EP1745008A1

EP1745008A1 - Composition, particularly a cosmetic composition, comprising ((dialkylamino)alkoxy) ethanol ester

Info

Publication number: EP1745008A1
Application number: EP05757130A
Authority: EP
Inventors: Maria Dalko
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 2004-05-06
Filing date: 2005-04-18
Publication date: 2007-01-24
Also published as: JP2007536352A; FR2869902B1; WO2005121067A1; FR2869902A1; US20080287537A1

Abstract

The invention relates to a method for cosmetic treatment of wrinkled skin, comprising topical application to the skin of a composition comprising at least one((dialkylamino)alkoxy) ethanol ester of formula (I). The invention also relates to novel compounds of formula (I) corresponding to fomulae (II) and (III) and to cosmetic compositions containing them.

Description

Composition, in particular cosmetic, comprising a ((dialkylamino) alkoxy) ethanoI ester

The present invention relates to a cosmetic treatment process for wrinkled skin, comprising the topical application to said skin of a composition comprising, in a physiologically acceptable medium, at least one ((dialkylamino) alkoxy) ethanol ester of particular formula . It also relates to a new family of such compounds, as well as the cosmetic compositions containing them.

Women, even men, currently tend to want to look young for as long as possible and therefore seek to fade the marks of aging skin, 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 for as long as possible, marks of young skin, especially since the physical appearance acts on the psyche and / or on morale.

Until now, wrinkles and fine lines have been treated with cosmetic products containing active agents which act on the skin, for example by moisturizing or improving its cell renewal or by promoting synthesis, or preventing degradation, elastic fibers that make up the skin tissue. Although these treatments make it possible to act on fine lines and wrinkles due to chronological or intrinsic aging, as well as on those due to photoaging, they have no effect on expression lines, which require intervention on the muscle contractile component of wrinkles present in the skin.

Up to now, the only means commonly used to act on expression lines is the botulinum toxin which is notably injected into the glabella lines which are the inter-eyebrow lines (see JD Carruters et al., J. Dermatol Onq. Oncol., 1992,

18, pp. 17-21). The Applicant has also proposed various compounds capable of offering a muscle relaxant effect when applied topically to the skin, thus making it possible to act by another route on expression wrinkles. Among these compounds, mention may especially be made of the antagonists of the receptors associated with calcium channels (FR-2 793 681), and in particular manganese and its salts (FR-2 809 005) and Palverine (FR-2 798 590); and agonists of receptors associated with chlorine channels, including glycine (EP-0 704 210) and certain extracts of Iris pallida (FR-2 746 641). However, there remains the need to have effective compounds for smoothing or blurring expression lines.

However, the Applicant has discovered with surprise that certain esters of ((dialkylamino) alkoxy) ethanol made it possible to satisfy this need.

Certain compounds used according to the invention, namely the ester of coconut fatty acids and (diethylamino) ethanol ethoxylates, have already been used in hair hygiene products. To the knowledge of the Applicant, however, it has never been suggested to use it on the skin of the face, in particular with a view to reducing expression lines.

The subject of the present invention is therefore a method of cosmetic treatment of wrinkled skin, in particular the skin of the face and / or forehead, comprising the topical application to said skin of a composition comprising, in a physiologically acceptable medium, at least one compound chosen from ((dialkylamino) alkoxy) ethanol esters of formula (I):

(0 in which:

R 1 and R ₂ independently denote: a linear or branched C ₁ -C ₁₀ alkyl or alkenyl group, optionally substituted by a saturated or unsaturated carbocycle comprising from 5 to 7 carbon atoms; or a saturated or unsaturated carbocycle having from 5 to 7 carbon atoms; or Ri and R ₂ form, with the nitrogen atom to which they are linked, a saturated or unsaturated heterocycle comprising from 5 to 6 atoms optionally substituted by an aryl group or by a Cι-C ₁₈ alkyl group optionally substituted by a aryl group;

Rs denotes an aryl group or a linear, branched or cyclic alkyl or alkenyl group, at CC ₂₅ , optionally substituted by at least one radical chosen from: a cycloalkyl, phenyl, OR ', -COOR', and -NR'R "radical, where R 'and R" independently denote a hydrogen atom or a linear or branched CC ₆ alkyl or alkenyl group;

n ranges from 1 to 10,

and their addition salts with an acid or a base.

In formula (I), the alkyl groups can in particular be chosen, depending on the case, from the groups: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl, octyl , nonyle, décyle, undécyle, dodécyle, myristyle, palmityl et stéaryl.

In addition, in the context of this application, the term “alkenyl” is understood to mean radicals which may comprise one or more double bonds, conjugated or not. They can in particular be chosen, as the case may be, from the groups: vinyl, allyl, butenyl or pentenyl.

The carbocycles can in particular be chosen from cyclopentyl, cyclohexyl and cycloheptyl radicals, the cyclopentyl and cyclohexyl radicals being preferred.

The nitrogen heterocycles can in particular be chosen from piperidine, pyrrolidine, piperazine, pyrimidine and morpholine. They can therefore include, in addition to the nitrogen atom, another nitrogen atom and / or an oxygen atom.

As the aryl group, it is preferred to use the phenyl radical.

As salts of the ester of formula (I), mention may be made of the salts obtained by adding the ester of formula (I) with an inorganic acid, chosen in particular from hydrochloric, sulfuric and phosphoric acids, or with an acid organic, chosen in particular from succinic, fumaric, lactic, glycolic, citric, tartaric, acetic and propionic acids. Mention may also be made of the salts obtained by adding the compound of formula (I) with an inorganic base, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, and carbonates or hydrogen carbonates of sodium, potassium or calcium; or with an organic base such as triethylamine or triethanolamine.

It is understood that the composition used according to the invention may comprise several compounds as defined above, in particular a statistical mixture of several compounds having different values of n and / or varying lengths of alkyl chain for R. This is in particular the case when the ester of formula (I) is synthesized from raw materials of plant origin.

The esters of formula (I) can in particular be prepared according to one of the conventional methods well known to those skilled in the art from amino (poly) ethoxy ethanol and acid or acid chloride correspondents.

It is thus possible to react the amino (poly) ethoxy ethanol with the acid chloride (route A), or with the acid activated by the reagents such as dicyclohexylcarbodiimide (DCC) or carbonyldiimidazole (CDI) for example (Route B), or directly with the carboxylic acid (route C).

To prepare the ester according to route A, it is possible, for example, to dissolve Pamino (poly) ethoxy ethanol in a non-protic organic solvent such as dichloromethane, DMF, dioxane or THF for example, add to this solution 1 to 10 equivalents (preferably 2 eq.) of organic base such as pyridine, triethylamine, ethyldiisopropylamine or of mineral base such as sodium bicarbonate, then slowly add 1 to 10 equivalents of acid chloride (preferably 1, 2 eq). The medium is kept stirring for 1 hour to 48 hours at a temperature of 10 ° C. to 70 ° C., the reaction time and the temperature being a function of the medium and of the reactivity of the acid chloride used. At the end of the reaction, the product obtained can be purified by chromatography on a column of silica gel, precipitation or recrystallization.

To prepare the ester according to route B, it is possible, for example, to activate the acid function in situ with reagents widely known to those skilled in the art as described for example p.393-396 in "Advanced Organic Chemistry, Reactions , Mechanisms, and Structure ", 4rd Edition, by Jerry March, Edition Wiley-lnterscience 1992. To prepare the ester according to route C, the amino (poly) ethoxy ethanol can be directly heated in the presence of the carboxylic acid with or without solvent. The water formed is distilled directly in the case of reaction without solvent, or distilled in the form of an azeotropic mixture with the solvent such as toluene, or even trapped by a desiccant introduced into the reaction medium such as a molecular sieve or any other agent. desiccant.

The starting amino (poly) ethoxy ethanol is commercially available for R ^ = R ₂ = ethyl or methyl and n equal to 1. When Ri and R ₂ are distinct from methyl or ethyl groups, the amino (poly) ethoxy ethanol can be prepared by reaction of the corresponding secondary amine on commercial 2- (2-chloroethyl-) ethylene glycol, in methanol or acetonitrile at reflux overnight. The product thus obtained can then be treated and purified on a silica column. For the other values of n, the amino (poly) ethoxy ethanol can be synthesized in particular according to the protocol described in application EP-0 300 323, starting from the corresponding polyol ether and dialkylamine.

These are processes well known to those skilled in the art.

According to a first preferred embodiment, the compound according to the invention is such that at least one of the following conditions, and preferably all of these conditions, are satisfied: • Ri, R ₂ are independently chosen from a methyl radical or ethyl; • R ₃ is an unsubstituted linear C ₂ -Cι ₉ alkyl or alkenyl radical; • n ranges from 1 to 9, preferably n is equal to 1, 2, 5 or 8.

According to a first variant of this embodiment, the compound according to this embodiment is such that: • Ri, R ₂ are each an ethyl radical; • R ₃ is a C ₅ -C ₁₇ unsubstituted linear alkyl or alkenyl radical; and • n is equal to 1.

According to a second variant, the compound used according to the invention is such that: • Ri, R ₂ are each an ethyl radical; • R ₃ is a linear C ₈ -C ₂ o unsubstituted alkyl or alkenyl radical; and • n is statistically between 4 and 5.

According to a second embodiment of the invention, the compound of formula (I) is such that: • Ri, R ₂ form, with the nitrogen atom to which they are linked, a piperidine or pyrrolidine ring substituted by a phenyl, benzyl, 2-phenyl-ethyl or 3-phenyl propyl; • R ₃ is a linear C ₅ -C ₁₇ unsubstituted alkyl radical, preferably an undecyl radical; and • n is equal to i.

The compounds according to this embodiment can be prepared according to a two-step process, comprising:

(a) the reaction of piperidine or pyrrolidine (RιR ₂ NH) on 2- (2-chloroethyl) ethylene glycol in methanol or acetonitrile at reflux, for example overnight, and

(b) the reaction of the product obtained in step (a) with the acyl chloride Rs-CO-CI, in the presence of triethylamine in dichloromethane, at room temperature, as indicated above (route A).

As will be demonstrated in the Examples below, the Applicant has demonstrated a dermo-relaxing and muscle relaxant effect of the compounds according to the invention, which makes it possible to envisage their use, more particularly in the smoothing of expression lines.

The invention therefore also relates to the cosmetic use of at least one compound as defined above, in a composition suitable for topical application to the skin, as an agent intended to smooth wrinkles, in particular of expression. .

The Applicant has moreover demonstrated that some of the compounds used according to the invention were new and exhibited an interesting dermo-relaxing or muscle relaxant activity. The invention therefore also relates to a subfamily of compounds derived from ((dialkylamino) alkoxy) ethanol, chosen from the esters which correspond to formula (II) below:

O

(II)

- few 's radicals n-iseptadecyl; esters of formula (II) are such that R is chosen from the radicals n- ,,,,,...: yl, n-nonyl, n-undecyl, n- tridecyl, n-pentadecyl, n-heptadecyl; ecadienyl (corresponding to linoleate). A preferred compound is such

. an n-nonyl radical. (S derived from

(i formula (III) cheerfully relates to another subfamily of compounds derived from alkoxy) ethanol, chosen from the esters which correspond to formula (III)

(III) ₄ denotes a linear, branched or cyclic C ₂ -C ₂₁ alkyl or alkenyl group or an aryl group which may be substituted by at least one radical chosen from: a cycloalkyl radical; phenyl optionally substituted by one or more radicals chosen from the radicals OR ', COOR', linear or branched CC ₆ and CF ₃ alkyl; GOLD'; -COOR '; and -NR'R "; where R 'and R" independently denote a hydrogen atom or a linear or branched CC ₆ alkyl or alkenyl group;

R ₅ denotes a phenyl, benzyl, 2-phenyl-ethyl or 3-phenyl propyl group;

m is 1 or 2.

and their addition salts with an acid or a base.

The acid or base used to salify the esters of formulas (II) and (III) may be any physiologically acceptable acid or base, as defined above.

The subject of the present invention is also a composition, in particular suitable for topical application to the skin, comprising, in a physiologically acceptable medium, at least one compound chosen from esters corresponding to formula (II) or (III) and their addition salts with an acid or a base.

The amount of esters of formula (I) -and therefore of formulas (II) or (III) - which can be used according to the invention and or their salts is of course dependent on the desired effect and can therefore vary to a large extent .

To give an order of magnitude, these compounds 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 representing 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 it 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 medium is advantageously cosmetically acceptable, that is to say that it does not cause itching, tingling or redness liable to to divert the user from the composition, and that he has a pleasant appearance, odor and touch.

This composition can be in all dosage forms normally used in the cosmetic field, and it can in particular be in the form of an optionally gelled solution, of a dispersion of the lotion type, optionally two-phase, of an emulsion obtained by dispersion of a fatty phase in an aqueous phase (O / W) or vice versa (W / O), or of a triple emulsion (W / O / W or O / W / O) or of a vesicular dispersion of ionic type and / or non-ionic. 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 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 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 used according to the invention may 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 materials. 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 event, these adjuvants, as well as their proportions, will be chosen so as not to harm the desired properties of the compounds 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 co-emulsifiers 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 (petroleum jelly oil), oils of vegetable origin (avocado oil, soybean oil), oils of animal origin (lanolin), synthesis (perhydrosqualene), silicone oils (cyclomethicone) and fluorinated oils (perfluoropolyethers). Fatty alcohols (cetyl alcohol), fatty acids, waxes (carnauba wax, ozokerite) can also be used as fat.

As emulsifiers and co-emulsifiers 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, and fatty acid and glycerin esters such as stearate glyceryl.

As hydrophilic gelling agents / thickeners, 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 gelling agents / thickeners lipophilic, there may be mentioned modified clays such as bentones, metal salts of fatty acids, and hydrophobic silica.

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; moisturizers; 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; other muscle relaxants and / or skin relaxants; tensing agents; anti-pollution and or anti-radical agents; agents acting on the microcirculation; agents acting on the energy metabolism of cells; and their mixtures.

Examples of such additional compounds are: retinol and its derivatives such as retinyl palmitate; ascorbic acid and its derivatives such as magnesium ascorbyl phosphate and ascorbyl glucoside; tocopherol and its derivatives such as tocopheryl acetate; nicotinic acid and its precursors such as nicotinamide; ubiquinone; glutathione and its precursors such as L-2-oxothiazolidine-4-carboxylic acid; plant extracts and in particular plant proteins and their hydrolysates, as well as phytohormones; marine extracts such as algae extracts; bacterial extracts; sapogenins such as diosgenin and Wild Yam extracts containing them; ceramides; hydroxy acids; hydroxy acids, such as salicylic acid and n-octanoyl-5-salicylic acid; resveratrol; oligopeptides and pseudodipeptides and their acylated derivatives; manganese and magnesium salts, in particular gluconates; and their mixtures.

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

The organic photo-protective agents can in particular 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 preferably Benzophenone-3 (Oxybenzone), or Benzophenone-4 (Uvinul MS40 available from BASF); benzylidenes-camphors, in particular 3-benzylidene-camphor, benzylidenecamphosulphonic acid, benzalkoniummethosulfate of camphor, polyacrylamidomethylbenzylidene camphor, terephthalylidene di-camphor sulfonic acid, and preferentially 4-methylbenzide 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 drometrizole trisiloxane, 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 preferably ethocrylene (Uvinul N35 ') octylmethoxycinnamate (Parsol MCX available from Hoffmann La Roche), or octocrylene (Uvinul 539 available from BASF); dibenzoylmethanes, in particular butyl methoxydibenzoylmethane (Parsol 1789); imidazolines, in particular ethylhexyl dimethoxybenzylidene dioxoimidazoline; PABA, in particular ethyl Dihydroxypropyl PABA, ethylhexyldimethyl PABA, glyceryl PABA, PABA, PEG-PABA, and preferably diethylhexylbutamido-triazone (Uvasorb HEB available from 3V Sigma), ethylhexyltriazone (Uvinul T1 available from BASF), or ethyl PABA (benzocaine); salicylates, in particular dipropylene glycol salicyclate, ethylhexyl salicylate, Phomosalate, or TEA salicylate; triazines, in particular anisotriazine (Tinosorb S available from Ciba); drometrizole trisiloxane.

The inorganic photo-protective agents preferably consist of zinc oxide and / or titanium dioxide, preferably of nanometric size, optionally coated with alumina and or stearic acid.

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

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

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

EXAMPLES

Example 1: Preparation of ((diethylamino) ethoxy) ethanol alkylesters

Various compounds according to the invention were prepared according to the synthetic scheme below:

This process includes the following steps. The commercial ((diethylamino) ethoxy) ethanol is dissolved in dichloromethane. 2.1 equivalents of triethylamine are then added, then slowly 1.05 equivalents of RCOCI acid chloride and the mixture is left to react for 20 h at room temperature. The medium is diluted with dichloromethane, then two aqueous washes are carried out. The organic phase is dried over sodium sulfate, filtered and then concentrated to dryness. The residue obtained is purified by column of silica or by precipitation.

The reagent (acyl chloride) used and the results obtained are collated in the table below.

Example 2: Preparation of the ester of coconut fatty acids and ethoxylated (diethylamino) ethanol (n≈1-9).

This mixture of compounds can be prepared by direct heating of a mixture of aminoethanol ethoxylates in the presence of coconut fatty acids, with or without solvent. The water formed is distilled directly in the case of reaction without solvent, or distilled in the form of an azeotropic mixture with the solvent such as toluene, or even trapped by a desiccant introduced into the reaction medium such as a molecular sieve or any other dehydrating agent. The mixture of compounds obtained has an amine number of 1.89 (meq / g) and the following structure:

where R corresponds to a residue of coconut fatty acids and n is statistically between 4 and 5.

Example 3 Demonstration of the Calcium Inhibitory Effect of the Compounds According to the Invention

For a substance to be recognized as an inhibitor of calcium channels, it must be able to reduce the intracellular calcium concentration or decrease the binding of calcium to intracellular proteins such as calmodulin, as described in particular by Galizzi, JP et al ., J. Biol. Chem. 1987, 262 p 6947; by Y. Okamiya et al., Eur. J. Pharmacol. 1991, 205, p 49; by J. A. Wagner et al., J. Neurosci. 1988, 8, p 3354; by H. R. Lee et al., Life Sci. 1984, 35, p 721; by Schoemaker H. and Lauger S. Eur. J. Pharmacol. 1985, 11, p 273 or also by I. J. Reynolds et al., J. Pharmacol. EXP. Ther. 1986, 237, p 731.

According to the protocol indicated in these documents, the applicant has determined the IC ₅ oc _a2 + for calcium flow inhibition of three compounds according to the invention. The results are given in Table 1 below. IC ₅₀ c _{a2 +} represents the inhibitory concentration of 50% of Ca 2+ release

From this table, it appears that the compounds according to the invention are indeed inhibitors of calcium channels. From these tests and from the teaching of application EP-1 053 745, it is deduced therefrom that they have a high probability of having a beneficial effect on wrinkles and in particular expression wrinkles.

Example 4: Demonstration of an Inhibitory Effect on L-type Calcium Channels a) Protocol

The capacity of the ((diethylamino) ethoxy) ethanol laurate of Example 1 (at 1 μM in DMSO) and of the mixture of compounds of Example 2 (at 10 μM in DMSO) was inhibited by competition. fixation of type L calcium channel agonists

The studies are carried out using homogenates of the cerebral cortex of rats (isolated membranes having calcium channels of the L type on their surface) according to the method described by Reynolds I.J. et al., 1986, J. Pharmacol. Exp. Ther., 237, p.731.

The experimental conditions are as follows:

No Test Ligand Conc. Incubation Specific detection of Ca ⁺ channel [ ³ H] (-) 0.5 nM D 600 (10 μM) 60 min. / 22 ° C Counting (L, site D 888 scintillation verapamil)

D888 which is [ ³ H] (-) desmethoxyverapamil serves as a specific radiolabelled ligand and D600 which is (±) methoxyverapamil hydrochloride serves as a reference molecule.

The specific binding of a ligand (labeled D888) to receptors (L-type calcium channels, verapamil site) is defined as the difference between total binding and non-specific binding determined in the presence of an excess of cold ligand (non-radioactive ). The results are expressed as a percentage of inhibition of the specific binding of the control in the presence of the test compound.

b) Results

The compound of Example 1 inhibits the specific binding of the control to calcium channels by 31%. The mixture of compounds of Example 2 inhibits by 95% the specific binding of the control to the calcium channels. From this test and from the teaching of application EP-1 053 745, it is deduced therefrom that these compounds have a high probability of having a beneficial effect on wrinkles and in particular expression wrinkles.

Example 5: Demonstration of the muscle relaxant effect of the compounds according to the invention

The mixture of compounds of Example 2 was tested on a nerve-muscle co-culture model which makes it possible to recreate a motor arc by innervating human striated muscle cells with explants of spinal cord and spinal ganglia of embryos of rat.

This test is predictive of an anti-wrinkle effect, as has been demonstrated by the Applicant in the case of diazepam, which inhibited muscle fiber contractions in this model and whose anti-wrinkle activity has been demonstrated in vivo.

a) Protocol Human muscle cells, obtained from striations of striated muscles from a healthy donor, are seeded in wells of 1.8 cm ² in section (24-well culture dishes). After 10 days of culture, these cells form a monolayer and fuse. At this stage, spinal cord explants of 13-day rat embryos containing the spinal ganglia are placed on the culture.

Neurite growth is visible outside of the spinal cord explant after one day of culture. The first contractions of the muscle fibers are observed after 5 to 6 days of co-culture and after 3 weeks, all the muscle fibers in the vicinity of the explants contract.

Co-cultures are used after 21 days, when the muscle fibers are striated and have mature differentiated neuromuscular junctions.

A muscle fiber having regular contractions (at least 60 contractions per minute) is then selected from three different culture wells and the number of contractions is counted over 30 seconds. The test compound, diluted in DMSO, is then incubated for 60 seconds in these wells, at the concentration of 10, 50 and 100 μM. At the end of the incubation, the number of contractions is again counted over 30 seconds. The test is carried out in triplicate.

b) Results

The mixture of compounds of Example 2 blocks the contractions of the three referenced muscle fibers, at concentrations of 10, 50 and 100 μM.

These compounds can therefore be used to relax facial features and smooth out expression lines.

Example 6 Cosmetic Composition

This composition is prepared in a conventional manner for a person skilled in the art. The quantities indicated are in percentages by weight. (Diethylamino) ethoxy) ethanol decanoate 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 monostearate (20 EO) 0.5% Oxyethylenated cetyl alcohol (20 EO) oxypropylene (5 OP) 1% Gelling agents 0.5%

Alkyl benzoates, C _12- 15 4% 3% Ethanol

0.12% sodium hydroxide

Preservatives 0.7%

Water qs 100%

This fluid is intended to be used in single- or twice-daily applications on the face and forehead to reduce expression wrinkles.

Claims

1. A method of cosmetic treatment of wrinkled skin, comprising the topical application to said skin of a composition comprising, in a physiologically acceptable medium, at least one compound chosen from esters of ((dialkylamino) alkoxy) ethanol of formula (I):

d) in which

Ri and R ₂ independently denote: a linear or branched C 1 -C 4 alkyl or alkenyl group, optionally substituted by a carbocycle comprising from 5 to 7 carbon atoms; or a saturated or unsaturated carbocycle having from 5 to 7 carbon atoms; or Ri and R ₂ form, with the nitrogen atom to which they are linked, a saturated or unsaturated heterocycle comprising from 5 to 6 atoms optionally substituted by an aryl group or by a C _r C ₁₈ alkyl group, optionally substituted by an aryl group or a C 1 -C ₈ alkyl group optionally substituted by an aryl group;

R ₃ denotes an aryl group or a linear, branched or cyclic alkyl or alkenyl group, at CC ₂₅ , optionally substituted by at least one radical chosen from: a cycloalkyl, phenyl, OR ', -COOR', and -NR'R radical ", where R 'and R" independently denote a hydrogen atom or a linear or branched CC ₆ alkyl or alkenyl group;

n ranges from 1 to 10,

and their addition salts with an acid or a base.

2. Method according to claim 1, characterized in that the salt of the ester of formula (I) is obtained by addition with an inorganic acid chosen from hydrochloric, sulfuric and phosphoric acids.

3. Method according to claim 1, characterized in that the salt of the ester of formula (I) is obtained by addition with an organic acid chosen from succinic, fumaric, lactic, glycolic, citric, tartaric, acetic and propionic acids .

4. Method according to claim 1, characterized in that the salt of the ester of formula (I) is obtained by addition with an inorganic base chosen from sodium hydroxide, potassium hydroxide, calcium hydroxide, and carbonates or hydrogen carbonates sodium, potassium or calcium.

5. Method according to claim 1, characterized in that the salt of the ester of formula (I) is obtained by addition with an organic base chosen from triethylamine and triethanolamine.

6. Method according to any one of claims 1 to 5, characterized in that said compound is such that at least one of the following conditions, and preferably all of these conditions, are satisfied: • Ri, R ₂ are independently chosen from a methyl or ethyl radical; • R ₃ is a linear C2-C ₁₉ unsubstituted alkyl or alkenyl radical; • n ranges from 1 to 5, preferably n is equal to 1, 2, 5 or 8.

7. Method according to claim 6, characterized in that said compound is such that: • Ri, R ₂ are each an ethyl radical; • R ₃ is a linear C ₅ -C ₁₇ unsubstituted alkyl or alkenyl radical; and • n is equal to 1.

8. Method according to claim 6, characterized in that said compound is such that: • Ri, R ₂ are each an ethyl radical; • Rs is a linear C ₈ -C ₂₀ unsubstituted alkyl or alkenyl radical; and • n is statistically between 4 and 5.

9. Method according to any one of claims 1 to 5, characterized in that said compound is such that: • Ri, R ₂ form, with the nitrogen atom to which they are connected, a piperidine or pyrrolidine ring substituted by a phenyl, benzyl, 2-phenyl-ethyl or 3-phenyl propyl group; • R ₃ is a linear C ₅ -C ₁₇ unsubstituted alkyl radical, preferably a dodecyl radical; and • n is equal to 1.

10. Method according to any one of claims 1 to 9, characterized in that said compound represents from 0.1 to 2% of the total weight of the composition.

11. Method according to any one of claims 1 to 10, characterized in that said composition additionally contains at least one compound chosen from: desquamating agents; moisturizers; 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; other muscle relaxants and / or skin relaxants; tensing agents; anti-pollution and / or anti-radical agents; agents acting on the microcirculation; agents acting on the energy metabolism of cells; and their mixtures.

12. Method according to any one of claims 1 to 11, characterized in that said composition is applied to the skin of the face and / or the forehead.

13. The method of claim 12, characterized in that said composition is applied to the areas of the face and / or forehead marked by expression lines and / or on people with expression lines.

14. Method according to claim 2, characterized in that said composition is applied to wrinkles arranged radially around the mouth and / or the eyes and / or horizontally on the forehead and / or located in the inter-eyebrow space.

15. Cosmetic use of at least one compound as defined in any one of claims 1 to 9, in a composition suitable for topical application to the skin, as an agent intended to smooth wrinkles.

16. Use according to claim 15, characterized in that said wrinkles are expression wrinkles.

17. Compounds derived from ((dialkylamino) alkoxy) ethanol chosen from esters which correspond to formula (II) below:

(II) in which:

R denotes a linear alkyl or alkenyl radical unsubstituted at C ₅ -Cι ₇ ,

and their addition salts with an acid or a base.

18. Compounds according to claim 17, characterized in that R denotes an n-nonyl radical.

19. Compounds derived from ((dialkylamino) alkoxy) ethanol, chosen from the esters which correspond to formula (III) below:

(III) in which R ₄ denotes a linear or branched or cyclic C ₂ -C ₂ alkyl or alkenyl group or an aryl group which may be substituted by at least one radical chosen from: a cycloalkyl radical; phenyl optionally substituted by one or more radicals chosen from the radicals OR ', COOR', linear or branched CC ₆ and CF ₃ alkyl; GOLD'; -COOR '; and -NR'R "; where R 'and R" independently denote a hydrogen atom or a linear or branched C-ι-C ₆ alkyl or alkenyl group;

R ₅ denotes a phenyl, benzyl, 2-phenyl-ethyl or 3-phenyl propyl group;

m is 1 or 2.

and their addition salts with an acid or a base.

20. Composition comprising at least one of the compounds according to any one of claims 17 to 19 in a physiologically acceptable medium.

21. Composition according to claim 20, characterized in that it is suitable for topical application to the skin.