WO2006053790A1 - Utilisation de composes de la famille des n-acylaminoamides en tant qu’agents calmants ou apaisants - Google Patents

Utilisation de composes de la famille des n-acylaminoamides en tant qu’agents calmants ou apaisants Download PDF

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Publication number
WO2006053790A1
WO2006053790A1 PCT/EP2005/013532 EP2005013532W WO2006053790A1 WO 2006053790 A1 WO2006053790 A1 WO 2006053790A1 EP 2005013532 W EP2005013532 W EP 2005013532W WO 2006053790 A1 WO2006053790 A1 WO 2006053790A1
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Prior art keywords
skin
compound
agents
use according
composition
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PCT/EP2005/013532
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English (en)
Inventor
Audrey Gueniche
Lionel Breton
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L'oreal
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Priority claimed from FR0452723A external-priority patent/FR2878156A1/fr
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Publication of WO2006053790A1 publication Critical patent/WO2006053790A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/75—Anti-irritant

Definitions

  • the field of the invention relates to protection of the skin and/or its integuments against stress-induced skin irritation or cutaneous inflammation.
  • stress means any stress of exogenous origin, such as stress of chemical origin (e.g.: xenobiotics, irritant chemical products, etc.), environmental origin (e.g.: temperature, climate, UV radiation, atmospheric pollution, especially: heavy metals, gaseous pollutants such as sulfur dioxide, ozone and nitrogen oxides, oxidative stress, cigarette smoke, etc.), mechanical origin (e.g.: friction on contact with a razor, etc.), infectious origin (e.g.: allergen, antigen, etc.) and/or any stress of endogenous origin, such as disorders involving an inflammatory and/or hormonal mechanism affecting the skin.
  • the stress is chosen from oxidative stress, a compound with an irritant side effect or strong irradiation with UV radiation.
  • the term "strong irradiation” means acute (strong irradiation) or intense solar exposure, in particular exposure to the zenithal sun or to solar radiation varying by an angle of 30° around this zenithal position and/or when the skin is subjected to UV radiation capable of inducing solar erythema characterized by redness commonly known as a "sunburn” and defined by a minimum erythemal dose (MED) .
  • This dose varies as a function of the individual's phototype and the UVA/UVB ratio.
  • the invention is especially directed towards preventing or reducing the pro-inflammatory mechanisms induced by short exposure to erythemal doses of solar radiation.
  • solar exposure conditions include UVB radiation, at doses of about the MED, in particular at a dose of greater than or equal to 1 MED.
  • strong solar exposure especially means solar exposure covering the real variations in solar radiation in terms of dose and UVA/UVB ratio, especially the zenithal condition, the said variations possibly corresponding to a solar exposure termed “erythemal” .
  • solar radiation especially means any radiation equivalent to the natural solar spectrum, in particular to the zenithal spectrum, and comprising at least UVA and UVB in a UVA/UVB ratio of between 10 and 17, preferably greater than or equal to 11 and less than or equal to 16.
  • the solar radiation according to the invention may comprise 92% UVA and 8% UVB, reproducing the conditions of the zenithal solar spectrum in the UVB region.
  • the proportion of UVB in the solar radiation defined according to the invention will be between 6% and 9%.
  • skin means the skin broadened to the scalp and mucous membranes.
  • integuments means the eyelashes, body hair, head hair and the nails.
  • the present invention relates especially to the use of at least one compound of the N-acylamino- amide family in a composition containing a physiologically acceptable medium, as a soothing or calming agent.
  • the said compound is intended to protect the skin and/or its integuments against the irritant effect of a chemical product, an atmospheric pollutant, UV radiation or mechanical friction, and consequently to protect the skin against the cutaneous signs associated with this irritant effect.
  • These cutaneous signs may range from the simple sensation of skin discomfort with tautness, itching, heating and redness, to more important cutaneous signs, for instance pruritus, dry patches and inflammatory erythema.
  • the invention thus relates also to the use of at least one compound of the N-acylaminoamide family for the preparation of a composition for preventing and/or treating dermatological complaints such as irritant dermatitis, acne, seborrhoeic dermatitis, psoriasis, vitiligo and atopic dermatitis.
  • the invention also relates to a cosmetic process for soothing the skin and/or the scalp, comprising the topical application of a composition comprising at least one compound of the N-acylamino ⁇ amide family. This process is especially advantageous for treating fair skin (phototype I, II and potentially III) and/or allergic and/or irritable skin types.
  • allergic and/or irritable skin and/or scalps especially means skin and/or scalps that react to external attacking factors, occasionally in an exaggerated manner. These skin types and/or scalps are consequently more subject to the development of a skin reaction that may be manifested by redness or pruritus and/or that may involve immunological or inflammatory mechanisms.
  • the preferred compounds used according to the invention are (2- (acetyl (3-trifluoromethylphenyl) - amino) -3-methylbutyrylamino) acetic acid or ethyl (2- (acetyl (3-trifluoromethylphenyl) amino) -3- methylbutylrylamino) acetate.
  • Human skin consists of two compartments, the epidermis and the dermis.
  • the epidermis is composed mainly of three types of cell, which are the keratinocytes (predominant) , the melanocytes and the Langerhans cells. Each of these cell types contributes by means of its intrinsic functions towards the essential role played in the body by the skin, especially the role of protecting the body against the abovementioned external attacking factors.
  • the dermis provides the epidermis with a solid support. It is also its nourishing factor. It consists mainly of fibroblasts and of an extracellular matrix, itself composed mainly of collagen, elastin and glycoproteins that constitute the ground substance. Leukocytes, mastocytes and tissue macrophages are also found therein. Finally, blood vessels and nerve fibres transverse the dermis.
  • atmospheric pollutants especially gaseous pollutants such as sulfur dioxide, ozone and nitrogen oxides on the constituents of the skin (fibres, cells and enzymes) is especially linked to their irritant activity, which causes cutaneous cell damage that may lead to inflammation, with vasodilation and release of mediators, and result especially in redness, heat and pain
  • ozone-induced lipid peroxidation may impair the skin in two ways :
  • the oxidation and degradation of the lipids of the stratum corneum may impair the barrier function of the stratum corneum, which appears to be one of the triggering factors in many forms of dermatosis (psoriasis, atopic dermatitis, irritant dermatitis) ; 2. the increased formation of lipid oxidation products in the upper layers of the skin may trigger attack in the adjacent cutaneous layers.
  • a significant oxidative attack of the surface layers of the stratum corneum may initiate underlying localized inflammatory processes, leading to the recruitment of phagocytes, which, by generating oxidizing agents, will amplify the initial oxidative processes; thus, the harmful effects of pollution on keratin materials affect the cell respiration of these keratin materials and are reflected by accelerated ageing of the skin, with a dull complexion and the early formation of wrinkles or fine lines, and also by a decrease in the strength of the hair, which also acquire a dull appearance. In addition, pollution causes the skin and the hair to become soiled more quickly.
  • pollution may cause irritation and allergy and inflammation phenomena on the skin; - the chemical products used in the usual products (household products, cosmetic products, etc.) may also have an irritant effect, i.e. may cause uncomfortable skin reactions such as heating, redness or, in certain cases, burning, or reactions of inflammatory or immunoallergic type; keratolytic agents or exfoliants, depigmenting agents, oxidizing agents, reducing agents and comedolytic agents are used, for example, in cosmetic compositions.
  • UV radiation with wavelengths of between 280 nm and 400 nm permit tanning of the human epidermis.
  • UVB rays cause erythema and skin burns.
  • UVA rays with wavelengths of between 320 and 400 nm are also liable to induce impairment of the skin: they in particular cause loss of elasticity of the skin (degradation of the elastic fibres) and the appearance of wrinkles, leading to premature ageing (this is referred to as photo-ageing) , and also promote triggering of the erythemal reaction or amplify this reaction in certain individuals and may even be the cause of phototoxic or photoallergic reactions.
  • UV rays are responsible at the cellular level for the generation of reactive oxygen species (oxidative stress) , which are themselves the cause of many biological effects, for instance the induction of oxidative damage to DNA (8 oxoguanine) or to many genes .
  • oxidative stress reactive oxygen species
  • the present invention is especially directed towards combating the pro-inflammatory and inflammatory mechanisms induced under stress conditions, in particular induced under conditions of oxidative stress, or induced by the presence of a compound with an irritant side effect or alternatively by UV radiation, in particular by a strong irradiation comprising UV rays capable of generating an erythemal reaction.
  • This erythemal reaction or solar erythema is generally reflected by redness of the skin observed within a few hours of exposure to sunlight. This effect is commonly known as “sunburn” and is associated simultaneously with the induction of damage to DNA, with the formation of sunburn cells and with the production of inflammatory cytokines such as IL-l ⁇ or TNF ⁇ .
  • the skin reacts by a cutaneous reaction that is intended to restore the broken homeostatic equilibrium or to repair the damage caused. It effects a cascade of reactions that can give rise to the persistent irritant process characterized mainly by irritation of the skin or an involution of the hair bulb and its matrix environment.
  • the primary cutaneous signs associated with skin irritation may be a simple sensation of skin discomfort (e.g. : stinging, itching, tautness, heating, redness, etc.) or pruritus, dry patches, inflammatory erythema or oedema, which may be found associated with dermatological complaints.
  • the skin irritation of inflammatory type is characterized by an initiation phase involving keratinocytes, which constitute the skin's first line of cellular defence.
  • stress proteins e.g. : HSP70 and HSP90
  • defensins e.g.: defensin 2
  • these keratinocytes release biological mediators and cytokines, which are prestored in the epidermis under normal conditions (e.g. : IL-l ⁇ , and arachidonic acid derivatives) .
  • IL-l ⁇ has an autocrine role, but is also capable of inducing the transcription of more than 90 genes (e.g.: cytokines IL-l ⁇ , IL-6, GM-CSF, TNF ⁇ , chemokines including IL-8, MCP-I, MIP-Ia and eotaxin, and also the expression of adhesion molecules such as E-selectin or ICAM-I and VCAM-I) in various skin cell types, for instance the keratinocytes, endothelial cells or fibroblasts.
  • genes e.g.: cytokines IL-l ⁇ , IL-6, GM-CSF, TNF ⁇ , chemokines including IL-8, MCP-I, MIP-Ia and eotaxin, and also the expression of adhesion molecules such as E-selectin or ICAM-I and VCAM-I
  • adhesion molecules such as E-selectin or ICAM-I and VCAM-I
  • Arachidonic acid is itself rapidly metabolized into numerous highly active compounds, eicosanoids such as prostaglandins, thromboxane and leukotrienes that act as local mediators with a short lifetime, which are involved in controlling proliferation, differentiation, apoptosis or the formation of oedema or leukocyte activation.
  • eicosanoids such as prostaglandins, thromboxane and leukotrienes that act as local mediators with a short lifetime, which are involved in controlling proliferation, differentiation, apoptosis or the formation of oedema or leukocyte activation.
  • TNF- ⁇ a major cytokine of cutaneous inflammation, which is prestored in the dermal mastocytes but is also produced by the keratinocytes and the Langerhans cells after stimulation, induces the transcription of adhesion molecules in synergism with IL-I, which play an essential role in the circulation and migration of leukocytes (in particular neutrophils) from the peripheral blood vessels to the dermis and the epidermis.
  • IL-I which play an essential role in the circulation and migration of leukocytes (in particular neutrophils) from the peripheral blood vessels to the dermis and the epidermis.
  • This initiation phase of skin irritation is then relayed by a phase of local amplification of the irritation, involving the production of IL-12 and IL-18 by the activated macrophages, and also the secretion of chemokines by the vascular cells and the keratinocytes (e.g.
  • IL-8 of the CC group and MCP-I of the CXC group which attract polymorphonuclear leukocytes, lymphocytes and monocytes/macrophages to the site of the inflammation.
  • IL-6 is also a cytokine secreted by activated keratinocytes, macrophages and vascular cells during inflammation, and which may reach the general circulation and trigger regional and systemic effects.
  • oxidative stress which can generate free radicals and reactive oxygen species (ROS) is another major factor of skin irritation and/or of inflammation.
  • ROS reactive oxygen species
  • skin irritation may be the cause of various cutaneous signs, ranging from simple sensations of skin discomfort (e.g.: tautness, itching, heating, redness, etc.) to more important cutaneous signs, for instance pruritus, dry patches, inflammatory erythema, oedema, or burning.
  • simple sensations of skin discomfort e.g.: tautness, itching, heating, redness, etc.
  • cutaneous signs for instance pruritus, dry patches, inflammatory erythema, oedema, or burning.
  • CID contact irritant dermatitis
  • Acute CID mainly characterized by inflammation
  • chronic CID characterized by hyperproliteration of the keratinocytes and transient hyperkeratosis
  • cutaneous penetration of chemical products associated with the degree of permeability of the skin (physiological state)
  • the physicochemical properties of the compounds molecular weight, polarity and state of ionization
  • the nature of their environment is a major parameter in establishing the physiopathology of the CID.
  • acne and seborrhoeic dermatitis also have an inflammatory component .
  • the early inflammatory processes may lead to cutaneous immune disorders such as atopic dermatitis, vitiligo and psoriasis.
  • the Applicant has been able to demonstrate, specifically, a regulatory effect of these compounds on the production of inflammation mediators and also an activating effect on the production of endogenous inhibitors of inflammatory cytokines.
  • the Applicant has been able to show that ⁇ 2- [acetyl (3-trifluoromethylphenyl) amino] -3- methylbutyrylamino ⁇ acetic acid, applied at a concentration of 0.1 mM or 1 mM to keratinocyte cultures subjected to an irritant stress (e.g. 0.1 ⁇ g/ml PMA or IFN-gamma), is capable of reducing the expression of inflammation mediators (e.g.
  • IL-I e.g. : type II interleukin-1 receptor
  • EP 1 269 989 with an antifungal agent or an antibacterial agent (EP 1 269 988) to prevent or reduce the mechanism of degradation of elastic fibres (upstream action) ; or with a hair-loss counteracting/hair-restoring compound (WO 03/000209) , with an agent for increasing elastin synthesis (FR 2 847 816) , with a metalloprotease inhibitor (EP 1 275 372) , or alternatively with a muscle relaxant (EP 1 269 990) , for combating the effects of degradation of elastic fibres on the skin or the scalp, such as ageing of the skin or hair loss (downstream action) .
  • the said compound is intended to: prevent and/or reduce a skin reaction induced by a stress; in particular, the stress is chosen from UV radiation, atmospheric pollution, oxidative stress, chemical products and mechanical friction, and mixtures thereof; it will preferably be oxidative stress or UV radiation, in particular strong UV irradiation; preventing and/or reducing the irritant effect of a cosmetic or dermatological composition containing one or more compounds with an irritant side effect; - preventing and/or reducing the sensations of skin discomfort, tautness of the skin, skin itching, skin redness or the sensation of heating of the skin, in particular induced by oxidative stress or stress linked to a compound with an irritant side effect or UV radiation, preferably strong irradiation comprising UVB rays.
  • the stress is chosen from UV radiation, atmospheric pollution, oxidative stress, chemical products and mechanical friction, and mixtures thereof; it will preferably be oxidative stress or UV radiation, in particular strong UV irradiation; preventing and/or reducing the irri
  • a compound of the N-acylaminoamide family thus has the advantage of eliminating or reducing the skin irritation that compounds with an irritant side effect might cause, and also of making it possible to increase the amount of compounds of irritant nature in cosmetic or dermatological compositions relative to the amount normally used, for the purpose of increased efficacy thereof.
  • compounds with an irritant side effect mention may be of keratolytic active agents, depigmenting agents, antiperspirants, slimming agents, hair removers, hair dyes or colorants, permanent-waving agents, retinoids, anti-pruriginous agents, anti-seborrhoeic agents, comedolytic agents or anti-acne agents, and mixtures thereof. Examples that may be mentioned include:
  • keratolytic agents such as ⁇ -hydroxy acids, for instance glycolic acid, lactic acid, dioic acid, malic acid, citric acid, tartaric acid and mandelic acid, and derivatives thereof; ⁇ -hydroxy acids, for instance salicylic acid and its derivatives; ⁇ -keto acids, for instance ascorbic acid or vitamin C and its derivatives; ⁇ -keto acids; retinoids, for instance retinol and its esters, retinal, retinoic acid and its derivatives, and those described in documents FR-A-2 570 377, EP-A-199 636, EP-A-325 540 and EP-A-402 072) ;
  • depigmenting agents e.g.: hydroquinone, vitamin C at high concentration, kojic acid, arbutin, ellagic acid, aminophenol derivatives, procysteine and derivatives, niacinamide, isothiocyanate and thiocyanate, and lucinol
  • hair removers or permanent-waving agents thiols, aqueous ammonia
  • hair dyes or colorants for instance para-phenylenediamine (p-PDA) and certain derivatives thereof such as N-phenyl-p-PDA and toluene-2, 5-diamine sulfate; meta-phenylenediamine (m-PDA) and certain derivatives thereof such as toluene-3,4-diamine; ortho-phenylenediamine Co- PDA) ;
  • comedolytic agents salicylic acid, dioic acid, Hepes, etc. ; and mixtures thereof.
  • N-acylaminoamide compounds according to the invention thus makes it possible to increase the amounts of the said compounds with an irritant side effect.
  • 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 the cutaneous signs associated with stress- induced skin irritation involving inflammatory mechanisms.
  • a composition for preventing and/or treating the cutaneous signs associated with stress- induced skin irritation involving inflammatory mechanisms.
  • it will be a skin irritation induced by oxidative stress, stress associated with an irritant side effect or a strong UV irradiation.
  • the said composition is intended for preventing and/or treating pruritus, dry patches, oedema, inflammatory erythema or burns.
  • the composition may also be used for preventing and/or treating dermatological complaints associated with a cutaneous inflammation or with early inflammatory processes responsible for cutaneous immune disorders . These dermatological complaints may be chosen especially from irritant dermatitis, acne, seborrhoeic dermatitis, atopic dermatitis, vitiligo and, preferably psoriasis
  • the compound according to the invention is also advantageous as an agent for preventing and/or treating the inflammatory component of androgenic alopecia or of hair loss.
  • the composition will not contain any hair-loss counteractant/hair restorer.
  • the said compound used according to the invention is intended for regulating the production of cutaneous inflammation mediators, by reducing the synthesis or release of pro-inflammatory or inflammatory cytokines and/or by activating the systems of negative regulation of inflammatory processes (e.g. : anti-inflammatory cytokines or inflammatory cytokine inhibitors) .
  • the said compound according to the invention is intended for reducing or inhibiting the production of TNF ⁇ , in particular induced in the presence of a compound with an irritant side effect or induced under conditions of strong UV irradiation.
  • the compounds of the N-acylaminoamide family that may be used in the present invention correspond to formula (I) below:
  • the radical Y represents O or S
  • the radical Rl represents: (i) a hydrogen atom; - (ii) a linear, branched or cyclic, saturated or unsaturated hydrocarbon-based radical containing 1 to 18 carbon atoms, optionally substituted with 1 to 5 groups, which may be identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH 2 ; -NHR; -NRR'; -NH-COR; -Hal (halogen) ; -CN; -COOR; -COR; -P(O)-(OR) 2 ; -SO 2 -OR; with R and R' representing, independently of each other, a linear, branched or cyclic, saturated or unsaturated hydrocarbon-based radical containing 1 to 6 carbon atoms, which is optionally halogenated, or even perhalogenated, the said radicals R and R' possibly forming,
  • radicals -OR a radical chosen from the radicals -OR; -NH 2 ; -NHR; -NRR'; -NH-COR; -COOR; -COR; with R and R' representing, independently of each other, a linear, branched or cyclic, saturated or unsaturated hydrocarbon-based radical containing 1 to 6 carbon atoms, which is optionally halogenated, or even perhalogenated, the said radicals R and R' possibly forming, together with N, a 5- or 6-membered carbon-based ring also possibly comprising at least one heteroatom chosen from 0, N and/or S in the ring, and/or possibly substituted with 1 to 5 groups, which may be identical or different, chosen from -OH; -OR"; -O-COR"; -SH; -SR"; -S-COR”; -NH 2 ; -NHR"; -NH-COR”; -Hal (halogen); -CN; -COOR”
  • A is a linear or branched, saturated or unsaturated divalent hydrocarbon-based radical containing 1 to 18 carbon atoms, optionally substituted with 1 to 5 groups, which may be identical or different, chosen from -OH; -OR; -0-COR; -SH; -SR; -S-COR; -NH 2 ; -NHR; -NRR'; -NH-COR; -Hal (halogen, even perhalogen) ; -CN; -COOR; -COR; -NO 2 ; -SO 2 -OR; with R and R' representing, independently of each other, a linear, branched or cyclic, saturated or unsaturated hydrocarbon-based radical containing 1 to 6 carbon atoms, which is optionally halogenated, or even perhalogenat ed , the said radicals R and R' possibly forming, together with N, a 5- or 6-membered carbon-based ring also possibly comprising at least one heteroatom chosen from 0, N and
  • B represents at least one group, which may be identical or different, chosen from -OH; -OR; -0-COR; -SH; -SR; -S-COR; -NH 2 ; -NHR; -NRR' ; -NH-COR; -Halogen; -CN; -COOR; -COR; -NO 2 ; -SO 2 -OR 7 or represents a linear or branched, saturated or unsaturated hydrocarbon-based radical containing 1 to 18 carbon atoms, optionally substituted with 1 to 5 groups, which may be identical or different, chosen from -OH; -OR; -0-COR; -SH; -SR; -S-COR; -NH 2 ; -NHR; -NRR'; -NH-COR; -Hal (halogen, even perhalogen) ; -CN; -COOR; -COR; -NO 2 ; -SO 2 -OR; with R and R'
  • linear, cyclic or branched hydrocarbon-based radical especially means radicals of alkyl, aryl, aralkyl, alkylaryl, alkenyl or alkynyl type.
  • the group C 6 H 5 present in the radical R3 should be understood as being an aromatic cyclic group.
  • the radical Y represents oxygen.
  • the radical Rl represents hydrogen or a linear or branched, saturated or unsaturated hydrocarbon-based radical containing 1 to 12 and especially 1, 2, 3, 4, 5 or 6 carbon atoms, which is optionally substituted.
  • the substituents may be chosen especially from -OH, -OR and/or -P(O)-(OR) 2 with R representing a linear, branched or cyclic, saturated or unsaturated hydrocarbon-based radical containing 1 to 6 carbon atoms, which is optionally halogenated, or even perhalogenated.
  • the radical Rl represents a methyl, ethyl, propyl or isopropyl radical, which is optionally substituted with an -OH or -P(O)-(OR) 2 group with R representing methyl, ethyl, propyl or isopropyl.
  • the radical R2 represents a linear, branched or cyclic, saturated or unsaturated hydrocarbon-based radical containing 1 to 12 and especially, 1, 2, 3, 4, 5 or 6 carbon atoms, which is optionally substituted.
  • the substituents may be chosen especially from -OH and -OR with R representing a linear, branched or cyclic, saturated or unsaturated hydrocarbon-based radical containing 1 to 6 carbon atoms, which is optionally halogenated, or even perhalogenated.
  • the radical R2 represents a methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl or isobutyl radical.
  • A is a linear or branched, saturated or unsaturated divalent hydrocarbon-based radical containing 1 to 12 carbon atoms, which is optionally substituted.
  • the substituents of A are preferably chosen from -Hal (halogen, or even perhalogen) ; -CN; -COOR; -NO 2 ; -SO 2 -OR; with R representing a linear, branched or cyclic, saturated or unsaturated hydrocarbon-based radical containing 1 to 6 carbon atoms, which is optionally halogenated, or even perhalogenated.
  • B represents at least one group -OR; -NHR; -CN; -COOR; -COR or represents a hydrocarbon-based radical chosen from a linear or branched, saturated or unsaturated hydrocarbon-based radical containing 1 to 12 carbon atoms, which is 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 linear, branched or cyclic hydrocarbon-based radical containing 1 to 6 carbon atoms, which is optionally halogenated, or even perhalogenated.
  • the radical R3 represents a group chosen from one of the following formulae:
  • the divalent radical A may especially be a methylene , an ethylene or a propylene .
  • 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-based radical chosen from a methyl, ethyl, propyl or isopropyl radical substituted with one or more halogens, especially chlorine, bromine, iodine or fluorine, and preferentially totally halogenated (perhalogenated) , such as perfluorinated. Mention may be made in particular of the perfluoro- methyl radical (-CF 3 ) as being most particularly preferred.
  • the radical X represents a radical chosen from -OH and -OR 4 with R 4 representing a linear, cyclic or branched, saturated or unsaturated hydrocarbon-based radical containing 1 to 6 carbon atoms, which is optionally substituted.
  • the substituents may be chosen from -OH and -OR with R representing a linear, branched or cyclic, saturated or unsaturated hydrocarbon-based radical containing 1 to 6 carbon atoms, which is optionally halogenated, or even perhalogenated.
  • the radical X represents a radical chosen from -OH, -OCH 3 , -OC 2 H 5 , -0-C 3 H 7 and -OC 4 H 9 .
  • a radical chosen from -OH, -OCH 3 , -OC 2 H 5 , -0-C 3 H 7 and -OC 4 H 9 is particularly preferred.
  • the amount of compound to be used in the compositions according to the invention may be readily determined by a person skilled in the art, as a function of the nature of the compound used, the individual to be treated and/or the desired effect. In general, this amount may be between 0.00001% and 20% by weight, especially between 0.001% and 10% by weight, preferably between 0.05% and 5% by weight, better still between 0.1% and 2% by weight and preferentially between 0.5% and 1% by weight, relative to the total weight of the composition.
  • the compounds of formula (I) may be used especially, alone or as a mixture, in a composition comprising a physiologically acceptable medium, especially in a cosmetic or pharmaceutical composition that thus moreover comprises a cosmetically or pharmaceutically acceptable medium.
  • a physiologically acceptable medium in which the compounds of the invention may be used, and also its constituents, the amount thereof, the galenical form of the composition and its mode of preparation may be chosen by a person skilled in the art on the basis of his general knowledge as a function of the desired type of composition.
  • the composition may especially be in the form of an aqueous or oily solution; a dispersion of the lotion or serum type; emulsions of liquid or semi-liquid consistency of the milk type obtained by dispersing a fatty phase in an aqueous phase (O/W) or, conversely, (W/0) ; suspensions or emulsions of soft, semi-solid or solid consistency of the cream or gel type, or alternatively multiple emulsions (W/O/W or 0/W/O) , microcapsules or microparticles; vesicular dispersions of ionic and/or nonionic type.
  • a dispersion of the lotion or serum type emulsions of liquid or semi-liquid consistency of the milk type obtained by dispersing a fatty phase in an aqueous phase (O/W) or, conversely, (W/0) ; suspensions or emulsions of soft, semi-solid or solid consistency of the cream or gel type, or alternatively multiple
  • the composition may be in the form of aqueous, alcoholic or aqueous- alcoholic solutions; in the form of creams, gels, emulsions or mousses; in the form of aerosol compositions also comprising a pressurized propellant.
  • aqueous form especially in the form of an aqueous dispersion, emulsion or solution, it may comprise an aqueous phase, which may comprise water, a floral water and/or a spring water.
  • the said aqueous phase may also comprise alcohols such as Ci-C 6 monoalcohols and/or polyols such as glycerol, butylene glycol, isoprene glycol, propylene glycol or polyethylene glycol.
  • alcohols such as Ci-C 6 monoalcohols
  • polyols such as glycerol, butylene glycol, isoprene glycol, propylene glycol or polyethylene glycol.
  • a surfactant preferably in an amount of from 0.01% to 30% by weight relative to the total weight of the composition.
  • 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 fatty acid esters of polyols such as glyceryl stearate.
  • the composition used according to the invention may also comprise a fatty phase, consisting especially of fatty substances that are liquid at 25°C, such as volatile or non-volatile oils of animal, plant, mineral or synthetic origin; fatty substances that are solid at 25 0 C such as waxes of animal, plant, mineral or synthetic origin; pasty fatty substances; gums; mixtures thereof.
  • composition used according to the invention may also comprise adjuvants that are common in the field under consideration, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, active agents, especially hydrophilic or lipophilic cosmetic or pharmaceutical active agents, preserving agents, antioxidants, solvents, fragrances, fillers, pigments, nacres, odour absorbers and dyes.
  • adjuvants may be introduced into the fatty phase, into the aqueous phase and/or into lipid spherules.
  • the said compound of formula (I) will be combined in the composition with at least one other soothing or calming agents.
  • the said soothing or calming agent will not be an anti ⁇ inflammatory agent.
  • Examples of other "soothing or calming agents" that may be mentioned include:
  • xanthin derivatives for instance diethylaminoethyltheophylline hydrochloride
  • aqueous extracts for example aqueous- alcoholic or water-glycol extracts
  • flowers or plants for instance cornflower water, camomile water, mint water, lime blossom water or rose water
  • extracts of Rosacea plants e.g. : Rosa gallic ⁇
  • extracts of peony extracts of hawthorn, extracts of yarrow, extracts of mallow, extracts of marigold, extracts of melilot, extracts of sage, extracts of elder, extracts of ginkgo biloba, extracts of arnica, extracts of oregano, extracts of green tea, extracts of waterlily blossom, extracts of iris, extracts of birch bark and extracts of Aloe vera
  • arnica extracts of oregano
  • extracts of green tea extracts of waterlily blossom
  • extracts of iris extracts of birch bark and extracts of Aloe vera
  • Aloe vera for example aqueous- alcoholic or water-glycol extract
  • fruit extracts for instance extract of pineapple, extract of papaya; extract of guava;
  • algae especially of the Laminaria type (for example red or brown algae) ;
  • oils of plant origin for instance canola seed oil and shea butter
  • essential oils for example of coriander, of balm, of lavender, of mint or of camomile, and mixtures thereof;
  • polysaccharides containing fucose for instance Fucogel 1000, sold by Solabia (aqueous solution containing 1% polysaccharide solids comprising fucose, galactose and galacturonic acid) ;
  • galactolipids derived, for example, from oat, for instance digalactosyl diglyceride or monogalalactosyl diglyceride;
  • amino acids, derivatives thereof and salts thereof such as the sodium salt of amino acids grafted onto cocoyl chains, sold in the form of a mixture under the name Sepicalm S by the company SEPPIC, capryloylglycine sold 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; • divalent strontium, zinc, manganese, magnesium and calcium salts, such as those described in documents WO-A-96/19184, WO-A-96/19182 and WO-A-96/19228; and mixtures thereof.
  • the compound used according to the invention may also be combined in the composition with a cosmetic or pharmaceutical active agent with an irritant side effect, chosen from the group of keratolytic active agents, depigmenting agents, antiperspirants, slimming agents, hair removers, hair dyes or colorants, permanent-waving agents, retinoids, anti-pruriginous agents, anti-seborrhoeic agents, comedolytic agents and anti-acne agents, and mixtures thereof.
  • a cosmetic or pharmaceutical active agent with an irritant side effect chosen from the group of keratolytic active agents, depigmenting agents, antiperspirants, slimming agents, hair removers, hair dyes or colorants, permanent-waving agents, retinoids, anti-pruriginous agents, anti-seborrhoeic agents, comedolytic agents and anti-acne agents, and mixtures thereof.
  • active agents with a potentially irritant side effect mention may be made of: • keratolytic agents such as ⁇ -hydroxy acids, for instance glycolic acid, lactic acid, dioic acid, malic acid, citric acid, tartaric acid and mandelic acid, and derivatives thereof; ⁇ -hydroxy acids, for instance salicylic acid and its derivatives; ⁇ -keto acids, for instance ascorbic acid or vitamin C and its derivatives; ⁇ -keto acids; retinoids, for instance retinol and its esters, retinal, retinoic acid and its derivatives, and those described in documents FR-A-2 570 377, EP-A-199 636, EP-A-325 540 and EP-A-402 072) ;
  • ⁇ -hydroxy acids for instance glycolic acid, lactic acid, dioic acid, malic acid, citric acid, tartaric acid and mandelic acid, and derivatives thereof
  • ⁇ -hydroxy acids for instance salicylic acid and its derivatives
  • ⁇ -keto acids
  • depigmenting agents e.g.: hydroquinone, vitamin C at high concentration, kojic acid, arbutin, ellagic acid, aminophenol derivatives, procysteine and derivatives, niacinamide, isothiocyanate and thiocyanate, and lucinol
  • hair dyes or colorants for instance para-phenylenediamine (p-PDA) and certain derivatives thereof such as N-phenyl -p-PDA and toluene-2 , 5 -diamine sulfate ; meta-phenylenediamine (m-PDA) and certain derivatives thereof such as toluene-3 , 4 -diamine ; ortho-phenylenediamine (o-PDA) and certain derivatives thereof such as N-phenyl -p-PDA and toluene-2 , 5 -diamine sulfate ; meta-phenylenediamine (m-PDA) and certain derivatives thereof such as toluene-3 , 4 -diamine ; ortho-phenylenediamine (o-PDA) and certain derivatives thereof such as N-phenyl -p-PDA and toluene-2 , 5 -diamine sulfate ; meta-phenylenediamine (m
  • comedolytic agents salicylic acid, dioic acid, Hepes, etc. ; and mixtures thereof.
  • an anti-pollution agent or free-radical scavenger, one or more UV-screening agents, or mixtures thereof, may also be added to the compositions of the invention.
  • anti-pollution agent or free- radical scavenger means any compound capable of trapping ozone, monocyclic or polycyclic aromatic compounds such as benzopyrene and/or heavy metals such as cobalt, mercury, cadmium and/or nickel.
  • free-radical scavenger means any compound capable of trapping free radicals.
  • vitamin C and its derivatives including ascorbyl glucoside; phenols and polyphenols, in particular tannins, ellagic acid and tannic acid; epigallocatechin and natural extracts containing it; extracts of olive tree leaf; extracts of tea, in particular of green tea; anthocyans; extracts of rosemary; phenol acids, in particular chorogenic acid; stilbenes, in particular resveratrol; sulfur-containing amino acid derivatives, in particular
  • agents for trapping monocyclic or polycyclic aromatic compounds which may 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 3-indolecarbinol; extracts of tea, in particular of green tea, extracts of water hyacinth or Eichhornia crassipes; and the water-soluble fraction of corn sold by the company Solabia under the trade name Phytovityl ® .
  • heavy-metal-trapping agents such as EDTA, the pentasodium salt of ethylenediaminetetramethylenephosphonic acid, and N,N'- bis (3,4, 5-trimethoxybenzyl) ethylenediamine or one of the salts, metal complexes or esters thereof; phytic acid; chitosan derivatives; extracts of tea, in particular of green tea; tannins such as ellagic acid; sulfur-containing amino acids such as cysteine; extracts of water hyacinth (Eichhornia crassipes) ; and the water-soluble fraction of corn sold by the company Solabia under the trade name Phytovityl .
  • chelating agents such as EDTA, the pentasodium salt of ethylenediaminetetramethylenephosphonic acid, and N,N'- bis (3,4, 5-trimethoxybenzyl) ethylenediamine or one of the salts, metal complexes or esters thereof
  • phytic acid chito
  • the free-radical scavengers that may be used in the composition according to the invention comprise, besides certain anti-pollution agents mentioned above, lycopene, vitamin E and its derivatives such as tocopheryl acetate; bioflavonoids; coenzyme QlO or ubiquinone; certain enzymes, for instance catalase, superoxide dismutase and extracts of wheat germ containing it, lactoperoxidase, glutathione peroxidase and quinone reductases; glutathione; benzylidenecamphor,- benzyleyelanones; substituted naphthalenon.es; pidolates; phytanetriol; gamraa- oryzanol; guanosine; lignans; and melatonin.
  • lycopene vitamin E and its derivatives such as tocopheryl acetate
  • bioflavonoids coenzyme QlO or ubiquinone
  • Sunscreens are molecules that absorb UV radiation and thus prevent this radiation from reaching the skin cells. They may absorb either mainly UVB or mainly UVA, depending on their nature. There are two major categories of sunscreen, either organic or mineral (zinc oxide or titanium oxide) . By using them in cosmetic compositions in combination and in sufficient amount, they can block the majority of UV radiation.
  • compositions in accordance with the invention may also comprise at least one organic photoprotective agent and/or at least one mineral photoprotective agent that is active in the UVA and/or UVB range (absorbers) , which are water-soluble or liposoluble, or even insoluble in the commonly used cosmetic solvents.
  • compositions in accordance with the invention may also comprise other additional organic or mineral UV-screening agents that are active in the UVA and/or UVB range, which are water-soluble or liposoluble, or even insoluble in the commonly used cosmetic solvents.
  • UV-screening agents include organic photoprotective agents chosen especially from anthranilates; cinnamic derivatives; dibenzoylmethane derivatives; salicylic derivatives; camphor derivatives; triazine derivatives such as those described in patent applications US 4 367 390, EP 863 145, EP 517 104, EP 570 838, EP 796 851, EP 775 698, EP 878 469, EP 933 376, EP 507 691, EP 507 692, EP 790 243 and EP 944 624; benzophenone derivatives; ⁇ , ⁇ -diphenylacrylate derivatives; benzotriazole derivatives; benzalmalonate derivatives; benzimidazole derivatives; imidazolines; bis-benzazolyl derivatives as described in patents EP 669 323 and US 2 463 264; p-aminobenzoic acid (PABA) derivatives; methylenebis (hydroxyphenylbenzotriazole) derivatives as
  • the mineral photoprotective agents are chosen from pigments or alternatively nanopigments (mean size of the primary particles : generally between 5 nm and 100 nm and preferably between 10 nm and 50 nm) of coated or uncoated metal oxides such as, for example, nanopigments of titanium oxide (amorphous or crystallized in rutile and/or anatase form) , of iron oxide, of zinc oxide, of zirconium oxide or of cerium oxide, which are all UV photoprotective agents that are well known per se. Standard coating agents are, moreover, alumina and/or aluminium stearate. Such coated or uncoated metal oxide nanopigments are described in particular in patent applications EP 518 772 and EP 518 773.
  • the screening agents 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 the total weight of the composition.
  • the amount of compound to be used according to the invention may be readily determined by a person skilled in the art, as a function of 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, especially between 0.001% and 10% by weight, preferably between 0.05% and 5% by weight, better still between 0.1% and 2% by weight and preferentially between 0.5% and 1% by weight relative to the total weight of the composition.
  • compositions of the invention do not contain any anti-inflammatory agent.
  • the invention also relates to a composition comprising, in a physiologically acceptable medium, at least one compound of the N-acylaminoamide family combined with at least one other soothing or calming agent as defined above, the said agent not being an anti-inflammatory agent.
  • the invention also relates to a composition
  • a composition comprising, in a physiologically acceptable medium, at least one compound of the N-acylaminoamide family combined with at least one cosmetic or pharmaceutical active agent with an irritant side effect, with the exception of antifungal agents, antibacterial agents or hair-loss counteractants.
  • This active agent may be chosen advantageously from the group of keratolytic active agents, depigmenting agents, antiperspirants, slimming agents, hair removers, hair dyes or colorants, permanent-waving agents, retinoids, anti-pruriginous agents, anti-seborrhoeic agents, comedolytic agents and anti-acne agents, and mixtures thereof.
  • active agents with a potentially irritant side effect examples include: • keratolytic agents such as ⁇ -hydroxy acids, for instance glycolic acid, lactic acid, dioic acid, malic acid, citric acid, tartaric acid and mandelic acid, and derivatives thereof; ⁇ -hydroxy acids, for instance salicylic acid and its derivatives; ⁇ -keto acids, for instance ascorbic acid or vitamin C and its derivatives; ⁇ -keto acids; retinoids, for instance retinol and its esters, retinal, retinoic acid and its derivatives, and those described in documents FR-A-2 570 377, EP-A-199 636, EP-A-325 540 and EP-A-402 072) ;
  • depigmenting agents e.g.: hydroquinone, vitamin C at high concentration, kojic acid, arbutin, ellagic acid, aminophenol derivatives, procysteine and derivatives, niacinamide, isothiocyanate and thiocyanate, and lucinol
  • hair dyes or colorants for instance para-phenylenediamine (p-PDA) and certain derivatives thereof such as N-phenyl-p-PDA and toluene-2, 5-diamine sulfate; meta-phenylenediamine (m-PDA) and certain derivatives thereof such as toluene-3,4-diamine; ortho-phenylenediamine (o- PDA) ;
  • p-PDA para-phenylenediamine
  • m-PDA meta-phenylenediamine
  • o- PDA ortho-phenylenediamine
  • comedolytic agents salicylic acid, dioic acid, Hepes, etc. ; and mixtures thereof .
  • physiologically acceptable medium means a medium that is compatible with the skin and/or the scalp and/or mucous membranes and/or the integuments.
  • This composition may be a cosmetic composition or a dermatological composition.
  • the amount of compound to be used in the compositions according to the invention may be readily determined by a person skilled in the art, as a function of 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, especially between 0.001% and 10% by weight, preferably between 0.05% and 5% by weight, better still between 0.1% and 2% by weight and preferentially between 0.5% and 1% by weight, relative to the total weight of the composition.
  • the invention also relates to a cosmetic process for soothing the skin and/or the scalp, characterized in that a cosmetic composition comprising at least one compound of the N-acylaminoamide family is applied to the skin and/or the scalp and/or mucous membranes.
  • the compound of the N-acylamino- amide family is combined with at least one agent chosen from another soothing or calming agent and a compound with an irritant side effect, and mixtures thereof.
  • the composition also comprises at least one UVB-screening agent.
  • at least one UVA-screening agent and at least one UVB- screening agent will be used to maximize the protection against all the radiation of the solar spectrum.
  • This cosmetic process will be intended especially for enhancing and/or improving the general appearance of the skin and/or the scalp and/or mucous membranes exposed to a stress.
  • the compound may be applied daily or several times a day and for a determined duration as a function of the individual to be treated.
  • the composition will be applied to the skin and/or the scalp before any solar exposure, and preferentially before a strong solar exposure. This type of process will be particularly advantageous in countries in which the sunshine is strong.
  • This process is particularly suited to application to irritable and/or allergic skin types and/or scalps and/or to fair skin types of phototype I , II and potentially III .
  • irritable and/or allergic skin types and/or scalps especially means skin types and/or scalps that react to external attacking factors , occasionally in an exaggerated manner . These skin types and/or scalps are consequently more subj ect to the development of a skin reaction that may be manifested by redness or pruritus and/or that may involve immunological or inflammatory mechanisms .
  • EXAMPLE 1 Effect of ⁇ 2 - [acetyl (3 -trif luoromethyl- phenyl) amino] -3 -methylbutyrylamino ⁇ acetic acid on the keratinocyte mediators expressed during exposure to an irritant product or during exposure to a hypoxiant stress a) Transcriptomic study (cDNA array)
  • the cellular model used comprises keratinocytes derived from human neonatal cells from Clonetics (Portland, OR) , cultured 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 0.25 ng/ml EGF and 25 ⁇ g/ml pituitary extract at 37 0 C and 5% CO 2 .
  • the keratinocytes were seeded in 25 cm 2 dishes and precultured in whole SFM medium. The cells were then placed in SFM medium containing no EGF or pituitary extract. Two series of 8 dishes were prepared: one series subjected to a hypoxiant stress (anaerobic condition) and one series subjected to a concentration of phorbol myristate acetate PMA (at 0.1 ⁇ g/ml) , the said series being placed in contact or otherwise with ⁇ 2- [acetyl (3-trifluoromethyl- phenyl) amino] -3-methylbutyrylamino ⁇ acetic acid at concentrations of 0.1 mM or 1 ⁇ iM.
  • the application of the ⁇ 2- [acetyl (3- trifluoromethylphenyl) amino] -3-methyl- butyrylamino ⁇ acetic acid may be performed under the following conditions: in a first experiment, the product is applied 4 hours before the exposure to PMA or to a hypoxia and then for 18 hours; in a second experiment, the product is applied at the same time as the exposure to PMA or to hypoxia, for 18 hours.
  • hypoxia control
  • a dish not treated with the product and placed at 37 0 C and 5% CO 2 were also prepared.
  • the cells are then rinsed with PBS and then lysed and the RNA is extracted using the tri-Reagent for genomic analysis.
  • the analysis of the various stress markers is performed according to the standard protocols of genomic analysis.
  • the DNA Microarrays methodology is preferably used.
  • the extraction/purification of the messenger RNA from each culture led to the isolation of amounts of messenger RNA (culture in small dishes) .
  • the 33 P-labelled DNA probes were produced by reverse transcription of the messenger RNAs, using a pool of primers specific for the sequences immobilized on the membranes (arrays) , in the presence of (alpha 33 P)-dATP. This step uses the reagents and the protocol recommended by Invitrogen.
  • the labelled probes are purified by exclusion column chromatography and the quality and equivalence of the labelled probes is evaluated by liquid scintillation counting.
  • the cDNAs immobilized on the membranes are hybridized (42 0 C, overnight) with the corresponding labelled 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 Phospholmager Cyclone (Packard) .
  • the results are expressed in relative expression units (RE, radioactivity of the spot corresponding to each gene, corrected for the background noise and the differences in intensity of the labelling of the probes) .
  • the membrane analysis was performed using the ImageQuant TL software (Ilage Analysis, Amersham Biosciences) . The results are finally expressed as % relative to the control.
  • ⁇ 2- [acetyl (3-trifluoromethyl- phenyl) amino] -3-methylbutyrylamino ⁇ acetic acid is applied at a concentration of 0.1 ⁇ iM or 1 mM to keratinocytes in culture 4 hours before exposure to PMA and then for 18 hours, reduced expression of genes involved in inflammation, such as beta-defensin 2 (inducible defensin) , inducible heme oxygenase 1 (quencheur of free radicals) and mitochondrial stress protein (induced especially during a thermal, inflammatory, infectious or oxidative stress, etc.) is observed.
  • beta-defensin 2 inducible defensin
  • inducible heme oxygenase 1 quencheur of free radicals
  • mitochondrial stress protein induced especially during a thermal, inflammatory, infectious or oxidative stress, etc.
  • ⁇ 2- [acetyl (3-trifluoromethyl ⁇ phenyl)amino] -3-methylbutyrylamino ⁇ acetic acid is applied at a concentration of 1 mM to keratinocytes in culture for 4 hours before exposure to PMA and then for 18 hours, an increase in the expression of genes involved in the systems of negative regulation of inflammation, such as the type II interleukin-1 receptor (IL-I inhibitor) intended to inhibit reactions that might occur during the release of IL-I by the action of PMA, is observed.
  • IL-I inhibitor type II interleukin-1 receptor
  • the selected markers correspond to the 4 genes identified during the cDNA-array study described in a) .
  • RNA remaining from the cDNA-array study is used.
  • the traces of potentially contaminant DNA are removed by treatment with DNAse and inactivation of the DNAse.
  • a reverse transcription reaction is then performed, followed by quantification, via fluorescence, of the synthesized cDNA.
  • the PCR reactions (polymerase 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-PCR is performed on the ⁇ -actin marker to check the homogeneity of the preparations to be compared.
  • Q-PCRs are then performed in triplicate using couples of primers specific for the ⁇ -actin sequences, and the markers to be studied.
  • 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 values of cycles of two independent PCRs according to the following formula: (i/ 2 number of c ⁇ cles ) x l ⁇ 6 .
  • EXAMPLE 2 Effect of ⁇ 2- [acetyl (3-trifluoromethyl- phenyl)amino] -3-methylbutyrylamino ⁇ acetic acid on the chemotaxis of polymorphonuclear neutrophils
  • Each well is separated as a lower chamber (in which the keratinocytes have been cultured) and an upper chamber (in which the polymorphonuclear neutrophils are deposited) .
  • the two chambers are separated by polycarbonate filters 6.5 mm in diameter pierced with 5 ⁇ m pores.
  • the migration of the polymorphonuclear neutrophils induced by the chemotaxic factors released by the keratinocytes is studied in the presence of ⁇ 2- [acetyl (3-trifluoromethylphenyl) amino] -3- methylbutyrylamino ⁇ acetic acid at different concentrations (0.1 ttiM or 0.2 ttiM) or of ⁇ -MSH 10 ⁇ M used as positive control of the inhibition of migration.
  • the polymorphonuclear neutrophils (1 x 10 6 in 100 ⁇ l) are placed in the upper chamber of the well equipped with a Transwell device. In the lower chamber, the keratinocytes were cultured to confluence. After incubation for 5 hours, the polymorphonuclear neutrophils that have migrated in the lower chamber in the direction of the keratinocytes are counted using a haemocytometer and the percentage of neutrophils that have migrated is calculated.
  • EXAMPLE 3 Effect of ⁇ 2- [acetyl (3-trifluoromethyl- phenyl) amino] -3-methylbutyrylamino ⁇ acetic acid on the production of TNF- ⁇ induced by a stress
  • Normal human epidermal keratinocytes are cultured at 37 0 C in SFM culture medium (serum free medium) supplemented by 5 ⁇ g/ml EGF (epidermal growth factor) and bovine pituitary extract (50 mg/ml) .
  • the culture medium is replaced with SFM medium containing DMSO (0.03% DMSO by volume) for the control condition, or ⁇ 2- [acetyl (3-trifluoromethyl- phenyl) amino] -3-methylbutyrylamino ⁇ acetic acid (1.0 or 0 . 1 TnM) .
  • the cells are incubated at 37 0 C for 24 hours and then stimulated with variable doses of IFN-gamma or of PMA/TPA: the IFN-gamma and the PMA/TPA are added to the culture medium to obtain final concentrations of IFN-gamma of 300 and 1000 units/ml of IFN-gamma corresponding, respectively, to 15 and 50 ng/ml; and a final concentration of 5.0 nM of PMA/TPA corresponding to 3.0 ng/ml of PMA/TPA.
  • the cells are stimulated for 24 hours; the culture medium is then removed and centrifuged at 16 000 x g for 5 minutes at 4 0 C and the supernatants are stored at -20 0 C until the time of analysis.
  • cytokines induced by IFN-gamma or PMA/TPA is measured using a ProteoplexTM kit according to the recommendations of the supplier (Novogen) .
  • the results obtained are presented in the following table: a % increase in the production of TNF ⁇ is measured in pg/ml relative to the total proteins, after stimulation with IFN-gamma or PMA.
  • Polysorbate 60 (Tween 60 from the 1.00% company ICI )
  • Salicylic acid 0.1% ⁇ 2- [Acetyl (3-trifluoromethylphenyl) amino] - 0.1% 3-methylbutyrylamino ⁇ acetic acid
  • Polysorbate 60 (Tween 60 sold by ICI) 1%

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Abstract

La présente invention concerne l’utilisation, en tant qu’agent calmant ou apaisant, d’au moins un composé de la famille des N-acylaminoamides dans une composition contenant un excipient acceptable sur le plan physiologique. Ledit composé a en particulier pour but d’empêcher et/ou réduire une réaction cutanée provoquée par un stress, ainsi que les signes cutanés associés, lesquels peuvent aller d’une simple sensation d'inconfort de la peau à des signes cutanés plus désagréables tels que prurit, plaques sèches ou érythème inflammatoire. Le composé est en particulier choisi parmi l’acide {2-[acétyl(3-trifluorométhylphényl)amino]-3-méthylbutyrylamino}acétique et le {2-[acétyl(3-trifluorométhylphényl)amino]-3-méthylbutyrylamino}acétate d’éthyle.
PCT/EP2005/013532 2004-11-22 2005-11-16 Utilisation de composes de la famille des n-acylaminoamides en tant qu’agents calmants ou apaisants WO2006053790A1 (fr)

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FR0452723A FR2878156A1 (fr) 2004-11-22 2004-11-22 Utilisation des composes de la famille des n-acylamino-amides comme agents apaisants
FR0452723 2004-11-22
US63810804P 2004-12-23 2004-12-23
US60/638,108 2004-12-23

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220313578A1 (en) * 2021-03-31 2022-10-06 L’Oreal Methods and compositions for improving skin
FR3122826A1 (fr) * 2021-05-12 2022-11-18 L'oreal Procedes et compositions pour l’amelioration de la peau

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0498728A1 (fr) * 1991-02-06 1992-08-12 L'oreal Amides de la glycyl-sérine et compositions cosmétiques, pharmaceutiques ou alimentaires les contenants
JP2001158732A (ja) * 1999-09-20 2001-06-12 Taisho Pharmaceut Co Ltd 皮膚洗浄剤
WO2001058854A1 (fr) * 2000-02-11 2001-08-16 Biophysica, Inc. Anti-androgene topique contre la chute des cheveux et d'autres conditions hyperandrogeniques
WO2001094381A2 (fr) * 2000-06-08 2001-12-13 L'oreal Nouveaux composes de la famille des n-acylamino-amides, compositions les comprenant, et utilisations
EP1269989A1 (fr) * 2001-06-26 2003-01-02 L'oreal Composition cosmétique ou dermatologique comprenant des dérivés d'acylaminoamides
EP1269988A1 (fr) * 2001-06-26 2003-01-02 L'oreal Composition cosmetique ou dermatologique comprenant des dérivés d'acylaminoamide
EP1269990A1 (fr) * 2001-06-26 2003-01-02 L'oreal Composition cosmètique ou dermatologique comprenant des dérivés d'acylaminoamide
WO2003000209A1 (fr) * 2001-06-26 2003-01-03 L'oreal Composition cosmetique ou dermatologique comprenant des derives des n-acylaminoamides
EP1275372A1 (fr) * 2001-06-26 2003-01-15 L'oreal, S.A. Composition cosmétique ou dermatologique comprenant un dérivé de N-Acylaminoamide et un inhibiteur de métalloprotéinase
FR2847816A1 (fr) * 2002-12-03 2004-06-04 Oreal Composition comprenant un pseudodipeptide et un agent augmentant la synthese d'elastine

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0498728A1 (fr) * 1991-02-06 1992-08-12 L'oreal Amides de la glycyl-sérine et compositions cosmétiques, pharmaceutiques ou alimentaires les contenants
JP2001158732A (ja) * 1999-09-20 2001-06-12 Taisho Pharmaceut Co Ltd 皮膚洗浄剤
WO2001058854A1 (fr) * 2000-02-11 2001-08-16 Biophysica, Inc. Anti-androgene topique contre la chute des cheveux et d'autres conditions hyperandrogeniques
WO2001094381A2 (fr) * 2000-06-08 2001-12-13 L'oreal Nouveaux composes de la famille des n-acylamino-amides, compositions les comprenant, et utilisations
EP1269989A1 (fr) * 2001-06-26 2003-01-02 L'oreal Composition cosmétique ou dermatologique comprenant des dérivés d'acylaminoamides
EP1269988A1 (fr) * 2001-06-26 2003-01-02 L'oreal Composition cosmetique ou dermatologique comprenant des dérivés d'acylaminoamide
EP1269990A1 (fr) * 2001-06-26 2003-01-02 L'oreal Composition cosmètique ou dermatologique comprenant des dérivés d'acylaminoamide
WO2003000209A1 (fr) * 2001-06-26 2003-01-03 L'oreal Composition cosmetique ou dermatologique comprenant des derives des n-acylaminoamides
EP1275372A1 (fr) * 2001-06-26 2003-01-15 L'oreal, S.A. Composition cosmétique ou dermatologique comprenant un dérivé de N-Acylaminoamide et un inhibiteur de métalloprotéinase
FR2847816A1 (fr) * 2002-12-03 2004-06-04 Oreal Composition comprenant un pseudodipeptide et un agent augmentant la synthese d'elastine

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CARLETTO ET AL.: "Oxidative stress and cutaneous ageing : the "toxic second messengers" concept and an interesting family of products, "pseudodipeptides"", INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, vol. 22, 2000, pages 361 - 370, XP002367306 *
PATENT ABSTRACTS OF JAPAN vol. 2000, no. 23 10 February 2001 (2001-02-10) *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220313578A1 (en) * 2021-03-31 2022-10-06 L’Oreal Methods and compositions for improving skin
FR3122826A1 (fr) * 2021-05-12 2022-11-18 L'oreal Procedes et compositions pour l’amelioration de la peau

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