.
[0249] The Obtained wet mass was granulated and dried.
[0250] Three aliquots of samples equivalent to 30 mg of Isoflavones
in 100 ml yogurt or tomato juice were prepared and their bitterness
evaluated:
[0251] Solgen-10 powder was typically bitter aftertaste and
unpleasant in the mouth.
[0252] Solgen-10 mixed with lecithin and solcon HV, was equally as
bitter while Isoflavones granules, prepared according to the
invention, was devoid of the original bitter taste and contained no
after taste at all for several weeks where kept under
refrigeration.
Example 24, Isoflavones and isolated soV proteins.
[0253] 1 gram of soybean lecithin was mixed and swelled in 10 ml of
water at room temperature.
[0254] 6 gram of Isoflavones (Nutragen-3, Solbar plant extracts,
Ashdodo, isarel) was added and well mixed to obtain a homogeneous
liquid paste.
[0255] 3 grams of functional isolated soy proteins (Supro 810,
Protein Technology International, St Louis, Mo., USA) were added
and well mixed to produce a homogeneous mass or dough, in an
appropriate consistency ready for passing through a granulating
net.
[0256] The Obtained wet mass was granulated and dried.
Example 25. Isoflavones and isolated soy proteins.
[0257] 17 gram of soybean lecithin was mixed and swelled in 10 ml
of water at room temperature.
[0258] 6 gram of Isoflavones (Soylife25, Soylife, Netherland) was
added and well mixed to obtain a homogeneous liquid paste.
[0259] 3 grams of functional isolated soy proteins (Supro 810,
Protein Technology International, St Louis, Mo., USA) were added
and well mixed to produce a homogeneous mass or dough, in an
appropriate consistency ready for passing through a granulating
net.
[0260] The Obtained wet mass was granulated and dried in a
microwave oven.
[0261] It will be evident to those skilled in the art that the
invention is not limited to the details of the foregoing
illustrative examples and that the present invention may be
embodied in other specific forms without departing from the
essential attributes thereof, and it is therefore desired that the
present embodiments and examples be considered in all respects as
illustrative and not restrictive, reference being made to the
appended claims, rather than to the foregoing description, and all
changes which come within the meaning and range of equivalency of
the claims are therefore intended to be embraced therein.
* * * * *