WO2002005764A1

WO2002005764A1 - Composition, in particular cosmetic, containing dhea and isoflavonoid

Info

Publication number: WO2002005764A1
Application number: PCT/FR2001/001787
Authority: WO
Inventors: Lionel Breton; Christel Liviero
Original assignee: L'oreal
Priority date: 2000-07-13
Filing date: 2001-06-08
Publication date: 2002-01-24
Also published as: FR2811562A1; FR2811562B1; AU2001266132A1; EP1303250A1

Abstract

The invention concerns a composition containing DHEA and/or a chemical or biological precursor or derivative thereof, characterised in that it further comprises at least an isoflavonoid. The invention also concerns the cosmetic and dermatological uses of said composition, in particular for preventing or treating actinic skin ageing symptoms.

Description

Composition, in particular cosmetic, containing DHEA and an isoflavonoid

The present invention relates to a composition containing DHEA and / or a precursor or chemical or biological derivative thereof, and at least one isoflavonoid, as well as to the use of said composition, in particular for preventing or treating signs of kinetic skin aging.

DHEA, or dehydroepiandrosterone, is a natural steroid produced mainly by the adrenal cortex. Exogenous DHEA, administered topically or orally, is known for its ability to promote keratinization of the epidermis (JP-07 196 467) and to treat dry skin by increasing endogenous production and sebum secretion and by strengthening thus the barrier effect of the skin (US Pat. No. 4,496,556). It has also been described in US Pat. No. 5,843,932 the use of DHEA for remedying atrophy of the dermis by inhibiting the loss of collagen and connective tissue. It has also been described in US Pat. No. 5J36,537 the oral use of DHEA esters, in particular DHEA salicylate, to regulate the atrophy of the skin due to thinning or general degradation of the skin. dermis.

It has now appeared to the Applicant that the combination of DHEA with an isoflavonoid makes it possible to more effectively prevent or treat the signs of skin aging, in particular of kinetic aging or photoaging.

The present invention therefore relates to a composition containing at least one compound chosen from: DHEA and / or a precursor or chemical or biological derivative thereof, characterized in that it also comprises at least one isoflavonoid.

DHEA has the following formula (I):

It is for example available from the company AKZO NOBEL. By DHEA precursors is meant its biological precursors which are capable of transforming into DHEA during metabolism, as well as its chemical precursors which can transform into DHEA by exogenous chemical reaction. Examples of biological precursors are Δ5-pregnenolone, 17α-hydroxy pregnenolone and 17α-hydroxy pregnenolone sulfate, without this list being limiting. Examples of chemical precursors are sapogenins such as diosgenin (or spirost-5-en-3-beta-ol), hecogenin, hecogenin acetate, smilagenin and sarsapogenin, as well as natural extracts thereof. containing, in particular fenugreek and Dioscorea extracts such as wild yam root or Wild Yam, without this list being exhaustive.

The term DHEA derivatives is understood to mean both its biological derivatives and its chemical derivatives. As biological derivatives, there may be mentioned in particular Δ5-androstene-3,17-diol and Δ4-androstene-3,17-dione, without this list being limiting. As chemical derivatives, mention may in particular be made of DHEA salts, in particular water-soluble salts, such as DHEA sulfate. Mention may also be made of esters, such as the esters of hydroxycarboxylic acids and of DHEA described in particular in US Pat. No. 5J36,537 or the other esters such as salicylate, acetate, valerate (or n-heptanoate) and DHEA enanthate. Mention may also be made of the DHEA derivatives (DHEA carbamates, DHEA 2-hydroxy malonate esters and DHEA amino acid esters) described in application FR 00/03846 in the name of the Applicant. This list is obviously not exhaustive.

The biological and chemical precursors and derivatives of DHEA will be designated below by "DHEA analogues".

The concentration of DHEA and / or precursors or derivatives in the composition according to the invention is advantageously between 0.0001% and 10% by weight, preferably between 0.001% and 5% by weight, relative to the total weight of the composition .

The composition according to the present invention contains, in combination with DHEA or the above analog, at least one isoflavonoid. Isoflavonoids constitute a subclass of flavonoids, formed of a 3-phenyl chroman skeleton which may contain substituents. varied and different levels of oxidation. Unlike flavonoids, they are only found in a very limited number of plants.

The term isoflavonoid groups together several classes of compounds among which mention may be made of isoflavones, isoflavanones, rotenoids, pterocarpans, isoflavanes, isoflavanes-3-enes, 3-arylcoumarins, 3-aryl-4-hydroxycoumarins, coumestanes, coumaronochromones, α-methyldeoxybenzoines or. 2-arylbenzofurans. In this regard, it will be advantageously reported for a complete review on isoflavonoids, their methods of analysis and their sources, in chapter 5 "Isoflavonids" written by P. M. Dewick, in The Flavonoid, Harbone editor, pp. 125-157 (1988).

The isoflavonoids suitable for use in the present invention can be of natural or synthetic origin. By "natural origin" is meant the isoflavonoid in the pure state or in solution at different concentrations, obtained by different extraction processes from an element, generally a plant, of natural origin. By "synthetic origin", we. means isoflavonoid in pure form or in solution at different concentrations, obtained by chemical synthesis.

We prefer to use isoflavonoids of natural origin. Among these, there may be mentioned: daidzin, genistin, daidzein, formonohetin, cuneatin, genistein, isoprunetin and prunetin, cajanin, orobol, pratensin, sandalwood, junipegenine A , glycitein, afrormosine, retusin, tectorigenin, irisolidone, jamaicin, and their analogs and metabolites. For a discussion of isoflavonoids, their methods of analysis and their sources, reference may be made to P.M. Dewick, The Flavonoïds. Chapman and Hall, pp. 125-157 (1988).

The isoflavonoid preferably represents from 10 ^"10 % to 10%, and preferably from 10 ^{" 8} to 5%, of the total weight of the composition. Of course, if the isoflavonoid is present in the form of a solution containing a plant extract, the skilled person will be able to adjust the amount of this solution in the composition according to the invention, so as to obtain the above ranges of isoflavonoid concentrations.

Isoflavones are preferred for use in the present invention. By this term is meant both the aglycone forms (daidzein, genistein, glyciteine) and the glycosylated forms (daidzine, genistin, glycitin) of isoflavones.

Processes for the preparation of isoflavones are in particular described in WO 95/10530, WO 95/10512, US-5,679,806, US-5,554,519, EP-812 837 and WO 97/26269.

However, for use in the present invention, it is preferred to use isoflavones in the form of soybean extracts marketed by ICHIMARU PHARCOS under the trade name Flavosterone SB® and by ARCHER DANIELS MIDLAND COMPANY under the trade name Novasoy®. These extracts mainly contain isoflavones in glycosylated form, capable of being metabolized in the body to their aglycone forms, and in the majority, isoflavones aglycones.

Isoflavones are in particular known as antioxidants, for their anti-radical and depigmenting properties, as well as for inhibiting the activity of the 'sebaceous glands (see in particular DE-44 32 947). They have also been described as agents to prevent signs of aging of the skin, including sagging skin and loss of radiance (JP 1-96106).

However, the Applicant has demonstrated that DHEA and / or its precursors or derivatives, applied topically, themselves have an activity on the signs of skin aging and in particular the atrophy of the epidermis, pigmentation spots, l papery appearance of the skin, wrinkles, sagging skin and dull complexion.

It is therefore understood that the combination of DHEA or analogues with isoflavonoids makes it possible to reinforce the anti-aging effects of the composition containing them, in particular when it is a question of preventing or treating the signs of cutaneous toctinic aging. In addition, without wishing to be bound by this theory, the Applicant believes that the seborrhea inhibiting effect exerted by isoflavonoids could make it possible to counter the increase in seborrhea generally observed by topical application of DHEA on the skin, and thus making the composition according to the invention suitable for oily skin.

Finally, isoflavonoids are all known to have an effect on hair repigmentation (US-5,639J85) and they are therefore capable of reinforcing the beneficial effect of DHEA on canities, already demonstrated by the Applicant.

The composition according to the invention can be in all dosage forms normally used for topical application to the skin, in particular in the form of an aqueous or oily solution, of an oil-in-water or water-in-oil emulsion or multiple, of a silicone emulsion, a microemulsion or nanoemulsion, an aqueous or oily gel, a liquid, pasty or solid anhydrous product, an oil dispersion in an aqueous phase in the presence of spherules , these spherules possibly being polymeric nanoparticles such as nanospheres and nanocapsules or, better, lipid vesicles of ionic and / or nonionic type.

This composition can be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a foam. or a gel. It can optionally be applied to the skin in the form of an aerosol. It can also be in solid form, and for example in the form of a stick. It can be used as a care product and / or as a skin makeup product.

In a known manner, the composition of the invention may also contain the adjuvants usual in the cosmetic and dermatological fields, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, perfumes, fillers, filters, pigments, odor absorbers and coloring matter. The amounts of these various adjuvants are those conventionally used in the fields under consideration, and for example from 0.01 to 20% of the total weight of the composition. These adjuvants, according to their nature, can be introduced in the fatty phase, in the aqueous phase, in the lipid vesicles and / or in the nanoparticles. These adjuvants, as well as their concentrations, must be such that they do not harm the advantageous properties of DHEA or of the isoflavonoids according to the invention.

When the composition according to the invention is an emulsion, the proportion of the fatty phase can range from 5 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition. The fats, emulsifiers and coemulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the field under consideration. The emulsifier and the coemulsifier are preferably present in the composition in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.

As fats which can be used in the invention, oils and in particular mineral oils (petroleum jelly oil), oils of vegetable origin (oil) can be used.

'- With avocado, soybean oil), oils of animal origin (lanolin), synthetic oils (perhydrosqualene), silicone oils (cyclomethicone) and fluorinated oils (perfluoropolyethers). Fatty alcohols such as cetyl alcohol, fatty acids, waxes and gums and in particular silicone gums can also be used as fats.

As emulsifiers and coemulsifiers which can be used in the invention, mention may, for example, be made of fatty acid and polyethylene glycol esters such as PEG-100 stearate, PEG-50 stearate and PEG-40 stearate; fatty acid and polyol esters such as glyceryl stearate, sorbitan tristearate and oxyethylenated sorbitan stearates available under the trade names Tween® 20 or Tween® 60, for example; and their mixtures.

As hydrophilic gelling agents, mention may be made in particular of carboxyvinyl polymers (carbomers), acrylic copolymers such as acrylate / alkyl acrylate copolymers, polyacrylamides, polysaccharides, natural gums and clays, and, as lipophilic gelling agents, quote clays modified such as bentones, metal salts of fatty acids and hydrophobic silica.

As active agents, depigmentants and keratolytic and / or scaling agents can be used in particular.

In the event of incompatibility, the active agents indicated above and / or DHEA or analogues and / or isoflavonoids according to the invention can be incorporated into spherules, in particular ionic or nonionic vesicles and / or nanoparticles (nanocapsules and / or nanospheres), so as to isolate them from each other in the composition.

According to a variant of the invention, the composition can be adapted for oral administration. In this case, it can be in the form of syrups, suspensions, solutions, emulsions, granules, capsules or tablets, for example.

The daily doses of DHEA or analogues administered orally can be between 1 and 100 mg / day, preferably between 25 and 75 mg / day. Preferably, DHEA or the like is present in the composition according to the invention in an amount allowing its administration at a dose of between 50 and 100 mg / day, said dosage being carried out in one or more doses, with a unit dose of 50 mg. .

In all cases, the composition according to the invention and / or the preparation obtained from it comprises an effective amount of DHEA or the like and isoflavonoid, sufficient to obtain the desired effect, and a physiologically acceptable medium.

The composition according to the invention finds in particular an application in the prevention and the treatment of the signs of skin aging, in particular of kinetic aging.

The present invention therefore also relates to the cosmetic use of the composition mentioned above for preventing or treating the signs of aging. skin, in particular kinetic aging. The composition according to the invention is thus preferably used:

- to prevent or reduce the papery appearance of the skin, and / or

- to improve the homogeneity of the skin color and / or to whiten the skin and / or revive the radiance of the complexion, and / or

- to treat fine lines and wrinkles, and / or

- to combat sagging skin, and / or

- to fight against or prevent atrophy of the epidermis.

The present invention also relates to the use of the composition mentioned above for manufacturing a preparation intended to attenuate pigmentation spots.

It also relates to the use of this composition for the cosmetic treatment of the scalp, in particular for preventing or treating canities. Finally, it relates to the use of the composition mentioned above for manufacturing a preparation intended for the treatment of canities.

The invention will now be illustrated by the following nonlimiting examples. In these examples, the quantities are indicated in percentage by weight.

Example 1: composition for topical application

Phase A1 2-octyldodecanol 20%

DHEA 1%

Phase A2

Polyglycerolated stearate (2 mol) 2% PEG mono-stearate (8 EO) 1.35%

Stearic acid 1%

Preservative 0.1% Β phase

Preservatives 0.35%

Neutralizers 0.25%

Propylene glycol 5% Aqueous extract of soybeans containing 0.2% isoflavones and 30% butylene glycol (Flavosterone SB - ICHIMARU PHARCOS) 5%

Water qs 100%

Phase C

0.5% gelling agent

Neutralizing 0.2% Water qs

This composition can be prepared in the following manner: phases A1, A2 and B are prepared separately by mixing their constituents under hot conditions, with stirring. Phases A1 and A2 are mixed hot, then phase B is added to them. The mixture thus obtained is transferred to a high pressure homogenizer where it is then subjected to three passages at 600 bars before incorporation of phase C.

This composition can be used in twice-daily applications to prevent or treat the signs of skin aging such as wrinkles, fine lines, the papery appearance of the skin, sagging skin and loss of radiance of the complexion.

Example 2: composition for topical application

The following composition is prepared:

Phase A1 Demineralized water 58.30%

Preservative 0.25%

Carbomer 0.40%

Glycerin 3.00% 0.10% xanthan gum

Aqueous extract of soybeans containing 0.2% isoflavones and 30% butylene glycol (Flavosterone SB - ICHIMARU PHARCOS)%

Phase A2

Oxyethylenated sorbitan stearate 20 EO

(Polysorbate 60) 0.90%

Phase B

PEG-100 stearate and glyceryl stearate 2.10%

Cetyl alcohol 2.60%

Isononyl isononanoate 11, 50%

Octyldodecanol 15.00% Diosgenin 0.50%

Butyl hydroxytoluene 0.10%

Octyl methoxycinnamate 1.00%

Preservatives 0.15%

Phase C

Demineralized water 2.00% Triethanolamine 0.30%

Phase D Demineralized water 1, 50% Preservative 0.30%

To do this, the constituents of phase A1 are mixed at 70 ° C., with stirring. The constituents of phases A2 and B are mixed and heated to 70 ° C. in a water bath, then the mixture is emulsified in phase A1 at the same temperature, with stirring at 600 rpm, for approximately two minutes. Phase C is prepared at room temperature, by dissolving triethanolamine in water, with magnetic stirring, then it is added at about 800 rpm in the above mixture which is then allowed to cool. Phase D is prepared in the same way as the phase C and added to the cooled mixture below 50 ° C. The composition is then allowed to cool to room temperature.

EXAMPLE 3 Depigmenting Lotion

A lotion is conventionally prepared by mixing the following constituents:

3-β-17-oxoandrost-5-en-3-yle glycinate 10%

Propylene glycol 15%

Ethanol 65% Aqueous extract of soybeans containing 0.2% isoflavones and 30% butylene glycol

(Flavosterone SB - ICHIMARU PHARCOS) 5%

Water qs 100%

This lotion can be used to reduce pigment spots on the hands and décolleté.

Example 4 Composition for Oral Administration

Soft capsules are prepared, conventionally for those skilled in the art, having the following composition:

Hydrogenated soybean oil 40 mg Wheat oil 95 mg

Soy lecithin 20 mg

Natural tocopherols 5 mg

Ascorbic acid 30 mg

Soy extract available under the name Novasoy® from AMD (corresponding to approximately 50 mg of isoflavones) 120 mg

DHEA 50 mg

Claims

1. Composition containing at least one compound chosen from: DHEA and / or a precursor or chemical or biological derivative thereof, characterized in that it also comprises at least one isoflavonoid.

2. Composition according to claim 1, characterized in that said precursor is a chemical precursor chosen from sapogenins and natural extracts containing it.

3. Composition according to claim 2, characterized in that said chemical precursor is chosen from diosgenin, hecogenin, smilagenin and sarsapogenin.

4. Composition according to claim 2, characterized in that said natural extract is chosen from fenugreek and Dioscorea extracts.

5. Composition according to claim 4, characterized in that said extract of Dioscorea is an extract of wild yam root.

6. Composition according to any one of the preceding claims, characterized in that said biological precursor is chosen from: Δ5-pregnenolone, 17α-hydroxy pregnenolone and 7-hydroxy pregnenolone sulfate.

7. Composition according to any one of the preceding claims, characterized in that the said biological derivative is chosen from: Δ5-androstene-3,17-diol and Δ4-androstene-3, 17-dione.

8. Composition according to any one of the preceding claims, characterized in that the said chemical derivative is chosen from: DHEA salts and esters of

DHEA.

9. Composition according to claim 8, characterized in that said DHEA salt is chosen from water-soluble salts, such as DHEA sulfate.

10. Composition according to claim 8, characterized in that said DHEA ester is chosen from: esters of hydroxycarboxylic acids and DHEA; DHEA salicylate; DHEA acetate; DHEA valerate; and DHEA enanthate.

11. Composition according to any one of the preceding claims, characterized in that it contains from 0.0001 to 10% by weight of DHEA and / or its precursors or derivatives, relative to the total weight of the composition.

12. Composition according to claim 11, characterized in that it contains from 0.001 to 5% by weight of DHEA and / or its precursors or derivatives, relative to the total weight of the composition.

13. Composition according to any one of the preceding claims, characterized in that said isoflavonoid is chosen from isoflavonoid of natural origin.

14. Composition according to claim 13, characterized in that said isoflavonoid is chosen from isoflavones.

15. Composition according to claim 13 or 14, characterized in that said isoflavonoid is chosen from: daidzine, genistin, daidzein, formononetin, cuneatin, genistein, isoprunetin and prunetin, cajanin, orobol, pratensin, sandalwood, junipegenine A, glycitein, afrormosin, retusin, tectorigenin, irisolidone, jamaicin, and their analogs and metabolites.

16. Composition according to claim 15, characterized in that said isoflavonoid is chosen from daidzein, genistein, glyciteine, daidzine, genistin and glycitin.

17. Composition according to any one of the preceding claims, characterized in that it comprises from 10 ^"10 % to 10% by weight of isoflavonoid, relative to the total weight of the composition.

18. Composition according to Claim 17, characterized in that it comprises from 10 ^"8 % to 5% by weight of isoflavonoid, relative to the total weight of the composition.

19 Cosmetic use of the composition according to any one of the preceding claims for preventing or treating the signs of skin aging, in particular kinetic aging.

20. Cosmetic use of the composition according to any one of claims 1 to 18 to prevent or reduce the papery appearance of the skin and / or to improve the uniformity of the color of the skin and / or to whiten the skin and / or revive the radiance of the complexion, and / or to treat fine lines and wrinkles and / or to fight against sagging skin, and / or to fight against or prevent atrophy of the epidermis.

21. Use of the composition according to any one of claims 1 to 18 for manufacturing a preparation intended to attenuate pigmentation spots.

22. Use of the composition according to any one of claims 1 to 18 for the cosmetic treatment of the scalp, in particular for preventing or treating canities.

23. Use of the composition according to any one of claims 1 to 18 for manufacturing a preparation intended for the treatment of canities.

AMENDED CLAIMS

[received by the International Bureau on November 16, 2001 (16.11.01); claims 1-23 replaced by claims 1-20 amended (3 pages)]

1. Cosmetic use for preventing or treating the signs of skin aging of a composition containing at least one compound chosen from: DHEA and / or a precursor or chemical or biological derivative thereof, and at least one isoflavonoid.

2. Use according to claim 1, characterized in that said precursor is a chemical precursor chosen from sapogenins and natural extracts containing it.

3. Use according to claim 2, characterized in that said chemical precursor is chosen from diosgenin, hecogenin, smilagenin and sarsapogenin.

4. Use according to claim 2, characterized in that said natural extract is chosen from fenugreek and Dioscorea extracts.

5. Use according to claim 4, characterized in that said Dioscorea extract is an extract of wild yam root.

6. Use according to any one of the preceding claims, characterized in that said biological precursor is chosen from: Δ5-pregnenolone, 17α-hydroxy pregnenolone and 17α-hydroxy pregnenolone sulfate.

7. Use according to any one of the preceding claims, characterized in that said biological derivative is chosen from: Δ5-androstene-3,17-diol and Δ4-androstene-3, 17-dione.

8. Use according to any one of the preceding claims, characterized in that the said chemical derivative is chosen from: DHEA salts and DHEA esters.

9. Use according to claim 8, characterized in that said DHEA salt is chosen from water-soluble salts, such as DHEA sulfate.

10. Use according to claim 8, characterized in that said DHEA ester is chosen from: esters of hydroxycarboxylic acids and DHEA; DHEA salicylate; DHEA acetate; DHEA valerate; and DHEA enanthate.

11. Use according to any one of the preceding claims, characterized in that it contains from 0.0001 to 10% by weight of DHEA and / or its precursors or derivatives, relative to the total weight of the composition.

12. Use according to claim 11, characterized in that it contains from 0.001 to 5% by weight of DHEA and / or its precursors or derivatives, relative to the total weight of the composition.

13. Use according to any one of the preceding claims, characterized in that said isoflavonoid is chosen from isoflavonoid of natural origin.

14. Use according to claim 13, characterized in that said isoflavonoid is chosen from isoflavones.

15. Use according to claim 13 or 14, characterized in that said isoflavonoid is chosen from: daidzin, genistin, daidzein, formononetin, cuneatin, genistein, isoprunetin and prunetin, cajanin, Porobol, pratensin, sandalwood, junipegenine A, glycitein, afrormosin, retusin, tectorigenin, irisolidone, jamaicin, and their analogs and metabolites.

16. Use according to claim 15, characterized in that said isoflavonoid is chosen from daidzein, genistein, glycitein, daidzin, genistin and glycitin.

17. Use according to any one of the preceding claims, characterized in that it comprises from 10 ^"10 % to 10% by weight of isoflavonoid, relative to the total weight of the composition.

18. Use according to claim 17, characterized in that it comprises from 10 ^"8 % to 5% by weight of isoflavonoid, relative to the total weight of the composition.

19. Use according to any one of the preceding claims, for preventing or treating the signs of kinetic skin aging.

20. Use according to any one of claims 1 to 18 for preventing or reducing the papery appearance of the skin and / or for improving the uniformity of the color of the skin and / or for whitening the skin and / or reviving the skin. 'radiance of the complexion, and / or to treat fine lines and wrinkles and / or to combat sagging skin, and / or to combat or prevent atrophy of the epidermis.