WO2002034228A1

WO2002034228A1 - Cosmetic composition comprising dhea and at least a muscle relaxant

Info

Publication number: WO2002034228A1
Application number: PCT/FR2001/003107
Authority: WO
Inventors: Isabelle Nonotte; Lionel Breton
Original assignee: L'oreal
Priority date: 2000-10-26
Filing date: 2001-10-09
Publication date: 2002-05-02
Also published as: FR2815860A1; AU2001295674A1; FR2815860B1

Abstract

The invention concerns the use of a composition comprising, in a physiologically acceptable medium, DHEA and/or a precursor or chemical or biological derivative thereof, combined with at least a muscle relaxant, for preventing and treating skin ageing symptoms, in particular for reducing wrinkles or fine lines and/or for smoothing the kin. The muscle relaxant can in particular consist in an anti-cholinergic agent, a substance agonist of the receptor associated with a chlorine channel or a substance antagonist of a receptor associated with a calcium channel.

Description

COSMETIC COMPOSITION COMPRISING DHEA AND AT LEAST ONE MYORELAXING AGENT

The invention relates to the cosmetic use of a composition comprising, in a physiologically acceptable medium, DHEA and / or a precursor or chemical or biological derivative thereof, in combination with at least one muscle relaxant agent, for preventing or treat the signs of skin aging.

Women, even men, currently tend to want to look young for as long as possible and therefore seek to fade the marks of skin aging, which are reflected in particular by wrinkles and fine lines. In this regard, advertising and fashion refer to products intended to keep glowing, wrinkle-free skin as long as possible, marks of young skin, all the more as the physical appearance induces on the psyche and / or on morale. However, it is important to feel physically and morally young.

Until now, wrinkles and fine lines have generally been reduced using cosmetic products containing active agents acting on the skin, for example by moisturizing or improving its cell renewal or by promoting the synthesis of the collagen that makes up skin tissue. It has also been proposed to act on wrinkles by intervening on the muscular elements present in the skin.

It is indeed known that the facial skin muscles are under the control of the motor nerve afferents of the facial nerve and that, moreover, the inter-lobular partitions of the hypodermis contain within them fibers which constitute striated muscle tissue (panniculus carnosus). On the other hand, it is also known that a subpopulation of fibroblasts of the dermis, which are called myofibroblasts, has characteristics in common with muscle tissue.

The Applicant has in particular observed, in certain pathological and therapeutic situations, the role played on facial wrinkles by the nerves controlling all of this muscle tissue. Thus, in the attacks of the facial nerve, in which the transmission of the nerve impulse is interrupted and / or diminished, one attends in the territory of innervation a paralysis of the muscles of the face. This facial paralysis is reflected, among other clinical signs, by a reduction or even disappearance of wrinkles. Conversely, in states of hyper muscular contraction of the face, the applicant has observed an accentuation of facial wrinkles. In addition, she also observed an accentuation of facial wrinkles in the states of muscular hypertonia of Parkinson's disease and the side effects induced by neuroleptics.

In addition, it has been shown that the botulinum toxin, originally used to decrease spasms, can act on states of muscle spasticity (see A. Blitzer et al., Arch. Otolaryngol. Head Nec Surg., 1993, 1 19, pages 1018 to 1022) and on the glabella lines which are inter-eyebrow lines (see JD Carruters et al., J. Dermatol. Surg. Oncol., 1992, 18, pages 17 to 21). This botulinum toxin is also conventionally used in plastic surgery in the treatment of wrinkles. Consequently, it is possible to act by a pharmacological action on the neuromuscular component of wrinkles.

After numerous tests, the Applicant has been able to determine that the contractile muscle fibers, which are under the direct control of the neuro-muscular impulse, play an essential role in the formation of wrinkles and that the modulation of the neuro-influx muscle not only reduced wrinkles but also fine lines and also had a "smoothing" effect on the skin microrelief.

Various compounds have therefore been proposed, designated in the following description by "muscle relaxants", capable of modifying muscle relaxation:

- either directly on the nerve / muscle junction,

- either directly on the nerve component of muscle contraction, - or directly on the muscle component of muscle contraction.

to act on wrinkles and fine lines.

However, these compounds do not always make it possible to fight sufficiently effectively against the signs of skin aging.

However, it appeared to the Applicant that DHEA and / or its precursors or chemical or biological derivatives could make it possible to improve the anti-aging effectiveness of the compositions comprising muscle relaxants. DHEA, or dehydroepiandrosterone, is a natural steroid produced primarily by the adrenal cortex. It is known for its ability to promote keratinization of the epidermis (JP-07 196 467), or in the treatment of dry skin, due to its ability to increase endogenous production and sebum secretion and to strengthen the skin. barrier effect of the skin (US Pat. No. 4,496,556). The use of DHEA to remedy dermal atrophy by inhibiting the loss of collagen and connective tissue has also been described in US Pat. No. 5,843,932. It has also been described in US Pat. No. 5,736,537 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 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).

It has certainly already been proposed to combine DHEA or its sulfate with muscle relaxants such as glycine or verapamil in pharmaceutical compositions intended to treat degenerative diseases of the nervous system, such as Alzheimer's disease (US -4,812,447), cardiovascular diseases or arthritis (US-6,048,846), ulcers (JP-06 183 979) or other pathologies generally linked to andropause or menopause (WO 00/37109). It has also been suggested to combine DHEA sulfate with a muscle relaxant such as glycine in the preparation of a gynecological ovum (EP-0 380 036).

However, to the knowledge of the Applicant, it has never been suggested to combine DHEA and / or its precursors or derivatives with a muscle relaxant in order to treat the skin signs of aging.

The subject of the invention is therefore the cosmetic use of a composition comprising, in a physiologically acceptable medium, DHEA and / or a precursor or chemical or biological derivative thereof, in combination with at least one muscle relaxant agent, to prevent or treat the signs of skin aging, in particular to prevent or treat wrinkles and fine lines and / or to smooth the skin.

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 Λ5-pregnenolone, 17-hydroxy pregnenolone and 17α-hydroxy pregnenolone sulfate, without this list being exhaustive. 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, without this list being limiting. 7α-OH DHEA is preferred for use in the present invention. A process for the preparation of 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 2 806 725 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".

In the composition according to the invention, DHEA or the like is associated with at least one muscle relaxant.

The muscle relaxant may in particular be an anti-cholinergic agent, a substance agonist of a receptor associated with a chlorine channel or a substance antagonistic of a receptor associated with a calcium channel.

Anti-cholinergic agents are compounds which decrease the release of acetylcholine or which oppose the binding of acetylcholine to its receptors or which accelerate the degradation of acetylcholine, for example by activating acetylcholinase. An example of an anti-cholinergic agent is in particular the botulinum toxin.

The agonist substances of a receptor associated with a chlorine channel can in particular be chosen from certain amino acids such as glycine (as described in application EP 0 704 210).

Examples of antagonistic substances of a receptor associated with a calcium channel are in particular given in application FR 99/06290 in the name of the Applicant, which is incorporated here by reference. As preferred examples of such substances, mention may in particular be made of alverine and its derivatives, in particular alverine citrate, and verapamil.

The muscle relaxant according to the invention can be of natural or synthetic origin. By "natural origin" is meant a compound in the pure state or in solution whatever its concentration in said solution, which can be obtained according to different extraction methods from a natural element. By "synthetic origin" is meant a compound in the pure state or in solution at any concentration, obtained by chemical synthesis.

The composition according to the invention is preferably applied topically to the skin.

The present invention therefore also relates to a cosmetic method for preventing or treating signs of skin aging, in particular wrinkles and fine lines, comprising topical application to the skin of a composition comprising DHEA and / or a precursor or chemical or biological derivative thereof, in combination with at least one muscle relaxant.

In this case, DHEA and / or its analogs can be present in an amount ranging from 0.0001 to 10% by weight, and preferably from 0.001 to 5% by weight, relative to the total weight of the composition. More preferably, DHEA and / or its analogs may be present in an amount of about 1% by weight, based on the total weight of the composition.

For its part, the muscle relaxant may represent from 10 ^"12 to 5% of the total weight of the composition, and preferably from 10 ^{" 10} to 2% of the total weight of the composition. Of course, if the muscle relaxant is used in the form of a solution of plant extract, for example, a person skilled in the art will know how to adjust the amount of solution to be used in the composition according to the invention so that the final amount of muscle relaxant in this composition is included in the concentration ranges indicated above.

The composition according to the invention can be in all the galenical forms normally used in the cosmetic and dermatological fields, and it can be in particular in the form of an aqueous solution possibly gelled, of a dispersion of the lotion type possibly biphasic, of an emulsion obtained by dispersing a fatty phase in an aqueous phase (O / W) or vice versa (W / O), or a triple emulsion (W / O / W or O / W / O). These compositions are prepared according to the usual methods.

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. . It can optionally be applied to the skin in the form of an aerosol. It can also be in solid form, in particular in the form of a stick. It can be used as a care product and / or as a make-up product for the skin.

In a known manner, the composition of the invention can also contain the adjuvants usual in the cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, perfumes, fillers, filters, pigments, odor absorbers and coloring matters. The amounts of these various adjuvants are those conventionally used in the field considered, 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. In any event, these adjuvants, as well as their proportions, will be chosen so as not to harm the desired properties of the combination of active agents according to the invention.

When the composition of 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 oils, 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 co-emulsifier are 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 oils which can be used in the invention, mention may be made of mineral oils (petrolatum oil), oils of vegetable origin (avocado oil, soybean oil), oils of animal origin (lanolin), oils of synthesis (perhydrosqualene), silicone oils (cyclomethicone) and fluorinated oils (perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids, waxes (camauba wax, ozokerite) 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-20 stearate, and fatty acid and glycerin esters such as glyceryl stearate .

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, hydrophobic silica and polyethylenes.

According to another possibility, the composition according to the invention can be administered orally. The present invention therefore also relates to a cosmetic method for preventing or treating signs of skin aging, in particular wrinkles and fine lines, comprising the oral administration of a composition comprising DHEA and / or a precursor or chemical derivative or biological thereof, in combination with at least one muscle relaxant.

In the case where the composition is administered orally, DHEA and / or its analogs can be administered at a rate of 1 to 100 mg / day, preferably from 25 to 75 mg / day and the muscle relaxant agent can be administered at 10 ^"10 to 500 mg / day, preferably 1 to 200 mg / day, better, 50 to 150 mg / day.

This composition can be in any dosage form suitable for this mode of administration, for example in the form of breakable tablets or not, granules, capsules, capsules, solutes, suspensions or solutions comprising an appropriate excipient.

In all cases, the composition according to the invention comprises a physiologically acceptable medium.

The invention will be better understood, and its advantages will emerge more clearly in the light of the following examples, which are given by way of illustration, and without limitation.

EXAMPLES

Example 1 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 Alverine citrate 100 mg

DHEA 50 mg

Example 2 -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:

7 OH-DHEA 1% Alverine citrate 0.8%

2% glycerol stearate

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

Stearic acid 1.4%

Triethanolamine 0.7% Carbomer 0.4%

Liquid fraction of shea butter 12%

Perhydrosqualene 12%

Perfume 0.5%

Preservative QS Water QSP 100%

Claims

1. Cosmetic use of a composition comprising, in a physiologically acceptable medium, DHEA and / or a precursor or chemical or biological derivative thereof, in combination with at least one muscle relaxant, for preventing or treating the signs of aging skin.

2. Cosmetic use of a composition comprising, in a physiologically acceptable medium, DHEA and / or a precursor or chemical or biological derivative thereof, in combination with at least one muscle relaxant, for preventing or treating fine lines and wrinkles and / or to smooth the skin.

3. Use according to claim 1 or 2, characterized in that said biological precursor is chosen from: Δ5-pregnenolone, 17α-hydroxy pregnenolone and 17α-hydroxy pregnenolone sulfate.

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

5. Use according to claim 4, characterized in that said chemical precursor is chosen from diosgenin, hecogenin, hecogenin acetate, smilagenin and sarsapogenin.

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

7. Use according to claim 6, characterized in that said Dîoscorée extract is an extract of wild yam root.

8. Use according to claim 1 or 2, characterized in that said biological derivative is chosen from: Δ5-androstene-3, 17-diol, Δ4-androstene-3,17-dione, 7αOH-DHEA, 7β -OH DHEA and 7-keto DHEA.

9. Use according to claim 1 or 2, characterized in that said chemical derivative is chosen from salts and esters of DHEA.

10. Use according to any one of the preceding claims, characterized in that the muscle relaxant is chosen from: an anti-cholinergic agent, a substance agonist of a receptor associated with a chlorine channel and a substance antagonist of a receptor associated with a calcium channel.

11. Use according to claim 10, characterized in that said anti-cholinergic agent is botulinum toxin.

12. Use according to claim 10, characterized in that said agonist substance of a receptor associated with a chlorine channel is chosen from glycine.

13. Use according to claim 10, characterized in that said antagonist substance of a receptor associated with a calcium channel is chosen from: alverine and its derivatives, and verapamil.

14. Use according to claim 13, characterized in that said antagonist substance of a receptor associated with a calcium channel is alverine citrate.

15. Use according to any one of the preceding claims, characterized in that the composition is applied topically to the skin.

16. Use according to claim 15, characterized in that the DHEA and / or its precursor or derivative are present in an amount ranging from 0.001 to 5% by weight, relative to the total weight of the composition.

17. Use according to claim 16, characterized in that the DHEA and / or its precursor or derivative are present in an amount of approximately 1% by weight, relative to the total weight of the composition.

18. Use according to any one of claims 15 to 17, characterized in that the muscle relaxant represents from 10 ^"10 to 2% of the total weight of the composition.

19. Use according to any one of claims 1 to 14, characterized in that the composition is administered orally.

20. Cosmetic method for preventing or treating signs of skin aging, in particular fine lines and wrinkles, comprising the oral administration of a composition comprising DHEA and / or a precursor or chemical or biological derivative thereof , in combination with at least one muscle relaxant.

21. The method of claim 20, characterized in that DHEA or its precursor or derivative is administered at a rate of 1 to 100 mg / day, preferably from 25 to 75 mg / day.

22. The method of claim 20 or 21, characterized in that the muscle relaxant is administered at a rate of 1 to 200 mg / day, preferably from 50 to 150 mg / day.

23. Cosmetic method for preventing or treating signs of skin aging, in particular wrinkles and fine lines, comprising the topical application to the skin of a composition comprising DHEA and / or a chemical or biological precursor or derivative thereof. ci, in combination with at least one muscle relaxant.