FR2831440A1 - COSMETIC COMPOSITION COMPRISING A DHEA DERIVATIVE AND A SOOTHING AGENT - Google Patents

Abstract

The invention relates to a composition containing, in a physiologically-acceptable medium, at least one DHEA derivative and at least one agent that can inhibit at least one enzyme selected from among phospholipases A2, lipoxygenases and/or human prostaglandin synthetases. The invention also relates to the cosmetic use of said composition, particularly in order to soothe cutaneous disorders including sensitive skin, cutaneous discomfort, skin tightness, pruritus, cutaneous irritations, cutaneous swelling, redness of the skin and/or cutaneous heat sensations. The invention also relates to a soothing cosmetic treatment method comprising the topical application of one such composition.

Description

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The invention relates to a composition containing, in a physiologically acceptable medium, at least one derivative of DHEA in combination with at least one agent capable of inhibiting at least one enzyme chosen from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases.

The invention also relates to the cosmetic use of this composition, especially for soothing cutaneous disorders and cutaneous disturbances chosen from sensitive skin, cutaneous discomfort, skin tightness, itchy skin, skin irritations, swelling. cutaneous, redness of the skin and / or sensations of cutaneous heat.

The invention also relates to a soothing cosmetic treatment method comprising the topical application of such a composition.

We know that the human being can undergo aggressive types of phenomena that are characterized by a feeling of cutaneous discomfort, tightness, itching, sensation of cutaneous heat, or redness.

For many years we have been looking for substances to fight against these types of aggression.

 Even if solutions have already been proposed, it is constantly interesting to have new compositions with soothing activity, especially for skin disorders such as, for example, sensitive skin, cutaneous discomfort, tight skin, itchy skin, skin irritations, skin swellings, redness of the skin, sensations of cutaneous heat.

 Among the factors responsible for these aggressive type phenomena include the enzymes involved in the cascade of arachidonic acid. The main enzymes involved in the arachidonic acid cascade are three in number. The first are phospholipases A2 (PLA2) whose physiological function is the release of esterified fatty acids in membrane phospholipids which are converted into arachidonic acid. Arachidonic acid is then enzymatically oxidized by lipoxygenases (Lox) or by human prostaglandin synthetases (PGHS) to provide pro-inflammatory mediators such as prostaglandins and leukotrienes (William L. Smith, 1989, Biochem J, 259, 315-324).

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Many substances are known in the prior art to inhibit at least one of these enzymes.

In this respect, for example, vegetable oils (Lipids, 32 (7), 759-767), triterpenes and fish oils (Heller et al., Lipdi mediators in inflammatory disorders, Drugs, 55 (4), 487-496).

However, there remains the need to enhance the effectiveness of these compounds to soothe certain disorders and disorders, including skin.

However, it has been found by the Applicant that the combination of a derivative of DHEA with an agent capable of inhibiting at least one enzyme chosen from phospholipases A2, lipoxygenases and / or prostaglandins human synthetases could make it possible to improve the effectiveness of the compositions comprising said agent inhibiting said enzymes.

DHEA or dehydroepiandrosterone is a natural steroid produced primarily by the adrenal cortex glands. Exogenous DHEA, administered topically or orally, is known for its ability to promote keratinization of the epidermis (JP-07196467) and to treat dry skin by increasing endogenous production and secretion of sebum and by strengthening Thus, the skin barrier effect (US Pat. No. 4,496,556). US Pat. No. 5,843,932 also describes the use of DHEA to remedy dermal atrophy by inhibiting the loss of collagen and of connective tissue. Finally, the Applicant has demonstrated the ability of DHEA to fight against the papery appearance of the skin (FR 2803513), to modulate the pigmentation of the skin and hair EP-1092423 and to fight against the atrophy of the skin. epidermis (FR 00/06154).

However, DHEA has effects of a hormonal nature that can make its use delicate.

Therefore, it is understood that it has been sought to have derivatives of DHEA having properties as interesting as DHEA itself, but having no hormonal effects.

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Parmi les dérivés de la DHEA, on connaît déjà la 3ss-acétoxy-7-oxo-DHEA ou A5- androstène-3ss-acétoxy-7, 17-dione, qui a été décrite comme étant efficace dans la modulation du système immunitaire (US-5,292, 730 ; US-5, 585,371 ; US-5,641, 766), le traitement de la maladie d'Alzheimer (US-5,707, 983) et le traitement du syndrome HIV (US-5,885, 977) et pour favoriser la perte de poids (US-5,296, 481 ; US-5,807, 848).

Among the derivatives of DHEA, 3ss-acetoxy-7-oxo-DHEA or A5-androstene-3ss-acetoxy-7,17-dione, which has been described as being effective in the modulation of the immune system (US -5,292,730 US-5,585,371; US-5,641,766), the treatment of Alzheimer's disease (US-5,707,983) and the treatment of the HIV syndrome (US-5,885,977) and to promote the weight loss (US-5,296,481; US-5,807,848).

The document WO 99/25333 also mentions the use, in particular topical use, of 3-acetoxy-7-oxo-DHEA in the prophylactic and curative treatment of lupus erythematosus, which is a disorder of the immune system capable of affecting several organs. and manifesting itself at the level of the skin by transverse redness of the face and / or by squamous erythema plaques disseminated on the body.

Document US Pat. No. 5,424,463 describes, in particular, 7-keto-DHEA (or Δ5-androstene-3β-ol-7,17-dione) and its hydrolyzable derivatives obtained by modification of the 3β-hydroxy group, said derivatives being capable of giving back 7-keto-DHEA after hydrolysis. The 3ss-hydroxy group is converted to carbamate or is esterified by (i) a C 2 -C 22, normal, branched, saturated or unsaturated aliphatic acid, (ii) a C 7 -C 22 aromatic acid, (iii) a dicarboxylic acid having C3 or more, for which only one carbonyl group is esterified with the 3-hydroxy group of the steroid, (iv) an inorganic acid such as sulfuric acid and phosphoric acid. US 5,424,463 discloses 7-keto-DHEA and its hydrolyzable derivatives as being effective for promoting weight loss.

The document WO98 / 40074 still describes the use of derivatives of 7-hydroxy-DHEA esterified at position 3 and / or 7 to treat cutaneous aging.

However, to the knowledge of the Applicant, it has never been suggested to associate DHEA derivatives with at least one agent capable of inhibiting at least one enzyme selected from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases.

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 The object of the present invention is therefore to be able to have new compositions thus having a reinforced soothing activity while not having any significant side effects.

This and other objects are achieved by the present invention which relates to a composition comprising, in a physiologically acceptable medium, at least one derivative of DHEA in combination with at least one agent capable of inhibiting at least one selected enzyme. among phospholipases A2, lipoxygenases and / or human prostaglandins synthetases, the said agent not being a 5-seductin inhibitor.

dans laquelle : - R1 est choisi parmi : - un atome d'hydrogène ; - un groupe alkyle en C1-C24, saturé ou insaturé, linéaire ou ramifié, cyclique pouvant éventuellement contenir un ou plusieurs hétéroatomes, et éventuellement substitué par un ou plusieurs groupes choisis parmi-OR'et/ou - SR'et/ou-COOR'et/ou-NR'R'et/ou halogène et/ou sulfate et/ou phosphate et/ou aryle et/ou hétérocycle, ledit hétérocycle pouvant avantageusement être choisi parmi un indole, une pyrimidine, une pipéridine, une morpholine, un pyrane, un furane, une pipérazine, une pyridine ; - un groupe alkylcarbonyl, dont la partie alkyle en C1-C24 est saturée ou insaturée, linéaire ou ramifiée, cyclique, et éventuellement substituée par un ou plusieurs groupes choisi parmi-OR'et/ou-SR'et/ou-COOR'et/ou-NR'R' et/ou halogène et/ou sulfate et/ou phosphate et/ou aryle et/ou hétérocycle, ledit hétérocycle pouvant avantageusement être choisi parmi un indole, une The derivative of the DHEA according to the invention corresponds to the following formula (1):

wherein: - R1 is selected from: - a hydrogen atom; a linear or branched, cyclic, saturated or unsaturated C1-C24 alkyl group which may optionally contain one or more heteroatoms, and optionally substituted with one or more groups chosen from -OR'and / or -SR'and / or -COOR and / or-NR'R 'and / or halogen and / or sulfate and / or phosphate and / or aryl and / or heterocycle, said heterocycle being advantageously chosen from indole, pyrimidine, piperidine, morpholine, pyran, furan, piperazine, pyridine; an alkylcarbonyl group, the C1-C24 alkyl part of which is saturated or unsaturated, linear or branched, cyclic, and optionally substituted with one or more groups chosen from -OR'and / or -SR'and / or -COOR'and and / or-NR'R 'and / or halogen and / or sulfate and / or phosphate and / or aryl and / or heterocycle, said heterocycle being advantageously chosen from an indole, a

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acide L-glutamique, la glycine, la L-histidine, la L-isoleucine, la L-leucine, la Llysine, la L-méthionine, la L-phénylalanine, la L-proline, la L-sérine, la L-thréonine, pyrimidine, piperidine, morpholine, pyran, furan, piperazine, pyridine; an arylcarbonyl group, preferably a phenylcarbonyl group, or an arylalkylcarbonyl group, preferably a benzylcarbonyl group, optionally substituted by one or more -OR 'and / or -SR'and / or -COOR'and / or -NR'R'groups; and / or halogen and / or aryl and / or heterocycle; a group O = P (OH) OR '; a group (OSOR '), a trialkylsilyl group (SiR'3) in which the 3 groups R' may be identical or different, a carbonyloxyalkyl group (R'OCO), a carbonylaminealkyl group (R'NHCO); which R 'is chosen from a hydrogen atom, a linear or branched, cyclic, linear or branched, C 1 -C 12, preferably C 1 -C 6, alkyl group which may optionally contain one or more heteroatoms, optionally functionalized with one or more -OR ", -COOR", halogen, -NR "R" groups, or an aryl group, preferably a phenyl group, optionally functionalized with one or more "OR", "COOR", halogen or -NR "R"groups; Preferably, R 1 represents a hydrogen atom, a methyl, an ethyl, a butyl, a propyl or an isopropyl, and R "represents a hydrogen atom, an alkyl chain, preferably a C 1 -C 6, saturated alkyl chain. or unsaturated, linear or branched or cyclic, preferably R "represents a hydrogen atom, u methyl, ethyl, butyl, propyl, isopropyl; it being understood that in each of the groups-NR'R 'and -NR "R", the substituents R', respectively R ", are identical or different, and that advantageously the group -NR'R'represents an amino acid, preferably selected from L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamine,

L-glutamic acid, glycine, L-histidine, L-isoleucine, L-leucine, Llysine, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine ,

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 L-tryptophan, L-tyrosine, L-valine; - R2 and R3 together represent a keto group (= O) or, when R2 represents a hydrogen atom, R3 represents a radical OR4 with R4 having the same definitions as those given previously for R 1.

The invention also relates to the optical and / or geometric isomers of the DHEA derivatives of formula (1) alone or in mixture in all proportions, as well as the physiologically acceptable salts of these derivatives.

In particular, the stereochemistry at the 7-position of the DHEA derivatives of formula (1) for which R3 represents an OR4 radical may be alpha (0 :), beta (ss) or a mixture of both in any proportion.

According to a preferred form of the invention, the preferred DHEA derivatives of formula (1) are those for which R2 and R3 together represent a keto group (= O) and R1 represents a hydrogen atom or a C1-C24 alkyl group. , preferably C1-C18, saturated or unsaturated, linear or branched, or cyclic may contain one or more heteroatoms, and optionally substituted with one or more groups selected from -OR'and / or -SR'and / or -COOR ' and / or NR'R'and / or halogen.

According to another preferred form of the invention, the preferred DHEA derivatives of formula (1) are those for which R2 and R3 together represent a keto group (= O) and R1 represents an alkylcarbonyl group, the C1-alkyl part of which -C24, preferably C1-C18, is saturated or unsaturated, linear or branched or cyclic and optionally substituted with one or more groups selected from-OR 'and / or-SR' and / or-COOR 'and / or -NR 'R' and / or halogen.

According to another preferred form of the invention, the preferred DHEA derivatives of formula (1) are those for which R 2 represents a hydrogen atom, R 3 represents an OR 4 radical, with R 4 having the same definitions as those previously given for preferred way for R1.

Among the derivatives of the DHEA of formula (1) according to the invention, all

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particulièrement au moins l'un des composés suivants : - A5-and rostène-3 P-hydroxy-7, 1 7-di one ou 7-oxo-déhydroépiandrostérone (7-oxoDHEA) ; - 3ss-0-acétyl-7-oxo-déhydroépiandrostérone (ou 3ss-acétyloxy-7 -oxo-DHEA commercialisée sous le nom de 7 Keto par la société Humanetics) ; - 3P-O-propionyl-7-oxo-déhydroépiandrostérone (ou 3p-propionyloxy-7-oxo-DHEA) -p-0-butanoyi-7-oxo-déhydroépiandrostérone (ou 3ss-butanoyloxy-7 -oxo-DHEA) ; - 3-0-iso-butanoyl-7-oxo-déhydroépiandrostérone ; -p-0-pentanoyl-7-oxo-déhydroépiandrostérone ; - 3P-O-hexanoyl-7-oxo-déhydroépiandrostérone -p-0-héptanoyl-7-oxo-déhydroépiandrostérone ; -p-0-octanoyl-7-oxo-déhydroépiandrostérone ; - 3P-O-nonanoyl-7-oxo-déhydroépiandrostérone -p-0-décanoyl-7-oxo-déhydroépiandrostérone ; -p-0-dodécanoyl-7-oxo-déhydroépiandrostérone ; -p-0-myristoyl-7-oxo-déhydroépiandrostérone ; -p-0-palmitoyl-7-oxo-déhydroépiandrostérone ; -p-0-stéaroyl-7-oxo-déhydroépiandrostérone ; -p-0-arachidoyl-7-oxo-déhydroépiandrostérone ; - 3ss-0-docosanoyl-7-oxo-déhydroépiandrostérone ; 3p-0- ! ! gnoceroy !-7-oxo-déhydroép ! androstérone ; - (3-0-oléoyl-7-oxo-déhydroépiandrostérone ; - (3-0-linoléoyl-7-oxo-déhydroépiandrostérone ; - (3-0-linolénoyl-7-oxo-déhydroépiandrostérone ; - 3P-O-pétroselinoyi-7-oxo-déhydroépiandrostérone - 3ss-O-méthyl-7 -oxo-déhydroépiandrostérone ; -p-0-éthyl-7-oxo-déhydroépiandrostérone ; -p-0-carboxyméthyl-7-oxo-déhydroépiandrostérone : -p-0-glucosyl-7-oxo-déhydroépiandrostérone ; -p-0-glucoronyl-7-oxo-déhydroépiandrostérone ; - 3-0- (2-tétrahydropyranyl)-7-oxo-déhydroépiandrostérone, - 3f-0- (2-tétrahydrofuranyl)-7-oxo-déhydroépiandrostérone - Glycinate de 3ss-O-7 -oxo-déhydroépiandrostérone ;

particularly at least one of the following compounds: A5-and rostene-3β-hydroxy-7,17-diol or 7-oxo-dehydroepiandrosterone (7-oxoDHEA); 3ss-O-acetyl-7-oxo-dehydroepiandrosterone (or 3ss-acetyloxy-7-oxo-DHEA sold under the name Keto by the company Humanetics); 3β-O-propionyl-7-oxo-dehydroepiandrosterone (or 3β-propionyloxy-7-oxo-DHEA) -β-O-butanoyl-7-oxo-dehydroepiandrosterone (or 3ss-butanoyloxy-7-oxo-DHEA); - 3-O-iso-butanoyl-7-oxo-dehydroepiandrosterone; p-O-pentanoyl-7-oxo-dehydroepiandrosterone; 3P-O-hexanoyl-7-oxo-dehydroepiandrosterone-p-O-heptanoyl-7-oxo-dehydroepiandrosterone; -p-O-octanoyl-7-oxo-dehydroepiandrosterone; 3 P-O-nonanoyl-7-oxo-dehydroepiandrosterone-p-O-decanoyl-7-oxo-dehydroepiandrosterone; p-O-dodecanoyl-7-oxo-dehydroepiandrosterone; p-O-myristoyl-7-oxo-dehydroepiandrosterone; p-O-palmitoyl-7-oxo-dehydroepiandrosterone; p-O-stearoyl-7-oxo-dehydroepiandrosterone; p-O-arachidoyl-7-oxo-dehydroepiandrosterone; 3ss-O-docosanoyl-7-oxo-dehydroepiandrosterone; 3p-0-! ! gnoceroyl-7-oxo-dehydroep! androsterone; (3-O-oleoyl-7-oxo-dehydroepiandrosterone; -3-O-linoleoyl-7-oxo-dehydroepiandrosterone; -3-O-linolenoyl-7-oxo-dehydroepiandrosterone; -3P-O-petroselinoyl-7 oxo-dehydroepiandrosterone-3ss-O-methyl-7-oxo-dehydroepiandrosterone; p-O-ethyl-7-oxo-dehydroepiandrosterone; p-O-carboxymethyl-7-oxo-dehydroepiandrosterone: p-O-glucosyl 7-oxo-dehydroepiandrosterone; -P-O-glucoronyl-7-oxo-dehydroepiandrosterone; 3-O- (2-tetrahydropyranyl) -7-oxo-dehydroepiandrosterone; -3f-O- (2-tetrahydrofuranyl) -7-oxo dehydroepiandrosterone - 3ss-O-7-oxo-dehydroepiandrosterone glycinate;

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Lysinate de 3P-0-7-oxo-déhydroépiandrostérone Sérinate de 3ss-O-7-oxo-déhydroépiandrostérone ; -c-Glutamate de 3ss-O-7 -oxo-déhydroépiandrostérone ; a-Aspartate de 3ss-O-7 -oxo-déhydroépiandrostérone ; 3p-Hemisuccinoyloxyandrost-5-ene-7, 17-dione ; 3p-0- (2-hydroxy-malonyl)-7-oxo-déhydroépiandrostérone ; 3p-0- (2-malonyl-amino-carbonyl)-7-oxo-déhydroépiandrostérone ; 3p-0- (2-succinyl-amino-carbonyl)-7-oxo-déhydroépiandrostérone ; 3p-0- (2-glutaryl-amino-carbonyl)-7-oxo-déhydroépiandrostérone ; 3p-méthylcarbonate-7-oxo-déhydroépiandrostérone ; 3p-0- (trifluroacétyl)-7-oxo-déhydroépiandrostérone ; 3P-O- (4-carboxy-butanoyl)-7-oxo-déhydroépiandrostérone 3p-0- (4-cyclopentyl-butanoyl)-7-oxo-déhydroépiandrostérone ; 3p-0-benzoyl-7-oxo-déhydroépiandrostérone ; 3p-0- (3, 4-dihyroxy-benzoyl)-7-oxo-déhydroépiandrostérone ; 3p-0- (ascorbyl-phosphate)-7-oxo-déhydroépiandrostérone ; 3f3-0- (ascorbyl-sulfate)-7-oxo-déhydroépiandrostérone ; 3p-0-phosphonyl-7-oxo-déhydroépiandrostérone ; 3p-0-monoacétyl-phosphonyl-7-oxo-déhydroépiandrostérone ; 3p-0-sulfonyl-7-oxo-déhydroépiandrostérone ; 3p-0- (tertio-butyl-diméthyl-silyl)-7-oxo-déhydroépiandrostérone ; 3p-0- (tertio-butyl-diphényl-silyl)-7-oxo-déhydroépiandrostérone ; 3 [3-0- (triméthyi si ! y !)-7-oxo-déhydroép ! androstérone ; A5-androstène-3p, 7p-dihydroxy-17-dione ou 7p-OH-déhydroépiandrostérone (7phydroxy-DHEA) ; A5-androstène-3p, 7a-dihydroxy-17-d ! one ou 7 a-OH-déhydroépiandrostérone (7 ahydroxy-DHEA) ; 3p-0-acétyl-7-hydroxy-déhydroépiandrostérone (3-béta-acétoxy-7-hydroxy-DHEA) ; 3p-0-propionyl-7-hydroxy-déhydroépiandrostérone (3-béta-propionyloxy-7hydroxy-DHEA) ; 3p-0-butanoyl-7-hydroxy-déhydroépiandrostérone (3-béta-butanoyloxy-7-hydroxyDHEA) ; 3P-O-iso-butanoyl-7-hydroxy-déhydroépiandrostérone

3P-O-7-Oxo-dehydroepiandrosterone Lysinate 3ss-O-7-Oxo-dehydroepiandrosterone Serinate; 3ss-O-7-oxo-dehydroepiandrosterone -c-Glutamate; 3ss-O-7-oxo-dehydroepiandrosterone a-Aspartate; 3β-Hemisuccinoyloxyandrost-5-ene-7,17-dione; 3β-O- (2-hydroxy-malonyl) -7-oxo-dehydroepiandrosterone; 3β-O- (2-malonyl-amino-carbonyl) -7-oxo-dehydroepiandrosterone; 3β-O- (2-succinylamino-carbonyl) -7-oxo-dehydroepiandrosterone; 3β-O- (2-glutaryl-aminocarbonyl) -7-oxo-dehydroepiandrosterone; 3β-methylcarbonate-7-oxo-dehydroepiandrosterone; 3β-O- (trifluroacetyl) -7-oxo-dehydroepiandrosterone; 3β-O- (4-carboxy-butanoyl) -7-oxo-dehydroepiandrosterone 3β-O- (4-cyclopentyl-butanoyl) -7-oxo-dehydroepiandrosterone; 3β-O-benzoyl-7-oxo-dehydroepiandrosterone; 3β-O- (3,4-dihydroxybenzoyl) -7-oxo-dehydroepiandrosterone; 3β-O- (ascorbyl-phosphate) -7-oxo-dehydroepiandrosterone; 3f3-0- (ascorbyl sulfate) -7-oxo-dehydroepiandrosterone; 3β-O-phosphonyl-7-oxo-dehydroepiandrosterone; 3β-O-monoacetylphosphonyl-7-oxo-dehydroepiandrosterone; 3β-O-sulfonyl-7-oxo-dehydroepiandrosterone; 3β-O- (tert-butyldimethylsilyl) -7-oxo-dehydroepiandrosterone; 3β-O- (tert-butyl-diphenyl-silyl) -7-oxo-dehydroepiandrosterone; 3 [3-O- (trimethylsilyl) -7-oxo-dehydroep! androsterone; A5-androstene-3β, 7β-dihydroxy-17-dione or 7β-OH-dehydroepiandrosterone (7-hydroxy-DHEA); A5-androstene-3β, 7α-dihydroxy-17-d! one or 7? -OH-dehydroepiandrosterone (7-hydroxy-DHEA); 3β-O-acetyl-7-hydroxy-dehydroepiandrosterone (3-beta-acetoxy-7-hydroxy-DHEA); 3β-O-propionyl-7-hydroxy-dehydroepiandrosterone (3-beta-propionyloxy-7hydroxy-DHEA); 3β-O-butanoyl-7-hydroxy-dehydroepiandrosterone (3-beta-butanoyloxy-7-hydroxyDHEA); 3P-O-iso-butanoyl-7-hydroxy-dehydroepiandrosterone

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3 (3-0-pentanoyl-7-hydroxy-déhydroépiandrostérone ; 3 (3-0-hexanoyl-7-hydroxy-déhydroépiandrostérone ; - 3p-0-héptanoyl-7-hydroxy-déhydroépiandrostérone ; 3p-0-octanoyl-7-hydroxy-déhydroépiandrostérone ; 3p-0-nonanoyl-7-hydroxy-déhydroépiandrostérone ; - 3p-0-décanoyl-7-hydroxy-déhydroépiandrostérone ; - 3ss-O-dodécanoyl-7 -hydroxy-déhydroépiandrostérone ; - 3ss-O-myristoyl-7 -hydroxy-déhydroépiandrostérone ; 3p-0-palmitoyl-7-hydroxy-déhydroépiandrostérone ; - 3ss-O-stéaroyl-7 -hydroxy-déhydroépiandrostérone ; - 3ss-O-arachidoyl-7 -hydroxy-déhydroépiandrostérone ; 3p-0-docosanoyl-7-hydroxy-déhydroépiandrostérone ; - 3ss-O-lignoceroyl-7 -hydroxy-déhydroépiandrostérone ; - 3ss-O-oléoyl-7 -hydroxy-déhydroépiandrostérone ; - 3p-0-linoléoyl-7-hydroxy-déhydroépiandrostérone ; 3p-0-linolénoyl-7-hydroxy-déhydroépiandrostérone ; - 3ss-O-pétroselinoyl-7 -hydroxy-déhydroépiandrostérone ; 3p-0-acétyl-7-hydroxy-déhydroépiandrostérone ; - 3ss-O-acétyl-7 -O-acétyl-déhydroépiandrostérone ; 3p-0-acétyl-7-0-propionyl-déhydroépiandrostérone ; - 3ss-O-acétyl-7 -O-butanoyl-déhydroépiandrostérone 1 - 3ss-O-acétyl-7 -O-iso-butanoyl-déhydroépiandrostérone ; 3p-O-acétyl-7-0-pentanoyl-déhydroépiandrostérone ; - 3ss-O-acétyl-7 -O-hexanoyl-déhydroépiandrostérone ; - 3ss-0-acétyl-7-0-héptanoyl-déhydroépiandrostérone ; - 3ss-O-acétyl-7 -O-octanoyl-déhydroépiandrostérone ; 3p-0-acétyl-7-0-nonanoyl-déhydroépiandrostérone ; - 3ss-O-acétyl-7 -O-décanoyl-déhydroépiandrostérone ; 3p-0-acétyl-7-0-dodécanoyl-déhydroépiandrostérone ; - 3p-0-acétyl-7-0-myristoyl-déhydroépiandrostérone ; 3p-0-acétyl-7-0-palmitoyl-déhydroépiandrostérone ; 3p-0-acétyl-7-0-stéaroyl-déhydroépiandrostérone ; 3p-0-acétyl-7-0-arachidoyl-déhydroépiandrostérone ;

3 (3-O-pentanoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-hexanoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-heptanoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-octanoyl-7-hydroxy; dehydroepiandrosterone, 3β-O-nonanoyl-7-hydroxy-dehydroepiandrosterone, 3β-O-decanoyl-7-hydroxy-dehydroepiandrosterone, 3β-O-dodecanoyl-7-hydroxy-dehydroepiandrosterone, 3β-O-myristoyl-7-hydroxy-dehydroepiandrosterone; hydroxy-dehydroepiandrosterone, 3β-O-palmitoyl-7-hydroxy-dehydroepiandrosterone, 3β-O-stearoyl-7-hydroxy-dehydroepiandrosterone, 3β-O-arachidoyl-7-hydroxy-dehydroepiandrosterone, 3β-O-docosanoyl-7-hydroxy-dehydroepiandrosterone; hydroxy-dehydroepiandrosterone; 3ss-O-lignoceroyl-7-hydroxy-dehydroepiandrosterone; 3ss-O-oleoyl-7-hydroxy-dehydroepiandrosterone; 3p-O-linoleoyl-7-hydroxy-dehydroepiandrosterone; 3p-O-linolenoyl-7 dehydroxy-dehydroepiandrosterone; 3β-O-petroselinoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-acetyl-7-hydroxy-dehydroepiandrosterone; 3β-O-acetyl-7-O-acetyl-dehydroepiandrosterone; 3β-O-acetyl-7-O-propionyl-dehydroepiandrosterone; 3ss-O-acetyl-7-O-butanoyldehydroepiandrosterone 1 - 3ss-O-acetyl-7-O-iso-butanoyldehydroepiandrosterone; 3β-O-acetyl-7-O-pentanoyl dehydroepiandrosterone; 3ss-O-acetyl-7-O-hexanoyldehydroepiandrosterone; 3ss-O-acetyl-7-O-heptanoyl dehydroepiandrosterone; 3ss-O-acetyl-7-O-octanoyldehydroepiandrosterone; 3β-O-acetyl-7-O-nonanoyl dehydroepiandrosterone; 3ss-O-acetyl-7-O-decanoyl dehydroepiandrosterone; 3β-O-acetyl-7-O-dodecanoyl dehydroepiandrosterone; 3β-O-acetyl-7-O-myristoyl dehydroepiandrosterone; 3β-O-acetyl-7-O-palmitoyldehydroepiandrosterone; 3β-O-acetyl-7-O-stearoyldehydroepiandrosterone; 3β-O-acetyl-7-O-arachidoyl dehydroepiandrosterone;

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3p-0-acétyl-7-0-docosanoyl-déhydroépiandrostérone ; 3j3-0-acétyl-7-0-lignoceroyl-déhydroépiandrostérone ; 3p-0-acétyl-7-0-oléoyl-déhydroépiandrostérone ; 3p-0-acétyl-7-0-linoléoyl-déhydroépiandrostérone ; 3p-0-acétyl-7-0-linolénoyi-déhydroépiandrostérone ; 3j3-0-acétyl-7-0-pétroselinoyl-déhydroépiandrostérone.

3β-O-acetyl-7-O-docosanoyl dehydroepiandrosterone; 3? -3-acetyl-7-O-lignoceroyl dehydroepiandrosterone; 3β-O-acetyl-7-O-oleoyldehydroepiandrosterone; 3β-O-acetyl-7-O-linoleoyl dehydroepiandrosterone; 3β-O-acetyl-7-O-linolenoyl dehydroepiandrosterone; 3j3-0-acetyl-7-0-pétroselinoyl-dehydroepiandrosterone.

-p-0-acétyl-7-oxo-déhydroépiandrostérone (ou 3ss-acétoxy-7 -oxo-DHEA) ; - 5-androstène-3ss, 7 a-dihydroxy-17 -dione ou 7 a-OH-déhydroépiandrostérone (7 a- hydroxy-DHEA). Advantageously, the compounds corresponding to formula (1) are chosen from at least one of the following compounds: # 5-androstene-3ss-hydroxy-7,17-dione or 7-oxo-dehydroepiandrosterone (7-oxo)
DHEA);

p-O-acetyl-7-oxo-dehydroepiandrosterone (or 3ss-acetoxy-7-oxo-DHEA); 5-androstene-3ss, 7α-dihydroxy-17-dione or 7α-OH-dehydroepiandrosterone (7α-hydroxy-DHEA).

The derivatives of the DHEA of formula (1) according to the invention are easily accessible from a synthetic point of view, in particular not the implementation of one of the synthetic methods described in US-5,424, 463; FR-2,771,105; US-5,869,709, US-6,111,118 or WO-94/085888.

sels, l'acide boswellique et ses sels ; l'acide bétullique et ses sels ; l'acide ss glycyrrhétinique et ses sels et/ou ses dérivés tels que l'acide glycyrrhétique monoglucuronide, le glycyrrhétinate de stéaryle, l'acide 3-stéaroyloxy glycyrrhétique) ; - les extraits de Paeonia suffruticosa ; - les extraits de Paeonia lactif/ora ; - l'huile de calophilum ; According to the invention, the agent capable of inhibiting at least one enzyme chosen from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases is chosen from at least one of the following substances: pentacyclic triterpenes and extracts of a plant (in particular Glycyrrhiza glabra) containing it, in particular oleanolic acid, ursolic acid and its

salts, boswellic acid and its salts; betullic acid and its salts; glycyrrhetinic acid and its salts and / or derivatives such as glycyrrhetic acid monoglucuronide, stearyl glycyrrhetinate, 3-stearoyloxy glycyrrhetic acid); - extracts of Paeonia suffruticosa; extracts of Paeonia lactif / ora; - calophilum oil;

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L'associatition de sodium palmitoylproline et de Nymphea alba, en particulier le Seppicalm VG de Séppic ; tes extraits du pygeum ;
Les extraits de Boswellia serrata, en particulier le Soothex# de Quest ; - Les extraits de Centipeda cunnighami, en particulier le phytoplenolin de Bio-
Botanica ;
Les extraits d'Hélianthus annuus, en particulier l'Hélioxine# de Silab ;
Les extraits de Linum usitatissimum, en particulier la Sensiline'de Silab les tocotrienols ;

- les extraits de Cola nitida ; le piperonal ; tes extraits de clou de girofle ; tes extraits d'épi lobe (Epilobium angustifolium) ; tes extraits d'Aloe vera. phycosaccharides, in particular hydrolysed algin # or hydrolysed algin and zinc sulfate, from the company Codif; Canola oil Tamanu oil; Calophillum oil is anabolic; chamomile extracts; allantoin; - The diesterphosphoric vitamin E and C, in particular Sepepital EPC from
Seppic; unsaturated omega 3 oils such as rosehip musk oil, black currant oil, ecchium oil, fish oil;
Plankton extracts, in particular Omega plankton # of Secma;

The associatition of sodium palmitoylproline and Nymphea alba, in particular Seppicalm VG of Séppic; your extracts from the pygeum;
Extracts of Boswellia serrata, especially the Soothex # of Quest; - The extracts of Centipeda cunnighami, in particular the phytoplenolin of Bio-
Botanica;
Extracts of Helianthus annuus, in particular Helioxin # from Silab;
Extracts of Linum usitatissimum, in particular Sensiline from Silab tocotrienols;

- extracts of Cola nitida; the piperonal; clove extracts; lobe epi (Epilobium angustifolium) extracts; your extracts of Aloe vera.

est choisi parmi au moins l'une des substances suivantes : - les extraits de Glycyrrhiza glabra, l'acide oléanolique et ses sels ; l'acide ursolique et ses sels ; l'acide boswellique et ses sels ; l'acide bétullique et ses sels ; l'acide ss glycyrrhétinique et ses sels et/ou ses dérivés tels que l'acide Advantageously, the agent capable of inhibiting at least one enzyme chosen from phospholipases A2, lipoxygenases and / or human prostaglandins synthetases

is selected from at least one of the following substances: - Glycyrrhiza glabra extracts, oleanolic acid and its salts; ursolic acid and its salts; boswellic acid and its salts; betullic acid and its salts; ss glycyrrhetinic acid and its salts and / or derivatives such as the acid

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glycyrrhétique monoglucuronide, le glycyrrhétinate de stéaryle, l'acide 3stéaroyloxy glycyrrhétique ; les extraits de Paeonia suffruticosa ; - les extraits de Paeonia lactiflora ; - les phycosaccharides, en particulier hydrolysed algin ou hydrolysed algin and zinc sulfate&commat; de la société Codif ; l'huile de calophillum ; l'alphabisabolol ; tes extraits de camomille ; t'allantoine ; - les tocotrienols ; tes extraits d'Aloe vera.

monoglucuronide glycyrrhetics, stearyl glycyrrhetinate, 3-stearoyloxy glycyrrhetic acid; extracts of Paeonia suffruticosa; extracts of Paeonia lactiflora; phycosaccharides, in particular hydrolysed algin or hydrolysed algin and zinc sulfate &commat; Codif company; calophillum oil; alphabisabolol; your extracts of chamomile; you are allantoin; - tocotrienols; your extracts of Aloe vera.

The respective amounts of DHEA derivative of formula (1) and of agent capable of inhibiting at least one enzyme chosen from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases present in the composition obviously depends on the effect research.

To give an order of magnitude, the composition according to the invention may contain from 0.0001% to 10% by weight, preferably from 0.01% to 5% by weight, of DHEA derivative of formula (1) such than previously defined, relative to the total weight of the composition.

To give another order of magnitude, the composition according to the invention may contain from 0.0001 to 10%, preferably from 0.001 to 5% by weight, of agent capable of inhibiting at least one enzyme chosen from phospholipases A2. , lipoxygenases and / or human prostaglandin synthetases as defined above, relative to the total weight of the composition.

Depending on the mode of administration, this composition may be in any of the galenical forms normally used.

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The compositions according to the invention may be intended for a cosmetic or pharmaceutical application, particularly dermatological. Preferably the compositions according to the invention are intended for a cosmetic application.

Thus, another subject of the invention relates to the cosmetic use of a composition containing, in a physiologically acceptable medium, at least one derivative of the DHEA of formula (1) as defined previously with at least one agent capable of inhibiting at least one enzyme selected from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases, to soothe the skin and / or the scalp.

Another subject of the invention also relates to the cosmetic use of a composition containing, in a physiologically acceptable medium, at least one derivative of the DHEA of formula (1) as defined previously with at least one agent capable of inhibiting at least one enzyme selected from phospholipases A2, lipoxygenases and / or prostaglandins human synthetases, for preventing and / or treating sensitive skin and / or cutaneous discomfort and / or tightness and / or itchy skin and skin irritations and / or skin swellings and / or redness and / or sensations of cutaneous heat.

 The compositions according to the invention are preferably suitable for topical application to keratin materials such as the skin, the scalp, the mucous membranes, the hair, the eyelashes or the nails. They may be in any of the galenical forms normally used for this type of application, especially in the form of an aqueous or oily solution, an oil-in-water or water-in-oil emulsion or a silicone emulsion. , a microemulsion or nanoemulsion, an aqueous or oily gel or a liquid, pasty or solid anhydrous product.

 These compositions may be more or less fluid and have the appearance of a white or colored cream, an ointment, a milk, a lotion, a serum, a paste, a mousse or a gel. They can optionally be applied to the skin in the form of an aerosol, patch or powder. They can also be in solid form, and for example in the form of a stick. They can be used

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 as a care product and / or as a make-up product for the skin. They can alternatively be in the form of shampoo or conditioner.

It is also possible to envisage a composition in the form of a foam or in the form of aerosol compositions also comprising a propellant under pressure.

les conservateurs, les antioxydants, les solvants, les parfums, les charges, les pigments, les absorbeurs d'odeur et les matières colorantes. Les quantités de ces différents adjuvants sont celles classiquement utilisées dans le domaine considéré, et par exemple de 0,01 à 20 % du poids total de la composition. Ces adjuvants, selon leur nature, peuvent être introduits dans la phase grasse ou dans la phase aqueuse. Ces adjuvants, ainsi que leurs concentrations, doivent être tels qu'ils ne nuisent pas aux propriétés avantageuses du dérivé de DHEA de formule (1) selon l'invention et de l'agent capable d'inhiber au moins une enzyme choisie parmi les phospholipases A2, les lipoxygénases et/ou les prostaglandines humaines synthétases. In known manner, the composition of the invention may also contain the usual adjuvants in the cosmetic field, such as hydrophilic or lipophilic gelling agents,

preservatives, antioxidants, solvents, perfumes, fillers, pigments, odor absorbers and dyes. The amounts of these various adjuvants are those conventionally used in the field under consideration, and for example from 0.01 to 20% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase or into the aqueous phase. These adjuvants, as well as their concentrations, must be such that they do not adversely affect the advantageous properties of the DHEA derivative of formula (1) according to the invention and of the agent capable of inhibiting at least one enzyme chosen from phospholipases. A2, lipoxygenases and / or human prostaglandins synthetases.

When the composition according to the invention is an emulsion, the proportion of the fatty phase can range from 2 to 80% by weight, and preferably from 5 to 50% by weight relative to the total weight of the composition. The fats, emulsifiers and coemulsifiers used in the composition in emulsion form are chosen from those conventionally used in the field under consideration. The emulsifier and the co-emulsifier are preferably present in the composition in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition. composition. The emulsion may further contain lipid vesicles.

When the composition is a solution or an oily gel, the fatty phase may represent more than 90% of the total weight of the composition.

In a known manner, the cosmetic composition may also contain adjuvants customary in the cosmetic field, such as hydrophilic gelling agents or

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 lipophilic, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, fragrances, fillers, filters, odor absorbers and dyes. The amounts of these various adjuvants are those conventionally used in the cosmetics field, and for example from 0.01% to 10% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase, into the aqueous phase and / or into the lipid spherules.

As oils or waxes that can be used in the invention, mention may be made of mineral oils (vaseline oil), vegetable oils (liquid fraction of shea butter, sunflower oil), animal oils (perhydrosqualene), synthetic oils ( Purcellin oil), silicone oils or waxes (cyclomethicone) and fluorinated oils (perfluoropolyethers), bees, carnauba or paraffin waxes. To these oils can be added fatty alcohols and fatty acids (stearic acid).

As emulsifiers and coemulsifiers that can be used in the invention, mention may be made, for example, of fatty acid and polyethylene glycol esters such as PEG-100 stearate, PEG-50 stearate and PEG-40 stearate; fatty acid esters of polyol such as glyceryl stearate, sorbitan tristearate and oxyethylenated sorbitan stearates available under the trade names Tween (D 20 or Tween &commat; 60, for example; and mixtures thereof.

As solvents that can be used in the invention, mention may be made of lower alcohols, in particular ethanol and isopropanol, and propylene glycol.

As hydrophilic gelling agents that may be used in the invention, mention may be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate / alkylacrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, ethylcellulose and polyethylene.

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 Whatever its mode of administration, the combination according to the invention can be used in cosmetics to soothe the skin and / or the scalp.

Thus, another subject of the present invention relates to the cosmetic use as a soothing agent, by topical application to the skin and / or the scalp, of the combination comprising at least one derivative of the formula DHEA. (1) as defined above with at least one agent capable of inhibiting at least one enzyme chosen from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases as defined above.

aliments, le vent, les frottements, le rasoir, le savon, les tensioactifs, l'eau dure à forte concentration de calcaire, les variations de température ou la laine. The present invention also relates to the cosmetic use as an agent for preventing and / or treating sensitive skin, cutaneous discomfort, skin tightness, itchy skin, skin irritations, skin swellings, skin rashes. and / or sensations of cutaneous heat, by topical application to the skin and / or the leather, of the combination comprising at least one derivative of the DHEA of formula (1) as defined previously with at least one agent capable of inhibiting at least one enzyme chosen from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases as defined above
"Sensitive skin" means skin that has been characterized by
Applicant in the patent EP 0 680 749 81. The Applicant has been able to show that the symptoms associated with sensitive skin consisted of more or less painful sensations felt in a cutaneous zone, such as tingling, tingling, itching or pruritus, burning, redness. , overheating, discomfort, tightness, etc. These symptoms can manifest themselves in response to various factors such as, among others, sweat, friction, emotions,

food, wind, rubbing, razor, soap, surfactants, hard water with high concentration of limestone, temperature variations or wool.

In addition, the term "sensitive skin" covers both irritable skin and intolerant skin.

The present invention also relates to a cosmetic treatment method

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 soothing keratin materials comprising the topical application thereto of a composition containing, in a physiologically acceptable medium, at least one derivative of the DHEA of formula (1) as defined previously with at least one agent capable of inhibiting at least one less an enzyme selected from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases.

It relates more particularly to a process for the cosmetic treatment of sensitive skin, cutaneous discomfort, skin tightness, itchy skin, skin irritations, skin swelling, redness of the skin, sensations of cutaneous heat including the application of topical treatment on the skin or the scalp of a composition containing, in a physiologically acceptable medium, at least one derivative of the DHEA of formula (1) as defined previously in association with at least one agent capable of inhibiting at least one enzyme selected from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases.

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 The following examples of compositions illustrate the invention without limiting it in any way. In the compositions, the proportions indicated are percentages by weight unless otherwise indicated.

Example 1: Gel for sensitive skin

<Tb>
<tb> A <SEP> Copolymer <SEP> acrylate / C10-30 <SEP> alkylacrylate <SEP> 0.50%
<tb> Water <SEP> 12, <SEP> 00 <SEP>%
<tb> B <SEP> Hexyldecanol <SEP> 10, <SEP> 00 <SEP>%
<tb> isononyl isononanoate <SEP><SEP> 10.00%
<tb> Octyl <SEP> methoxycinnamate <SEP> 1, <SEP> 00%
<tb> 7-Keto-DHEA <SEP> 0, <SEP> 50%
<tb> C <SEP> Triethanolamin <SEP> 0, <SEP> 50%
<tb> Water <SEP> Qsp <SEP> 100, <SEP> 00 <SEP>%
<tb> Glycerin <SEP> 6, <SEP> 00%
<tb> Preservatives <SEP> 0, <SEP> 25%
<tb> Allantoin <SEP> 0, <SEP> 10%
<tb> a-bisabolol <SEP> 0, <SEP> 10%
<tb> D <SEP> Polyacrylamide <SEP> and <SEP> C13-14 <SEP> isoparaffin <SEP> and <SEP> Laureth <SEP> 7
<tb> (Sepigel <SEP> 305 <SEP> provided <SEP> by <SEP> the <SEP> company <SEP> SEPPIC) <SEP> 0, <SEP> 50%
<Tb>
Procedure: The above composition can be prepared in the following manner: the polymer of phase A is dispersed in water at 40 ° C. The constituents of phase B are heated to 70 C until complete dissolution and the temperature is reduced to 40 C. The constituents of phase C are mixed with 50 C.

B is introduced into A at 40 C with stirring and phase C is added thereto. Phase D is introduced into the previously obtained mixture.

This cream is particularly well suited to the treatment of sensitive skin in mono or bi daily application.

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Example 2: Lotion for sensitive skin

<Tb>
<tb> - <SEP> Extract <SEP> of <SEP> Paeonia <SEP> suffruticosa <SEP> 0,50%
<tb> - <SEP> 3ss-acetoxy-7-keto-DHEA <SEP> 0, <SEP> 01%
<tb> - <SEP> Propylene <SEP> glycol <SEP> 20, <SEP> 00%
<tb> - <SEP> Hydroxy <SEP> propycellulose <SEP> 3.50%
<tb> - <SEP> Alcohol <SEP> ethyl <SEP> Qsp <SEP> 100, <SEP> 00%
<tb> -Water <SEP> 50.00%
<Tb>
EXAMPLE 3 Cleaning Gel for Sensitive Skins All percentages are expressed by weight of raw materials as such.

<Tb>
<Tb>

- <SEP> Lauryl <SEP> phosphate <SEP> (1) <SEP> 6.50%
<tb> - <SEP> Decyl <SEP> Glucoside <SEP> (2) <SEP> 16, <SEP> 25%
<tb> -Polyquaternium-7 <SEP> (3) <SEP> 5, <SEP> 70%
<tb> - <SEP> PEG-150 <SEP> Pentaerythrityl <SEP> Tetrastearte <SEP> (4) <SEP> 0, <SEP> 50%
<tb> - <SEP> Glycerin <SEP> 3.50%
<tb> - <SEP> Sorbitol <SEP> 3, <SEP> 50%
<tb> - <SEP> potassium <SEP> Hydroxide <SEP> 1, <SEP> 70%
<tb> - <SEP> Hydroxypropylcellulose <SEP> 0.20%
<tb> - <SEP> Disodium <SEP> EDTA <SEP> 0.05%
<tb> - <SEP> Sodium <SEP> chloride <SEP> 0.10%
<tb> - <SEP> 7-Keto-DHEA <SEP> 0, <SEP> 10%
<tb> -Acid <SEP> ss <SEP> Glycyrrhetinic <SEP> 1, <SEP> 00%
<tb> - <SEP> Methylparaben <SEP> 0, <SEP> 15%
<tb> - <SEP> imidazolidinyl <SEP> urea <SEP> 0.15%
<tb> - <SEP> Water <SEP> Qsp <SEP> 100, <SEP> 00%
<Tb>
(1) Lauryl monophosphate (75% mono-ester); MAP 20 # of KAO CHEMICALS (2) Alkyl (C9 / 11) polyglucoside (1,4) in 40% solution; Mydol 100 from KAO CHEMICALS

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(3) Copolymer di-methyl di-allyl ammonium chloride / acrylamide in water at 8%; Merquat S'de CALGON (4) Pentaerythrityl oxyethylene tetrastearate (150 EO) CROTHIX from CRODA Example 4: Tinted cream for the treatment of oily and sensitive skin

<Tb>
<tb> - <SEP> Hydrogenated Lecithin <SEP><SEP> 2,4 <SEP>%
<tb> - <SEP> Apricot almond <SEP><SEP> oil <SEP> 6.0 <SEP>%
<tb> - <SEP> Oil <SEP> of <SEP> seed <SEP> of <SEP> rosewood <SEP> musca <SEP> 1, <SEP> 0 <SEP>%
<tb> -Copolymer <SEP> Dimethacrylate <SEP> of Ethylene Glycol / Methacrylate <SEP> of <SEP> Lauryl <SEP> 1.0%
<tb> - <SEP> Sterols <SEP> of <SEP> soybean <SEP> oxyethylenated <SEP> (5 <SEP> OE) <SEP> 1, <SEP> 6 <SEP>%
<tb> - <SEP> 7 <SEP> alpha <SEP> hydroxy-DHEA <SEP> 0.5 <SEP>%
<tb> - <SEP> Serenoa <SEP> repents <SEP> 1, <SEP> 0 <SEP>%
<tb> - <SEP> Oxides <SEP> of <SEP> Iron <SEP> 0, <SEP> 9 <SEP>%
<tb> - <SEP> Oxide <SEP> of <SEP> Titanium <SEP> 5.0 <SEP>%
<tb> - <SEP> Polyacrylamide / C13-C14-lsoparaffin / Laureth-7 <SEP> (Sepigel <SEP> 305) <SEP> 4.0 <SEP>%
<tb> -Cyclopentadimethylsiloxane <SEP> 6.0 <SEP>%
<tb> - <SEP> Glycerin <SEP> 6.0 <SEP>%
<tb> - <SEP> Propylene <SEP> Glycol <SEP> 6.0 <SEP>% <SEP>%
<tb> - <SEP> Aloes <SEP> vera <SEP> 1, <SEP> 0 <SEP>%
<tb> - <SEP> Perfume <SEP> qs
<tb> - <SEP> Demineralized <SEP> water <SEP> Qsp <SEP> 100, <SEP> 0 <SEP>%
<Tb>
This cream is beige and is suitable for the treatment of the skin, by application to the face twice a day.

Claims (21)

 wherein: - R1 is selected from: - a hydrogen atom; a linear or branched, cyclic, saturated or unsaturated C1-C24 alkyl group which may optionally contain one or more heteroatoms, and optionally substituted with one or more groups chosen from -OR'and / or -SR'and / or -COOR and / or-NR'R 'and / or halogen and / or sulfate and / or phosphate and / or aryl and / or heterocycle, said heterocycle being advantageously chosen from indole, pyrimidine, piperidine, morpholine, pyran, furan, piperazine, pyridine; an alkylcarbonyl group, the C1-C24 alkyl part of which is saturated or unsaturated, linear or branched, cyclic, and optionally substituted with one or more groups chosen from -OR'and / or -SR'and / or -COOR'and and / or-NR'R 'and / or halogen and / or sulfate and / or phosphate and / or aryl and / or heterocycle, said heterocycle being advantageously chosen from indole, pyrimidine, piperidine, morpholine, pyran, furan, piperazine, pyridine; an arylcarbonyl group, preferably a phenylcarbonyl, or a group

1. A composition comprising, in a physiologically acceptable medium, at least one derivative of DHEA in combination with at least one agent capable of inhibiting at least one enzyme selected from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases, said agent not being a water sediment inhibitor, characterized in that said DHEA derivative has the following formula (1): <Desc / Clms Page number 22> R ', respectively R ", are identical or different; - R2 and R3 together represent a keto group (= O) or, when R2 represents a hydrogen atom, R3 represents a radical OR4 with R4 having the same definitions as those given previously for R1. R "represents a hydrogen atom, a linear or branched or cyclic saturated or unsaturated C 1 -C 6 alkyl group, it being understood that in each of the NR'R'and -NR" R "groups, the substituents C12, saturated or unsaturated, linear or branched, cyclic optionally containing one or more heteroatoms, optionally functionalized with one or more groups-OR ", -COOR", halogen, -NR "R"; or with an aryl group, preferably a phenyl, optionally functionalized with one or more - OR ", -COOR", halogen or -NR "RtI groups;  arylalkylcarbonyl, preferably a benzylcarbonyl, optionally substituted with one or more -OR 'and / or -SR'and / or -COOR'and / or -NR'R'and / or halogen and / or aryl and / or heterocycle groups; a group O = P (OH) OR '; a group (OSOR '), a trialkylsilyl group (SiR'3) in which the 3 groups R' may be identical or different, a carbonyloxyalkyl group (R'OCO), a carbonylaminealkyl group (R'NHCO); which R is chosen from a hydrogen atom, a C1-C6 alkyl group 2. Composition according to the preceding claim, characterized in that the derivatives of the DHEA of formula (1) are those for which R2 and R3 together represent a keto group (= O) and R1 represents a hydrogen atom or a C1-C18 alkyl group. saturated or unsaturated, linear or branched, or cyclic may contain one or more heteroatoms, and optionally substituted with one or more groups selected from -OR'and / or -SR'and / or -COOR'and / or -NR'R ' and / or halogen. <Desc / Clms Page number 23> 3. Composition according to Claim 1, characterized in that the DHEA derivatives of formula (1) are those for which R2 and R3 together represent a keto group (= O) and R1 represents an alkylcarbonyl group, the alkyl part of which is C1-C18, is saturated or unsaturated, linear or branched or cyclic and optionally substituted with one or more groups selected from -OR'and / or -SR'and / or -COOR 'and / or -NR'R'and / or hatogène. 4 Composition according to Claim 1, characterized in that the preferred DHEA derivatives of formula (1) are those for which R2 represents a hydrogen atom, R3 represents an OR4 radical, with R4 having the same definitions as those given for R 1 in claim 3. 5. Composition according to any one of the preceding claims, characterized in that each of the groups R 'and R "represents a group chosen from a hydrogen atom and a C1-C6 alkyl group. 6. Composition according to any one of the preceding claims, characterized in that each of R'and R "represents a group selected from a hydrogen atom, a methyl, an ethyl, a butyl, a propyl, an isopropyl. 7. Composition according to any one of the preceding claims, characterized in that each of the groups-NR'R 'and -NR "R" represents an amino acid, preferably chosen from L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamine, L-glutamic acid, glycine, L-histidine, Lisoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-proline, L-serine, L-threonine, L-tryptophan, L-tyrosine, L-valine. 8. Composition according to any one of claims 1 to 5, characterized in that the derivative of the DHEA of formula (1) is chosen from at least one of the following derivatives: - A5-androstene-3p-hydroxy-7, 17 -dione or 7-oxo-dehydroepiandrosterone (7-oxo DHEA); 3-O-acetyl-7-oxo-dehydroepiandrosterone (or 3β-acetoxy-7-oxo-DHEA); <Desc / Clms Page number 24>  3β-O-propionyl-7-oxo-dehydroepiandrosterone (or 3β-propionyloxy-7-oxo-DHEA) -3ss-O-butanoyl-7-oxo-dehydroepiandrosterone (or 3ss-butanoyloxy-7-oxo-DHEA); 3β-O-iso-butanoyl-7-oxo-dehydroepiandrosterone 3β-O-pentanoyl-7-oxo-dehydroepiandrosterone; 30-O-hexanoyl-7-oxo-dehydroepiandrosterone 3P-O-heptanoyl-7-oxo-dehydroepiandrosterone 3P-O-octanoyl-7-oxo-dehydroepiandrosterone 3p-O-nonanoyl-7-oxo-dehydroepiandrosterone; 3β-O-decanoyl-7-oxo-dehydroepiandrosterone; 3β-O-dodecanoyl-7-oxo-dehydroepiandrosterone 3β-O-myristoyl-7-oxo-dehydroepiandrosterone; 3β-O-palmitoyl-7-oxo-dehydroepiandrosterone; 3-0-stearoyl-7-oxo-dehydroepiandrosterone; 3β-O-arachidoyl-7-oxo-dehydroepiandrosterone; 3f3-0-docosanoyl-7-oxo-dehydroepiandrosterone; 3p-O-ignoceroyl-7-oxo-dehydroepiandrosterone; 3β-O-oleoyl-7-oxo-dehydroepiandrosterone; 3j3-0-linoleoyl-7-oxo-dehydroepiandrosterone; 3p-O-linolenoyl-7-oxo-dehydroepiandrosterone; 3β-O-petroselinoyl-7-oxo-dehydroepiandrosterone; 30-O-methyl-7-oxo-dehydroepiandrosterone 3p-O-ethyl-7-oxo-dehydroepiandrosterone; 3β-O-carboxymethyl-7-oxo-dehydroepiandrosterone: 3β-O-glucosyl-7-oxo-dehydroepiandrosterone; 3β-O-glucoronyl-7-oxo-dehydroepiandrosterone; 3- [3- (2-tetrahydropyranyl) -7-oxo-dehydroepiandrosterone; 3β-O- (2-tetrahydrofuranyl) -7-oxo-dehydroepiandrosterone; 3P-O-7-oxo-dehydroepiandrosterone glycinate 3ss-O-7-oxo-dehydroepiandrosterone lysinate; 3ss-O-7-oxo-dehydroepiandrosterone serinate; 3ss-O-7-oxo-dehydroepiandrosterone a-Glutamate; 3ss-O-7-oxo-dehydroepiandrosterone a-Aspartate; 3 Hemisuccinoyloxyandrost-5-ene-7,17-dione;

<Desc / Clms Page number 25>  3β-O- (2-hydroxy-malonyl) -7-oxo-dehydroepandrosterone; 3β-O- (2-malonylamino-carbonyl) -7-oxo-dehydroepiandrosterone; 3β-O- (2-succinylamino-carbonyl) -7-oxo-dehydroepiandrosterone; 3ss-O- (2-glutaryl-aminocarbonyl) -7-oxo-dehydroepiandrosterone; 3β-methylcarbonate-7-oxo-dehydroepiandrosterone; 3β-O- (trifluroacetyl) -7-oxo-dehydroepiandrosterone 3β-O- (4-carboxy-butanoyl) -7-oxo-dehydroepiandrosterone; 3β-O- (4-cyclopentyl-butanoyl) -7-oxo-dehydroepiandrosterone; 3β-O-benzoyl-7-oxo-dehydroepiandrosterone; 3β-O- (3,4-dihydroxybenzoyl) -7-oxo-dehydroepiandrosterone; 3P-O- (ascorbyl-phosphate) -7-oxo-dehydroepiandrosterone 3p-O- (ascorbyl-sulfate) -7-oxo-dehydroepiandrosterone; 3β-O-phosphonyl-7-oxo-dehydroepiandrosterone; 3β-O-monoacetylphosphonyl-7-oxo-dehydroepiandrosterone; 3β-O-sulfonyl-7-oxo-dehydroepiandrosterone; 3β-O- (tert-butyldimethylsilyl) -7-oxo-dehydroepiandrosterone; 3β-O- (tert-butyl-diphenyl-silyl) -7-oxo-dehydroepiandrosterone; 3β-O- (trimethylsilyl) -7-oxo-dehydroepiandrosterone; - 15-Androstene-3ss, 7ss-dihydroxy-17-dione or 7ss-OH-dehydroepiandrosterone (7-hydroxy-DHEA); A5-androstene-3β, 7α-dihydroxy-17-d! one or 7a-OH-dehydroepiandrosterone (7-hydroxy-DHEA); 3β-O-acetyl-7-hydroxy-dehydroepiandrosterone (3-beta-acetoxy-7-hydroxy-DHEA); 3β-O-propionyl-7-hydroxy-dehydroepiandrosterone (3-beta-propionyloxy-7hydroxy-DHEA); 3β-O-butanoyl-7-hydroxy-dehydroepiandrosterone (3-beta-butanoyloxy-7-hydroxyDHEA); 3β-O-iso-butanoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-pentanoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-hexanoyl-7-hydroxy-dehydroepiandrosterone-3β-O-heptanoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-octanoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-nonanoyl-7-hydroxy-dehydroepiandrosterone;

<Desc / Clms Page number 26>  3β-O-decanoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-dodecanoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-myristoyl-7-hydroxydehydroepiandrosterone; 3p-O-palmitoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-stearoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-arachidoyl-7-hydroxy-dehydroepiandrosterone; 3p-O-docosanoyl-7-hydroxy-dehydroepiandrosterone; 3ss-O-lignoceroyl-7-hydroxydehydroepiandrosterone; 3ss-O-oleoyl-7-hydroxydehydroepiandrosterone; 3p-O-linoleoyl-7-hydroxy-dehydroepiandrosterone; 3j3-0-)! nolenoyl-7-hydroxy-dehydroepiandrosterone; 3p-O-petroselinoyl-7-hydroxy-dehydroepiandrosterone; 3β-O-acetyl-7-hydroxy-dehydroepiandrosterone; 3β-O-acetyl-7-O-acetyl-dehydroepiandrosterone; 3ss-O-acetyl-7-O-proponyl dehydroepiandrosterone; 3β-O-acetyl-7-O-butanoyldehydroepiandrosterone; 3β-O-acetyl-7-iso-butanoyldehydroepiandrosterone; 3β-O-acetyl-7-O-pentanoyl dehydroepiandrosterone; 3) 3-O-acetyl-7-O-hexanoyldehydroepiandrosterone; 3ss-O-acetyl-7-O-heptanoyldehydroepiandrosterone; 3β-O-acetyl-7-O-octanoyl-dehydroepiandrosterone; 3β-O-acetyl-7-O-nonanoyl dehydroepiandrosterone; 3β-O-acetyl-7-O-decanoyl dehydroepiandrosterone; 3β-O-acetyl-7-O-dodecanoyl dehydroepiandrosterone; 3-O-acetyl-7-O-myristoyl dehydroepiandrosterone; 3ss-O-acetyl-7-O-palmitoyldehydroepiandrosterone; 3β-O-acetyl-7-O-stearoyldehydroepiandrosterone; 3β-O-acetyl-7-O-arachidoyl dehydroepiandrosterone; 3β-O-acetyl-7-O-docosanoyl dehydroepiandrosterone; 3ss-O-acetyl-7-O-lignoceroyl dehydroepiandrosterone; 3ss-O-acetyl-7-O-oleoyldehydroepiandrosterone; 3β-O-acetyl-7-O-linoleoyl dehydroepiandrosterone; 3β-O-acetyl-7-O-linolenoyl dehydroepiandrosterone;

<Desc / Clms Page number 27> 3ss-O-acetyl-7-O-pétroselinoyl-dehydroepiandrosterone. 9. Composition according to any one of claims 1 to 5 and 8, characterized in that the derivative of the DHEA of formula (1) is chosen from at least one of the following derivatives: - # 5-androstene-3ss-hydroxy- 7,17-dione or 7-oxo-dehydroepiandrosterone (7-oxo) DHEA);

 p-O-acetyl-7-oxo-dehydroepiandrosterone (or 3ss-acetoxy-7-oxo-DHEA); - 5-Androstene-3β, 7α-dihydroxy-17-dione or 7α-OH-dehydroepiandrosterone (7α-hydroxy-DHEA). 10. Composition according to any one of the preceding claims, characterized in that the agent capable of inhibiting at least one enzyme selected from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases is selected from at least one the following substances: - pentacyclic triterpenes and plant extracts containing them; - extracts of Paeonia suffruticosa; extracts of Paeonia lactiflora - phycosaccharides,; - Canola oil; - Tamanu oil; - calophyllum oil; - alphabisabolol; - chamomile extracts; - allantoin; Diesterphosphoric vitamin E and C - unsaturated oils in omega 3 such as rosehip musca oils, black currant oils, ecchium oils, fish oils; Plankton extracts; sodium palmitoylproline and nymphea alba; extracts of the pygeum; Extracts of Boswellia serrata; Extracts of Centipeda cunnighami; Extracts of Helianthus annuus; <Desc / Clms Page number 28>  your ear extracts (Ep / '/ ob /' um angush'fo / m); extracts of Aloe vera.

Extracts of Linum usitatissimum; - tocotrienols; your extracts of Cola nitida; the piperonal; clove extracts 11. Composition according to the preceding claim, characterized in that the agent capable of inhibiting at least one enzyme chosen from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases is chosen from at least one of the following substances:

 extracts of Glycyrrhiza glabra, oleanolic acid and its salts; ursolic acid and its salts; boswellic acid and its salts; betullic acid and its salts; glycyrrhetinic acid and its salts and / or derivatives such as monoglucuronide glycyrrhetic acid, stearyl glycyrrhetinate, 3-stearoyloxy-glycyrrhetic acid; - extracts of Paeonia suffruticosa; extracts of Paeonia lactiffora phycosaccharides; - calophyllum oil; - alphabisabolol; - chamomile extracts; - allantoin; - tocotrienols; - Aloe vera extracts. 12. Composition according to any one of the preceding claims, characterized in that it contains from 0.0001% to 10% by weight of derivative of the DHEA of formula (1) as defined in one of claims 1 at 9, relative to the total weight of the composition. <Desc / Clms Page number 29> 13. Composition according to the preceding claim, characterized in that it contains from 0.01% to 5% by weight of derivative of the DHEA of formula (1) as defined in one of claims 1 to 9, by relative to the total weight of the composition. 14. Composition according to any one of the preceding claims, characterized in that it contains from 0.0001 to 10% by weight of agent capable of inhibiting at least one enzyme selected from phospholipases A2, lipoxygenases and / or or human prostaglandin synthetases, relative to the total weight of the composition. 15. Composition according to the preceding claim, characterized in that it contains from 0.001 to 5% by weight, of agent capable of inhibiting at least one enzyme chosen from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases, relative to the total weight of the composition. 16. Cosmetic use of a composition containing, in a physiologically acceptable medium, at least one derivative of the DHEA of formula (1) as defined in any one of Claims 1 to 9 with at least one agent capable of inhibiting less an enzyme chosen from phospholipases A2, lipoxygenases and / or prostaglandins human synthetases, to soothe the skin and / or the scalp. 17. Cosmetic use of a composition containing, in a physiologically acceptable medium, at least one derivative of the DHEA of formula (1) as defined in any one of Claims 1 to 9 with at least one agent capable of inhibiting less an enzyme chosen from phospholipases A2, lipoxygenases and / or prostaglandins human synthetases, for preventing and / or treating sensitive skin and / or cutaneous discomfort and / or tightness and / or itching of the skin and / or skin irritations and / or skin swelling and / or redness and / or sensations of cutaneous heat. 18. Cosmetic use as a soothing agent, by topical application to the skin and / or the scalp, of the combination comprising at least one derivative of the DHEA of formula (1) as defined in any one of the Claims 1 to 9 with at least one agent capable of inhibiting at least one enzyme selected from the group consisting of <Desc / Clms Page number 30>  phospholipases A2, lipoxygenases and / or human prostaglandins synthetases. 19. Cosmetic use as an agent for preventing and / or treating sensitive skin, cutaneous discomfort, skin tightness, itchy skin, skin irritations, skin swellings, skin rashes and / or heat sensations cutaneous, by topical application to the skin and / or the leather, of the combination comprising at least one derivative of the DHEA of formula (1) as defined in any one of claims 1 to 9 with at least one agent capable inhibiting at least one enzyme selected from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases. 20. Cosmetic treatment process soothing keratinous materials by topical application thereto of a composition containing, in a physiologically acceptable medium, at least one derivative of the DHEA of formula (1) as defined in any one of the Claims 1 to 9 with at least one agent capable of inhibiting at least one enzyme selected from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases. 21. Process for the cosmetic treatment of sensitive skin, cutaneous discomfort, skin tightness, itchy skin, skin irritations, skin swelling, redness of the skin, sensations of cutaneous heat including topical application to the skin or the scalp of a composition containing, in a physiologically acceptable medium, at least one derivative of the DHEA of formula (1) as defined in any one of claims 1 to 9 with at least one agent capable of inhibiting at the less an enzyme selected from phospholipases A2, lipoxygenases and / or human prostaglandin synthetases.