FR2846882A1 - Use of phenyl-substituted secondary or tertiary amines to prepare compositions for topical application to the skin to smooth out wrinkles - Google Patents

Abstract

Phenyl-substituted secondary or tertiary amines (I) are used to prepare compositions for topical application to the skin to smooth out wrinkles and fine lines. Phenyl-substituted secondary or tertiary amines of formula (I) or their acid addition salts are used to prepare compositions for topical application to the skin to smooth out wrinkles and fine lines: R1-R8 = H or 1-12C (un)saturated alkyl, or adjacent pairs can form double bonds; R9 = H or 1-12C (un)saturated alkyl; R10 = 1-12C (un)saturated alkyl; R = alkyl, OR11, SR11, NR11R12, COOR11, CONR11R12, CF3 or halo; R11, R12 = H, 1-4C alkyl or aryl, optionally substituted with OR', NR'R, COOR' or CF3; R', R = H, 1-4C alkyl or aryl; m = 0-5; and n = 0-1.

Description

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The present invention relates to the use of a secondary or tertiary phenyl amine of given formula, for producing a composition adapted for topical application to the skin, intended to smooth wrinkles and fine lines. It also relates to the use of such an amine in a composition suitable for topical application to the skin, as an agent for smoothing out fine lines and wrinkles.

Women, even men, tend to want to look young as long as possible and therefore seek to fade the marks of aging skin, which result in particular in the form of wrinkles and fine lines. In this regard, advertising and fashion mention products intended to keep as long as possible a glowing skin without wrinkles, marks of a young skin, especially as the physical aspect acts on the psyche and / or on morale.

Until now, wrinkles and fine lines have been treated with cosmetic products containing active agents acting on the skin, for example by moisturizing it or improving its cell renewal, or by promoting the synthesis of the collagen that makes up the skin. cutaneous tissue.

Although these treatments can act on wrinkles and fine lines due to chronological or intrinsic aging, as well as those due to photoaging, they have no effect on wrinkles and fine lines of expression, which require intervention on the contractile muscle component of wrinkles present in the skin.

Until now, the only way commonly used to act on expression wrinkles is botulinum toxin which is in particular injected into the wrinkles of the glabella which are inter-eyebrow wrinkles (see JD Carruters et al., J. Dermatol Surg, Oncol, 1992, 18, pp. 17-21).

The Applicant has furthermore proposed various compounds capable of offering a myorelaxant effect when applied topically to the skin, thus making it possible to act by another route on expression lines. Among these compounds, mention may in particular be made of calcium channel-associated receptor antagonists (FR-2 793 681), and in particular manganese and its salts (FR-2 809 005) and alverine (FR-2 798 590) ; andthe receptor agonists associated with the chlorine channels, including glycine (EP-0 704 210) and certain extracts of Iris pallida (FR-2 746 641).

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 However, there remains the need for effective compounds to smooth or fade wrinkles and fine lines of expression.

Now, the Applicant has discovered with astonishment that certain secondary and tertiary phenyl amines make it possible to satisfy this need.

EP-1 090 630 discloses certain amines having the property of increasing collagen synthesis by fibroblasts and of moisturizing the skin, which are useful against dry skin and atopic dermatitis, and which also have an efficacy. on wrinkles. However, the phenyl amines recited herein are all primary amines. In addition, they have no effect on expression lines and wrinkles.

WO 93/05763 discloses certain amines di- and trisubstituted by at least two chains each carrying at least one hydroxyl group. These amines increase the differentiation of keratinocytes, limit the UV-induced thickening of the epidermis and are useful for preventing and treating UVB-induced wrinkles. It is not suggested that these amines, different from those of the present invention, have any effect on expression lines and wrinkles.

Similarly, EP-0 691 327 discloses a very large family of mono-, di- or trisubstituted amines described as effective for smoothing wrinkles.

The amines exemplified in this patent application are polyhydroxylated or polyalkoxylated, unlike the amines object of the present invention. In addition, it is not suggested that they have any effect on expression lines and wrinkles.

The Applicant has now discovered that by selecting certain primary and secondary amines of simple structure, comprising a phenyl group, it was possible to obtain effective cosmetic compositions for smoothing wrinkles and fine lines of expression.

The subject of the present invention is therefore the use of at least one compound of formula (I):

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Ri, R2, R3, R4, R5, R6, R7, R8. identiques ou différents, sont choisis parmi : un atome d'hydrogène, un groupe alkyle linéaire ou ramifié, saturé ou insaturé, en C1-C12, non substitué, Rg est choisi parmi : un atome d'hydrogène, un groupe alkyle linéaire ou ramifié, saturé ou insaturé, en C1-C12, non substitué, R10 est un groupe alkyle linéaire ou ramifié, saturé ou insaturé, en C1-C12, non substitué, les substituants R sont indépendamment choisis parmi : un groupe alkyle, -OR11, SR11, -NR11R12, -COORn, -CONR11R12, -CF3 et un atome d'halogène, où R11 et R12, identiques ou différents, sont choisis parmi : un atome d'hydrogène, un groupe alkyle en C1-C4, linéaire ou ramifié, et un groupe aryle, éventuellement substitués par un groupe-OR',-NR'R", -COOR' ou -CF3, où R' et R", identiques ou différents, sont choisis parmi : un atome d'hydrogène, un groupe alkyle en C1-C4, linéaire ou ramifié, et un groupe aryle non substitués, m est compris entre 0 et 5, n est compris entre 0 et 1 étant entendu que les groupes Ri, R3 ; R3, R5 ; R5, R7 , R2, R4 ; R4, R6 ; Re, Rs respectivement pris ensemble, peuvent former une double liaison, ou son sel d'addition avec un acide, pour fabriquer une composition adaptée à une application topique sur la peau, destinée à lisser les rides et ridules.

R1, R2, R3, R4, R5, R6, R7, R8. identical or different, are chosen from: a hydrogen atom, a linear or branched, unsaturated, saturated or unsubstituted C1-C12 alkyl group, Rg is chosen from: a hydrogen atom, a linear or branched alkyl group; saturated or unsaturated, unsubstituted C1-C12, R10 is unsubstituted or unsubstituted, C1-C12 linear or branched, unsaturated alkyl group, the substituents R are independently selected from: an alkyl group, -OR11, SR11 , -NR11R12, -COORn, -CONR11R12, -CF3 and a halogen atom, wherein R11 and R12, which may be identical or different, are chosen from: a hydrogen atom, a linear or branched C1-C4 alkyl group, and an aryl group, optionally substituted by a group-OR ', -NR'R ", -COOR' or -CF3, where R 'and R", which are identical or different, are chosen from: a hydrogen atom, a group C1-C4 alkyl, linear or branched, and unsubstituted aryl, m is 0-5, n is 0-1 only groups R1, R3; R3, R5; R5, R7, R2, R4; R4, R6; Re, Rs respectively taken together, can form a double bond, or its acid addition salt, to make a composition suitable for topical application to the skin, for smoothing out fine lines and wrinkles.

It also relates to the use of at least one compound of formula (I) as defined above, in a composition suitable for topical application to the skin, as an agent for smoothing out fine lines and wrinkles.

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In the formula (1), the C 1 -C 12 alkyl group may be chosen from the following groups: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl , decyl, undecyl and dodecyl, while the C1-C4 alkyl group may be selected from: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl.

For its part, the aryl group may be chosen from a benzyl group and a phenyl group.

The halogen atom can be a fluorine, chlorine, bromine or iodine atom.

As salts of the compound of formula (1), mention may be made of the salts obtained by adding the compound of formula (I) with an inorganic acid, chosen in particular from hydrochloric, sulfuric, nitric and phosphoric acids, or with an organic acid, chosen from in particular, among succinic, fumaric, lactic, glycolic, citric and tartaric acids.

. R3 = R4 = R5 = Rg = R7 = Rs = H # Rg= H dans la formule (1). According to a preferred embodiment of the invention, the compound of formula (I) is such that at least one of the following conditions, and preferably all these conditions, are satisfied: # m = 0 # n = 0

. R3 = R4 = R5 = Rg = R7 = Rs = H # Rg = H in formula (1).

As will be demonstrated in the Examples below, the Applicant has demonstrated a myorelaxant effect of the compounds of formula (I) according to the invention, which allows to consider their use, especially in the smoothing of wrinkles and fine lines of 'expression.

The composition according to the invention is therefore advantageously intended to be applied to the areas of the face or the forehead marked by expression lines and wrinkles, and / or to persons with wrinkles and fine lines of expression.

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 The wrinkles and fine lines concerned are preferably those arranged radially around the mouth and / or eyes, in particular crow's feet wrinkles, and / or located at the forehead, in particular the so-called lion's wrinkle, at the level of the glabella, in the space inter-sourcillier, and / or arranged horizontally on the forehead.

 The amount of compound (s) formula (I) 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, this compound can be used in an amount representing from 0.01% to 10% of the total weight of the composition, preferably in an amount representing from 0.05% to 5% of the total weight of the composition. more preferably in an amount of from 0.1% to 2% of the total weight of the composition.

The composition according to the invention is suitable for topical application to the skin and therefore contains a physiologically acceptable medium, that is to say compatible with the skin and optionally with its integuments (eyelashes, nails, hair) and / or mucous.

This composition may be in any galenical form normally used in the cosmetics field, and it may especially be in the form of an optionally gelled aqueous solution, an optionally biphasic lotion-type dispersion, an emulsion obtained by dispersion of a fatty phase in an aqueous phase (O / W) or conversely (W / O), or a triple emulsion (W / O / W or W / O / H) or a vesicular dispersion of ionic type and or nonionic. These compositions are prepared according to the usual methods. It is preferred to use according to this invention a composition in the form of an oil-in-water emulsion.

This composition may 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 mousse . It can optionally be applied 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.

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In a known manner, the composition used according to the invention may also contain the usual adjuvants 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 dyestuffs. The amounts of these various adjuvants are those conventionally used in the field 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, into the aqueous phase or into the lipid vesicles. In any case, these adjuvants, as well as their proportions, will be chosen so as not to interfere with the desired properties of the compounds of formula (I) according to the invention.

When the composition used 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 oils, emulsifiers and coemulsifiers used in the composition in emulsion form are chosen from those conventionally used in the field under consideration. The emulsifier and the coemulsifier 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 (vaseline oil), vegetable oils (avocado oil, soya oil), animal oils (lanolin), vegetable oils and the like. synthesis (perhydrosqualene), silicone oils (cyclomethicone) and fluorinated oils (perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids, waxes (carnauba wax, ozokerite) can also be used as fats.

As emulsifiers and coemulsifiers that can be used in the invention, mention may be made, for example, of fatty acid and polyethylene glycol esters such as PEG-100 stearate, and fatty acid and glycerine esters such as glyceryl stearate. .

As hydrophilic gelling agents, mention may in particular be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as copolymers of acrylates / alkylacrylates, polyacrylamides, polysaccharides, natural gums and clays, and, as lipophilic gelling agents, it is possible to mention quote the clays

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 modified such as bentones, metal salts of fatty acids, hydrophobic silica and polyethylenes.

As active agents, it will be advantageous to introduce into the composition used according to the invention at least one compound chosen from: desquamating agents; moisturizing agents; depigmenting or propigmenting agents; anti-glycation agents; NO-synthase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; muscle relaxants; tensors; anti-pollution and / or anti-radical agents; agents acting on microcirculation; agents acting on the energetic metabolism of cells; and their mixtures.

Examples of such additional compounds are given below.

1. desquamating agents "desquamating agent" means any compound capable of acting: - either directly on desquamation by promoting exfoliation, such as sshydroxyacids, in particular salicylic acid and its derivatives (including the acid n-octanoyl 5-salicylic); α-hydroxy acids, such as glycolic, citric, lactic, tartaric, malic or mandelic acids; urea; gentisic acid; oligofucoses; cinnamic acid; Saphora japonica extract; resveratrol; or on the enzymes involved in the desquamation or degradation of corneodesmosomes, glycosidases, stratum corneum chymotryptic enzyme (SCCE) or even other proteases (trypsin, chymotrypsin-like). Mention may be made of the chelating agents for mineral salts: EDTA; N-acyl-N, N ', N', ethylene diaminetriacetic acid; aminosulfonic compounds and in particular (N-2-hydroxyethylpiperazine-N-2-ethane) sulfonic acid (HEPES); derivatives of 2oxothiazolidine-4-carboxylic acid (procysteine); glycine-type alpha amino acid derivatives (as described in EP-0 852 949, as well as the sodium methyl glycine diacetate marketed by BASF under the trade name TRILON M);

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 honey ; sugar derivatives such as O-octanoyl-6-D-maltose and N-acetyl glucosamine.

2. Moisturizing agent By "moisturizing agent" is meant: - either a compound acting on the barrier function, with a view to maintaining the hydration of the stratum corneum, or an occlusive compound. There may be mentioned ceramides, sphingoid-based compounds, lecithins, glycosphingolipids, phospholipids, cholesterol and its derivatives, phytosterols (stigmasterol, sssitosterol, campesterol), essential fatty acids, 1-2 diacylglycerol, 4chromanone pentacyclic triterpenes such as ursolic acid, petrolatum and lanolin; or a compound directly increasing the water content of the stratum corneum, such as thralose and its derivatives, hyaluronic acid and its derivatives, glycerol, pentanediol, sodium pidolate, serine, xylitol, lactate sodium, glycerol polyacrylate, ectoin and its derivatives, chitosan, oligo- and polysaccharides, cyclic carbonates, N-lauroyl pyrrolidone carboxylic acid, and Na-benzoyl-L-arginine; or an activating compound for the sebaceous glands, such as DHEA and its derivatives, and vitamin D and its derivatives.

3. Depigmenting or Proligating Agent The depigmenting agents that may be incorporated into the composition according to the present invention comprise, for example, the following compounds: kojic acid; ellagic acid; arbutin and its derivatives such as those described in EP-895,779 and EP-524,109; hydroquinone; aminophenol derivatives such as those described in applications WO 99/10318 and WO 99/32077, and in particular Ncholesteryloxycarbonyl-para-aminophenol and N-ethyloxycarbonyl-para-aminophenol; iminophenol derivatives, in particular those described in application WO 99/22707; L-2-oxothiazolidine-4-carboxylic acid or procysteine, as well as its salts and esters;

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 ascorbic acid and its derivatives, especially ascorbyl glucoside; and plant extracts, in particular licorice, mulberry and skullcap, without this list being limiting.

As a pro-pigmenting agent, mention may be made of burnet extract (Sanguisorba officinalis) marketed by the company MARUZEN and extracts of chrysanthemum (Chrysanthemum morifolium).

4. Anti-glycation agent By "anti-glycation agent" is meant a compound that prevents and / or decreases the glycation of skin proteins, in particular dermal proteins such as collagen.

Examples of anti-glycation agents are plant extracts of the family Ericaceae, such as a bilberry extract (Vaccinium angustifolium); ergothioneine and its derivatives; and hydroxystilbenes and their derivatives, such as resveratrol and 3,3 ', 5,5'-tetrahydroxystilbene.

5. NO-synthase inhibitor Examples of NO-synthase inhibitors that are suitable for use in the present invention include, in particular, a plant extract of the Vitis vinifera species which is sold in particular by the company Euromed under the name Leucocyanidines of Grapes. extra, or by the company Indena under the name Leucoselect #, or finally by the company Hansen under the name Extract of marc de raisin; a plant extract of the species Olea europaea which is preferably obtained from olive leaves and is especially marketed by VINYALS in the form of dry extract, or by Biologia & Technologia under the trade name Eurol BT ; and an extract of a plant of the Gingko biloba species which is preferably a dry aqueous extract of this plant sold by Beaufour under the trade name Ginkgo biloba standard extract.

6. Agent stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation

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 Among the active agents stimulating the macromolecules of the dermis or preventing their degradation, there may be mentioned those which act: either on the synthesis of collagen, such as extracts of Centella asiatica; asiaticosides and derivatives; ascorbic acid or vitamin C and its derivatives; synthetic peptides such as iamin, the biopeptide CL or palmitoyloligopeptide marketed by SEDERMA; peptides extracted from plants, such as the soy hydrolyzate marketed by the company Coletica under the trade name Phytokine; and plant hormones such as auxins.

or on the synthesis of elastin, such as the extract of Saccharomyces Cerivisiae sold by the company LSN under the trade name Cytovitin; and the algae extract Macrocystis pyrifera marketed by SECMA under the trade name Kelpadelie #; or on the synthesis of glycosaminoglycans, such as the product of fermentation of milk with lactobacillus vulgaris, marketed by BROOKS under the trade name Biomin yogourth #; the extract of the brown alga Padina pavonica marketed by the company Alban Müller under the trade name HSP3; and the Saccharomyces cerevisiae extract available in particular from the company Silab under the trade name Firmalift or from the company LSN under the trade name Cytovitin; or on the synthesis of fibronectin, such as the Salina zooplankton extract marketed by Seporga under the trade name GP4G #; the yeast extract available in particular from the company Alban Mueller under the trade name Drieline #; and the palmitoyl pentapeptide marketed by SEDERMA under the trade name Matrixil; - Or on the inhibition of metalloproteinases (MMP) such as more particularly the MMP 1, 2,3, 9. There may be mentioned: retinoids and derivatives, oligopeptides and lipopeptides, lipoamino acids, malt extract marketed by the company Coletica under the trade name Collalift #; extracts of blueberry or

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 rosemary; lycopene; isoflavones, their derivatives or plant extracts containing them, in particular extracts of soya (marketed for example by the company Ichimaru Phacos under the trade name Flavosterone SB #), red clover, flax, kakkon or sage; or on the inhibition of serine proteases such as leucocyte elastase or cathepsin G. Mention may be made of: the peptide extract of leguminous seeds (Pisum sativum) sold by the company LSN under the trade name Parelastyl; heparinoids; and pseudodipeptides.

Among the active agents stimulating epidermal macromolecules, such as fillagrin and keratins, mention may be made in particular of the lupine extract marketed by SILAB under the trade name Structurine; the extract of beech buds Fagus sylvatica marketed by the company GATTEFOSSE under the trade name Gatuline #; and Salina zooplankton extract marketed by the company SEPORGA under the trade name GP4G #.

7. Agent stimulating the proliferation of fibroblasts or keratinocytes and / or the differentiation of keratinocytes The agents stimulating the proliferation of fibroblasts that can be used in the composition according to the invention may for example be chosen from plant proteins or polypeptides, extracted especially from soybean ( for example a soybean extract marketed by the company LSN under the name Eleseryl SH-VEG 8 # or sold by the company SILAB under the trade name Raffermine #); and plant hormones such as giberrellins and cytokinins.

The agents stimulating the proliferation of keratinocytes, usable in the composition according to the invention, include retinoids such as retinol and its esters, including retinyl palmitate; phloroglucinol; nut cake extracts sold by the company GATTEFOSSE; and extracts of Solanum tuberosum marketed by SEDERMA.

Agents stimulating the differentiation of keratinocytes include, for example, minerals such as calcium; the lupine extract marketed by SILAB

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 under the trade name Photopreventine #; sodium beta-sitosteryl sulphate marketed by Seporga under the trademark Phytocohesine; and the corn extract marketed by SOLABIA under the trade name Phytovityl.

8. Muscle Relaxing Agent In addition to the compound of formula (I) described above, the composition according to the invention may comprise other muscle-relaxing agents, among which mention may in particular be made of alverine and its salts, in particular alverine citrate, manganese gluconate, sapogenins such as diosgenin and natural extracts containing them (such as extracts of Wild Yam), as well as the hexapeptide argireline R marketed by LIPOTEC.

9. Tensing agent "Tensing agent" means a compound capable of exerting traction on the skin, which has the effect of temporarily reducing the irregularities on the surface of the skin, such as wrinkles and fine lines.

Among the tensing agents that may be used in the composition according to the present invention, mention may be made in particular of: (1) synthetic polymers, such as polyurethane latices or acrylic-silicone latexes, in particular those described in patent application EP-1038519 such as propylthio (methyl polyacrylate), propylthio (polymethyl methacrylate) and propylthio (polyacrylic acid) graft polydimethyl siloxane, or a propylthio (isobutyl polymethacrylate) and propylthio (polyacrylic acid) grafted polydimethyl siloxane. Such grafted silicone polymers are in particular sold by the company 3M under the trade names VS 80, VS 70 or LO21, (2) polymers of natural origin, in particular (a) polyholosides, for example (i) in the form of starch obtained especially from rice, maize, potato, cassava, peas, wheat, oats, etc ... or (ii) in the form of carrageenans, alginates, agars, gellans, cellulosic polymers and pectins , advantageously in dispersion

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 aqueous gel microparticles, and (b) latexes consisting of shellac resin, sandarac gum, dammars, elemis, copals, cellulosic derivatives, and mixtures thereof, (3) protein and vegetable protein hydrolysates , in particular maize, rye, wheat, buckwheat, sesame, pepper, pea, bean, lentil, soybean and lupine, (3) mixed silicates, in particular phyllosilicates, and in particular Laponites, (4) wax microparticles, chosen, for example, from Carnauba, Candelila or Alfa waxes, (5) colloidal particles of inorganic filler having a number average diameter of between 0.1 and 100 nm. , preferably between 3 and 30 nm, and chosen for example from: silica, cerium oxide, zirconium oxide, alumina, calcium carbonate, barium sulphate, calcium sulphate, zinc oxide and titanium dioxide.

10. Anti-pollution or anti-radical agent By the term "anti-pollution agent" is meant any compound capable of trapping ozone, mono- or polycyclic aromatic compounds such as benzopyrene and / or heavy metals such as cobalt, mercury, cadmium and / or nickel. By "anti-radical agent" is meant any compound capable of trapping free radicals.

As ozone-trapping agents that may be used in the composition according to the invention, mention may be made in particular of vitamin C and its derivatives including ascorbyl glucoside; phenols and polyphenols, in particular tannins, ellagic acid and tannic acid; epigallocatechin and natural extracts containing it; olive leaf extracts; tea extracts, especially green tea; anthocyanins; rosemary extracts; phenolic acids, in particular chorogenic acid; stilbenes, in particular resveratrol; sulfur-containing amino acid derivatives, in particular Scarboxymethylcysteine; ergothioneine; N-acetylcysteine; chelating agents such as N, N'-bis- (3,4,5-trimethoxybenzyl) ethylenediamine or a salt thereof, metal complexes or esters; carotenoids such as crocetin; and various raw materials such as the mixture of arginine, histidine ribonucleate, mannitol, adenosinetriphosphate, pyridoxine, phenylalanine, tyrosine and hydrolysed RNA marketed by Serobiological Laboratories under the name

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 commercial CPP LS 2633-12F #, the water-soluble corn fraction marketed by the company SOLABIA under the trade name Phytovityl, the mixture of fumitory extract and lemon extract marketed under the name Unicotrozon C-49 # by the company Induchem , and the mixture of extracts of ginseng, apple, peach, wheat and barley sold by the company PROVITAL under the trade name Pronalen Bioprotect.

As scavengers for mono- or polycyclic aromatic compounds that can be used in the composition according to the invention, mention may be made in particular of tannins such as ellagic acid; indole derivatives, in particular indol-3-carbinol; tea extracts especially green tea, extracts of water hyacinth or eichornia crassipes; and the water soluble fraction of corn marketed by the company SOLABIA under the trade name Phytovityl.

Finally, as scavengers for heavy metals that may be used in the composition according to the invention, there may be mentioned in particular chelating agents such as EDTA, the pentasodium salt of ethylenediamine tetramethylene phosphonic acid, and N, N'-bis- ( 3,4,5-trimethoxybenzyl) ethylenediamine or a salt thereof, metal complexes or esters; phytic acid; chitosan derivatives; tea extracts, especially green tea; tannins such as ellagic acid; sulfur-containing amino acids such as cysteine; water hyacinth (Eichornia crassipes) extracts; and the water soluble fraction of corn marketed by the company SOLABIA under the trade name Phytovityl.

The anti-radical agents that can be used in the composition according to the invention comprise, in addition to certain anti-pollution agents mentioned above, vitamin E and its derivatives such as tocopheryl acetate; bioflavonoids; coenzyme Q10 or ubiquinone; enzymes such as catalase, superoxide dismutase, lactoperoxidase, glutathione peroxidase and quinone reductases; glutathione; benzylidene camphor; benzylcyclanones; substituted naphthalenones; pidolates; phytantriol; gamma-oryzanol; lignans; and melatonin.

11. Agents acting on microcirculation

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 The active agents acting on microcirculation (vasoprotective or vasodilatory), are found in particular among the flavonoids, ruscogenins, esculosides, escin extracted from horse chestnut, nicotinates, heparidin methyl chalcone, essential oils of lavender or of rosemary, extracts from Ammi Visnaga.

12. Agents acting on the energetic metabolism of the cells By this expression, we mean the active agents acting on the cutaneous energetic metabolism such as, for example, and in a nonlimiting manner, the synthesis of ATP, as well as those which intervene on the respiratory chain of the cell or energy reserves. These include Coenzyme Q10 (ubiquinone), cytochrome C, creatine or phosphocreatine.

As indicated above, the composition according to the invention may also contain UVA and / or UVB filters, in the form of organic or inorganic compounds, the latter being optionally coated to make them hydrophobic.

The organic screening agents may especially be chosen from: anthranilates, in particular menthyl anthranilate; benzophenones, in particular benzophenone-1, benzophenone-3, benzophenone-5, benzophenone-6, benzophenone-8, benzophenone-9, benzophenone-12, and preferentially benzophenone-3 (oxybenzone), or Benzophenone-4 (Uvinul MS40 available from BASF); benzylidenecamphers, in particular 3-benzylidene camphor, benzylidenecamphosulfonic acid, camphor benzalkonium methosulphate, polyacrylamidomethylbenzylidene camphor, terephthalylidene di-camphorsulfonic acid, and preferentially 4-methylbenzylidene camphor (Eusolex 6300 available). at Merck); benzimidazoles, in particular benzimidazilate (Neo Heliopan AP available from Haarmann and Reimer), or phenylbenzimidazole sulfonic acid (Eusolex 232 available from Merck); benzotriazoles, in particular trisiloxane drometzol, or methylene bis-benzotriazolyltetramethylbutylphenol (Tinosorb M available from Ciba); cinnamates, in particular cinoxate, DEA methoxycinnamate, diisopropyl methylcinnamate, dimethoxycinnamate glyceryl ethylhexanoate, isopropyl methoxycinnamate, isoamyl cinnamate, and

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 preferentially ethocrylene (Uvinul N35 available from B.A.S.F.), octylmethoxycinnamate (Parsol MCX available from Hoffmann La Roche), or octocrylene (Uvinul 539 available from B.A.S.F.); dibenzoylmethanes, especially butyl methoxydibenzoylmethane (Parsol 1789); imidazolines, in particular ethylhexyl dimethoxybenzylidene dioxoimidazoline; PABAs, in particular ethyl dihydroxypropyl PABA, ethylhexyldimethyl PABA, glyceryl PABA, PABA, PEG-25 PABA, and preferentially diethylhexylbutamido-triazone (Uvasorb HEB available from 3V Sigma), ethylhexyltriazone (Uvinul T150 available from BASF), or ethyl PABA (benzocaine); salicylates, especially dipropylene glycol salicyclate, ethylhexyl salicylate, homosalate, or TEA salicylate; triazines, in particular anisotriazine (Tinosorb S available from Ciba); drometrizole trisiloxane.

The inorganic filters are preferably made of zinc oxide and / or titanium dioxide, preferably of nanometric size, optionally coated with alumina and / or stearic acid.

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

Exemple 1 : synthèse de l'heptyl-(3-phényl-propyl -amine

EXAMPLES

Example 1 Synthesis of Heptyl- (3-Phenylpropylamine)

10 g of 3-phenyl-1-propylamine solubilized in 100 ml of methanol are added, 8.9 g of heptaldehyde are added and the mixture is left to react for 6 hours at 50 ° C. 3.64 g of NaBH 4 is then added and the mixture is left to react for 3 hours. at room temperature. 100 ml of water are added and the methanol is evaporated under vacuum. The residual aqueous phase is extracted with 2 × 100 ml of CH 2 Cl 2. The organic phases are dried over sodium sulphate before concentration under reduced pressure. The yield is 98%.

Example 2 Synthesis of Rethyl-heptyl-3-phenyl-propyl-amine

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A 0,4g d'heptyl-(3-phényl-propyl)-amine solubilisée dans 10 ml de DMF anhydre, on ajoute 72 mg de NaH à 60% en dispersion dans l'huile. On laisse réagir 30 minutes à température ambiante sous argon, puis on additionne 0,2 ml d'iodure d'éthyle eton laisse réagir 5h. On dilue le milieu par 20 ml d'une solution saturée en NaHCO3, et on extrait par 2x50 ml de dichlorométhane. Les phases organiques sont séchées sur sulfate de sodium, et purifiées sur colonne de silice en éluant par du dichlorométhane et en faisant un gradient de méthanol jusqu'à 5%. Le rendement est de 22%.

To 0.4 g of heptyl- (3-phenyl-propyl) -amine solubilized in 10 ml of anhydrous DMF is added 72 mg of 60% NaH in dispersion in oil. Allowed to react for 30 minutes at room temperature under argon, then 0.2 ml of ethyl iodide is added and allowed to react 5h. The medium is diluted with 20 ml of a saturated solution of NaHCO 3 and extracted with 2x50 ml of dichloromethane. The organic phases are dried over sodium sulphate and purified on a silica column, eluting with dichloromethane and making a methanol gradient of up to 5%. The yield is 22%.

Example 3: synthesis of butyl- (3-phenyl-propyl) -amine

To 1 g of 3-phenyl-1-propylamine solubilized in 20 ml of methanol, 0.56 g of butyraldehyde is added and the mixture is left to react for 2 hours at 50 ° C. Then 0.25 g of NaBH 4 are added and the reaction is left to react for 3 hours. room. 15 ml of water are added and the methanol is evaporated under vacuum. The residual aqueous phase is extracted with 2x 50ml of AcOEt. The organic phases are dried over sodium sulphate, before concentration under reduced pressure and purification on a silica column. The yield is 50%.

Example 4 Synthesis of Ethyl- (3-phenyl-propyl) -amine

1 equivalent of 3-phenylpropylamine (36.98 mmol, 5.3 ml), 1 equivalent of acetaldehyde (36.98 mmol, 2.1 ml) and 25 ml of ethanol are mixed and heated at 50 ° C. for 3 hours . 1.4 equivalents of sodium borohydride (9.320 mmol, 353 mg) are added in small spatulas and stirred at room temperature for 2 hours. The reaction medium is concentrated and taken up in water. The organic phase is then extracted with 2 portions of 20 ml of dichloromethane and the organic phase is then dried over anhydrous sodium sulphate and concentrated to dryness.

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6.0 g of a yellow oil are obtained. The yield is 99%. Example 5 Synthesis of dodecyl-ethyl- (3-phenyl-propyl) -amine

In a 50 ml three-necked mixture, 1 equivalent of ethyl (3-phenylpropyl) amine (6.135 mmol, 1 g), 1 equivalent of potassium carbonate (6.135 mmol, 850 mg), 15 ml of dimethylformamide and 1 , 5 ml of bromododecane. Stir at room temperature for 12 hours. The reaction medium is diluted with dichloromethane and the organic phase is washed with a saturated solution of sodium hydrogencarbonate, then dried over anhydrous sodium sulphate and concentrated to dryness before purification on a silica column, eluting with dichloromethane and making a gradient of methanol up to 5%. 530 mg of a yellow oil are obtained. The yield is 30%.

Example 6 Synthesis of 3- (3,4-Dimethoxy-phenyl) -propyl-heptyl-amine

To 1 equivalent of 3- (3,4-dimethoxy-phenyl) propionaldehyde (2.577 mmol, 500 mg) solubilized in 10 ml of absolute ethanol, 1 equivalent of heptylamine (2.577 mmol, 0.384 ml) was added and stirred at 50.degree. C for 6 hours. The reaction medium is allowed to return to ambient temperature and 1.4 equivalents of sodium borohydride (3.608 mmol, 136 mg) are added. The mixture is stirred at ambient temperature for 10 hours, then the reaction mixture is concentrated to dryness and taken up with water. Extracted with 2 dichloromethane fractions, the organic phases are dried over anhydrous sodium sulphate and concentrated to dryness. 680 mg of a yellow oil are obtained.

The yield is 90%.

Example 7 Synthesis of r3- (3,4-dimethoxy-phenyl) propyll-ethyl-heptyl-amine

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In 100 ml tricolors are mixed 1 equivalent of [3- (3,4-dimethoxyphenyl) propyl] heptylamine (5.037 mmol, 1.47 g), 1.1 equivalents of potassium carbonate (5.541 mmol; 766 mg) and 25 ml of dimethylformamide. 1.1 equivalents of iodoethane (5.541 mmol, 0.443 ml) are then added dropwise. The medium is stirred at room temperature for 10 hours. The reaction medium is diluted with dichloromethane and washed with a saturated solution of sodium hydrogencarbonate. The organic phase is dried over anhydrous sodium sulphate, concentrated to dryness and purified on a silica (dichloromethane) column. 45 mg of a yellow oil are recovered. The yield is 10%.

Example 8 Synthesis of Ethyl- (3-phenyl-allyl) -amine

To 1 equivalent of cinnamaldehyde (0.038 mmol, 5 g) mixed with 10 ml of ethanol is added dropwise 1 equivalent of 70% ethylamine in water (0.038 mmol, 2.44 g). Stir at room temperature for 1 hour, then 2 equivalents of sodium borohydride (0.076 mmol, 2.86 g) are added by small spatulas (exothermic reaction) and allowed to stir at room temperature for 1 hour. A large amount of water is then added and the organic phase is extracted with dichloromethane and then dried over anhydrous sodium sulphate and concentrated to dryness. 5.51 g of a yellow oil are obtained. The yield is 90%.

EXAMPLE 9 Demonstration of the Musorelaxant Effect of the Compounds According to the Invention The compounds of Examples 1 and 2 were tested on a nerve / muscle junction model (motor plate) obtained in a preparation isolated from the phrenic nerve / diaphragm of a rat (striated muscle) (Pollard BJ et al, Br. J. Anaesth., 1988, 61, 419-424).

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This test is predictive of an anti-wrinkle effect, as has been verified by the Applicant on diazepam, which is both active in vivo in humans and in this test at 10-4M.

The phrenic nerve and diaphragm are carefully isolated and placed in a 50 ml vessel filled with survival fluid (Krebs Henseleit fluid) maintained at 37 C and oxygenated with oxygen / CO 2 (95%). / 5).

Variations in diaphragm voltage are recorded with an initial pre-charge of several grams.

After a relaxation period of 30 minutes, the diaphragm is stimulated indirectly via the phrenic nerve.

On each preparation, the effect of the products to be tested was evaluated on contractions induced by indirect stimulation via stimulation on the phrenic nerve (0.1 to 0.5 volts, 0.3 ms, 0.1 Hz). Alverine, known as a myorelaxant compound with an anti-wrinkle effect according to the application FR-2 798 590, is used as a control.

The results obtained in the model of motor plate with the compounds according to the invention are presented in the table below:

<Tb>
<tb> PRODUCT <SEP> CONCENTRATION <SEP>% <SEP> INHIBITION
<tb> DES
<tb> CONTRACTIONS
<tb> Alverine <SEP> 10 <SEP> M <SEP> 100%
<tb> 10-5 <SEP> M <SEP> 0%
<tb> Compound <SEP> of <SEP> Example <SEP> 1 <SEP> 10-5 <SEP> M <SEP> 100%
<tb> Compound <SEP> of <SEP> Example <SEP> 2 <SEP> 10-4 <SEP> M <SEP> 100% <SEP>
<Tb>
Thus, the compounds according to the invention are muscle relaxants at least as effective as alverine and useful for this purpose in smoothing expression lines and wrinkles.

Example 10 Cosmetic Composition

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 This composition is prepared in a conventional manner for the skilled person. The quantities indicated are in percentages by weight.

Compound of Example 1 1% Propylene glycol isostearate 13% Polyethylene glycol (8 EO) 5% Propylene glycol 3% Pentylene glycol 3% Glyceryl stearate and polyethylene glycol stearate (100 EO) 5% Oxyethylenated sorbitan mono-stearate (20 EO) 0.5% oxyethylenated (20 EO) oxypropylenated cetyl alcohol (5 PO) 1% Gelling agents 0.5% C12-15 alkyl benzoates 4% Ethanol 3% Sodium hydroxide 0.12% Preservatives 0, 7% Water qs 100% This fluid is intended to be applied on the face and forehead to reduce wrinkles and fine lines of expression.

Claims (17)

 R 1, R 2, R 3, R 4, R 5, R 6, R 7 and R 8, which are identical or different, are chosen from: a hydrogen atom, a linear or branched, saturated or unsaturated C 1 -C 12 alkyl group, unsubstituted, R 8 is chosen from: a hydrogen atom, a linear or branched, unsaturated, unsubstituted or unsubstituted C1-C12 alkyl group, R10 is a linear or branched, unsubstituted or saturated or unsubstituted C1-C12 alkyl group, the substituents R are independently chosen from: an alkyl group, -OR11, SR11, -NR11R12, -COORn, -CONR11R12, -CF3 and a halogen atom, where R11 and R12, which are identical or different, are chosen from: an atom hydrogen, a linear or branched C1-C4 alkyl group, and an aryl group, optionally substituted with a group-OR ', -NR'R ", -COOR' or -CF3, where R 'and R", identical or different, are chosen from: a hydrogen atom, a linear or branched C1-C4 alkyl group, and an unsubstituted aryl group, m is between 0 and 5, n is t between 0 and 1 with the proviso that the groups R 1, R 3; R3, R5; R5, R7; R2, R4; R4, R6; R6, R8 respectively taken together, can form a double bond, or its acid addition salt, to make a composition suitable for topical application to the skin, for smoothing out fine lines and wrinkles.

 1. Use of at least one compound of formula (I): <Desc / Clms Page number 23> 2. Use of at least one compound of formula (I) as defined in claim 1, in a composition adapted for topical application to the skin, as an agent for smoothing wrinkles and fine lines. 3. Use according to claim 1 or 2, characterized in that said C1-C12 alkyl group is chosen from the following groups: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl. , octyl, nonyl, decyl, undecyl and dodecyl. 4. Use according to claim 1 or 2, characterized in that said alkyl group C1-C4 is selected from: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl. 5. Use according to claim 1 or 2, characterized in that said aryl group is selected from: a benzyl group and a phenyl group. 6. Use according to claim 1 or 2, characterized in that said halogen atom is selected from fluorine, chlorine, bromine and iodine atoms. 7. Use according to any one of claims 1 to 6, characterized in that the salt of the compound of formula (I) is obtained by addition with an inorganic acid selected from hydrochloric, sulfuric, nitric and phosphoric acid. 8. Use according to any one of claims 1 to 6, characterized in that the salt of the compound of formula (I) is obtained by addition with an organic acid selected from succinic acid, fumaric acid, lactic acid, glycolic acid, citric acid and tartaric acid. . 9. Use according to claim 1 or 2, characterized in that m = 0 in the formula (1).  10. Use according to claim 1,2 or 9, characterized in that n = 0 in the formula (I).  11. Use according to claim 1,2, 9 or 10, characterized in that R3 = R4 = R5 = R6 = R7 = R8 = H in the formula (1). <Desc / Clms Page number 24>  12. Use according to claim 1,2, 9,10 or 11, characterized in that Rg = H in the formula (1). 13. Use according to any one of claims 1 to 12, characterized in that said compound of formula (I) represents from 0.1 to 2% of the total weight of the composition. 14. Use according to any one of claims 1 to 13, characterized in that said composition also contains at least one compound selected from: desquamating agents; moisturizing agents; depigmenting or propigmenting agents; anti-glycation agents; NO-synthase inhibitors; agents stimulating the synthesis of dermal or epidermal macromolecules and / or preventing their degradation; agents stimulating the proliferation of fibroblasts and / or keratinocytes or stimulating the differentiation of keratinocytes; muscle relaxants; tensors; anti-pollution and / or anti-radical agents; agents acting on microcirculation; agents acting on the energetic metabolism of cells; and their mixtures. 15. Use according to any one of claims 1 to 13, characterized in that said lines and wrinkles are wrinkles and fine lines of expression. 16. Use according to claim 15, characterized in that said wrinkles and fine lines are arranged radially around the mouth and / or eyes and / or horizontally on the front and / or located in the space inter-sourcillier. 17. Use according to any one of claims 1 to 16, characterized in that said composition is applied to the areas of the face or the forehead marked by lines and wrinkles of expression and / or on persons with wrinkles and fine lines. expression.