FR2878156A1 - Use of compound of N-acylamino-amides family in a composition containing medium e.g. as alleviating agent, to prevent and/or decrease cutaneous reaction induced by a stress and dermatological effects e.g. acne and atopic dermatitis - Google Patents

Abstract

Use of at least a compound (I) of the family of N-acylamino-amides in a composition containing a physiologically acceptable medium, as alleviating agent. Independent claims are also included for: (1) a cosmetic composition (A) comprising: either (I) associated with at least another alleviating agent (not an anti-inflammatory agent) in a physiologically acceptable medium; or (I) associated with at least a compound having irritating side effects (keratolytic agents, depigmentants, antitranspirants, thinners, depilatory, dyeings or capillary dyes, permanent agents, retinoids, antipruritic, antiseborrheic, comedolytic and/or anti-acne; and (2) a cosmetic method, for alleviating the skin and/or the scalp, comprising applying (A) to the skin and/or scalp. ACTIVITY : Tranquilizer; Antipruritic; Virucide; Antiinflammatory; Dermatological; Vulnerary; Antiseborrheic; Antipsoriatic. MECHANISM OF ACTION : Interleukin-1 inhibitor expression enhancer; Tumor necrosis factor-alpha inhibitor expression enhancer.

Description

The field of the invention relates to the protection of the skin and / or its

  dander against skin irritation or skin inflammation induced by stress.

  'Stress' means any stress of exogenous origin, such as chemical stress (eg xenobiotics, irritating chemicals, etc.) or environmental stress (eg temperature, climate, UV radiation, atmospheric pollution, in particular: heavy metals, gaseous pollutants such as sulfur dioxide, ozone and nitrogen oxides, oxidative stress, cigarette smoke ...), mechanical (eg rubbing on contact with the razor ...), infectious (ex: allergen, antigen ...), and / or any stress of endogenous origin, such as disorders involving an inflammatory and / or hormonal mechanism affecting the skin.

  By "skin" is meant according to the invention the skin enlarged to the scalp and mucous membranes. By "dander" is meant according to the invention the eyelashes, hair, hair and nails.

  The present invention relates in particular to the use of at least one compound of the family of N-acylamino amides in a composition containing a physiologically acceptable medium, as a soothing agent.

  In particular, said compound is intended to protect the skin and / or its integuments against the irritating effect of a chemical, an atmospheric pollutant, a UV radiation or a mechanical friction, and therefore protect the skin against the cutaneous signs associated with this irritating effect. These signs of skin can range from the simple sensation of cutaneous discomfort with tightness, itching, warming, redness to more important cutaneous signs such as pruritus, scabs, inflammatory erythema.

  The invention therefore also relates to the use of at least one compound of the family of N-acylamino amides for the preparation of a composition intended to prevent and / or treat dermatological conditions such as irritant dermatitis, acne , seborrheic dermatitis, psoriasis, vitiligo and atopic dermatitis.

  The invention also relates to compositions comprising at least said compound associated with at least one other soothing agent distinct from an anti-inflammatory agent or compositions comprising at least said compound associated with at least one agent with a particular irritating side effect (ex : cosmetic active ingredients, dermatological active ingredients).

  The preferred compounds used according to the invention are (2- (acetyl (3-trifluoromethylphenyl) -amino) -3-methyl-butylrylamino) acetic acid or (2- (acetyl- (3-trifluoromethylphenyl) -amino) - Ethyl 3-methyl-butylrylamino) acetate.

  Human skin consists of two compartments, the epidermis and the dermis.

  The epidermis is composed mainly of three types of cells which are keratinocytes (majority), melanocytes and Langerhans cells. Each of these cell types contributes, through its specific functions, to the essential role played in the body by the skin, in particular the protective role of the body with respect to the aforementioned external aggressions.

  The dermis provides the epidermis with a solid support. It is also its nurturing element. It consists mainly of fibroblasts and an extracellular matrix composed mainly of collagen, elasloin and glycoproteins which constitute the fundamental substance. There are also leucocytes, mast cells and tissue macrophages. Finally, the dermis is crossed by blood vessels and nerve fibers.

  The skin and in particular the epidermis, the outermost of its compartments, are directly and frequently exposed to external aggressions.

  It is known in particular that: - the toxicity of atmospheric pollutants, in particular gaseous pollutants such as sulfur dioxide, ozone and nitrogen oxides on the constituents of the skin (fibers, cells, enzymes), is particularly related to their irritating activity which causes cutaneous cellular damage which can induce inflammation, with vasodilation and release of mediators, and notably lead to redness, heat and pain; in particular, ozone-induced lipid peroxidation can alter the skin in two ways: 1 / the oxidation and degradation of stratum corneum lipids can alter the barrier function of the stratum corneum, which seems to be one of the triggering factors in 30 many dermatoses (psoriasis, atopic dermatitis, irritant dermatitis); 2 / the increased formation of lipid oxidation products in the upper skin layers may trigger damage to the adjacent skin layers. Thus, significant oxidative damage at the level of the superficial stratum corneum can initiate underlying localized inflammatory processes, leading to the recruitment of phagocytes which, by generating oxidants, will amplify the initial oxidative processes; Thus, the harmful effects of pollution on keratinous substances affect the cellular respiration of these keratin materials and result in accelerated aging of the skin, with a dull complexion and the early formation of wrinkles or fine lines, and also by a decrease in the vigor of the hair, which also looks dull. In addition, because of pollution, skin and hair get dirty more quickly. In addition, pollution can cause irritation and allergy and inflammation on the skin; the chemicals used in the usual products (household, cosmetic ...) can also have an irritating effect, that is to say can cause cutaneous reactions of discomfort of the type heating, redness, or in some cases burns or inflammatory or immunoallergic reactions; Keratinolytic agents or exfoliating agents, depigmenting agents, oxidizing agents, reducing agents and comedolytic agents are used, for example, in the cosmetic compositions. And even certain compounds which are considered as inert in a cosmetic or dermatological composition, such as, for example, preservatives, surfactants, perfumes, solvents or propellants, may be irritating when they are applied to keratin materials, this irritating nature depending on the compound used and the reactivity of the skin and the resident skin flora of the user; UV radiation with wavelengths between 280 nm and 400 nm allows the browning of the human epidermis. But it is also known that wavelength rays between 280 and 320 nm, known under the name of UVB, cause erythema and skin burns. Moreover, the UV-A rays, of wavelengths between 320 and 400 nm, are also likely to induce an alteration of the skin: they cause in particular a loss of elasticity of the skin and the appearance of wrinkles leading to premature aging, and also promote the triggering of the erythematous reaction or amplify this reaction in some subjects and may even be the cause of phototoxic or photoallergic reactions.

  Faced with these attacks, the skin reacts with a cutaneous reaction that aims to restore the broken homeostatic balance or repair the damage caused. It involves a cascade of reactions that can give rise to the persistent irritating process that is mainly characterized by skin irritation or involution of the hair bulb and its matrix environment.

  The primary skin signs associated with skin irritation may be a simple sensation of cutaneous discomfort (eg tingling, itching, tightness, warming, redness ...) or pruritus, scars, inflammatory erythema, edema that we can find associated with dermatological conditions.

  Generally, inflammatory-type skin irritation is characterized by an initial phase involving keratinocytes, which constitute the first line of cellular defense of the skin. At an early stage, stress proteins (eg HSP70 and HSP90) and defensins (eg defensin 2) are induced under cutaneous stress at the keratinocyte level. In addition, these keratinocytes release biological mediators and cytokines, which are pre-stored in the epidermis in the normal state (eg IL-1a, arachidonic acid derivatives). In particular, IL-1a has an autocrine role but is also capable of inducing the transcription of more than 90 genes (eg cytokines IL-1 [3, IL-6, GM-CSF, TNFα, chemokines whose IL-8, MCP-1, MIF'-1a and eotaxin, as well as the expression of adhesion molecules such as E-selectin or ICAM-1 and VCAM-1) in different cell types of skin such as keratinocytes, endothelial cells or fibroblasts. Arachidonic acid is rapidly metabolized to many highly active compounds, eicosanoids such as prostaglandins, thromboxane and leukotrienes acting as local mediators with low lifespan, involved in the control of proliferation, differentiation, apoptosis or the formation of edema or leukocyte activation.

  It is also known that TNF-a, a major cytokine of cutaneous inflammation, which is pre-stored in dermal mast cells but also produced by keratinocytes and Langerhans cells after stimulation, induces the transcription of adhesion molecules. synergy with IL-1, which play: an essential role in the circulation and migration of leukocytes (especially neutrophils) from the peripheral blood vessels to the dermis and epidermis.

  The initialization phase of the inflammation is then relayed by a local amplification phase of the irritation, involving the production of IL-12 and IL-18 by the activated macrophages, as well as the secretion of chemokines by vascular cells and keratinocytes (ex: IL-8 of the CC group and M'CP-1 of the CXC group), which will attract polynuclear, lymphocytes, monocytes / macrophages to the site of inflammation.

  IL-6 is also a cytokine secreted by keratinocytes, macrophages, vascular cells activated during inflammation and can gain general circulation and trigger regional and general effects.

  Moreover, it is known that oxidative stress, which can generate free radicals and reactive oxygen species (ROS) is another major player in skin irritation and / or inflammation.

  There is also a negative regulation system of the previously described proinflammatory and inflammatory processes, involving anti-inflammatory cytokines such as TGF-5 and IL-10, inflammatory cytokine inhibitors such as inhibitors of IL1 or TNFot, as well as stress proteins known as modulating any danger signal (ex: BiP (grp78) and HSP27).

  These mediators can be synthesized in particular by keratinocytes and are capable of inhibiting the production of pro-inflammatory cytokines and chemotactic cytokines.

  It is known that skin irritation can cause various signs of skin, ranging from simple sensations of cutaneous discomfort (ex: tugging, itching, heating, redness ...) to more important skin signs such as pruritus, scabs, inflammatory erythema, edema, or burns.

  These can be found in particular skin conditions such as herpes, psoriasis, vitiligo, atopic dermatitis, irritant dermatitis, eczema, seborrheic dermatitis, acne, and inflammatory hyperpigmentations. In particular, it is known that skin irritation may account for approximately 60% to 80% of clinical cases of irritant contact dermatitis (IDD). IDD is a multifactorial disease whose onset depends both on intrinsic factors (eg, genetic background, sex, age) and extrinsic factors (eg, irritants). Acute DIC, mainly characterized by inflammation, is distinguished from chronic DIC characterized by hyper-proliferation of keratinocytes and transient hyperkeratosis. And the cutaneous penetration of chemicals, related to the degree of permeability of the skin (physiological state), the physicochemical properties of the compounds (molecular weight, polarity, ionization stage) and the nature of their environment (excipient, vehicle), is a major parameter in establishing the pathophysiology of IDD.

  It is also known that acne and seborrheic dermatitis also have an inflammatory component.

  Finally, early inflammatory processes can lead to skin immune disorders such as atopic dermatitis, vitiligo, and psoriasis.

  It is therefore understood from the above that it is advantageous to find compounds capable in particular of preventing and / or reducing the irritating effect of cosmetic or dermatological compositions containing one or more compounds with an irritating side effect, and of preventing and / or treating disorders. skin associated with skin irritation or skin inflammation.

  Now the Applicant has just demonstrated that the compounds of the family of N-acylamino amides described in the application EP 1 292 608 B1 and known hitherto for their anti-elastase activity, also had an anti-irritant activity and / or anti-inflammatory. It has indeed been able to highlight a regulatory effect of these compounds on the production of mediators of inflammation and an activating effect on the production of endogenous inhibitors of inflammatory cytokines.

  In particular, the Applicant has been able to show that {2- [acetyl- (3-trifluoromethylphenyl) -amino] -3-methyl-butyrylamino} acetic acid, applied at a concentration of 0.1 mM or 1 mM on keratinocyte cultures subjected to irritant stress (eg PMA 0, ipg / ml), was able to decrease the expression of mediators of inflammation (eg beta-defensin 2, mitochondrial stress protein 70, inducible heme oxygenase 1) and increase the expression of inflammatory cytokine inhibitor such as IL-1 (ex: type II interleukin-1 receptor).

  The present invention therefore relates to the use of a compound of the family of N acylamino amide in a composition containing a physiologically acceptable medium, as a soothing agent.

  In particular, said compound is intended to: - prevent and / or reduce a cutaneous reaction induced by stress; in particular the stress is selected from UV radiation, atmospheric pollution, oxidative stress, chemicals, mechanical friction and mixtures thereof; to prevent and / or reduce the irritating effect of a cosmetic or dermatological composition containing one or more compounds with an irritating side effect; - prevent and / or reduce feelings of cutaneous discomfort, skin tightness, itchy skin, redness of the skin, or sensation of cutaneous heat.

  The use of a compound of the family of N acylamino amide therefore has the advantage of eliminating skin irritation that could have caused the compounds with irritating side effect, and also to increase the amount of compounds to irritating nature in cosmetic or dermatological compositions compared to the quantity normally used, with a view to an increased efficiency of the latter.

  The invention also relates to the use of a compound of the N acylaminoamide family for the preparation of a composition for preventing and / or treating cutaneous signs related to stress-induced skin irritation.

  In particular, said composition is intended to prevent and / or treat pruritus, oars, edema, inflammatory erythema, or burns.

  The composition may also be used to prevent and / or treat dermatological conditions related to cutaneous inflammation or early inflammatory processes responsible for cutaneous immune disorders.

  These dermatological conditions may especially be chosen from irritant dermatitis, acne, seborrheic dermatitis, atopic dermatitis, vitiligo, and psoriasis.

  In particular, said compound used according to the invention is intended to regulate the production of mediators of cutaneous inflammation, by decreasing the synthesis or the release of pro-inflammatory or inflammatory cytokines and / or by activating the negative regulation systems of the processes. inflammatory (eg anti-inflammatory cytokines or inflammatory cytokine inhibitors).

  The compounds of the family of N-acylamino amides that may be used in the present invention have the following formula (I): ## STR3 ## in which: the radical Y represents O or S, - the radical R1 represents: - (i) a hydrogen atom; (ii) a linear, branched or cyclic hydrocarbon radical, saturated or unsaturated, having 1 to 18 carbon atoms, optionally substituted with 1 to 5 groups, identical or different, chosen from - OH; -GOLD; -O-COR; - SH; -SR; -S-COR; NH2; NHR; -NRR '; -NH-COR; -Hal (halogen); - CN; -000R; -HORN; -P (0) - (OR) 2; -SO 2 OR; with R and R 'representing, independently of one another, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated, said radicals R and R; which can form together with N a 5- or 6-membered carbon ring which may furthermore comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted with 1 to 5 groups, which may be identical or different selected from -OH; -OR "; -O-COR"; SH; -SR "-S-COR"; NH2; - NHR "-NH- COR"; -Hal (halogen); CN; -COOR "; -COR"; with R "representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated or even perhalogenated; (iii) a radical chosen from the radicals -OR; -NH 2; -NHR -NRR '; -NH-COR; COOR; -COR; with R and R' representing, independently of one another, a linear, branched or cyclic hydrocarbon radical, saturated or unsaturated, having 1 to 6 atoms; of carbon, optionally halogenated or even perhalogenated, said radicals R and R 'being able to form together with N a 5- or 6-membered carbon ring which may furthermore comprise at least one heteroatom selected from O, N and / or S in the ring, and / or may be substituted with 1 to 5 groups, identical or different, chosen from -OH; -OR "; -O-COR -SH; -SR "; -S-COR"; NH2; -NHR "-NH-COR"; -Hal (halogen); CN; -COOR "; -COR"; with R "representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated or even perhalogenated; - radical R2 represents a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 18 carbon atoms, optionally substituted with 1 to 5 groups, identical or different, selected from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH 2; NHR; -NRR '; -NH-COR; -Hal (halogen); CN; -COOR; -COR; wherein R and R' represent, independently of one another, a linear, branched, hydrocarbon radical; or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated or even perhalogenated, said radicals R and R 'being able to form together with N a 5- or 6-membered carbon ring which may furthermore comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or may be substituted with 1 to 5 groups, identi or different, selected from -OH; -O-COR "; -SH; -SR"; -S-COR "-NH2; -NHR"; -NH-COR "-Hal (halogen); -CN; - COOR"; -COR "with R" representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated; the radical R 3 represents a radical chosen from those of formula (II) or (III): embedded image in which: y is an integer between 0 and 5 inclusive, and y 'is an integer between 1 and 5 inclusive; - A is a divalent hydrocarbon radical, linear or branched, saturated or unsaturated, having 1 to 18 carbon atoms, optionally substituted with 1 to 5 groups, identical or different, selected from - OH; -GOLD; -O-COR; SH; -SR; -S- COR; NH2; NHR; -NRR '; -NH-COR; -Hal (halogen, even perhalogenous); CN; -000R; -HORN; -NO 2; -SO 2 OR; with R and R 'representing, independently of one another, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated, said radicals R and R; which can form together with N a 5- or 6-membered carbon ring which may furthermore comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted with 1 to 5 groups, which may be identical or different selected from -OH; -OR "; -O-COR"; SH; -SR "-S-COR"; NH2; - NHR "-NH- COR"; -Hal (halogen); CN; -COOR "; -COR"; with R "representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated or even perhalogenated; B represents at least one group, identical or different, selected from -OH; OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NF R; -NRR '; -NH-COR; -Halogen; -CN; -COOR; -COR; -NO2; -SO2; -OR, or represents a hydrocarbon radical, linear or branched, saturated or unsaturated, having 1 to 18 carbon atoms, optionally substituted with 1 to 5 groups, identical or different, selected from -OH; -OR; -O- COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR '; -NH-COR; -Hal (halogen, or even perhalogen); -CN; -000R; -COR; -NO2; -SO2-; OR, with R and R 'representing, independently of one another, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated, said radicals R and R 'can form together with N a 5- or 6-membered carbon ring which may further comprise at least one heteroatom selected from O, N and / or S in the ring, and / or may be substituted with 1 to 5 groups, identical or different, selected from -OH; -OR "; -O-COR"; SH; -SR "; -S-COR"; NH2; -NHR "-NH-COR"; -Hal (halogen); CN; -COOR "; -COR"; with R "representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated or even perhalogenated; - radical X represents a radical chosen from -OH, -OR4, -NH2, -NHR4, -NR4R5, -SR4, -COOR4; -COR4, with R4 and R5 representing, independently of each other, a hydrocarbon radical, linear, cyclic or branched, saturated or unsaturated, having 1 to 6 atoms carbon, optionally substituted with 1 to 5 groups, identical or different, selected from OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR '; -NH; -COR; -Hal (halogen, or even perhalogen); -CN; -COOR; -COR; with R and R 'representing, independently of one another, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated; , having 1 to 6 carbon atoms, optionally halogenated or even perhalogenated, said radicals R and R 'being able to form together with N a 5- or 6-membered carbon ring which can further comprising at least one heteroatom selected from O, N and / or S in the ring, and / or may be substituted with 1 to 5 groups, identical or different, selected from -OH; -OR "; -O-COR"; SH; -SR "-S-COR"; NH2; -NHR "-NH-COR"; -Hal (halogen); CN; - COOR "; -COR"; with R "representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated or even perhalogenated, said radicals R4 and R5 being able to form together with N a 5- or 6-membered carbon ring which may further comprise at least one heteroatom selected from O, N and / or S in the ring, and / or may be substituted with 1 to 5 groups, identical or different, chosen from -OH; -OR "; -O-COR "; -SH; -SR"; -S-COR "; -NH2; -NHR"; -NH-COR "-Hal (halogen); -CN; -COOR"; -COR "with R" representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated.

  Also included in this definition are the mineral or organic acid salts of said compounds, as well as their optical isomers, in isolated form or in a racemic mixture.

  The term "linear, cyclic or branched hydrocarbon-based radical" is intended especially to mean alkyl, aryl, aralkyl, alkylaryl, alkenyl or alkynyl radicals.

  The C6H5 group present in the radical R3 must be understood as an aromatic cyclic group.

  Preferably, the radical Y represents oxygen.

  Preferably, the radical R 1 represents hydrogen or a linear or branched, saturated or unsaturated hydrocarbon-based radical having 1 to 12, in particular 1, 2, 3, 4, 5 or 6 carbon atoms, which is optionally substituted.

  In particular, the substituents may be chosen from -OH, -OR and / or P (O) - (OR) 2 with R representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated or even perhalogenous.

  Preferentially, the radical R 1 represents a methyl, ethyl, propyl or isopropyl radical, optionally substituted with an OH or P (O) - (OR) 2 group with R representing methyl, ethyl, propyl or isopropyl.

  Preferably, the radical R 2 represents a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 12, in particular 1, 2, 3, 4, 5 or 6 carbon atoms, optionally substituted.

  In particular, the substituents may be chosen from -OH and -OR with R representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated.

  Preferentially, the radical R 2 represents a methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl or isobutyl radical.

  Preferably, the radical R3 represents a radical of formula -CeH (5_y.) By. for which y '1, 2 or 3; or a radical of formula -A-C6H (5-y) -By for which y = 0, 1 or 2.

  Preferably, A is a divalent hycrocarbon radical, linear or branched, saturated or unsaturated, having 1 to 12 carbon atoms, optionally substituted.

  The substituents of A are preferably selected from -Hal (halogen, or even perhalogen); CN; -000R; -NO 2; -SO 2 OR; with R representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated.

  Preferably, B represents at least one -OR group; NHR; CN; -000R; -COR or represents a hydrocarbon radical chosen from a hydrocarbon radical, linear or branched, saturated or unsaturated, having 1 to 12 carbon atoms, optionally substituted.

  The substituents of B are preferably chosen from -Hal (halogen, or even perhalogen); CN; COOR; -NO 2; -SO 2 OR; with R representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated.

  Preferentially, the radical R3 represents a group chosen from one of the following formulas: in which A and B have the meanings given above.

  In particular, the divalent radical A may be a methylene, an ethylene or a propylene.

  Preferably, the radical B represents at least one group -OR; NHR; CN; - COOR; -COR for which R denotes a methyl, ethyl, propyl or isopropyl radical, or represents a hydrocarbon radical chosen from a methyl, ethyl, propyl or isopropyl radical, substituted by one or more halogens, in particular chlorine, bromine, iodine or fluorine, and preferentially totally halogenated (perhalogenated), such as perfluorinated. In particular, mention may be made of the perfluoromethyl (-.CF 3) radical as particularly preferred.

  Preferably, the radical X represents a radical chosen from -OH or OR4 with R4 representing a hydrocarbon radical, linear, cyclic or branched, saturated or unsaturated, having 1 to 6 carbon atoms, optionally substituted.

  The substituents may be chosen from -OH and -OR with R representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated.

  Preferably, the radical X represents a radical chosen from OH, OCH3, -OC2H5, -O-C3H7 or OC4H9.

  Among the particularly preferred compounds, mention may be made of: [2 - (acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} acetic acid, - {2- [acetyl- (3-trifluoromethyl)} -phenyl) -amino] -3-methyl-butyrylamino} ethyl acetate, [2- (acetyl-benzylamino) -3-methylbutyrylamino] acetic acid, [2- (acetyl-benzyl-amino) ) -3-methylbutyrylamino] ethyl acetate, ethyl (2- {benzyl - [(diethoxy-phosphoryl) acetyl] -amino} -3-methyl-butyrylamino) acetate.

  Even more preferentially, {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butyrylamino} -acetic acid or {2-acetyl (3-trifluoromethyl-phenyl) -10-amino] will be used. 3-methyl-butyrylamino} ethyl acetate.

  The amount of compound to be used in the compositions according to the invention can be easily determined by those skilled in the art, depending on the nature of the compound used, the person to be treated and / or the desired effect. In general, this amount may be between 0.00001 and 20% by weight relative to the total weight of the composition, in particular between 0.001 and 10% by weight, and preferably between 0.05 and 5% by weight. more preferably between 0.1 and 2% by weight, and preferably between 0.5 and 1% by weight.

  The compounds of formula (I) may in particular be employed, alone or as a mixture, in a composition which comprises a physiologically acceptable medium, especially in a cosmetic or pharmaceutical composition which therefore also comprises a cosmetically or pharmaceutically acceptable medium.

  The physiologically acceptable medium in which the compounds according to the invention may be employed, as well as its constituents, their quantity, the galenic form of the composition and its method of preparation, may be chosen by those skilled in the art on the basis of their general knowledge according to the type of composition sought.

  For topical application to the skin, the composition may be in the form of an aqueous or oily solution; dispersion of the lotion or serum type; emulsions of liquid or semi-liquid consistency of the milk type obtained by dispersion of a fatty phase in an aqueous phase (O / W) or conversely (W / O); suspensions or emulsions of soft, semi-solid or solid consistency of the cream or gel type, or multiple emulsions (E / H / E or H / E / H), microcapsules or microparticles; vesicular dispersions of ionic and / or nonionic type.

  For an application on the hair, the composition may be in the form of aqueous, alcoholic or aqueous-alcoholic solutions; in the form of creams, gels, emulsions, foams; in the form of aerosol compositions also comprising a propellant under pressure.

  When the composition is in aqueous form, especially in the form of a dispersion, an emulsion or an aqueous solution, it may comprise an aqueous phase, which may comprise water, floral water and / or mineral water.

  Said aqueous phase may further comprise alcohols such as C1-C6 monoalcohols and / or polyols such as glycerol, butylene glycol, isoprene glycol, propylene glycol, polyethylene glycol.

  When the composition used according to the invention is in the form of an emulsion, it may optionally further comprise a surfactant, preferably in an amount of 0.01 to 30% by weight relative to the total weight of the composition. The composition according to the invention may also comprise at least one co-emulsifier which may be chosen from oxyethylenated sorbitan monostearate, fatty alcohols such as stearyl alcohol or cetyl alcohol, or esters of fatty acids and of polyols such as glyceryl stearate.

  The composition used according to the invention may also comprise a fatty phase, in particular consisting of liquid fats at 25 ° C., such as oils of animal, vegetable, mineral or synthetic origin, volatile or otherwise; solid fats at 25 ° C., such as waxes of animal, vegetable, mineral or synthetic origin; pasty fatty substances; gums; of their mixtures.

  In known manner, the composition used according to the invention may furthermore comprise the usual adjuvants in the field in question, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, active agents, in particular cosmetic or pharmaceutical hydrophilic or lipophilic agents, preservatives, antioxidants, solvents, fragrances, fillers, pigments, nacres, odor absorbers and dyes. These adjuvants, depending on their nature, can be introduced into the fatty phase, into the aqueous phase and / or into lipid spherules.

  The nature and amount of these adjuvants may be chosen by those skilled in the art, on the basis of their general knowledge, so as to obtain the desired form of presentation for the composition. In any case, those skilled in the art will take care to choose any possible additional compounds and / or their quantity, in such a way that the advantageous properties of the composition according to the invention are not, or not substantially, impaired by the envisaged addition.

  Advantageously, said compound of formula (I) will be associated in the composition with at least one other soothing agent, said agent not being an anti-inflammatory agent.

  As "other soothing agent", there may be mentioned, for example: allantoin; Beta-glycyrrhetinic acid, the extracts containing them, for example Glycyrrhiza Glabra extract (liquorice) and the complexes containing them, such as the allantoin / glycyrrhetinic acid complex; É escin and plant extracts containing such as chestnut extract; Xanthine derivatives such as diethylaminoethyl theophylline hydrochloride; Water and aqueous extracts (eg hydroalcoholic or hydroglycolic) of flowers and plants, such as blueberry water, chamomile water, mint water, linden water, rose water , rosaceae extracts (ex: Rosa gallica), peony extracts, hawthorn extracts, millefeuille extracts, mauve extracts, marigold extracts, melilot extracts, sage extracts, elderberry water, ginkgo biloba extracts, arnica extracts, oregano extracts, green tea extracts, water lily flower extracts, iris extracts, birch bark extracts, Aloe vera extracts; Asian acid and plant extracts containing it such as Centella Asiatica; Bisabolol; É fruit extracts, such as pineapple extract, papaya extract; guava; • algae, particularly of the Laminaria type (for example red or brown); Pyrrolidone carboxylates and in particular zinc (Zn-PCA) or copper (Cu-PCA); É vegetable oils, such as canola seed oil and shea oil; É essential oils, for example coriander, lemon balm, lavender, mint, chamomile and their blends; Acexamic acid and transexamic acid (trans-4, aminomethylcyclohexane carboxylic acid); Ursolic acid and extracts containing it such as rosemary leaf extract; Fucose-containing polysaccharides, such as FUCOGEL 1000, sold by Solabia (aqueous solution comprising 1% of polysaccharide solids comprising fucose, galactose and galacturonic acid); Electrolytes and in particular an aqueous mixture comprising from 30 to 35% of magnesium chloride, from 20 to 28% of potassium chloride, from 3 to 10% of sodium chloride, from 0.2 to 1% of calcium, from 0.1 to 0.6% of magnesium bromide and from 0.1 to 0.5% of insolubles, the so-called mixture being here called "Dead Sea Bath Salts" for it corresponds to the principal salts contained in the Dead Sea; Galactolipids, for example from oats, such as, for example, digalactosyl diglyceride or monogalactosyl diglyceride; Amino acids, their derivatives and their salts, such as the sodium salt of amino acids grafted onto cocoyl chains, marketed in the form of a mixture under the name SEPICALM S by the company SEPPIC, capryloylglycine marketed under the name LIPACIDE; C8G by the company SEPPIC and the mixture of capryloylglycine, cinnamon and sarcosine sold under the name SEPICONTROL A5 by the company SEPPIC; É divalent salts of strontium, zinc, manganese, magnesium, calcium, such as those described in documents VVO-A-96/19184, WO-A-96/19182 and WO-A-20 96/19228 ; and their mixtures.

  The compound used according to the invention may also be combined in the composition with a cosmetic or pharmaceutical active ingredient with an irritating side effect selected from the group of keratolytic active ingredients, depigmenting agents, antiperspirants, slimming agents, depilatories, dyes or hair dyes. , permanent agents, retinoids, antipruriginous, antiseborrhoeic, comedolytic or antiacne agents and mixtures thereof.

  It may also be added in the compositions of the invention an anti-pollution or anti-radical agent, a UV filter or mixtures thereof.

  As an anti-pollution or anti-radical 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 "antiradical 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 and epigallocatechin and natural extracts containing them; olive leaf extracts tea extracts, especially green tea; anthocyanins; rosemary extracts phenolic acids, especially chorogenic acid; stilbenes, in particular resveratrol; sulfur-containing amino acid derivatives, in particular S-carboxymethylcysteine; 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 trade name CPP LS 2633-12F, the water-soluble fraction of corn 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, lycopene, vitamin E and its derivatives such as tocopheryl acetate; bioflavonoids; coenzyme Q10 or ubiquinone; certain enzymes such as catalase, superoxide dismutase and wheat germ extracts containing it, lactoperoxidase, glutathione peroxidase and quinone reductases; glutathione; benzylidene camphor; benzylcyclanones; substituted naphthalenones; pidolates; phytantriol; gamma-oryzarol; guanosine; lignans; and melatonin.

  As UV filters, mention may be made of organic photoprotective agents, chosen in particular from anthranilates; cinnamic derivatives; dibenzoylmethane derivatives; salicylic derivatives, camphor derivatives; triazine derivatives such as those described in patent applications US 4367390, EP863145, EP517104, EP570838, EP796851, EP775698, EP878469, EP933376, EP507691, EP507692, EP790243, EP944624; benzophenone derivatives; derivatives of (3, 3-diphenylacrylate, benzotriazole derivatives, benzalmalonate derivatives, benzimidazole derivatives, imidazolines, bis-benzoazolyl derivatives as described in patents EP669323 and US 2,463,264; paminobenzoic acid (PABA); methylene bis (hydroxyphenyl benzotriazole) derivatives as described in US5,237,071, US5,166, 355, GB2303549, DE 197 26 184 and EP893119; filter polymers and silicone filters such as those described in particular in the application WO 93/04665, dimers derived from α-alkylstyrene such as those described in the patent application DE19855649, 4,4-diarylbutadienes as described in applications EP0967200, DE19746654, DE19755649, EP-A -1008586, EP1133980 and EP133981 and mixtures thereof.

  The inorganic photoprotective agents are chosen from pigments or even nanopigments (average size of the primary particles: generally between 5 nm and 100 nm, preferably between 10 nm and 50 nm) of coated or uncoated metal oxides such as, for example, nanopigments titanium oxide (amorphous or crystallized in rutile and / or anatase form), iron, zinc, zirconium or cerium which are all UV photoprotective agents well known per se. Conventional coating agents are, moreover, alumina and / or aluminum stearate. Such nanopigments of metal oxides, coated or uncoated, are in particular described in patent applications EP518772 and EP518773.

  The filters are generally present in the compositions according to the invention in proportions ranging from 0.1 to 20% by weight relative to the total weight of the composition, and preferably ranging from 0.2 to 15% by weight relative to total weight of the composition.

  The amount of compound to be used according to the invention can be easily determined by those skilled in the art, depending on the nature of the compound used, the person to be treated and / or the desired effect. In general, this amount may be between 0.00001 and 20% by weight relative to the total weight of the composition, in particular between 0.001 and 10% by weight, and preferably between 0.05 and 5% by weight. by weight, more preferably between 0.1 and 2% by weight, and preferably between 0.5 and 1% by weight.

  Preferably, the compositions of the invention do not contain an anti-inflammatory agent.

  The invention also relates to a composition comprising, in a physiologically acceptable medium, at least one compound of the family of N-acylaminoamides associated with at least one other soothing agent as defined above, said agent not being an anti-inflammatory agent. inflammatory.

  The invention also relates to a composition comprising, in a physiologically acceptable medium, at least one compound of the family of Nacylaminoamides associated with at least one cosmetic or pharmaceutical active ingredient with irritating side effect with the exception of antifungal or antibacterial agents or agents. Anti fall.

  This active agent may advantageously be chosen from the group of keratolytic active agents, depigmentants, antiperspirants, slimming agents, depilatories, hair dyes or dyes, permanent agents, retinoids, antipruriginous agents, antiseborrhoeic agents, comedolytic agents or anti-viral agents. acne and their mixtures.

  As examples of potentially irritating side effect active agents, mention may be made of: E keratolytic agents such as α-hydroxy acids, such as glycolic, lactic, dioic, malic, citric, tartaric and mandelic acids, and their derivatives; β-hydroxy acids such as salicylic acid and its derivatives; α-ketoacids such as ascorbic acid or vitamin C and its derivatives; 13-keto acids; retinoids such as retinol and its esters, retinal, retinoic acid and its derivatives, those described in documents FR-A-2 570 377, EP-A-199 636, EP-A-325 540, EP-A -402,072); Depigmenting agents (eg hydroquinone, vitamin C in high concentration, kojic acid, arbutin, ellagic acid, aminophenol derivatives, procysteine and derivatives, niacinamide, isothiocyanate and thiocyanate, lucinol); Antiperspirant agents (certain aluminum salts); É certain slimming active agents with a heating effect; É depilatory or permanent active agents (thiols, ammonia); Hair dyes or dyes such as para-phenylene diamine (p-PDA) and some of its derivatives such as N-phenyl p-PDA and toluene 2,5-diamine sulphate; meta-phenylene diamine (m-PDA) and some of its derivatives such as toluene 3,4-diamine; orthophenylene diamine (o-PDA); E retinoids; Comedolytic agents (salicylic acid, dioic acid, Hepes, etc.) and their mixtures.

  "Physiologically acceptable medium" means a medium compatible with the skin and / or the scalp and / or mucous membranes and / or integuments.

  This composition may be a cosmetic composition or a dermatological composition.

  And it can be in all the galenic forms described above, adapted to topical application.

  The amount of compound to be used in the compositions according to the invention can be easily determined by those skilled in the art, depending on the nature of the compound used, the person to be treated and / or the desired effect. In general, this amount may be between 0.00001 and 20% by weight relative to the total weight of the composition, in particular between 0.001 and 10% by weight, and preferably between 0.05 and 5% by weight. more preferably between 0.1 and 2% by weight, and preferably between 0.5 and 1% by weight.

  The invention also relates to a soothing cosmetic process for the skin and / or the scalp, characterized in that a cosmetic composition as defined above is applied to the skin and / or the scalp and / or the mucous membranes.

  This cosmetic process will be especially intended to embellish and / or improve the general appearance of the skin and / or scalp and / or mucous membranes exposed to stress.

  The composition may be applied daily or several times a day and for a period of time depending on the subject to be treated.

  The invention will now be illustrated by the following nonlimiting examples.

  EXAMPLE 1 Effect of {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butylylamino} -acetic Acid on Keratinocyte Mediators Expressed During Exposure to an Irritant or During a Treatment exposure to hypoxidic stress a) transcriptomic study (cDNA array) To investigate the protective activity of {2- [acetyl- (3trifluoromethyl-phenyl) -amino] -3-methyl-butylylamino} acetic acid vis-à-vis -vis of a cutaneous stress, one analyzes the effect of the product on the expression of genes known to be modulated in response to a stress. The analysis is performed using dedicated minichips, consisting of cDNA arrays containing several tens of genes in relation to cellular stress such as cytokines, defensins, chemokines, stress proteins, stress inhibitors oxidative inhibitors of IL1 or TNFa, anti-inflammatory cytokines.

  The cellular model used includes keratinocytes derived from human neonatal cells of Clonetics (Portland, OR), grown as reported by Boyce ST and Ham RG (J Invest Dermatol, 1983, Vol 81, pp 33S-40S). The keratinocytes are cultured in SFM medium with EGF 0.25 ng / ml and pituitary extract 25 μg / ml at 37 ° C. and 5% CO2.

  The keratinocytes were inoculated into 25 cm 2 dishes and pre-cultured in complete SFM medium. The cells were then placed in SFM medium without EGF or pituitary extract. Two series of 8 boxes were made: a series subjected to hypoxic stress (anaerobic condition) and a series subjected to a concentration of Phorbol Myristate Acetate PMA (at 0.1 μg / ml), said series being placed in the presence or absence of {2 [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methylbutylamino} acetic acid at concentrations of 0.1mM or 1mM.

  The application of {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butylylamino} -acetic acid (product) can be carried out under the following conditions: in a first experiment, the product is applied 4 h before exposure to PMA or hypoxia and then for 18h; in a second experiment, the product is applied at the same time as exposure to PMA or hypoxia and this for 18h.

  For the 'stress hypoxia' series, a box that was not treated with the product and placed in hypoxia (control) and a box that was not treated with the product and placed at 37 ° C and 5% CO2 (controlled without hypoxia stress) were also produced. .

  For the 'PMA irritant stress' series, a box that was not treated with the product and treated with PMA (control) and a box not treated with the product and without PMA (control without PMA) were also produced.

  The cells are then rinsed in PBS and lysed and the RNA is extracted using tri-Reagent for genomic analysis.

  The analysis of the different stress markers is done according to the standard protocols of genomic analysis. The methodology of DNA Microarrays is preferably used. The extraction / purification of messenger RNA from each culture led to the isolation of amounts of messenger RNA (small box culture).

  The 33 P-labeled DNA probes were made by reverse transcription of the mRNAs, using a pool of primers specific for immobilized sequences on the membranes (arrays), in the presence of (alpha 33 P) -dATP. This step uses the reagents and the protocol recommended by Invitrogen. The labeled probes are purified by exclusion column chromatography and the quality and equivalence of the labeled probes is evaluated by liquid scintillation counting.

  Immobilized cDNAs on the membranes are hybridized (42 C, overnight) to the corresponding labeled probes. The filters are then washed and placed in individual plastic bags for exposure and analysis.

  The analysis corresponds to a direct quantification of the radioactivity of the spots using a Cyclone phospholmager (Packard). The results are expressed in relative units of expression (RE, spot radioactivity corresponding to each gene, corrected for background noise and differences in the intensity of labeling of the probes). Membrane analysis was performed using ImageQuant TL software (Ilage Analysis, Amersham Biosciences). The results are expressed in fine in% relative to the control.

  The results obtained in the 'stress + product to be tested' condition are compared with the results of the 'stress without product' and control conditions (without stress or product).

  The results obtained in the application condition of the product 4h before the exposure to the PMA then for 18h, are presented in the following table: Control Genes (without Control (with With PMA With PMA PMA or PMA without +0.1 mM +1 mM product) product) product produced in% by% by% relative to the ratio to the ratio to the control control control betadefensin 2 (hBD2, 35.3 221 209 165 DEFB2) Heme oxygenase 1 7.9 334 282 240 inducible (HO1; HMOX1) mitochondrial stress protein 3,3 234 102 142 Interleukin-1 receptor 4,6,294 251,498 of type II (IL-1R2); IL-1Rbeta When {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methylbutylylamino} acetic acid is applied at a concentration of 0.1 mM or 1 mM on keratinocytes in culture 4h before exposure to PMA and then for 18h, a lower expression of genes involved in inflammation such as beta-defensin 2 (inducible defensin), inducible heme oxygenase 1 (free radicals) and mitochondrial stress protein (induced in particular during thermal stress, inflammatory, infectious, or oxidative ...). These results indicate that the keratinocytes pretreated 4h with {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butylylamino} acetic acid undergo less stress under the action of PMA. {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methyl-butylylamino} -acetic acid thus protects the keratinocytes.

  Moreover, when {2- [acetyl- (3-trifluoromethyl-phenyl) amino] -3-methylbutylylamino} acetic acid is applied at a concentration of 1 mM on keratinocytes in culture 4h before exposure to PMA and then during 18h, there is an increase in the expression of genes involved in the negative regulation of inflammation systems such as the receptor interleukin-1 type II (IL-1 inhibitor) intended to inhibit the reactions that may be involved in the release of IL-1 by action of PMA.

  All these results were confirmed by the quantitative measurement by ELISA of these mediators induced in the supernatants and in the cell extracts and by the analysis of the expression of the stress proteins at the intracellular nuclear level by immunocytochemistry.

  b) study RT-Q-PCR 3 conditions are tested: - control: without product and without PMA - control: without product with PMA - test: with product (1 mM) and PMA.

  The markers selected correspond to the 4 genes identified during the cDNA-array study described in a).

  The total remaining RNA from the cDNA-array study is used. Traces of potentially contaminating DNA are removed by DNAse treatment and DNAse inactivation. A reverse transcription reaction is then carried out followed by quantification, by fluorescence, of the synthesized cDNA.

  PCR reactions (polymerise chain reactions) were performed by quantitative PCR with the Light Cycler system (Roche Molecular Systems Inc.) and according to the procedures recommended by the supplier.

  A first series of Q-PCRs are carried out on the Ractin marker to verify the homogeneity of the preparations to be compared. Triplicate Q-PCRs are then carried out using primer pairs specific for the sequences (3-actin and the markers to be studied) and the fluorescence analysis in the amplified DNA is measured continuously during the PCR cycles. The average value of the relative expression (RE) is expressed in Arbitrary Units (AU) calculated from the cycle values of two independent PCRs according to the following formula: (1/2 cycle shadow) x 106.

  The differential expression results of the 4 markers are compared with that of the actin.

  EXAMPLE 2 Effect of {2- [acel: yl- (3-trifluoromethyl-phenyl) amino] -3-methyl-butylylamino} acetic Acid on the Chemotaxis of Neutrophil Polynuclear Neutrophil Migromites in the Presence of Keratinocytes in a Monolayer at confluence is studied using Transwell filters (Costar).

  Each well is separated into a lower chamber (where the keratinocytes were cultured) and an upper chamber (where the neutrophils are deposited). The two chambers are separated by 6.5mm diameter polycarbonate filters pierced with 5pm pores.

  The neutrophil migration induced by the chemotactic factors released by the keratinocytes is studied in the presence of {2- [acetyl- (3-trifluoromethyl-phenyl) -amino] -3-methylbutylylamino} acetic acid at different concentrations (0, 1mM or 0.2mM) or 10pM α-MSH used as a positive control of migration inhibition.

  The neutrophils (1x106 in 100 μl) are placed in the upper chamber of the well equipped with a Transwell device. In the lower chamber, the keratinocytes were grown at confluence. After 5 hours of incubation neutrophils having migrated into the lower chamber towards the keratinocytes are counted with the aid of a hemocytometer and the% of neutrophils having migrated is calculated.

  EXAMPLE 3: Soothing Cream Compositions - {2- [acetyl- (3-trifluoromethyl-phenyl) -arnino] -3-methyl-butylylamino} acetic acid 1% bisabolol 0.5% - aloe vera extract 1% - stearate glycerol 2% polysorbate 60 (Tween 60 from ICI) 1.00% - stearic acid 1.4% triethanolamine 0.7% - carbomer 0.4% - sunflower oil 10.00% -parfume 0.50% - preservative 0.30% -water qs 100% Anti-acne cream - 0.1% salicylic acid - {2- [acetyl- (3-trifluoromethyl-phenyl) -arnino] -3-methyl-butylylamino} acetic acid 0 , 1% - glycerol stearate 2% polysorbate 60 (Tween 60 sold by 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 qs 100

Claims (18)

  1. Use of at least one compound of the family of N-acylamino amides in a composition containing a physiologically acceptable medium, as a soothing agent.   2. Use according to claim 1, characterized in that said compound is intended to prevent and / or reduce a cutaneous reaction induced by a stress selected from chemicals, UV radiation, air pollution, oxidative stress, mechanical friction and their mixtures.   3. Use according to any one of claims 1 or 2, characterized in that said compound is intended to prevent and / or reduce the irritating effect of a cosmetic or dermatological composition containing one or more compounds with irritating side effect.   4. Use according to any one of claims 1 to 3, characterized in that the compound is intended to prevent and / or reduce sensations of cutaneous discomfort, tight skin, itchy skin, redness of the skin, or sensation cutaneous heat.   Use of at least one compound of the N-acylamino amide family for the preparation of a composition for preventing and / or treating stress-induced skin irritation.   6. Use according to claim 5, characterized in that said compound is intended to prevent and / or treat cutaneous signs related to skin irritation selected from pruritus, scabs, edema, inflammatory erythema, and burns.   7. Use of at least one compound of the family of N-acylamino amides for the preparation of a pharmaceutical composition intended to prevent and / or treat dermatological affections related to cutaneous inflammation or to early inflammatory processes responsible for disorders cutaneous immune system.   8. Use according to claim 7, characterized in that the dermatological conditions are selected from irritant dermatitis, acne, seborrheic dermatitis, atopic dermatitis, vitiligo, and psoriasis.   9. Use according to any one of claims 1 to 8, characterized in that said compound is intended to regulate the production of mediators of cutaneous inflammation.   10. Use according to claim 9, characterized in that said compound is capable of decreasing the expression of mediators involved in cutaneous inflammation, and / or increase the expression of inflammatory cytokine inhibitors.   11 Use according to any one of claims 1 to 10 characterized in that said compound of the family of N-acylamino amides is chosen from: - {2- [acetyl- (3-trifluoromethyl-phenyl) -amino acid ] 3-methyl-butyrylamino} acetic acid; ethyl {2- [acetyl- (3-trifluoromethylphenyl) amino] -3-methyl-butyrylamino} acetate; [2 (acetyl-benzylamino) -3-methyl-butyrylamino] acetic acid; ethyl [2- (acetylbenzyl-amino) -3-methyl-butyrylamino] acetate; ethyl (2- {benzyl [(diethoxy-phosphoryl) -acetyl] -amino} -3-methyl-butyrylamino) acetate.   12 Use according to any one of revendicaions 1 to 11 characterized in that the composition is suitable for topical administration.   13 Use according to any one of claims 1 to 12 characterized in that the compound of the family of N-acylamino amides is present in the composition in an amount ranging from 0.00001 to 20% by weight relative to the total weight of the composition, preferably from 0.5 to 5%, more preferably from 0.1 to 2% by weight relative to the total weight of the composition.   14. Cosmetic composition comprising, in a physiologically acceptable medium, at least one compound of the family of N-acylamino amides combined with at least one other soothing agent, said soothing agent not being an anti-inflammatory agent.   15. Composition comprising, in a physiologically acceptable medium, at least one compound of the family of N-acylamino amides associated with at least one compound with an irritating side effect selected from the group of keratolytic active agents, depigmenting agents, antiperspirants and slimming agents. depilatories, hair dyes or dyes, perming agents, retinoids, antipruritic, antiseborrhoeic, comedolytic or antiacne agents, and mixtures thereof.   16. Composition according to claim 15, characterized in that the amount of compound (s) with irritating side effect is between 0.0001 to 50% by weight and preferably from 0.01 to 30% by weight relative to the total weight of the composition.   17. Composition according to any one of claims 14 to 16, characterized in that the compound of the family of N-acylamino amides is present in the composition in an amount ranging from 0.00001 to 20% by weight relative to the total weight of the composition, preferably from 0.05 to 5%, more preferably from 0.1 to 2% by weight relative to the total weight of the composition.   18. Cosmetic soothing process of the skin and / or scalp, characterized in that it is applied to the skin and / or the scalp a composition as defined in one of claims 14 to 17.