WO2002034230A1

WO2002034230A1 - Cosmetic composition containing dhea and an anti-irritant

Info

Publication number: WO2002034230A1
Application number: PCT/FR2001/003313
Authority: WO
Inventors: Isabelle Nonotte
Original assignee: L'oreal
Priority date: 2000-10-26
Filing date: 2001-10-25
Publication date: 2002-05-02
Also published as: AU2002214100A1; FR2815858A1; FR2815858B1

Abstract

The invention concerns a composition containing DHEA and/or a precursor or a chemical or biological derivative thereof, characterised in that it further comprises at least an agent capable of inhibiting irritation of neurogenic origin selected among: an agent blocking sodium channels, a substance P antagonist, a CGRP antagonist and a bradykinin antagonist. The invention also concerns cosmetic and dermatological uses of said composition, in particular for preventing or treating skin ageing symptoms.

Description

COSMETIC COMPOSITION CONTAINING DHEA AND ANTI-IRRITANT AGENT

The present invention relates to a composition containing at least one compound chosen from DHEA and / or a precursor or a chemical or biological derivative thereof, and at least one agent capable of inhibiting irritation of given neurogenic origin. , as well as the use of said composition, in particular for preventing or treating the signs of skin aging.

DHEA, or dehydroepiandrosterone, is a natural steroid produced primarily 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 the endogenous production and the secretion of sebum and thereby strengthening 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. 5,736,537 the oral use of DHEA esters, in particular DHEA salicylate, for regulating the atrophy of the skin due to thinning or general degradation of the dermis. Finally, it has been proposed to use DHEA sulfate to treat various signs of aging such as wrinkles, loss of radiance of the skin and sagging skin (EP-0 723 775).

However, it appeared to the Applicant that ^' the association of DHEA with certain agents capable of inhibiting irritation of neurogenic origin could make it possible to prevent or more effectively treat the signs of skin aging.

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 agent capable of inhibiting neurogenic irritation selected from: a sodium channel blocking agent, a substance P antagonist, a CGRP antagonist and a bradykinin antagonist.

DHEA has the following formula (I):

It is for example available from the company AKZO NOBEL.

By precursors of DHEA 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 and their derivatives, such as diosgenin (or spirost-5-en-3-beta-ol), hecogenin, hecogenin acetate, smilagenin and sarsapogenin, as well as natural extracts containing it, in particular fenugreek and extracts of Dioscorea 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, as well as 7α-OH DHEA, 7β-OH DHEA and 7-keto-DHEA , without this list being exhaustive. 7α-OH DHEA is preferred for use in the present invention. A process for preparing this compound is described in particular in patent applications FR-2 771 105 and WO 94/08588 ..

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. 5,736,537 or the other esters such as salicylate, acetate, valerate (or n-heptanoate) and enanthate of DHEA. 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 chemical and biological precursors and derivatives of DHEA will hereinafter be referred to as "DHEA analogues".

The concentration of DHEA and / or the like 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 and / or its analogs, at least one agent capable of inhibiting irritation of neurogenic origin.

By "agent capable of inhibiting irritation of neurogenic origin" is meant according to the invention, certain molecules, salts of these molecules and / or plant and / or bacterial and / or marine extracts which exhibit anti-irritant activity :

1) by totally or partially blocking the activity of sensitive nerve endings and therefore by reducing the release of neuromediators in the skin tissue,

2) and / or by blocking the action on the cutaneous target cells of these same neuromediators and / or of the neurohormones provided by the superficial blood microcirculation,

3) and / or by lowering the reactivity threshold of the cutaneous target cells to these neuromediators and / or neurohormones.

More specifically, according to the invention, anti-irritants are used: - sodium channel blocking agents, and / or

agents which interact specifically with receptors for neuromediators or neurohormones, chosen from antagonists of substance P, antagonists of CGRP, and antagonists of bradykinin.

By "sodium channel blocking agent" is meant, according to the present invention, a substance responding as a sodium antagonist substance in the model described by Y. Jacques et al. (J. Biol. Chem., 1987, 253, page 7383) and / or a response substance such as a specifically binding substance in the sodium channel attachment models, described by WA Catterall et al. (J. Biol. Chem., 1979, 254, page 11379) or by GB Brown, (J. Neuroscience, 1986, 6, page 2064). By way of examples, the following can be used in the invention as sodium channel inhibitors: Amiloride, Quinidine, Quinidine sulfate, Apamine, Cyproheptadine, Loperamide and N-acetylprocainamide.

Preferably according to the invention, Amiloride is used.

These sodium channel blocking agents, including those described in patent application WO 99/44579, which is incorporated here by reference.

By "substance P antagonist" is meant, according to the present invention, a substance of organic or inorganic origin capable of producing an inhibition of the receptor fixation of substance P or of producing an inhibition of the synthesis and / or of the release of substance P from sensitive nerve fibers.

For a substance to be recognized as a substance P antagonist, it must induce a consistent pharmacological response in at least one of the following tests:

- the antagonist substance must have a selective affinity for the NK1 tachykinin receptors, and / or

- the antagonist substance must cause an inhibition of the release and / or the synthesis of substance P and / or the antagonist substance must cause an inhibition of the contraction of the smooth muscles induced by the administration of substance P.

For a more precise definition of the substance P antagonists and their mechanism of action, reference may for example be made to application EP-0 680 749, the content of which is incorporated here by reference.

Examples of substance P antagonists include: strontium salts; thermal waters and in particular thermal water from the Vichy basin and thermal water from La Roche Posay; bacterial extracts and in particular the extract of non-photosynthetic filamentous bacteria described in patent application EP-0 761 204, preferably prepared from bacteria belonging to the order of Beggiatoales, and more particularly to the genera Beggiatoa, Vitreoscilla, Flexithrix or Leucothrix. Preferably, a strain of Vitreoscilla filiformis is used according to the invention.

By "CGRP antagonist" is meant, according to the present invention, a substance of organic or inorganic origin capable of producing an inhibition of receptor binding of CGRP or of producing an inhibition of the synthesis and / or release of CGRP by sensitive nerve fibers.

For a substance to be recognized as a CGRP antagonist, it must have a pharmacological activity as a CGRP antagonist, that is to say inducing a coherent pharmacological response in particular in one of the following tests:

- the antagonist substance must have a selective affinity for the CGRP receptor and / or

- the antagonist substance must cause inhibition of the release of CGRP by sensitive nerve fibers and / or

- the antagonist substance must decrease an inhibition of the contraction of the smooth muscle of the vas deferens induced by CGRP.

For a more precise definition of the CGRP antagonists and of their mechanism of action, reference may for example be made to application EP-0 734 729, the content of which is incorporated here by reference.

A non-limiting example of a CGRP antagonist which can be used in the present invention consists of an extract of cells (preferably undifferentiated) from at least one plant of the Iridaceae family, obtained by culture in vitro. The iridaceae preferably belongs to one of the following genera: Romulea, Crocus, Iris, Gladiolus, Sisyrinchium and Hermodactylus. For use in the present invention, it is preferred to use an extract of plant material originating from Iris, better still, from Iris pallida, as described in application EP-0 765 668.

By "bradykinin antagonist" is meant, according to the present invention, a substance capable of inhibiting the release and / or the synthesis and / or the receptor fixation of bradykinin. Antagonists inhibiting receptor binding of bradykinin are specific agents of the type 1 (B.) and / or type 2 receptor (B ₂ ) of bradykinin. Their mechanism of action is notably described in patent application EP-0 756 862, the content of which is incorporated here by reference.

A non-limiting example of a bradykinin antagonist which can be used in the present invention consists of an extract of at least one plant from the Rosaceae family, preferably cultivated in vivo. The Rosacea extract can preferably belong to the following genera: Agrimonia, Amygdalus, Armeniaca, Cerasus, Malus, Mespilus, Persica, Pirus, Prunus, Rosa, Rubus.

Preferably, according to the invention, a plant belonging to the genus Rosa is used, advantageously prepared from material obtained from at least one plant belonging to a species chosen from Rosa alba, Rosa alpina, Rosa canina, Rosa cinnamonea, Rosa gallica, Rosa repens, Rosa rubrifolia, Rosa rubiginosa, Rosa sempervirens, Rosa spinosissima, Rosa stylosa, Rosa tomentosa, Rosa villosa. Better still, the plant belongs to the Rosa gallica species as described in patent application EP-0 909 556.

The anti-irritant agent used according to the invention can be of natural or synthetic origin. By natural origin is meant an inhibitor in the pure state or in solution whatever its concentration in said solution, obtained by different processes from a natural element. By synthetic origin is meant an anti-irritant agent in the pure state or in solution, whatever its concentration in said solution, obtained by chemical synthesis.

The amount of anti-irritant agent usable according to the invention is of course a function of the desired effect and can therefore vary to a large extent.

To give an order of magnitude, the anti-irritant agent may be present, in the composition according to the invention, in an amount representing from 10 ^"12 % to 20% of the total weight of the composition and preferably in an amount representing 10 ^'8 % to 10% of the total weight of the composition.

Of course, a person skilled in the art, if he uses the anti-irritant agent in the form of a solution, a plant extract for example, knows how to adjust the amount of solution he uses in its composition so that the amount final anti-irritant agent in the composition is in agreement with the previously defined usable quantities. 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 or a liquid, pasty or solid anhydrous product.

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 known manner, the composition of the invention may also contain the adjuvants customary 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, depending on their nature, can be introduced into the fatty phase or into the aqueous phase. These adjuvants, as well as their concentrations, must be such that they do not harm the advantageous properties of the combination of active agents 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, elulsants 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 (avocado oil, soybean oil), oils of animal origin (lanolin) can be used. ), 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, there may be mentioned, for example, fatty acid esters of polyethylene glycol such as PEG-100 stearate, PEG-50 stearate and PEG-40 stearate; fatty acid esters of polyols such as glyceryl stearate, sorbitan tristearate and the oxyethylenated sorbitan stearates available under the tradenames Tween ^® 20 or Tween ^® 60, for example; and their mixtures. .

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

The composition according to the invention comprises an effective amount of DHEA and / or the like and of anti-irritant agent, sufficient to obtain the desired effect, and a physiologically acceptable medium. By "physiologically acceptable medium" is meant a medium suitable for topical application to the skin and / or its integuments.

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

The present invention therefore also relates to the cosmetic use of the composition mentioned above for preventing or treating the signs of skin aging. 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

A treatment cream (oil-in-water emulsion) having the following composition is prepared, conventionally for a person skilled in the art:

Hydroglycolic extract of rose petals * 1% DHEA: 1%

2% glycerol stearate

Polysorbate 60 (Tween 60 ® sold by the company ICI) 1%

1.4% stearic acid

Triethanolamine 0.7% Carbomer 0.4%

Liquid fraction of shea butter 12%

Perhydrosqualene 12%

Perfume 0.5%

Preservative QS Water QSP 100%

* Herbasol Extract Rose Flower 218250/1/2 supplied by the company COSMETOCHEM

Example 2 - Composition for topical application

Iris pallida extract * 1% 7 -OH DHEA. ' 0.5%

Glycerol stearate ^' . 2%

Polysorbate 60 (Tween 60 ® sold by the company ICI) ..... 1%

1.4% stearic acid

Triethanolamine 0.7% Carbomer: 0.4% Liquid fraction of shea butter 12%

Perhydrosqualene 12%

Perfume 0.5%

Preservative QS Water QSP 100%

* Prepared according to the process described in application EP-0765 668.

Claims

1. Composition containing at least one compound chosen from DHEA and / or a precursor or a chemical or biological derivative thereof, characterized in that it also comprises at least one agent capable of inhibiting the irritation of neurogenic origin chosen from: a sodium channel blocking agent, a substance P antagonist, a CGRP antagonist and a bradykinin antagonist.

2. Composition according to claim 1, characterized in that said chemical precursor of DHEA is chosen from sapogenins and their derivatives, and natural extracts containing them.

3. Composition according to claim 2, characterized in that said chemical precursor is chosen from diosgenin, hecogenin, hecogenin acetate, 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 17α-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, Δ4-androstene-3, 17-dione, 7α-OH DHEA , 7β-OH DHEA and 7-keto-DHEA.

8. Composition according to claim 7, characterized in that said biological derivative of DHEA is 7α-OH DHEA.

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

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

11. Composition according to claim 9, characterized in that said DHEA ester is chosen from: esters of hydroxycarboxylic acids and of DHEA; DHEA salicylate; DHEA acetate; DHEA valerate; and DHEA enanthate.

12. Composition according to any one of the preceding claims, characterized in that it contains from 0.001 to 5% by weight of DHEA and / or precursor or derivative, relative to the total weight of the composition.

13. Composition according to any one of claims 1 to 12, characterized in that said sodium channel blocking agent is chosen from: Amiloride, Quinidine, Quinidine sulfate, Apamine, Cyproheptadine, Loperamide and N- acetylprocainamide.

14. Composition according to any one of claims 1 to 12, characterized in that said substance P antagonist is chosen from: strontium salts; thermal waters and in particular thermal water from the Vichy basin and thermal water from La Roche Posay; and an extract of non-photosynthetic filamentous bacteria.

15. Composition according to claim 14, characterized in that said bacteria extract is prepared from bacteria belonging to the order of Beggiatoales.

16. Composition according to claim 15, characterized in that said bacteria extract is extracted from a strain of Vitreoscilla filiformis.

17. Composition according to any one of claims 1 to 12, characterized in that said CGRP antagonist is an extract of cells from at least one plant of the Iridaceae family.

18. Composition according to claim 17, characterized in that said CGRP antagonist is an extract of plant material originating from Iris pallida.

19. Composition according to any one of claims 1 to 12, characterized in that said bradykinin antagonist is an extract of at least one plant from the Rosaceae family.

20. Composition according to claim 19, characterized in that said bradykinin antagonist is extracted from a plant belonging to the genus Rosa.

21. Composition according to claim 20, characterized in that said plant belongs to the species Rosa gallica.

22. Composition according to any one of the preceding claims, characterized in that it comprises from 10 ^"8 % to 10% by weight of agent capable of inhibiting irritation of neurogenic origin, relative to the total weight of the composition.

23. Cosmetic use of the composition according to any one of claims 1 to 22 for preventing or treating the signs of skin aging.