U.S. patent application number 10/057660 was filed with the patent office on 2002-08-08 for primary composition comprising a lipophilic bioactive compound.
Invention is credited to Baur, Markus, Bortlik, Karlheinz, Duruz, Eliane, Lambelet, Pierre, Pfeifer, Andrea M.A., Richelle, Myriam, Saucy, Francoise.
Application Number | 20020107292 10/057660 |
Document ID | / |
Family ID | 8168868 |
Filed Date | 2002-08-08 |
United States Patent
Application |
20020107292 |
Kind Code |
A1 |
Bortlik, Karlheinz ; et
al. |
August 8, 2002 |
Primary composition comprising a lipophilic bioactive compound
Abstract
A primary composition that includes at least one lipophilic
bioactive compound and a whey protein in an amount effective to
increase the bioavailability of the lipophilic bioactive compound,
and methods of forming the same. Also, an oral composition that
contains the primary composition in a foodstuff, in a food
supplement, in a cosmetic preparation or in a pharmaceutical
preparation, and methods of forming the same.
Inventors: |
Bortlik, Karlheinz;
(Savigny, CH) ; Saucy, Francoise; (Blonay, CH)
; Duruz, Eliane; (Epalinges, CH) ; Richelle,
Myriam; (Savigny, CH) ; Lambelet, Pierre;
(Saint-Legier, CH) ; Baur, Markus; (Aran, CH)
; Pfeifer, Andrea M.A.; (Saint- Legier, CH) |
Correspondence
Address: |
WINSTON & STRAWN
PATENT DEPARTMENT
1400 L STREET, N.W.
WASHINGTON
DC
20005-3502
US
|
Family ID: |
8168868 |
Appl. No.: |
10/057660 |
Filed: |
January 25, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10057660 |
Jan 25, 2002 |
|
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PCT/EP01/06145 |
May 29, 2001 |
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Current U.S.
Class: |
514/773 |
Current CPC
Class: |
A23L 33/105 20160801;
A23V 2002/00 20130101; A61K 8/9789 20170801; A61K 8/9728 20170801;
A61K 8/9794 20170801; A61K 2800/52 20130101; A61K 8/31 20130101;
A61K 8/986 20130101; A61K 35/20 20130101; A61K 8/64 20130101; A23L
5/44 20160801; A61P 17/16 20180101; A61Q 19/00 20130101; A61P 3/02
20180101; A61K 8/99 20130101; A23L 33/19 20160801; A61Q 19/08
20130101; A61P 17/00 20180101; A23V 2002/00 20130101; A23V 2250/213
20130101; A23V 2250/54252 20130101 |
Class at
Publication: |
514/773 |
International
Class: |
A01N 025/00 |
Foreign Application Data
Date |
Code |
Application Number |
May 30, 2000 |
EP |
00111542.7 |
Claims
What is claimed is:
1. Primary composition comprising at least one lipophilic bioactive
compound and a whey protein in an amount effective to increase the
bioavailability of the lipophilic bioactive compound.
2. Primary composition according to claim 1, wherein the lipophilic
bioactive compound is obtained, extracted, enriched or purified
from a plant, microorganism, yeast or product of animal origin.
3. Primary composition according to claim 2, wherein the plant is
tomatoes, soya, green tea, green coffee beans, spices, grapes,
cocoa, ginger or cereals.
4. Primary composition according to claim 2, wherein the
microorganism is any type of bacterium which produces a lipophilic
bioactive compound.
5. Primary composition according to claim 2, wherein the yeast is a
yeast which produces a lipophilic bioactive compound.
6. Primary composition according to claim 2, wherein the product of
animal origin is chosen from the group consisting of a liver
extract and a milk fraction.
7. Primary composition according to claim 1, wherein the lipophilic
bioactive compound is a carotenoid, polyphenol, lipophilic vitamin,
flavonoid, isoflavone, curcuminoid, ceramide, proanthocyanidin,
terpenoid, sterol, phytosterol, sterol ester, tocotrienol,
squalene, or retinoid, alone or as a mixture.
8. Primary composition according to claim 1, wherein the lipophilic
bioactive compound is a tomato extract, a soybean extract or a
mixture thereof.
9. Primary composition according to claim 1 in the form of a
powder, gel or liquid and which further comprises at least one of
vitamin C or tocopherol.
10. Primary composition according to claim 1, which further
comprises at least one of an emulsifier, a stabilizer or another
additive.
11. Primary composition according to claim 1, wherein the
lipophilic bioactive compound is present in an amount of about 0.05
to 50% by weight of the composition and the whey protein is present
in an amount of about 5 to 90% of the composition.
12. Primary composition according to claim 11, wherein the whey
protein and lipophilic bioactive compound are present in a weight
ratio of about 1:1 to 500:1.
13. A primary composition comprising at least one lipophilic
bioactive compound of a tomato oleoresin, a soybean extract, or a
mixture thereof, and a whey protein in an amount effective to
increase the bioavailability of the lipophilic bioactive
compound.
14. Oral composition comprising the primary composition according
to claim 1 in a foodstuff, in a food supplement, in a cosmetic
preparation or in a pharmaceutical preparation.
15. Oral composition according to claim 14, wherein the foodstuff
is a yogurt, a liquid drink, a chocolate containing product, an ice
cream, cereal, coffee or animal food.
16. Oral composition according to claim 14, wherein the food
supplement further comprises at least one of a sweetener, a
stabilizer, a flavoring and a colorant and is provided in the form
of sugar-coated tablets, pills, gelatin capsules, a syrup, a gel or
a cream.
17. Oral composition according to claim 14, wherein the cosmetic
preparation additionally comprises a compound active with respect
to the skin.
18. Oral composition according to claim 14, wherein the content of
the primary composition is between about 0.001 and 100%.
19. Oral composition according to claim 18, wherein the content of
the primary composition is between about 10 and 50%.
20. Cosmetic composition comprising the primary composition
according to claim 1.
21. Cosmetic composition according to claim 20, wherein the content
of primary composition is between about 10.sup.-10% and 10%.
22. A method for protecting skin tissue against ageing which
comprises administering to a subject in need of such protection the
primary composition of claim 1.
23. A method for protecting skin tissue against ageing which
comprises administering to a subject in need of such protection the
oral composition of claim 14.
24. A method for protecting skin tissue against ageing which
comprises administering to a subject in need of such protection the
cosmetic composition according to claim 20.
23. A process for the preparation of a primary composition
according to claim 1, which comprises associating the whey protein
with the lipophilic bioactive compound under conditions sufficient
to form the composition a mixture.
24. The process according to claim 23, wherein the composition is
formed by dissolving the whey protein in water to form a first
solution, dissolving the lipophilic bioactive compound in a solvent
to form a second solution, combining the two solutions, and
evaporating the solvent to form the composition as a
dispersion.
25. The process according to claim 23, wherein the composition is
formed by mixing the lipophilic bioactive compound with a solvent
to form a first mixture, mixing the first mixture with the whey
protein in the form of a powder to form a second mixture and
evaporating the solvent from the second mixture to produce the
composition as a dry powder.
26. The process according to claim 24, wherein the solvent is
acetone, ethanol, isopropanol or mixtures thereof.
27. The process according to claim 25, wherein the solvent is
acetone, ethanol, isopropanol or mixtures thereof.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of the US
national phase designation of International application
PCT/EP01/06145 filed May 29, 2001, the content of which is
expressly incorporated herein by reference thereto.
TECHNICAL FIELD
[0002] The present invention relates to a primary composition
comprising a lipophilic bioactive compound and to an oral
composition comprising the primary composition and its process of
preparation.
BACKGROUND
[0003] Compositions available on the market that include a
lipophilic bioactive compound, namely lycopene, are already known.
Lycopene is a natural product which is known to have multiple
roles, in particular that of an antioxidant. Lycopene is present in
various natural products, in particular tomatoes, melons, guavas
and grapefruit. The composition generally available on the market
which comprises lycopene is an oleoresin. The problem with this
oleoresin is that it has been found that the lycopene present
therein is insufficiently bioavailable.
[0004] For example, European patent 278 284 relates to a
pulverulent composition comprising a synthetic carotenoid. The
problem with this composition is that it cannot be used in the food
field and, moreover, it is envisaged for a coloring purpose.
[0005] Thus, there is a need for a lycopene-containing product
which has better bioavailability than the products currently on the
market.
SUMMARY OF THE INVENTION
[0006] A primary composition that includes at least one lipophilic
bioactive compound and a whey protein in an amount effective to
increase the bioavailability of the lipophilic bioactive compound.
The lipophilic bioactive compound is advantageously obtained,
extracted, enriched or purified from a plant, microorganism, yeast
or product of animal origin.
[0007] The preferred form of the primary composition is as an
additive in a foodstuff for oral administration, such as in a food
supplement, in a cosmetic preparation or in a pharmaceutical
preparation.
[0008] The invention also relates to methods of forming the primary
composition, the food supplement, cosmetic preparation or
pharmaceutical preparation containing the same, and to a method for
protecting skin tissue against ageing by administering to a subject
in need of such protection one of the primary, oral, or cosmetic
compositions disclosed herein.
[0009] The process for the preparation of a primary composition
comprises associating the whey protein with the lipophilic
bioactive compound under conditions sufficient to form the
composition a mixture. The composition may be formed by dissolving
the whey protein in water to form a first solution, dissolving the
lipophilic bioactive compound in a solvent to form a second
solution, combining the two solutions, and evaporating the solvent
to form the composition as a dispersion. Alternatively, the
composition may be formed by mixing the lipophilic bioactive
compound with a solvent to form a first mixture, mixing the first
mixture with the whey protein in the form of a powder to form a
second mixture and evaporating the solvent from the second mixture
to produce the composition as a dry powder.
DETAILED DESCRIPTION OF THE INVENTION
[0010] The present invention relates to a primary composition
comprising a lipophilic bioactive compound and a whey protein. The
term "bioactive compound" is understood to mean a compound having a
beneficial effect on the human or animal metabolism. The present
invention now makes available to the consumer an improved
composition obtained from natural products. As will be explained
further below, protection and enhancement of the lipophilic
bioactive compound is also targeted according to the invention.
[0011] The lipophilic bioactive compound is obtained, extracted,
enriched or purified starting from a plant, microorganism, yeast or
product of animal origin. The term "obtained" is understood to mean
that the bioactive product is directly available commercially. The
term "extracted" is understood to mean that the bioactive principle
has been extracted. The term "enriched" is understood to mean that
the non-bioactive compounds have been separated as much as
possible. The term "purified" is understood to mean that only the
bioactive compound is recovered.
[0012] In the case of a bioactive compound originating from a
plant, the plant is chosen from the group consisting of tomatoes
(i.e., whole tomato, tomato extract, tomato flesh, tomato puree,
tomato skin, with or without the seeds), soya, green tea, green
coffee beans, spices such as ginger or others, grapes, cocoa and
cereals. The microorganism can be any type of bacterium which
produces a lipophilic bioactive compound. For example, a probiotic
microorganism, in particular a lactic acid bacterium, can be
envisaged as microorganism. The yeast can be any yeast which
produces a lipophilic bioactive compound, for example a
Saccharomyces. The product of animal origin is chosen from the
group consisting of a liver extract and a milk fraction. The term
"milk fraction" is understood to mean any part of the milk.
[0013] In the primary composition according to the invention, the
lipophilic bioactive compound is chosen from the group consisting
of carotenoids, polyphenols, lipophilic vitamins, flavonoids,
isoflavones, curcuminoids, ceramides, proanthocyanidins,
terpenoids, sterols, phytosterols, sterol esters, tocotrienols,
squalene and retinoids, alone or as a mixture. Carotenoids are
present in particular in tomatoes, carrots, yellow peaches,
apricots and oranges. Lycopene is a carotenoid which is
particularly favored in the present composition. Polyphenols are
present in particular in green tea, coffee, cocoa or red wine.
Lipophilic vitamins are present in particular in numerous
vegetables. Flavonoids and isoflavones are present in particular in
soya, tea, onions or wine. Curcuminoids are present in particular
in ginger. Ceramides are glycolipids present in particular in yeast
derivatives and derivatives of animal origin. Proanthocyanidins are
flavonoids present in particular in grapes. Terpenoids are present
in spices. Sterols, phytosterols and sterols esters are present in
particular in vegetable oils, seeds, nuts and vegetables.
Tocotrienols are present in particular in rice bran, barley, wheat,
palm oil, rye and oats. Squalene is present in particular in fish
liver, olive oil, wheat germ oil or rice bran oil. Finally,
retinoids are present in particular in liver, egg yolk and dairy
products.
[0014] In a preferred embodiment of the primary composition
according to the invention, the lipophilic bioactive compound is
obtained from tomatoes, for example tomato puree or a tomato
extract. The presence of lycopene in tomatoes is advantageous for
the present invention. The bioactive compound can also be a soybean
extract. It is also possible to have a mixture of tomato extract
and of soybean extract. These extracts are obtained by conventional
methods, with the preferred totmato extract being a lipidic extract
obtained by use of a solvent such as ethyl acetate, and the soybean
extract being obtained from the ethanol/hot water extraction of soy
which has been initially defatted by treatment by hexane.
[0015] The composition according to the invention can be provided
in the form of a powder, liquid or gel.
[0016] As already mentioned above, the present invention provides a
composition comprising a lipophilic bioactive compound which has a
better bioavailability than the compound alone. Also, these
compositions may be in the form of a highly water-dispersible
composition, if the powder form is chosen. In this instance, the
powder is dispersible in water at ambient temperature. Another
feature of the invention is to protect and preserve the activity of
the lipophilic bioactive compound with whey protein.
[0017] In the compositions according to the invention, the
preferred additive for increasing bioactivity of the compound is
whey protein, for example in the form of whey protein isolate. The
term "whey protein" is understood to mean a product comprising at
least 80% of whey proteins.
[0018] The primary composition according to the invention can
additionally comprise vitamin E and vitamin C. Vitamin E
(tocopherol) can be of exogenous or endogenous origin. If desired,
vitamin C in any conventional form may be added to the
composition.
[0019] The composition additionally comprises one or more of
emulsifiers, stabilizers and other additives. Use is made of
emulsifiers compatible in the food field, such as phospholipids,
for example lecithin, polyoxyethylene sorbitan mono- or
tristearate, monolaurate, monopalmitate, mono- or trioleate, a
mono- or diglyceride. Use may also be made of any type of
stabilizer that is known in the food business, in cosmetics or in
pharmaceuticals. Use is made, as additives, of flavorings,
colorants and any other additive known in the food business, in
cosmetics or in pharmaceuticals. These emulsifiers, stabilizers and
additives are added according to the final use of the primary
composition.
[0020] In the primary composition, the lipophilic bioactive
compound is preferably present in an amount of about 0.05 to 50% by
weight of the composition and the whey protein is present in an
amount of about 5 to 90% of the composition. Also, the whey protein
and lipophilic bioactive compound may be present in a weight ratio
of at least about 1:1 to 500:1, preferably from about 1.5:1 to
250:1 and more preferably about 2:1 to 20:1.
[0021] In a preferred embodiment of the invention, the primary
composition comprises tomato oleoresin, soybean extract and whey
protein. The term "tomato oleoresin" is understood to mean, in the
present description, a lipid extract of the tomato plant, including
carotenoids, such as lycopene, triglycerides, phospholipids,
tocopherol and other less significant compounds. The term "soybean
extract" is understood to mean a soybean extract comprising a high
content of isoflavone. It is also possible to envisage other
carotenoid-comprising plants, in particular melons, guavas,
grapefruit, apricots, rosehips, carrots, peaches and oranges.
[0022] The present invention additionally relates to an oral
composition comprising the primary composition described above in a
foodstuff, in a food supplement, in a cosmetic preparation or in a
pharmaceutical preparation.
[0023] This orally ingestible composition makes it possible to
enhance the bioavailability of the lipophilic bioactive compound in
the body and to slow down the ageing of the skin. Mention may be
made, as foodstuff supplemented by the above primary composition,
of yogurts, liquid drinks, chocolate, ice creams, cereals,
chocolate powders, coffee, culinary products, such as mayonnaise,
tomato puree or salad dressings, infant nutrition products, enteral
nutrition products or pet foods. In this case, the powder is
dissolved in the above-mentioned foods or drinks so as to have a
daily intake of between about 0.001 and 50 mg of lipophilic
bioactive compound, for example such as lycopene. A daily intake of
the order of about 5 to 20 mg per day is preferably envisaged.
[0024] It is also possible to envisage, according to the invention,
a food supplement in the form of sugar-coated tablets, pills,
gelatin capsules, a syrup, a gel, a cream or lozenges with a dose
of about 0.001 to 100% of the primary composition, which can then
be taken directly with water or by any other known means. This
supplement may also include a sweetener, a stabilizer, an additive,
a flavoring or a colorant.
[0025] The oral composition can also be a cosmetic preparation
comprising the primary composition and a compound active with
respect to the skin known to a person skilled in the art.
[0026] The oral composition can also be a pharmaceutical
preparation comprising the primary composition and a pharmaceutical
compound, for example a compound in topical application or which
can be orally ingested.
[0027] The invention also relates to a cosmetic composition
comprising the primary composition described above. In this case,
the content of primary composition is between 10.sup.-10 and 10%.
The cosmetic composition preferably comprises between 10.sup.-8 and
5% of lipophilic bioactive compound.
[0028] This composition which can be used topically additionally
comprises a fat or an oil which can be used in cosmetics, for
example those mentioned in the CTFA work, Cosmetic Ingredients
Handbook, Washington. It is also possible to add other cosmetically
active ingredients. The composition additionally comprises a
structuring agent and an emulsifier.
[0029] Other excipients, colorants, fragrances or opacifiers can
also be added to the composition.
[0030] The present invention additionally relates to the use of the
oral composition or of the cosmetic composition described above for
protecting the tissues of the skin against ageing, in particular
for inhibiting damage to the skin and/or mucous membranes by
inhibiting collagenases and enhancing the synthesis of
collagen.
[0031] The present invention additionally relates to the process
for the preparation of the primary composition described above, in
which the whey protein is mixed with the lipophilic bioactive
compound.
[0032] In a first embodiment of the process according to the
invention,
[0033] the whey protein is dissolved in water,
[0034] the lipophilic bioactive compound is dissolved in a
solvent,
[0035] the two solutions are mixed,
[0036] the solvent is evaporated, and
[0037] a dispersion is obtained.
[0038] In a first alternative form of the process according to the
invention, a dispersion is obtained. In a second alternative form,
the dispersion is heat-treated to produce a gel. And, in a third
alternative form, the dispersion is dried by spraying or by
lyophilization to produce a powder. The composition according to
the invention may be directly usable as is or as a mixture, as will
be explained below.
[0039] The whey protein is dissolved in water at a temperature in
the region of or slightly greater than ambient temperature. An
oleoresin which comprises between 1 and 40% of lycopene is used.
The amounts are given as weight/weight. When the oleoresin is
dissolved in the solvent, the ratio of the said oleoresin to the
solvent is of the order of 1:1 to 1:900 by weight.
[0040] The solvent is any type of solvent compatible with the food
business, cosmetics or pharmaceuticals. The solvent is preferably
acetone, ethanol or isopropanol. When the aqueous phase is mixed
with the solvent, a solvent/water ratio by volume of the order of
60/40 is chosen.
[0041] After mixing the two phases, the mixture is left to stand
for 30 to 60 min at a temperature slightly higher than ambient
temperature, for example of the order of 30.degree. C., and the
first operation is to drive off the solvent under a moderate
vacuum. The term "moderate vacuum" is understood to mean a vacuum
of between 200 and 300 mbar. If a powder is desired, the water is
removed, either under vacuum or by spraying or by lyophilization.
The term "vacuum" is understood to mean a vacuum of between 40 and
50 mbar. If a gel is desired, the emulsion is heated or any other
technique known to a person skilled in the art for preparing the
said gel is employed.
[0042] In a second embodiment of the process according to the
invention,
[0043] the lipophilic bioactive compound is mixed with a
solvent,
[0044] the composition obtained is mixed with the whey protein
powder, and
[0045] the solvent is evaporated to produce a powder
composition.
[0046] The solvent used is the same as that mentioned above.
[0047] In a third embodiment, the lipophilic bioactive compound,
either in the oleoresin form or in the powder form or in any other
dry form (for example, the oleoresin is absorbed on a support), is
mixed directly with the whey powder (optionally comprising a
soybean extract) to produce the primary composition according to
the invention.
EXAMPLES
[0048] The continuation of the description is now made with
reference to the examples which illustrate preferred embodiments of
the invention.
Example 1
[0049] Preparation of the Composition in the Powder Form
[0050] 13.3 kg of whey protein isolate are dissolved in 330 l of
demineralized water and the mixture is stirred for 6 hours at
25-30.degree. C. Separately, 550 g of oleoresin from Lycored,
comprising 6% of lycopene, are mixed in 438 l of acetone and the
mixture is stirred.
[0051] The 2 solutions are subsequently mixed for 60 min at
30.degree. C. The final mixture is moderately heated and the
acetone is driven off at a moderate pressure. Finally, water is
partially driven off at a pressure of 40-50 mbar. An aqueous
solution of 200 kg of whey protein isolate and of oleoresin is
obtained.
[0052] This solution is subsequently spray dried.
[0053] Starting from this powder, tests were carried out with
people who were daily given this powder comprising 25 mg of
lycopene and other carotenoids present in the oleoresin and 12.5 g
of whey proteins: the powder was taken by dissolving it in apple
juice. In comparison with the reference, which was tomato puree
comprising the same amount of lycopene, a bioavailability of the
lycopene starting from the powder according to the invention equal
to that starting from the tomato puree was observed. This study was
carried out over a period of 8 weeks. It should be remembered that
tomato puree is regarded by a person skilled in the art as the
product having the best bioavailability of lycopene. This
demonstration was carried out by quantitative determination of the
lycopene in the blood plasma.
Example 2
[0054] Preparation of Sugar-coated Tablets
[0055] A dispersion of 550 g of oleoresin of Example 1 with an
emulsifier in ethanol is prepared. This dispersion is mixed with 1
100 g of whey protein and 1 100 g of soybean extract (comprising
40% of isoflavone). The solvent is driven off to produce a
powder.
[0056] The powder thus obtained is mixed with ascorbic acid and
other additives, such as one or more sweeteners, thickeners and
food additives, making possible preparation in the form of
sugar-coated tablets. The mixture obtained is subsequently
sugar-coated.
[0057] Sugar-coated tablets of the order of 700 mg, comprising 33
mg of lycopene, 70 mg of soybean extract, 70 mg of whey protein, 40
mg of ascorbic acid, the remainder being sweeteners, thickeners and
food additives, to arrive at 700 mg, are thus prepared.
Example 3
[0058] Cosmetic Composition
[0059] A milk for the face is prepared comprising 7% of liquid
petrolatum, 2% of powder according to Example 1, 3% of glyceryl
monostearate, polyethylene glycol stearate, 0.4% of carboxyvinyl
polymer, 0.7% of stearyl alcohol, 3% of soybean proteins, 0.4% of
NaOH and a preservative, and the remainder to 100 being water.
Example 4
[0060] Cosmetic Composition
[0061] A gel for the face is prepared comprising 10% of glycerol,
2% of powder according to Example 1, 1% of disodium
cocoamphodiacetate and a preservative, and the remainder to 100
being water.
Example 5
[0062] Study of the Stability of Lycopene
[0063] It is known that light and oxygen cause lycopene to
decompose. An aqueous-phase analysis of the stability of lycopene
alone and of lycopene in combination with the whey protein
according to the invention was carried out. After one day in the
aqueous phase for lycopene alone, only 40% of the lycopene remains,
whereas, with the whey, virtually 90% of it remains. After two
days, 60% of it remains with the whey, whereas the lycopene is
virtually completely decomposed if it is alone.
[0064] A protective effect on the lycopene by the whey protein
therefore clearly exists.
* * * * *