US 20030054021A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2003/0054021 A1 Dalko et al. (43) Pub. Date: Mar. 20, 2003

(54) 7-OXO-DHEACOMPOUNDS FOR TREATING (30) Foreign Application Priority Data KERATINOUS CONDITIONS/AFFLICTIONS Jun. 14, 2001 (FR)...... 01/07804 (76) Inventors: Maria Dalko, Gif Sur Yvette (FR); Publication Classification Alexandre Cavezza, Tremblay-En-France (FR); Elisabeth (51) Int. Cl." ...... A61K 31/695; A61K 31/66; Picard-Lesboueyries, Velizy (FR); A61K 31/58; A61K 31/56; Beatrice Renault, Saint Maurice (FR); A61K 7/OO Veronique Burnier, Paris (FR) (52) U.S. Cl...... 424/401; 514/63; 514/172; 514/176; 514/177; 514/143 Correspondence Address: (57) ABSTRACT Norman H. Stepno, Esquire BURNS, DOANE, SWECKER & MATHIS, 7-Oxo-DHEA derivatives, various of which are themselves L.L.P. novel compounds, are well Suited for cosmetically/therapeu P.O. Box 1404 tically treating adverse conditions/afflictions of a keratinous Alexandria, VA 22313-1404 (US) Substrate/material, notably of human skin, hair, eyelashes and nails, to improve the appearance thereof, in particular to prevent or treat Signs of aging of the Skin and/or a dull (21) Appl. No.: 10/170,679 complexion and/or skin or hair pigmentation disorders and/ or dryneSS of the skin and/or hyperSeborrhoea and/or hyper Seborrhoea-related imperfections and/or Sensitive skin and/ (22) Filed: Jun. 14, 2002 or dandruff and/or natural hair loSS and/or baldness. US 2003/0054021 A1 Mar. 20, 2003

7-OXO-DHEACOMPOUNDS FOR TREATING KERATINOUS CONDITIONS/AFFLICTIONS (I) Me O CROSS-REFERENCE TO PRIORITY APPLICATION Me 0001. This application claims priority under 35 U.S.C. S 119 of FR-01/07804, filed Jun. 14, 2001, hereby expressly incorporated by reference. R No O BACKGROUND OF THE INVENTION 0010. Among these compounds, 3 B-acetoxy-7-oxo 0002) 1. Technical Field of the Invention DHEA or A5-androstene-3,3-acetoxy-7,17-dione is already 0003. The present invention relates to novel 7-oxo known and has been described as being effective in modu DHEA derivatives, to a process for Synthesizing Such novel lating the immune system (U.S. Pat. Nos. 5,292,730, 5,585, compounds and to cosmetic/therapeutic compositions com 371 and 5,641,766), treating Alzheimer's disease (U.S. Pat. prising Same. No. 5,707,983), treating HIV syndrome (U.S. Pat. No. 5,885,977) and for promoting weight loss (U.S. Pat. Nos. 0004. The present invention also relates to cosmetic 5,296,481 and 5,807,848). applications of at least one 7-oxo-DHEA derivative to 0011 WO-99/25333 also indicates the administration, improve the appearance of keratin materials and Substrates, especially topically, of 3,3-acetoxy-7-oxo-DHEA in the pro Such as the skin, the hair, the eyelashes and the nails, in phylactic and curative treatment of lupus erythematosus, particular to prevent or treat adverse signs of aging of the which is a disorder of the immune system that is liable to skin and/or a dull complexion and/or skin or hair pigmen affect Several organs and that is manifested in the skin by tation disorders and/or dryness of the skin and/or hyperse transverse redness of the face and/or by Squamous erythemal borrhoea and/or hyperSeborrhoea-related imperfections and/ plaques disseminated over the body. or Sensitive Skin and/or dandruff and/or natural hair loSS 0012 U.S. Pat. No. 5,424,463 especially describes and/or baldness. 7-keto-DHEA (or A5-androstene-3B-ol-7,17-dione) and 0005. This invention also relates to a cosmetic regime/ derivatives thereof wherein one or more of the hydroxyl or regimen for treating keratinous Substrates/materials by topi keto Substituents is a group convertible thereto by hydroly cal application thereon of a composition containing at least Sis. Hydrolyzable groups include hydroxyl groups esterified one 7-oxo-DHEA derivative, formulated into a physiologi with an acid selected from the group consisting of (i) a cally acceptable medium therefor. normal, branched, Saturated or unsaturated C-C aliphatic acid, (ii) a C7-C aromatic acid, (iii) a C- or more dicar 0006 2. Description of the Prior Art boxylic acid, for which only one carbonyl group is esterified with the 3-hydroxy group of the Steroid, (iv) an inorganic 0007 DHEA, or dehydroepiandrosterone, is a natural acid such as Sulfuric acid and phosphoric acid. U.S. Pat. No. Steroid produced essentially by the adrenal glands. EXOg 5,424,463 describes the 7-keto- and hydrolyzable deriva enous DHEA, administered topically or orally, is recognized tives thereof as being effective for promoting weight loSS. for its capacity to promote epidermal keratinization (JP-07, 0013 In addition, the following derivatives are also 196,467) and to treat dry skin by increasing the endogenous described as being effective for promoting weight loSS production and Secretion of Sebum and thus by reinforcing (Steroids, 1998, 63(3), pp. 158-165): 3 B-O-acetyl-7-oxo the skin's barrier effect (U.S. Pat. No. 4,496.556). U.S. Pat. dehydroepiandrosterone (or 3,3-acetyl-7-oxo-DHEA); No. 5,843,932 has also described the administration of 3|8-O-propionyl-7-oxo-dehydroepiandrosterone (or 3 B-pro DHEA to remedy dermal atrophy by inhibiting the loss of pionyl-7-oxo-DHEA); 3.3-O-butanoyl-7-oxo-dehydroepi collagen and of connective tissue. Too, the assignee hereof androsterone (or 3,3-butanoyl-7-oxo-DHEA); 3 B-O-isobu has demonstrated the capacity of DHEA to combat the tanoyl-7-oxo-dehydroepiandrosterone; 3 B-O-heptanoyl-7- weathered appearance of the skin (FR-00/00349), to modify OXO-dehydroepiandrosterone; 3f6-O-dodecanoyl-7-oxo skin and hair pigmentation (FR-99/12773) and to combat dehydroepiandrosterone; 3f6-O-palmitoyl-7-oxo epidermal atrophy (FR-00/06154). These properties of dehydroepiandrosterone; 3f6-O-stearoyl-7-oxo DHEA make it a candidate of choice as an anti-aging active dehydroepiandrosterone; 3.3-O-hemisuccinate-7-oxo agent. dehydroepiandrosterone. 0008. However, DHEA has hormonal effects that may 0014) Among the 7-oxo-DHEA derivatives of formula (I) prove difficult as regards the administration of Same. There that are described in the prior art are the following deriva need Still exists to provide DHEA analogs with properties as tives: advantageous as DHEA itself, but without eliciting any 0.015 (1) The derivative of formula (I) in which R is hormonal effects. a 2-tetrahydropyran group (RN 102 890-86-8). 0009. It was first considered by applicants that the 7-oxo 0016 (2) The compound of formula (I) in which R DHEA derivatives of general formula (I) below could satisfy is a CHOCO group, described as Suppressing the this need: transactivation of the androgenic receptor induced US 2003/0054021 A1 Mar. 20, 2003

by an androstenediol in human prostate cancer cells and/or Sulfate and/or phosphate and/or aryl and/or hetero (Proc. Natl. Acad. Sci. USA, 1999, 96(20), pp. cycle, Said heterocycle advantageously being an indole, a 11173-11177). pyrimidine, a piperidine, a morpholine, a pyran, a furan, a piperazine or a pyridine, an alkylcarbonyl radical, with the 0017 (3) Derivatives of formula (I) in which R is an exception of the CH-CO-radical, the C-C alkyl moiety of O=P(OH)OCOCH group or a group which is Saturated or unsaturated, linear or branched, or cyclic, and optionally Substituted with one or more Substitu CO2H ents selected from among -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 het erocycle advantageously being an indole, a pyrimidine, a piperidine, a morpholine, a pyran, a furan, a piperazine or a pyridine, an arylcarbonyl radical, preferably a phenylcarbo nyl radical, or an arylalkylcarbonyl radical, preferably a benzylcarbonyl radical, optionally Substituted with one or more of the Substituents -OR" and/or -SR' and/or COOR and/or -NR'R' and/or halogen and/or aryl and/or hetero cycle; a group O=P(OH)OR'; a group (O)SOR"; a trialkyl 0018) described in U.S. Pat. No. 5,837,269 as silyl radical (SiR') in which the 3 groups R' may be identical agents for increasing the immune response to a or different; an alkyloxycarbonyl group (R'OCO); an alky Vaccine. laminocarbonyl group (R'NHCO); wherein R' is a hydrogen 0.019 (4) The derivative of formula (I) in which R is atom, a Saturated or unsaturated, linear or branched, or a group molPhCO, described in an epoxidation cyclic C-C and preferably C-C alkyl radical, which may process for the synthesis of steroids (J. Chem. Soc. optionally contain one or more hetero atoms, optionally Perkin Trans. I, 1975 (4), pp. 323-6). functionalized with one or more of the groups -OR", -COOR", halogen, -NR"R", or with an aryl group, pref 0020 (5) Derivatives of formula (I) in which R is an erably a phenyl group, optionally functionalized with one or NaSOH group or an SOH group, noted in Endo more of the groups -OR", -COOR", halogen or crinol. Exp., 1971, 5(4), pp. 205-210, which -NR"R", and preferably wherein R' is a hydrogen atom, a describes the properties of these derivatives when methyl, an ethyl, a butyl, a propyl or an isopropyl radical; they are subjected to various hydrolysis conditions. and R" is a hydrogen atom or a Saturated or unsaturated, linear or branched or cyclic alkyl radical, preferably C-C, 0021 (6) The derivative of formula (I) in which R is preferably R" is a hydrogen atom, a methyl, an ethyl, abutyl, a tEuSi(Me) group, described in a steroid prepara a propyl or an isopropyl radical; with the proviso that, in tion process (Heterocycles, 1994, 38(5), pp. 1053 each of the groups -NR'R' and -NR"R", the substituents 60). R" and R", respectively, are identical or different, and that, 0022. However, to the knowledge of applicants, it was advantageously, the group -NR'R' represents an amino heretofore unknown to administer the 7-oxo-DHEA deriva acid, preferably Selected from among L-alanine, L-arginine, tives of general formula (I) for cosmetic purposes, in par L-asparagine, L-aspartic acid, L-cysteine, L-glutamine, ticular for treating the adverse Signs of aging. L-glutamic acid, glycine, L-histidine, L-isoleucine, L-leu cine, L-lysine, L-methionine, L-phenylalanine, L-proline, SUMMARY OF THE INVENTION L-serine, L-threonine, L-tryptophan, L-tyrosine and L-va 0023 The present invention thus features cosmetic appli line. cations for improving the appearance of keratinous Sub Strates/materials, by administering to a candidate Subject in DETAILED DESCRIPTION OF BEST MODE need of Such treatment, a thus-effective amount of at least AND SPECIFIC/PREFERRED EMBODIMENTS one 7-oxo-DHEA compound of formula (I) below: OF THE INVENTION 0025 More particularly according to the present inven (I) tion, by “cyclic C-C alkyl radical” is intended a Me O cycloalkyl radical having from 3 to 12 carbon atoms. 0026. The present invention also features the optical Me isomers and/or geometric isomers of the 7-oxo-DHEA derivatives of formula (I), either alone or in admixture in all proportions, and also the physiologically acceptable Salts of R these derivatives, Said optical and/or geometric isomers No O deriving from the group R. 0027. By the expression “keratin materials or substrates' 0024 in which R is a saturated or unsaturated, linear or is intended skin, hair fibers (head hair and eyelashes) and the branched, or cyclic C-C alkyl radical optionally contain nails. ing one or more hetero atoms and optionally Substituted with 0028. According to one preferred embodiment of the one or more Substituents Selected from among -OR" and/or invention, the 7-oxo-DHEA compounds of formula (I) are -SR' and/or -COOR" and/or -NR'R' and/or halogen those in which R is a C-C, Saturated or unsaturated, linear US 2003/0054021 A1 Mar. 20, 2003 or branched, or cyclic alkyl radical optionally containing 0051 3B-O-arachidoyl-7-oxo-dehydroepiandroster one or more hetero atoms, and optionally Substituted with One, one or more Substituents Selected from among -OR" and/or 0052 3B-O-docosanoyl-7-oxo-dehydroepiandros -SR' and/or -COOR and/or -NR'R' and/or halogen. terone, 0029. In another preferred embodiment of the invention, the 7-oxo-DHEA compounds of formula (I) are those in 0053 3B-O-lignoceroyl-7-oxo-dehydroepiandros which R is an alkylcarbonyl radical, the C-Co and prefer terone, ably C-C alkyl moiety of which is Saturated or unsatur 0054 3B-O-oleoyl-7-oxo-dehydroepiandrosterone; ated, linear or branched or cyclic and optionally Substituted with one or more substituents selected from among -OR' 0055 3B-O-inoleoyl-7-oxo-dehydroepiandroster and/or -SR' and/or -COOR and/or -NR'R'' and/or halo One, gen. 0056 3B-O-linolenoyl-7-oxo-dehydroepiandroster 0030 Among the compounds of formula (I) according to One, the invention, the following are the most particularly pre 0057 3B-O-petroselinoyl-7-oxo-dehydroepiandros ferred: terone, 0031 3B-O-methyl-7-oxo-dehydroepiandrosterone; 0058 3B-O-7-oxo-dehydroepiandrosterone glyci 0032 3B-O-ethyl-7-oxo-dehydroepiandrosterone; nate, 0033 3B-O-carboxymethyl-7-oxo-dehydroepi 0059) 3B-O-7-oxo-dehydroepiandrosterone lysi androsterone; nate, 0034 33-O-glucosyl-7-oxo-dehydroepiandroster 0060 3B-O-7-oxo-dehydroepiandrosterone serin One, ate, 0035 3B-O-glucoronyl-7-oxo-dehydroepiandroster 0061 3B-O-7-oxo-dehydroepiandrosterone One, C-glutamate; 0036 3.B-O-(2-tetrahydropyranyl)-7-oxo-dehydroe 0062 3B-O-7-oxo-dehydroepiandrosterone C.-as piandrosterone; partate, 0037 3/8-O-(2-tetrahydrofuranyl)-7-oxo-dehydroe 0063. 3?-hemisuccinoyloxyandrost-5-ene-7,17-di piandrosterone; One, 0038 3B-O-propionyl-7-oxo-dehydroepiandroster 0064 3.B-O-(2-hydroxymalonyl)-7-oxo-dehydroe one (or 3,3-propionyloxy-7-oxo-DHEA); piandrosterone; 0039) 33-O-butanoyl-7-oxo-dehydroepiandroster 0065 3,B-O-(2-malonylaminocarbonyl)-7-oxo-de one (or 3,3-butanoyloxy-7-oxo-DHEA); hydroepiandrosterone, 0040 3B-O-isobutanoyl-7-oxo-dehydroepiandros 0066 3.B-O-(2-succinylaminocarbonyl)-7-oxo-de terone, hydroepiandrosterone, 0041 3B-O-pentanoyl-7-oxo-dehydroepiandroster 0067 3/8-O-(2-glutarylaminocarbonyl)-7-oxo-dehy One, droepiandrosterone; 0042 3B-O-hexanoyl-7-oxo-dehydroepiandroster 0068 33-methylcarbonate-7-oxo-dehydroepi One, androsterone; 0043 33-O-heptanoyl-7-oxo-dehydroepiandroster 0069. 3.3-O-(trifluoroacetyl)-7-oxo-dehydroepi One, androsterone; 0044) 3B-O-octanoyl-7-oxo-dehydroepiandroster 0070 3(3-O-(4-carboxybutanoyl)-7-oxo-dehydroe One, piandrosterone; 0045 3B-O-nonanoyl-7-oxo-dehydroepiandroster 0071 3f6-O-(4-cyclopentylbutanoyl)-7-oxo-dehy One, droepiandrosterone; 0046) 3B-O-decanoyl-7-oxo-dehydroepiandroster 0072 3B-O-benzoyl-7-oxo-dehydroepiandroster One, One, 0047 3B-O-dodecanoyl-7-oxo-dehydroepiandros 0.073 3/3-O-(3,4-dihydroxybenzoyl)-7-oxo-dehy terone, droepiandrosterone; 0048 3B-O-myristoyl-7-oxo-dehydroepiandroster 0074 3.3-O-(ascorbyl phosphate)-7-oxo-dehydroe One, piandrosterone; 0049 3B-O-palmitoyl-7-oxo-dehydroepiandroster 0075 3,B-O-(ascorbyl sulfate)-7-oxo-dehydroepi One, androsterone; 0050 3B-O-Stearoyl-7-oxo-dehydroepiandroster 0076 3B-O-phosphonyl-7-oxo-dehydroepiandros One, terone, US 2003/0054021 A1 Mar. 20, 2003

0077 3B-O-monoacetylphosphonyl-7-oxo-dehy 0088. By the expression “physiologically acceptable droepiandrosterone, medium' is intended a medium that is compatible with the 0078 3B-O-sulphonyl-7-oxo-dehydroepiandroster skin and/or its integuments. One, 0089. To provide an order of magnitude, the composi tions according to the invention advantageously contain 0079) 33-O-(tert-butyldimethylsilyl)-7-oxo-dehy from 0.00001% to 10% by weight of 7-oxo-DHEA deriva droepiandrosterone, tive of formula (I) as defined above, relative to the total 0080) 3(3-O-(tert-butyldiphenylsilyl)-7-oxo-dehy weight of the composition. Preferably, however, the subject droepiandrosterone, compositions will contain from 0.001% to 5% by weight of 7-oxo-DHEA derivative of formula (I) relative to the total 0081 3f6-O-(trimethylsilyl)-7-oxo-dehydroepi weight of the composition. androsterone. 0090 The above compositions are well Suited for cos 0082 More particularly, the present invention also fea metic purposes, to improve the appearance of keratin Sub tures the cosmetic administration of at least one 7-OXO Strates/materials. DHEA compound of formula (I) for preventing or treating the adverse signs of aging of the skin and/or a dull com 0091. The subject compositions may thus be adminis plexion and/or skin or hair pigmentation disorders and/or tered to prevent or treat the Signs of aging of the skin and/or skin dryneSS and/or hyperSeborrhoea and/or hyperSebor a dull complexion and/or skin or hair pigmentation disorders rhoea-related imperfections and/or Sensitive skin and/or and/or skin dryneSS and/or hyperSeborrhoea and/or hyper dandruff and/or natural hair loSS and/or baldness. Seborrhoea-related imperfections and/or Sensitive skin and/ or dandruff and/or natural hair loSS and/or baldness. 0.083. By the expression “signs of aging of the skin' are intended wrinkles and fine lines, loss of firmness and/or 0092 Various compounds that may be formulated into elasticity of the skin, cutaneous atrophy, a more irregular the compositions according to the invention will now be skin grain with presence of dilated pores, loSS of radiance of more fully described. the skin and/or pigmentary markS. 0093 1. Desquamating Agents and Moisturizers: 0084. By the expression “sensitive skin' is intended skin that has been characterized in EP-0,680,749 B1, hereby 0094. By the term “desquamating agent” is intended any incorporated by reference. It has thus been shown that the compound capable of acting: Symptoms associated with Sensitive skin included more or 0.095 (a) either directly on descuamation by pro less painful Sensations experienced in an area of skin, Such moting exfoliation, Such as B-hydroxy acids, in par as Stinging, tingling, itching or pruritus, burning, redness, ticular Salicylic acid and derivatives thereof (includ hotness, discomfort, tautness, etc. These Symptoms may be ing 5-n-octanoylsalicylic acid), C-hydroxy acids, manifested in response to various factorS Such as, inter alia, Such as glycolic acid, citric acid, lactic acid, tartaric Sweat, friction, the emotions, foods, the wind, Shaving, Soap, acid, malic acid or mandelic acid; urea, gentisic acid; Surfactants, hard water with a high calcium concentration, oligofucoses, cinnamic acid; extract of Saphora temperature variations or wool. japonica, hydroxyStilbenes including, in particular, 0085 Thus invention also features cosmetic composi reSVeratrol; tions containing, in a physiologically acceptable medium therefor (vehicle, diluent or carrier), at least one 7-oxo 0096 (b) or on the enzymes involved in the descqua DHEA derivative of formula (I) and at least one other active mation or degradation of corneodesmoSomes, gly agent compound Selected from among: a descquamating cosidases, Stratum corneum chymotryptic enzyme agent, a moisturizer, a depigmenting or propigmenting (SCCE), or even other proteases (trypsin, chymot agent, an anti-glycation agent, an NO-Synthase inhibitor, a rypsin-like). Exemplary agents for chelating mineral 5C-reductase inhibitor, a lysyl and/or prolyl hydroxylase salts are EDTA; N-acyl-N,N',N'-ethylenediaminetri inhibitor, an agent for Stimulating the Synthesis of dermal or acetic acid; amino-Sulfonic compounds and in par epidermal macromolecules and/or for preventing their deg ticular (N-2-hydroxyethylpiperazine-N-2-ethane radation, an agent for Stimulating the proliferation of fibro )sulfonic acid (HEPES), 2-oxothiazolidine-4- blasts and keratinocytes and/or keratinocyte differentiation, carboxylic acid (procysteine); C-amino acid a muscle relaxant, a compound for reducing irritation, an derivatives of the type Such as glycine (as described antimicrobial agent, a tensioning agent, an anti-pollution in EP-0,852,949); honey; sugar derivatives such as agent or a free-radical Scavenger. O-octanoyl-6-D-maltose and N-acetylglucosamine. 0.086 The present invention also features cosmetic com 0097. By the term “moisturizer” is intended: positions containing, in a physiologically acceptable 0098 (a) either a compound acting on the barrier medium, at least one 7-oxo-DHEA compound of formula (I) function, in order to maintain the moisturization of and at least one UV-Screening agent Selected from among the Stratum corneum, or an occlusive compound. certain UVA and/or UVB Screening agents and/or at least Exemplary are the ceramides, Sphingoid-based com one optionally coated inorganic pigment. pounds, lecithins, glycosphingolipids, phospholip 0087. The compositions according to the invention are ids, cholesterol and derivatives thereof, phytosterols well Suited for topical application onto keratin Substrates/ (Stigmasterol, f-sitosterol or campesterol), essential materials Such as the skin, keratin fibers (head hairs and fatty acids, 1,2-diacylglycerol, 4-chromanone, pen eyelashes) and the nails. tacyclic triterpenes, petroleum jelly and lanolin; US 2003/0054021 A1 Mar. 20, 2003

0099 (b) or a compound that directly increases the 0111. The compositions of the invention comprising an water content of the Stratum corneum, Such as thre anti-glycation agent as defined above are well Suited to alose and derivatives thereof, hyaluronic acid and prevent or treat the Signs of aging of the skin, in particular derivatives thereof, glycerol, pentanediol, pidolates, to prevent or treat the loSS of tonicity and/or elasticity of the Serine, Xylitol, Sodium lactate, polyglyceryl acrylate, skin. ectoin and derivatives thereof, chitosan, oligosaccha rides and polysaccharides, cyclic carbonates, N-lau 0112 4. NO-synthase Inhibitors: royl-pyrrollidonecarboxylic acid and N-C-benzoyl-L- 0113 Exemplary NO-synthase inhibitors that are suitable arginine; for formulation into the compositions of the present inven tion especially comprise a plant extract of the Species Vitis 0100 (c) or a compound that activates the sebaceous vinifera which is marketed by Euromed as Leucocyanidines glands, Such as Steroid derivatives (including de raisins extra, or by Indena under the trademark Leucose DHEA) and vitamin D and derivatives thereof. lectOR), or also by Hansen as EXtrait de marc de raisin; a plant 0101 These compounds advantageously constitute from extract of the Species Olea europaea which is preferably 0.001% to 30% and preferably from 0.01% to 20% of the obtained from olive tree leaves and is marketed by Vinyals total weight of the composition according to the invention. in the form of a dry extract, or by Biologia & Technologia under the trademark Eurol BT, and a plant extract of the 0102) The compositions according to the present inven Species Gingko biloba which is preferably a dry acqueous tion comprising the descquamating agents and moisturizers indicated above are well Suited for preventing or treating extract of this plant marketed by Beaufour as Gingko biloba skin dryneSS and especially Xerosis. eXtrait Standard. 0114. The compositions according to the invention com 0103 2. Depigmenting or Propigmenting Agents: prising an NO-synthase inhibitor as defined above are well 0104 Exemplary depigmenting agents that may be for Suited to prevent or treat the Signs of aging of the skin and/or mulated into the compositions according to the present Sensitive skin. invention comprise the following compounds: kojic acid; ellagic acid; arbutin and derivatives thereof Such as those 0115 5.5C-reductase Inhibitors: described in EP-895,779 and EP-524,109; hydroquinone; 0116. When the compositions according to the invention aminophenol derivatives such as those described in WO-99/ comprise a 5C.-reductase inhibitor, Such inhibitor is advan 10318 and WO-99/32077, and in particular N-cholestery tageously Selected from among: loxycarbonyl-para-aminophenol and N-ethyloxycarbonyl para-aminophenol; iminophenol derivatives, in particular 0117 retinoids, and in particular retinol; those described in WO-99/22707; L-2-oxothiazolidine-4- 0118 sulfur and sulfur derivatives; carboxylic acid or procysteine, and also its Salts and esters, ascorbic acid and derivatives thereof, especially ascorbyl 0119 Zinc Salts. Such as Zinc lactate, gluconate, glucoside; and plant extracts, in particular extracts of liquo pidolate, carboxylate, Salicylate and/or cysteate; rice, of mulberry and of Skullcap, this list not intended to be limiting. 0120 selenium chloride; 0105 Propigmenting agents that are exemplary include 0121 vitamin B6 or pyridoxine; the extract of burnet (Sanguisorba officinalis) marketed by 0.122 mixture of capryloyl glycine, sarcosine and Maruzen, and extracts of chrysanthemum (Chrysanthemum extract of Cinnamomum zeylanicum marketed by morifolium). Seppic under the trademark Sepicontrol A5(R); 0106 The compositions according to the present inven 0123 an extract of Laminaria Saccharina marketed tion comprising the depigmenting agents indicated above are by SECMA under the trademark Phlorogine(R); well Suited for preventing or treating hyperpigmentation, in particular pigmentary marks related to aging of the skin. 0.124 an extract of Spiraea ulmaria marketed by 0107 The compositions containing the propigmenting Silab under the trademark Sebonormine(E); agents indicated above are well Suited for treating baldness. 0.125 plant extracts from the species Arnica mon tana, Cinchona Succirubra, Eugenia Caryophyllata, 0108) 3. Anti-glycation Agents: Humulus lupulus, Hypericum perforatum, Mentha 0109. By the term “anti-glycation agent” in intended a piperita, RoSmarinus Officinalis, Salvia Oficinalis and compound for preventing and/or reducing the glycation of Thymus vulgaris, all marketed, for example, by skin proteins, in particular of dermal proteins Such as Maruzen; collagen. 0.126 an extract of Serenoa repens marketed by 0110 Exemplary anti-glycation agents are plant extracts Euromed; of the Ericacea family, Such as an extract of blueberry (Vaccinium angustifolium), ertothioneine and derivatives 0127 plant extracts of the genus Silybum; thereof; and hydroxyStilbenes and derivatives thereof, such 0128 plant extracts containing Sapogenins and in as resveratrol and 3,3',5,5'-tetrahydroxyStilbene. These anti particular extracts of diosgenin-rich or hecogenin glycation agents are described in FR-99/16166, FR-00/ rich DioScorea plants, and 08.158, FR-99/09267 and FR-99/16168, respectively. Res veratrol is particularly preferred for formulation into the 0.129 extracts of Eugenia caryophyllata containing compositions of the invention. eugenol or eugenylglucoside. US 2003/0054021 A1 Mar. 20, 2003

0130. The 5C.-reductase inhibitor advantageously consti 0141 (e) or on metalloprotease (MMP) inhibition, tutes, for example, from 0.001% to 10% and preferably from such as, more particularly, MMP 1, 2, 3 or 9: 0.01% to 5% of the total weight of the composition accord exemplary are the retinoids and derivatives, isofla ing to the invention. When this composition contains Such a vonoids, oligopeptides and lipopeptides, lipoamino compound, it is particularly Suitable for preventing or treat acids, the malt extract marketed by Coletica under ing Seborrhoea and/or hirsutism and/or androgen-dependent the trademark Collalift(R); extracts of blueberry or of alopecia. rosemary; carotenoids including, in particular, lyco 0131 6. Lysyl and/or Prolyl Hydroxylase Inhibitors: pene; isoflavones, their derivatives or plant extracts 0132) Preferred examples of lysyl and/or propyl hydroxy containing them, in particular extracts of Soybean lase inhibitors that may be formulated into the compositions (marketed, for example, by Ichimaru Pharcos under according to the present invention are 2,4-diaminopyrimi the trademark Flavosterone SB(R), of red clover, of dine 3-oxide or 2,4-DPO described in WO-96/09048 and flax, of kakkon, of Sage or extracts of Sage (as 2,4-diamino-6-piperidinopyrimidine 3-oxide or “Minoxidil” described in French patent application No. described in U.S. Pat. Nos. 4,139,619 and 4,596,812. 00/10203); 0133. These compounds are advantageously present, for 0142 (f) or on the inhibition of serine proteases such example, in the compositions of the invention in a propor as leukocyte elastase or cathepsin G: exemplary are tion of from 0.001% to 5% by weight and preferably in a the peptide extract of Leguminosa Seeds (Pisum proportion of from 0.01% to 5% by weight relative to the sativum) marketed by LSN under the trademark total weight of the composition. Parelastyl(R), and heparinoids and pseudodipeptides. 0134) The compositions containing the lysyl and/or pro 0.143 Among the active agents that stimulate epidermal lyl hydroxylase inhibitor and the 7-oxo-DHEA derivative of macromolecules, Such as fillagrin and keratins, especially formula (I) are advantageously used for treating alopecia. representative are the extract of lupin marketed by Silab 0135 7. Agents for Stimulating the Synthesis of Dermal under the trademark Structurine(E; the extract of beech or Epidermal Macromolecules and/or for Preventing Their Fagus Sylvatica buds marketed by Gattefosse under the Degradation: trademark Gatuline(R), and the extract of the Zooplankton 0.136 Among the active agents for Stimulating dermal Salina marketed by Seporga under the trademark GP4G(R). macromolecules, exemplary are those that act: 0144. The compositions according to the invention con 0137 (a) either on collagen synthesis, such as taining one or more of the above compounds are particularly extracts of Centella asiatica, asiaticosides and Suitable for preventing or treating the Signs of aging of the derivatives thereof; ascorbic acid or vitamin C and skin, in particular loSS of firmness and/or elasticity of the derivatives thereof; synthetic peptides Such as lamin, skin. biopeptide CL or the palmitoyloligopeptide mar 0145 8. Agents for Stimulating the Proliferation of keted by Sederma; peptides extracted from plants, Fibroblasts or Keratinocytes and/or Keratinocyte Differen Such as the Soybean hydrolysate marketed by tiation: Coletica under the trademark Phytokine(R); plant hor mones Such as auxins and cinnamic acid and deriva 0146 Exemplary agents for stimulating the proliferation tives thereof, as described in the European patent of fibroblasts that may be formulated into the compositions application published under No. 0.925,779; of the invention include plant proteins or polypeptides, extracts, especially of Soybean (for example an extract of 0138 (b) or on elastin synthesis, such as the extract soybean marketed by LSN under the trademark Eleseryl of Saccharomyces cerivisiae marketed by LSN under SH-VEG 8(R) or marketed by Silab under the trademark the trademark Cytovitin(R); and the extract of the alga Raffermine(E); and plant hormones Such as giberrellins and Macrocystis pyrifera marketed by SECMA under the cytokinins. trademark KelpadelieCR; 0147 The agents for stimulating keratinocyte prolifera 0.139 (c) or on glycosaminoglycan Synthesis, Such tion that may be formulated into the compositions according as the product of fermentation of milk with Lacto to the invention especially comprise retinoids Such as retinol bacillus vulgaris, marketed by Brooks under the and its esters, including retinyl palmitate; extracts of nut trademark Biomin yogourthE); the extract of the cakes marketed by Gattefosse, and extracts of Solanum brown alga Padina pavonica marketed by Alban tuberosum marketed by Sederma. Miller under the trademark HSP3(E); and the extract of Saccharomyces cerevisiae available from Silab 0.148. The agents for stimulating keratinocyte differen under the trademark Firmalift(E) or from LSN under tiation comprise, for example, minerals Such as calcium; the the trademark Cytovitin(R); extract of lupin marketed by Silab under the trademark Photopreventine(R); sodium beta-sitosteryl sulfate marketed 0140 (d) or on fibronectin synthesis, such as the by Seporga under the trademark Phytocohesine(R); and the extract of the Zooplankton Salina marketed by extract of corn marketed by Solabia under the trademark Seporga under the trademark GP4G(R); the yeast Phytovityl(R). extract available from Alban Miller under the trade mark Drieline(E); and the palmitoyl pentapeptide 014.9 The compositions according to the invention com marketed by Sederma under the trademark prising these compounds are preferably used for preventing Matrixil(R); or treating the Signs of aging of the skin. US 2003/0054021 A1 Mar. 20, 2003

0150. 9. Muscle Relaxants: grafted polydimethylsiloxane. Such grafted Silicone 0151. The muscle relaxants that may be included in the polymers are marketed by 3M under the trademark compositions according to the invention comprise calcium VS 80, VS 70 or LO21. inhibitorS Such as alverine and its Salts, chlorine-channel 0162 (2) soybean or wheat plant proteins, and/or openerS Such as diazepam, and catecholamine and acetyl 0163 (3) sodium magnesium silicates (Laponites). choline inhibitors, Such as the hexapeptide argireline R 0164. The compositions according to the invention com marketed by Ilipotec. prising the above tensioning agents are well Suited for 0152 The compositions of the invention comprising treating the Signs of aging of the skin, in particular wrinkles these compounds are used for preventing or treating the and fine lines. Signs of aging of the Skin and in particular wrinkles. 0.165 12. Anti-pollution Agents or Free-radical Scaven 0153. 10. Antimicrobial Agents: gerS. 0154) Exemplary antimicrobial agents that may be for 0166 By the term “anti-pollution agent” is intended any mulated into the compositions according to the invention compound capable of trapping OZone, monocyclic or poly include 2,4,4-trichloro-2'-hydroxydiphenyl ether (or tri cyclic aromatic compounds Such as benzopyrene and/or closan), 3,4,4'-trichloro-banilide, phenoxyethanol, phenox heavy metals Such as cobalt, mercury, cadmium and/or ypropanol, phenoxy-isopropanol, hexamidine isethionate, nickel. By the term “free-radical Scavenger' is intended any metronidazole and its Salts, micronazole and its Salts, itra compound capable of trapping free radicals. conazole, terconazole, econazole, ketoconazole, Sapercona 0.167 Exemplary ozone-trapping agents that may be for Zole, fluconazole, clotrimazole, butoconazole, oxiconazole, mulated into the compositions according to the invention Sulphaconazole, Sulconazole, terbinafine, ciclopiroX, ciclo are, in particular, Vitamin C and derivatives thereof, includ piroXolamine, undecylenic acid and its Salts, benzoyl per ing ascorbyl glucoside; phenols and polyphenols, in particu oxide, 3-hydroxybenzoic acid, 4-hydroxy-benzoic acid, lar tannins, elagic acid and tannic acid; epigallocatechin and phytic acid, N-acetyl-L-cysteine acid, lipoic acid, azelaic natural extracts containing Same; extracts of olive tree leaf; acid and its Salts, arachidonic acid, resorcinol, 2,4,4'- extracts of tea, in particular of green tea; anthocyans, trichloro-2'-hydroxydiphenyl ether, 3,4,4'-trichlorocarba extracts of rosemary; phenol acids, in particular chlorogenic nalide, OctopiroX, Octoxyglycerine, octanoylglycine, capry acid; Stilbenes, in particular resveratrol; Sulfur-containing lyl glycol, 10-hydroxy-2-decanoic acid, amino acid derivatives, in particular S-carboxymethylcyS dichlorophenylimidazole dioxolane and its derivatives teine; ergothioneine, N-acetylcysteine, chelating agents, for described in WO-93/18743, farnesol and phytosphingosines, instance N,N'-bis(3,4,5-trimethoxybenzyl)ethylenediamine and mixtures thereof. or one of its Salts, metal complexes or esters, carotenoids O155 The preferred antimicrobial agents are triclosan, Such as crocetin; and various starting materials, for instance phenoxyethanol, octoxyglycerine, octanoyl-glycine, 10-hy the mixture of arginine, histidine ribonucleate, mannitol, droxy-2-decanoic acid, caprylylglycol, farneSol and azelaic adenosine triphosphate, pyridoxine, phenyl-alanine, tyrosine acid. and hydrolysed RNA, marketed by Laboratoires Sérobi ologiques under the trademark CPP LS 2633-12F(R), the 0156 By way of example, the antimicrobial agents may water-soluble fraction of corn marketed by Solabia under the be formulated into the compositions of the invention in trademark Phytovityle), the mixture of extract of fumitory amounts advantageously representing from 0.1% to 20% and of extract of lemon marketed under the trademark and preferably from 0.1% to 10% of the total weight of the Unicotrozon C-49(R) by Induchem, and the mixture of composition. extracts of ginseng, of apple, of peach, of wheat and of barley, marketed by Provital under the trademark Pronalen O157 The compositions containing the 7-oxo-DHEA Bioprotect(R). derivative of formula (I) and the antimicrobial agent are particularly Suitable for treating acne-prone greasy skin, 01.68 Exemplary agents for trapping out monocyclic or acne or dandruff of the Scalp. polycyclic aromatic compounds according to the invention are, in particular, tannins Such as elagic acid; indole deriva 0158 11. Tensioning Agents: tives, in particular 3-indolecarbinol; extracts of tea, in par 0159. By the term “tensioning agent” is intended a com ticular of green tea, extracts of water hyacinth or Eichhornia pound capable of exerting tension on the skin, the effect of crasSipes, and the water-Soluble fraction of corn marketed which is to temporarily fade out irregularities on the skin's by Solabia under the trademark Phytovityle. Surface, Such as wrinkles and fine lines. 0169 Finally, exemplary heavy-metal-trapping agents 0160 Among the tensioning agents that may be formu that may be formulated into the compositions according to lated into the compositions of the present invention, espe the invention include, in particular, chelating agents Such as cially representative are: EDTA, the pentasodium salt of ethylenediamine tetrameth ylenephosphonic acid, and N,N'-bis(3,4,5-trimethoxyben 0161 (1) polyurethane latices or acrylic-silicone Zyl)ethylenediamine or one of the Salts, metal complexes or latices, in particular those described in EP-1,038, esters thereof; phytic acid; chitosan derivatives, extracts of 519, Such as a propylthio(polymethylacrylate), pro tea, in particular of green tea; tannins Such as elagic acid; pylthio(polymethyl methacrylate) or propylthi Sulfur-containing amino acids Such as cysteine; extracts of O(polymethacrylic acid) grafted polydimethyl water hyacinth (Eichhornia crassipes); and the water Siloxane, or alternatively a propylthio(polyisobutyl soluble fraction of corn marketed by Solabia under the methacrylate) and propylthio(polymethacrylic acid) trademark Phytovityle). US 2003/0054021 A1 Mar. 20, 2003

0170 The free-radical scavengers that may be included in methylenebis(5-(2H-benzotriazol-2-yl)-4-(1,1,3,3- the compositions according to the invention comprise, other tetramethylbutyl)phenol available from Ciba Geigy than certain anti-pollution agents indicated above, Vitamin E under the trademark Tinosorb M, and derivatives thereof Such as tocopheryl acetate; biofla vonoids, coenzyme Q10 or ubiquinone; certain enzymes, for 0189 (3) benzene-1,4-bis(3-methylidene-10-cam example, catalase, Superoxide dismutase, lactoperoxidase, phorSulfonic acid), optionally in partially or totally glutathione peroxidase and quinone reductases, glutathione; neutralized form, and benzylidenecamphor; benzylcyclanones; Substituted naptha 0.190 (4) mixtures thereof. lenones, pidolates, phytanetriol, gamma-ory Zanol, lignans, 0191 Exemplary compounds for screening out UVB and melatonin. radiation include: 0171 The compositions of the invention comprising the 0192 (1) salicylic acid derivatives, in particular anti-pollution agents and/or free-radical Scavengers indi homomenthyl Salicylate and octyl Salicylate; cated above are well Suited for preventing or treating the Signs of aging of the skin, in particular wrinkles, and loSS of 0193 (2) cinnamic acid derivatives, in particular firmness and elasticity of the skin and dehydration. AS a 2-ethylhexyl p-methoxycinnamate, available from variant, Same are useful for preventing or treating a dull Givaudan under the trademark Parsol MCX; complexion. 0194 (3) liquid B.B'-derivatives, in particular 2-eth 0172 13. UVA and/or UVB Screening Agents and ylhexyl C-cyano-C.f3'-diphenylacrylate, or Octoc Optionally Coated Inorganic Pigments: rylene, available from BASF under the trademark Uvinul N539; 0173 The compositions according to the invention may contain one or more UV-Screening agents capable of Screen 0195 (4) p-aminobenzoic acid derivatives; ing out UVA and/or UVB radiation. 0196) (5) 4-methylbenzylidenecamphor available 0.174 Exemplary compounds for screening out UVA from Merck under the trademark EuSolex 6300; radiation include, especially: 0197) (6) 2-phenylbenzimidazole-5-sulfonic acid marketed under the trademark “Eusolex 232' by 0175 (1) benzophenone derivatives, for example: Merck; 0176) 2,4-dihydroxybenzophenone (benzophe 0198 (7) 1,3,5-triazine derivatives, in particular: none-1); 0199 2,4,6-trisp-(2-ethylhexyl-1'-oxycarbony 0177) 2,2,4,4-tetrahydroxybenzophenone l)anilino-1,3,5-triazine, available from BASF (benzo-phenone-2); under the trademark Uvinul T150, and 0.178 2-hvdroXV-4-methoxvbenzophenoney y y p 0200 the compound having the formula (A) (benzo-phenone-3), available from BASF under below: the trademark Uvinul M40; 0179 2-hydroxy-4-methoxybenzophenone-5-sul fonic acid (benzophenone-4) and also its Sulfonate (A) form (benzophenone-5), available from BASF under the trademark Uvinul MS40; 0180 2,2'-dihydroxy-4,4'-dimethoxybenzophe none (benzophenone-6); 0181 5-chloro-2-hydroxybenzophenone (ben Zophenone-7); NH 0.182) 2,2'-dihydroxy-4-methoxybenzophenone (benzo-phenone-8); 1s N 0183 the disodium salt of 2,2'-dihydroxy-4,4'- O O dimethoxybenzophenone-5,5-disulfonic acid RO-C NH l Nels NH C-OR (benzophenone-9); 0.184 2-hydroxy-4-methoxy-4'-methylbenzophe none (benzophenone-10); 0201 in which R" is a 2-ethylhexyl radical and R is a tert-butyl radical, available from Sigma 3V under the trade 0185 benzophenone-11; mark Uvasorb HEB; 0186 2-hydroxy-4-(octyloxy)benzophenone (benzo-phenone-12); 0202) (8) mixtures thereof. 0203 Exemplary compounds for screening out UVA and 0187 benzophenones 3 and 5 being preferred; UVB radiation are, in particular: 0188 (2) triazine derivatives, and in particular 2,4- 0204 (1) plant extracts, in particular of rosemary bis(4-(2-ethylhexyloxy)-2-hydroxyphenyl-6-(4- (roSmarinic acid) and of the genus Leontopodium, in methoxy-phenyl)-1,3,5-triazine available from Ciba particular a plant species Leontopodium alpinum or Geigy under the trademark Tinosorb S and 2,2'- LeOntopodium Stracheyi, US 2003/0054021 A1 Mar. 20, 2003

0205 (2) the benzotriazole silicone having the gen dine Sulfate, Apamine, Cyproheptadine, Loperamide eral formula (B) below: and N-acetylprocainamide 0218 (9) potassium-channel openers, especially Minoxidil and derivatives thereof. (B) 0219. In addition to the compound(s) described above, HC-Si-O-Si-O-Si-CH the compositions according to the invention generally con tain an effective amount of 7-oxo-DHEA derivatives of CH CH formula (I) as defined above, that is sufficient to elicit the HC desired effect. It thus contains, for example, from 0.00001% to 10% by weight of the 7-oxo-DHEA derivative of formula HO (I), relative to the total weight of the composition, and 2N preferably from 0.001% to 5% by weight of the 7-oxo N DHEA derivative of formula (I) relative to the total weight S. M of the composition. N 0220. This invention also features novel 7-oxo-DHEA CH derivatives of formula (I) that may be formulated into cosmetics and that are readily Synthetically available, espe cially by carrying out one of the processes more fully 0206. This benzotriazole silicone, and also the method described hereinbelow. for preparing it, are especially described in FR-A-2,642,968. 0221) Thus, the present invention features novel 7-oxo 0207 Exemplary optionally coated inorganic pigments DHEA compounds of general formula (I) described above, include nanopigments of titanium dioxide, of iron oxide, of comprising: Zinc oxide, of Zirconium oxide or of cerium oxide optionally coated with alumina and/or with aluminum Stearate. O222 a group O=P(OH)OR"U= Withwith theth exception o f the O=P(OH) group and the O=P(OH)OCOCH 0208. 14. Compounds of Neurogenic Origin for Reduc grOup, ing Irritation: 0209 Exemplary compounds of neurogenic origin for 0223) a group (O)SOR" with the exception of the reducing irritation include: Na. SOH group and the SOH group; 0210 (1) Substance Pantagonists and in particular 0224 a traKVISIialkylsilyl groupOU (SiR) inIn Whichwhich the 3 those described in EP-0,680,749, extracts of at least groups R' may be identical or different, with the one non-photosynthetic filamentous bacterium, par exception of the tBu Si(Me) group; ticularly strains of Vitreoscilla filiformis described in 0225 an alkyloxycarbonyl group (ROCO) with the EP-0,761,204, the spring waters described in EP-0, exception of the CHOCO group; 764,440, extracts of at least one plant of the Rosacea family, particularly of the Species ROSa gallica 0226 an alkylaminocarbonyl group (R'NHCO) described in the European patent application pub wherein the alkyl moiety is necessarily Substituted with one or more of the groups -OR" and/or -SR' lished under No. 0,906,752 and the alkaline earth and/or -COOR" and/or -NR'R' and/or halogen metals described in the European patent applications and/or Sulfate and/or phosphate and/or glycoside published under Nos. 0.737,471 and 0.770,302; and/or aryl and/or heterocycle, Such heterocycle 0211 (2) CGRP antagonists, in particular those preferably being an indole, a pyrimidine, a piperi described in EP-0,765,668 and especially Iridacea dine, a morpholine, a pyran, a furan, a piperazine, or extracts, particularly of the Species Iris pallida, a pyridine, 0212 (3) NO-synthase inhibitors; 0227 in which RR", -NR'R' and -NR"R" have the 0213 (4) bradykinin antagonists and in particular Same definitions as described above; and compounds of those described in the European patent application formula (I) selected from among: published under No. 0,909,556; 0228 3B-O-pentanoyl-7-oxo-dehydroepiandroster 0214 (5) cytokine antagonists; One, 0215 (6) histamine antagonists; 0229) 33-O-hexanoyl-7-oxo-dehydroepiandroster 0216 (7) antagonists of interleukin 1 and/or of One, tumor necrosis factor of C. type (TNFC) and in 0230 3B-O-octanoyl-7-oxo-dehydroepiandroster particular those described in the European patent One, applications published under Nos. 0.892,642 and 0231 3B-O-nonanoyl-7-oxo-dehydroepiandroster 0.764,444, particularly peptide Modulene, the trip eptide Lysine-Proline-Valine (KPV) and an extract One, of at least one plant from the Labiae family, particu 0232 3B-O-decanoyl-7-oxo-dehydroepiandroster larly of the Species ROSmarinus Oficinalis, One, 0217 (8) sodium-channel blockers preferably 0233 3B-O-myristoyl-7-oxo-dehydroepiandroster Selected from among: Amiloride, Quinidine, Quini One, US 2003/0054021 A1 Mar. 20, 2003

0234 33-O-arachidoyl-7-oxo-dehydroepiandroster 0261 3f6-O-(1-butyldiphenylsilyl)-7-oxo-dehydroe One, piandrosterone; 0235 3B-O-docosanoyl-7-oxo-dehydroepiandros 0262 3,3-O-(trimethylsilyl)-7-oxo-dehydroepi terone, androsterone. 0236 3.B-O-lignoceroyl-7-oxo-dehydroepiandros 0263. This invention also features compositions compris terone, ing, in a physiologically acceptable medium, at least one 0237 3B-O-oleoyl-7-oxo-dehydroepiandrosterone; novel 7-oxo-DHEA derivative as defined above. 0238 3B-O-linoleoyl-7-oxo-dehydroepiandroster 0264. Too, the compositions according to the invention One, may comprise the novel 7-OXO-DHEA compounds as described above either alone or as mixtures in all propor 0239) 3B-O-linolenoyl-7-oxo-dehydroepiandroster tions. One, 0240 3B-O-petroselinoyl-7-oxo-dehydroepiandros 0265. The amount of novel 7-oxo-DHEA derivatives as described above that may be formulated into the composi terone, tions according to the invention obviously depends on the 0241 3B-O-methyl-7-oxo-dehydroepiandrosterone; desired effect and must be in an effective amount that is 0242 3B-O-ethyl-7-oxo-dehydroepiandrosterone; Sufficient to obtain or elicit the desired effect. 0243 3B-O-carboxymethyl-7-oxo-dehydroepi 0266 To provide an order of magnitude, the composi androsterone; tions of the invention advantageously contain at least one novel 7-oxo-DHEA derivative as described above in an 0244 33-O-glucosyl-7-oxo-dehydroepiandroster amount representing from 0.00001% to 10% of the total One, weight of the composition and preferably in an amount 0245 3,B-O-(2-tetrahydrofuranyl)-7-oxo-dehydroe representing from 0.001% to 5% of the total weight of the piandrosterone; composition. 0246 3.B-O-(trifluoroacetyl)-7-oxo-dehydroepi 0267 The novel DHEA compounds are readily synthe androsterone; sized: Said compounds are prepared in one Step from 7-OXO 0247 3/8-O-(4-cyclopentylbutanoyl)-7-oxo-dehy DHEA, especially via various synthetic methods that will be droepiandrosterone, more fully described hereinbelow. 0268. The 7-oxo-DHEA, which constitutes one of the 0248 3,B-O-(3,4-dihydroxybenzoyl)-7-oxo-dehy Starting materials used in Said Synthetic methods, is itself droepiandrosterone. obtained in two steps from 3.f3-O-acetyl-DHEA. 0249 Among the novel derivatives of formula (I), the 0269. The first step is an oxidation reaction in the allylic following compounds are most particularly preferred: position of 3f-O-acetyl-DHEA according to a technique 0250 3B-O-7-oxo-dehydroepiandrosterone glyci described, for example, in Tetrahedron Letters, 1997, 38, nate, 119-122, which permits obtaining 3 B-O-acetyl-7-oxo 0251 3B-O-7-oxo-dehydroepiandrosterone lysi DHEA nate, 0270. The second step is a deprotection reaction which prepares 7-oxo-DHEA from the 3.3-O-acetyl-7-oxo-DHEA 0252 3B-O-7-oxo-dehydroepiandrosterone serin obtained in the preceding Step by a transesterification reac ate, tion, which essentially entails dissolving the 3B-O-acetyl-7- 0253) 3 B-O-7-oxo-dehydroepiandrosterone OXO-DHEA in an alcoholic Solvent, adding an alkali metal C-glutamate; alkoxide, Stirring the reaction medium and then, after reac tion, processing the reaction medium under conditions con 0254 3B-O-7-oxo-dehydroepiandrosterone C.-as ventionally employed in organic chemistry, the residue partate, obtained being recrystallized or purified on a column of 0255 3 B-O-(2-hydroxymalonyl)-7-oxo-dehydroe Silica. piandrosterone; 0271 According to the invention, by the expression 0256 3.B-O-(2-malonylaminocarbonyl)-7-oxo-de “inert atmosphere' is intended argon or nitrogen and by the hydro-epiandrosterone; expression "room temperature' is intended a temperature 0257 3/8-O-(2-succinylaminocarbonyl)-7-oxo-de ranging from between 15 to 25 C. hydro-epiandrosterone; 0272. The purification techniques that may optionally be employed at the end of each of the Steps of the processes 0258 3,B-O-(2-glutarylaminocarbonyl)-7-oxo-dehy according to the invention are performed according to dro-epiandrosterone; Standard methodology of organic Synthesis. 0259) 3 B-O-(ascorbyl phosphate)-7-oxo-dehydroe piandrosterone; 0273) The novel 7-keto-DHEA compounds described above are obtained in one step from 7-oxo-DHEA according 0260 3.3-O-(ascorbyl sulphate)-7-oxo-dehydroepi to various synthetic methods that will now be more fully androsterone; described. US 2003/0054021 A1 Mar. 20, 2003

0274. According to one preferred embodiment of the materials. Such as the skin, the hair, the eyelashes or the nails. invention, a first general method for Synthesizing the novel They may be in any presentation form normally used for this 3f6-O-alkylcarbonyl-7-oxo-DHEA derivatives entails plac type of application, especially in the form of an aqueous or ing 7-OXO-DHEA in a polar aprotic Solvent and then adding oily Solution, an oil-in-water or water-in-oil emulsion, a an organic base and an acid chloride thereto. After reaction Silicone emulsion, a microemulsion or nanoemulsion, an and processing the reaction medium under conditions con aqueous or oily gel or a liquid, pasty or Solid anhydrous ventionally employed in organic chemistry, the residue product. obtained is then crystallized or purified on a column of Silica. 0283 The subject compositions may be more or less fluid and may have the appearance of a white or colored cream, 0275. The acid chlorides not commercially available may an ointment, a milk, a lotion, a Serum, a paste, a mousse or be prepared via Standard methods of organic chemistry. a gel. They may optionally be topically applied onto the skin 0276 According to another preferred embodiment of the in the form of an aerosol, a patch or a powder. They may also invention, a Second general method for Synthesizing the be in solid form, for example, in the form of a stick. They novel 3 B-O-alkylcarbonyl-7-oxo-DHEA compounds entails may be used as care products and/or as makeup products for adding a carbonyldiimidazole dissolved in a polar aprotic the skin. Alternatively, they may be formulated as Shampoos Solvent to carboxylic acid dissolved in the same Solvent, and or conditioners. then, to the Solution Stirred without heating, adding 7-OXO 0284. In known fashion, the compositions of the inven DHEA dissolved in the same solvent, stirring the mixture tion may also contain additives and adjuvants that are under cold conditions and then at room temperature over common in cosmetics, Such as hydrophilic or lipophilic night and then, after reaction, processing the reaction gelling agents, preservatives, antioxidants, Solvents, fra medium under conditions conventionally employed in grances, fillers, pigments, odor absorbers and dyestuffs. The organic chemistry, and the residue is then purified by chro amounts of these various additives and adjuvants are those matography or by recrystallization. conventionally employed in the field under consideration, 0277 According to another preferred embodiment of the and range, for example, from 0.01% to 20% of the total invention, a general method for Synthesizing the novel weight of the composition. Depending on their nature, these 3f6-O-alkyl-7-oxo-DHEA derivatives entails placing 7-oxo additives and adjuvants may be introduced into the fatty DHEA in a polar aprotic Solvent and then adding an alkali phase or into the aqueous phase. These additives and adju metal hydride under cold conditions, Stirring the reaction Vants, and the concentrations thereof, must be Such that they medium and then, after adding an alkyl halide, maintaining do not adversely affect the advantageous properties of the the reaction medium at room temperature, and, after reac 7-oxo-DHEA derivatives of formula (I) according to the tion, processing the reaction medium under conditions con invention. ventionally employed in organic chemistry, and the residue 0285) When the composition according to the invention is obtained is then recrystallized or purified on a column of an emulsion, the proportion of the fatty phase advanta Silica. geously ranges from 2% to 80% by weight and preferably 0278. According to yet another preferred embodiment of from 5% to 50% by weight relative to the total weight of the the invention, a general method for Synthesizing the 7-keto composition. The fatty Substances, emulsifiers and co-emul DHEA carbamates entails placing 7-oxo-DHEA in an anhy sifiers included in the composition in emulsion form are drous aprotic Solvent, heating the reaction medium after Selected from among those conventionally formulated in the addition, under inert atmosphere, of an isocyanate and an field under consideration. The emulsifier and co-emulsifier organic base, and, after reaction, processing the reaction are preferably present in the composition in a proportion medium under conditions conventionally employed in ranging from 0.3% to 30% by weight and preferably from organic chemistry, and the residue obtained is then recryS 0.5% to 20% by weight relative to the total weight of the tallized or purified by chromatography. composition. 0279 Specific examples of the preparation of the novel 0286 Exemplary fatty Substances according to the inven 7-OXO-DHEA compounds according to the invention are Set tion include the oils and especially mineral oils (liquid forth in the examples to follow. petroleum jelly), oils of plant origin (avocado oil, Soybean 0280 The compositions according to the invention are oil), oils of animal origin (lanolin), Synthetic oils (perhy well Suited for cosmetic or pharmaceutical applications, droSqualene), Silicone oils (cyclomethicone) and fluoro oils particularly dermatological use. Preferably, the composi (perfluoro polyethers). Fatty alcohols Such as cetyl alcohol, tions of the invention are well Suited for cosmetic applica fatty acids, waxes and gums and in particular Silicone gums tions. are also representative fatty Substances. 0281. The compositions according to the invention may 0287 Exemplary emulsifiers and co-emulsifiers accord be administered for cosmetic purposes, to improve the ing to the invention include fatty acid esters of polyethylene appearance of keratin materials, in particular to prevent or glycol, such as PEG-100 stearate, PEG-50 Stearate and treat the adverse signs of aging of the skin and/or a dull PEG-40 Stearate; fatty acid esters of polyols, Such as glyc complexion and/or skin or hair pigmentation disorders and/ eryl Stearate, Sorbitan triStearate and oxyethylenated Sorbitan or skin dryneSS and/or hyperSeborrhoea and/or hyperSebor Stearates commercially available under the trademark rhoea-related imperfections and/or Sensitive skin and/or Tween(E) 20 or Tween(F) 60, for example; and mixtures dandruff and/or natural hair loSS and/or baldness. thereof. 0282. The compositions according to the invention are 0288 And exemplary hydrophilic gelling agents include preferably formulated for topical application to keratin in particular, carboxyvinyl polymers (carbomer), acrylic US 2003/0054021 A1 Mar. 20, 2003 copolymerS Such as acrylate/alkyl acrylate copolymers, until completely dissolved, and the temperature was then polyacrylamides, polysaccharides, natural gums and clayS. reduced to 40 C. The constituents of phase C were mixed Exemplary lipophilic gelling agents include, in particular, together at 50 C. Phase B was then introduced into phase modified clays, for example bentones, metal Salts of fatty A at 40 C. with stirring, and phase C was then added acids and hydrophobic Silica. thereto. 0289. The present invention also features a cosmetic regime/regimen for treating keratin Substrates by topical 0296. The above composition rehydrates dry skin and application thereon of a composition containing, formulated renders it Smooth. into a physiologically acceptable medium (vehicle, diluent or carrier), at least one 7-oxo-DHEA derivative having the above formula (I), either alone or in combination with at Composition 2; Moisturizing Cream: least one other compound as described above. The composition below was formulated in conventional manner. 0290 This invention relates more particularly to a cos Phase A: metic regime or regimen for treating the adverse Signs of Demineralized water CS 100% aging of the skin and/or a dull complexion and/or skin or Preservatives O.5% hair pigmentation disorders and/or skin dryneSS and/or Carbomer O.4% hyperSeborrhoea and/or hyperSeborrhoea-related imperfec Glycerol 7.0% tions and/or Sensitive skin and/or dandruff and/or natural Phase B1: hair loSS and/or baldness, comprising the topical application Oxyethylenated (200 EO) sorbitan stearate O.9% onto the skin or the hair, for Such period of time as required Phase B2: to elicit the desired cosmetic/therapeutic response, of a composition containing, formulated into a physiologically PEG-100 stearate and glyceryl stearate 2.1% Isononyl isononanoate 10.0% acceptable medium, at least one 7-oxo-DHEA derivative Petroleum jelly 2.0% having the above formula (I), either alone or in combination Octyldodecanol 10.0% with at least one other compound as described above. 3B-O-sulfonyl-7-oxo-DHEA O.2% Butylhydroxytoluene O.1% 0291 Each citation indicated above, whether of the open UV-screening agent 1.0% literature, patent, patent application, or otherwise, is hereby Ceramides O.5% expressly incorporated by reference. Phase C: Water 2.0% 0292. In order to further illustrate the present invention Triethanolamine O.5% and the advantages thereof, the following Specific examples Urea 1.0% are given, it being understood that same are intended only as This cream is useful for caring for dry skin. illustrative and in nowise limitative. Composition 3; Anti-Aging Cream: 0293. In said examples to follow, all parts and percent ages are given by weight. Phase A: Acrylate/Co-so acrylate copolymer O.5% EXAMPLE 1. Water 12.0% 0294. This example describes a variety of specific com Phase B: positions according to the invention. Isononyl isononanoate 5.0% 3B-O-(2-Malonylaminocarbonyl)-7-oxo-DHEA O.5% Cyclohexasiloxane 5.0% Octyl methoxycinnamate 1.0% Composition 1; Moisturizing Cream: Phase C: Phase A: Triethanolamine 1.0% Glycerol 6.0% Acrylate/Co-so acrylate copolymer O.5% Preservatives O.5% Water 12.0% Polyacrylamide and C13-14 isoparaffin and laureth-7 1.0% Phase B: Water CS 100% Hydrogenated polyisobutene 5.0% 3f-O-7-oxo-DHEA C-glutamate O.5% Cyclohexasiloxane 6.0% 0297. This composition was prepared in the following Phase C: manner. The polymer of phase A was dispersed in water at Triethanolamine 1.0% 40° C. The constituents of phase B were heated to 70° C. Glycerol 6.0% until completely dissolved, and the temperature was then EDTA O.2% reduced to 40 C. The constituents of phase C were mixed Preservatives O.5% Glycine 2.0% together at 50 C. Phase B was then introduced into phase Polyacrylamide and C-1 isoparaffin and laureth-7 1.0% A at 40 C. with stirring, and phase C was then added Water CS 100% thereto. 0298 This cream is advantageously topically applied 0295) This composition was prepared in the following once or twice a day for treating the Signs of aging of the skin, manner. The polymer of phase A was dispersed in water at and in particular for reducing or fading out wrinkles and fine 40° C. The constituents of phase B were heated to 70° C. lines. US 2003/0054021 A1 Mar. 20, 2003 13

EXAMPLE 2 0299 Synthesis of 3 B-O-acetyl-7-oxo-DHEA Composition 4: Anti-Aging Cream: The composition below was formulated in conventional manner.

Phase A:

Demineralized water CS 100.0% Preservatives 0.5% Carbomer O.4% Glycerol 7.0% Phase B1: Oxyethylenated (200 EO) sorbitan stearate O.9% t Phase B2: PEG-100 stearate and glyceryl stearate 2.1% 0300 Asolution of 10 g of 3|B-O-acetyl-DHEAin 200 ml Isononyl isononanoate 10.0% of acetonitrile was prepared. 60 mg of copper iodide (CuI) Octyldecanol 10.0% 3f-O-Butanoyl-7-oxo-DHEA O.2% were added thereto under an inert atmosphere. The Solution Butylhydroxytoluene O.1% was cooled to between 5 and 10° C. and 19.6 ml of 80% UV-screening agent 1.0% t-BuOOH were added dropwise. At the end of the addition, Phase C: the reaction medium was allowed to return to room tem Water 2.0% perature and was stirred for 2 hours, followed by heating at Triethanolamine 0.5% 50° C. for 20 hours. The reaction medium was then cooled Extract of Centella asiatica 1.0% and poured into 300 g of 10% sodium bicarbonate Palmitoyl pentapeptide O.1% Matrixwly (R) marketed bwy Sederma (NaHCO) solution. This mixture was extracted three times This cream is useful as a firming day cream. with diethyl ether and the organic Solution was then washed with saturated NaHCO Solution, and then with saturated Composition 5; Gel For Cleansing Greasy Skin: sodium chloride (NaCl) solution. After drying and evapo The following composition was formulated in conventional manner. rating to dryness, the crude product was obtained in the form of a Solid. The residue was recrystallized from an acetone/ Lauryl phosphate 6.50% hexane mixture. Decyl glucoside 16.25% Polyquaternium-7 5.70% Oxyethylenated (150 EO) pentaerythrityl tetrastearate O.50% 0301 (a) Melting point: 190-192 C.; Glycerol 3.50% Sorbitol 3.50% 0302) (b) Yield: 91%; Potassium hydroxide 1.70% Hydroxypropylcellulose O.20% 0303 (c) C=-76 (methanol); Disodium EDTA O.05% 0304) (d) H NMR and mass spectrometry in agree Sodium chloride O.10% ment. 3f-O-heptanoyl-7-oxo-DHEA O.10% Preservatives O.30% Water CS 100% EXAMPLE 3 This gel is useful to control the secretions of sebum and to attenuate skin imperfections. 0305 Synthesis of 7-oxo-DHEA Composition 6: Anti-Blemish Patch: A patch comprising the composition below was assembled:

Water 40.0% Alcohol CS Glycerol 7.0% 3f-O-(ascorbyl sulfate)-7-oxo-DHEA 0.5% Polyvinyl alcohol 5.0% Kojic acid 0.5% HO O This patch may be applied to the hands and the neckline to fade out pigmentary marks, in particular age marks. Composition 7; Lotion For Preventing Hair Loss: 0306 A solution of 3 B-O-acetyl-7-oxo-DHEA obtained The composition below was formulated in conventional manner. in Example 2 in methanol was prepared. 1 molar equivalent of sodium methoxide (NaOMe) was added and the mixture Water 25.0% was stirred for a period of between 3 and 12 hours. The Glycerol 7.0% 3f-O-Stearoyl-7-oxo-DHEA 0.5% methanol was evaporated off and the residue was diluted Alcohol CS 100% with water and extracted with dichloromethane. The organic This lotion is effective for preventing natural hair loss. Solution was dried and then evaporated to dryneSS. The residue was purified by chromatography to give the 7-OXO DHEA US 2003/0054021 A1 Mar. 20, 2003 14

EXAMPLE 4 0307 Synthesis of 3 B-O-linoleoyl-7-oxo-DHEA

O HC (CH2)3us O

0308) 1 equivalent of 7-oxo-DHEA obtained in Example romethane at 0° C. 0.5 mmol of carbonyldiimidazole dis 3 was dissolved in 70 ml of dichloromethane in a reactor. 1.5 Solved in 2 ml of dichloromethane was added. The Solution equivalents of triethylamine and 1.25 equivalents of linoleic was stirred at 0° C. for 20 minutes, followed by addition of acid chloride were then added. The mixture was reacted at 0.45 mmol of 7-oxo-DHEA (obtained in Example 3) dis room temperature for 20 hours. The medium was then Solved in 2 ml of dichloromethane. The mixture was stirred diluted with dichloromethane, washed with Saturated at 0° C. for 1 hour and then at room temperature for 15 NaHCO, solution and then washed a second time with water. hours. The reaction medium was evaporated to dryneSS and The organic phase was dried over Sodium Sulfate, filtered then taken up in 5 ml of ethyl acetate. The solution was and concentrated to dryneSS under vacuum. The residue washed with 5 ml of Saturated acqueous NaCl Solution, then obtained was recrystallized or purified on a column of Silica. with 5 ml of 1N sulfuric acid, then with 5 ml of water, then EXAMPLE 5 with 5 ml of Saturated aqueous Sodium bicarbonate Solution and then with 5 ml of water. The residual organic phase was 0309 Synthesis of 3 B-O-methyl-7-oxo-DHEA dried over Sodium Sulfate and then evaporated to dryneSS. The residue was purified by chromatography on a column of O Silica to give the protected expected product. 0313 Deprotection was carried out by treatment with 2 ml of a dichloromethane/trifluoroacetic acid mixture (1:1 ratio) for 30 minutes at room temperature. The mixture was then evaporated to dryness to give 3.f3-O-7-oxo-DHEA MeO O C-glutamate. 0310 1 equivalent of 7-oxo-DHEA obtained in Example EXAMPLE 7 3 was dissolved in 70 ml of dimethylformamide in a reactor. 0314 Synthesis of 3.3-O-(2-glutarylaminocarbonyl)-7- 1.2 equivalents of sodium hydride (60% in oil) was then OXO-DHEA added at 0° C. and the mixture was stirred for half an hour. 1.5 equivalents of methyl iodide were then added and the mixture was reacted at room temperature for 20 hours. The medium was then diluted with diethyl ether, washed with saturated NaHCO Solution and then washed a second time with water. The organic phase was dried over Sodium Sulphate, filtered and concentrated to dryneSS under vacuum. The residue obtained was recrystallized or purified on a HOOC O column of Silica. EXAMPLE 6 ...~s N lsO H 0311 Synthesis of 3,3-O-7-oxo-DHEAO-glutamate 0315) A solution of 7-oxo-DHEA obtained in Example 3 in an anhydrous aprotic Solvent, for example anhydrous toluene (benzene) or anhydrous THF, was prepared. 1 molar equivalent of 2-isocyanate ester of Succinic acid and 2 molar equivalents of pyridine were added under an inert atmo sphere. The solution was heated at 80° C. (or in refluxing THF, 70° C.) for 1-12 hours. The reaction medium was HO evaporated to dryneSS and the residue was then taken up in NH2 a Solvent, for instance ethyl acetate or dichloromethane. After Several acidic, basic and neutral washes, the organic Solution was dried and then evaporated to dryneSS. The 0312. A solution of 0.5 mmol of 5-tert-butyl N-tert residue was purified by chromatography or by recrystalli butoxycarbonyl-L-glutamate was prepared in 2 ml of dichlo Zation to give the protected expected product. US 2003/0054021 A1 Mar. 20, 2003

0316 Deprotection was carried out by treatment with a 2. The regime or regimen as defined by claim 1, wherein mixture of dichloromethane/trifluoroacetic acid (in a 1:1 formula (I), R is a C-C, Saturated or unsaturated, linear or ratio) for 30 minutes at room temperature. The mixture was branched, or cyclic alkyl radical optionally containing one then evaporated to dryness to give 3(3-O-(2-glutarylami or more hetero atoms, and optionally Substituted with one or nocarbonyl)-7-oxo-DHEA. more groups selected from among -OR" and/or -SR and/or -COOR" and/or -NR'R' and/or halogen. 0317. While the invention has been described in terms of 3. The regime or regimen as defined by claim 1, wherein various Specific and preferred embodiments, the skilled formula (I), R is an alkylcarbonyl radical, the C-Co alkyl artisan will appreciate that various modifications, Substitu moiety of which is Saturated or unsaturated, linear or tions, omissions, and changes may be made without depart branched or cyclic and optionally Substituted with one or ing from the Spirit thereof. Accordingly, it is intended that more groups selected from among -OR" and/or -SR the scope of the present invention be limited solely by the and/or -COOR" and/or -NR'R' and/or halogen. Scope of the following claims, including equivalents thereof. 4. The regime or regimen as defined by claim 3, wherein formula (I), R is an alkylcarbonyl radical comprising a What is claimed is: C-Cls alkyl moiety. 1. A regime or regimen for cosmetically/therapeutically 5. The regime or regimen as defined by claim 1, wherein treating an adverse condition/affliction of a keratinous Sub formula (I), each of the groupSR' and R" is a hydrogen atom Strate/material to improve the appearance thereof, compris or a C-C alkyl radical. ing topically applying onto Such keratinous Substrate/mate 6. The regime or regimen as defined by claim 1, wherein rial, an appearance-enhancing effective amount of at least formula (I), each of the groupSR' and R" is a hydrogen atom, one 7-oxo-DHEA compound having the structural formula or a methyl, ethyl, butyl, propyl or isopropyl radical. (I): 7. The regime or regimen as defined by claim 1, wherein formula (I), at least one of R and R' is an amino acid group -NR'R' or -NR"R" selected from among L-alanine, (I) L-arginine, L-asparagine, L-aspartic acid, L-cysteine, Me L-glutamine, L-glutamic acid, glycine, L-histidine, L-iso leucine, L-leucine, L-lysine, L-methionine, L-phenylala nine, L-proline, L-serine, L-threonine, L-tryptophan, L-ty rosine and/or L-Valine. 8. The regime or regimen as defined by claim 1, Said at least one 7-OXO-DHEA compound comprising: 3f6-O-methyl-7-oxo-dehydroepiandrosterone; in which R is a Saturated or unsaturated, linear or branched, 3f6-O-ethyl-7-oxo-dehydroepiandrosterone; or cyclic C-C alkyl radical optionally containing one or 3f6-O-carboxymethyl-7-oxo-dehydroepiandrosterone; more hetero atoms and optionally Substituted with one or more substituents selected from among -OR" and/or -SR' 3f3-O-glucosyl-7-OXO-dehydroepiandrosterone, and/or -COOR" and/or -NR'R' and/or halogen and/or 3f3-O-glucoronyl-7-OXO-dehydroepiandrosterone; Sulfate and/or phosphate and/or aryl and/or heterocycle; an alkylcarbonyl radical, with the exception of the CH-CO 3.3-O-(2-tetrahydropyranyl)-7-oxo-dehydroepiandroster radical, the C-C alkyl moiety of which is Saturated or One, unsaturated, linear or branched, or cyclic, and optionally Substituted with one or more Substituents selected from 3.3-O-(2-tetrahydrofuranyl)-7-oxo-dehydroepiandroster among -OR" and/or -SR' and/or -COOR" and/or One, -NR'R' and/or halogen and/or sulfate and/or phosphate 3f-O-propionyl-7-OXO-dehydroepiandrosterone (or and/or aryland/or heterocycle; an arylcarbonyl radical, or an 3B-propionyloxy-7-oxo-DHEA); arylalkylcarbonyl radical, optionally Substituted with one or more of the Substituents -OR" and/or -SR' and/or COOR 3.3-O-butanoyl-7-oxo-dehydroepiandrosterone (or 3B-bu and/or -NR'R' and/or halogen and/or aryl and/or hetero tanoyloxy-7-oxo-DHEA); cycle; a group O=P(OH)OR'; a group (O)SOR"; a trialkyl 3f6-O-isobutanoyl-7-oxo-dehydroepiandrosterone; silyl radical (SiR') in which the 3 groups R' may be identical or different; an alkyloxycarbonyl group (ROCO); an alky 3f-O-pentanoyl-7-OXO-dehydroepiandrosterone; laminocarbonyl group (R'NHCO); wherein R' is a hydrogen 3.f3-O-hexanoyl-7-oxo-dehydroepiandrosterone; atom, a Saturated or unsaturated, linear or branched, or cycliC C-C alkyl radical, which may optionally contain 3f3-O-heptanoyl-7-OXO-dehydroepiandrosterone; one or more hetero atoms, optionally functionalized with 3f-O-Octanoyl-7-OXO-dehydroepiandrosterone, one or more of the groups -OR', -COOR", halogen, -NR"R", or with an aryl group, optionally functionalized 3f-O-nonanoyl-7-oxo-dehydroepiandrosterone; with one or more of the groups -OR", -COOR", halogen 3f-O-decanoyl-7-OXO-dehydroepiandrosterone; or -NR"R"; and R" is a hydrogen atom or a saturated or unsaturated, linear or branched or cyclic alkyl radical; with 3f6-O-dodecanoyl-7-oxo-dehydroepiandrosterone; the proviso that, in each of the groups -NR'R' and 3f6-O-myristoyl-7-oxo-dehydroepiandrosterone; -NR"R", the Substituents R' and R", respectively, are identical or different. 3f6-O-palmitoyl-7-oxo-dehydroepiandrosterone; US 2003/0054021 A1 Mar. 20, 2003 16

3.3-O-Stearoyl-7-oxo-dehydroepiandrosterone; Seborrhoea-related imperfections and/or Sensitive skin and/ 3.3-O-arachidoyl-7-oxo-dehydroepiandrosterone; or dandruff and/or natural hair loSS and/or baldness. 11. The regime or regimen as defined by claim 10, 3f3-O-docOSanoyl-7-OXO-dehydroepiandrosterone; comprising treating wrinkles and fine lines, cutaneous atro 3f3-O-lignoceroyl-7-OXO-dehydroepiandrosterone; phy, loSS offirmness and/or elasticity of the skin, an irregular skin grain with presence of dilated pores, loSS of radiance of 3.3-O-oleoyl-7-oxo-dehydroepiandrosterone; the skin and/or pigmentary markS. 3.3-O-linoleoyl-7-oxo-dehydroepiandrosterone; 12. The regime or regimen as defined by claim 1, com prising topically co-applying onto Such keratinous Substrate/ 3.3-O-linolenoyl-7-oxo-dehydroepiandrosterone; material, an effective amount of at least one other active 3f3-O-petroSeinoyl-7-OXO-dehydroepiandrosterone; agent compound Selected from among descquamating agents, moisturizers, depigmenting or propigmenting agents, anti 3f3-O-7-OXO-dehydroepiandrosterone glycinate; glycation agents, NO-synthase inhibitors, 5C-reductase 3.3-O-7-oxo-dehydroepiandrosterone lysinate; inhibitors, lysyl and/or prolyl hydroxylase inhibitors, agents for Stimulating the Synthesis of dermal or epidermal mac 3f3-O-7-OXO-dehydroepiandrosterone Serinate; romolecules or for preventing their degradation, agents for 3f3-O-7-OXO-dehydroepiandrosterone C-glutamate, Stimulating the proliferation of fibroblasts and keratinocytes and/or keratinocyte differentiation, muscle relaxants, com 3f3-O-7-OXO-dehydroepiandrosterone C.-aspartate; pounds for reducing irritation of neurogenic origin, antimi 3.3-hemisuccinoyloxyandrost-5-ene-7,17-dione; and/or crobial agents, tensioning agents, anti-pollution agents, and/ or free-radical Scavengers. 3B-O-(2-hydroxymalonyl)-7-oxo-dehydroepiandroster 13. The regime or regimen as defined by claim 1, com OC. prising topically co-applying onto Such keratinous Substrate/ 9. The regine or regimen as defined by claim 1, Said at material, an effective amount of at least one optionally least one 7-OXO-DHEA compound comprising: coated inorganic pigment and/or at least one UV-Screening 3B-O-(2-malonylaminocarbonyl)-7-oxo-dehydroepi agent Selected from among: androsterone; (a) a benzophenone derivative; 3B-O-(2-succinylaminocarbonyl)-7-oxo-dehydroepi (b) a triazine derivative; androsterone; (c) benzene-1,4-bis(3-methylidene-10-camphorsulfonic 3B-O-(2-glutarylaminocarbonyl)-7-oxo-dehydroepi acid), optionally in partially or totally neutralized State; androsterone; 3.3-methylcarbonate-7-OXO-dehydroepiandrosterone, (d) a Salicylic acid derivative; 3B-O-(trifluoroacetyl)-7-oxo-dehydroepiandrosterone; (e) a cinnamic acid derivative; 3B-O-(-carboxybutanoyl)-7-oxo-dehydroepiandroster (f) a liquid B.f3'-diphenylacrylate derivative; One, (g) a p-aminobenzoic acid derivative; 3B-O-(4-cyclopentylbutanoyl)-7-oxo-dehydroepiandros (h) 4-methylbenzylidenecamphor; terone, 3.3-O-benzoyl-7-oxo-dehydroepiandrosterone; (i) 2-phenylbenzimidazole-5-Sulfonic acid; 3B-O-(3,4-dihydroxybenzoyl)-7-oxo-dehydroepiandros (i) a 1,3,5-triazine derivative; terone, (k) a plant extract which comprises an extract of ROS marinus Officinalis, LeOntopodium alpinum and/or 3B-O-(ascorbyl phosphate)-7-oxo-dehydroepiandroster LeOntopodium Stracheyi, One, 3B-O-(ascorbyl sulfate)-7-oxo-dehydroepiandrosterone; (l) a benzotriazole Silicone having the formula: 3f3-O-phosphonyl-7-OXO-dehydroepiandrosterone; 3f3-O-monoacetylphosphonyl-7-OXO-dehydroepiandros CH CH CH terone, HC-Si-O-Si-O-Si-CH. 3.3-O-sulfonyl-7-oxo-dehydroepiandrosterone; CH CH 3B-O-(tert-butyldimethylsilyl)-7-oxo-dehydroepiandros HC terone, HO 3B-O-(tert-butyldiphenylsilyl)-7-oxo-dehydroepiandros terone; and/or eN N 3B-O-(trimethylsilyl)-7-oxo-dehydroepiandrosterone. S. M 10. The regime or regimen as defined by claim 1, for N preventing or treating the Signs of aging of the skin and/or CH a dull complexion and/or skin or hair pigmentation disorders and/or skin dryneSS and/or hyperSeborrhoea and/or hyper US 2003/0054021 A1 Mar. 20, 2003 17

14. The regime or regimen as defined by claim 1, Said 3f6-O-7-oxo-dehydroepiandrosterone lysinate; keratinous Substrate/material comprising human skin, hair, eyelashes and/or nails. 3f-O-7-OXO-dehydroepiandrosterone Serinate; 15. A 7-oxo-DHEA compound having the formula (I) as 3f-O-7-OXO-dehydroepiandrosterone C-glutamate; defined by claim 1, in which R is: a group O=P(OH)OR' with the exception of the 3f-O-7-OXO-dehydroepiandrosterone C.-aspartate, O=P(OH), group and the O=P(OH)OCOCH group; 3.3-O-(2-hydroxymalonyl)-7-oxo-dehydroepiandroster a group (O)SOR" with the exception of the Na. SOH One, group and the SOH group; 3.3-O-(2-malonylaminocarbonyl)-7-oxo-dehydroepi a trialkylsilyl group (SiR') in which the 3 groups R' may androsterone; be identical or different, with the exception of the tBu Si(Me) group; 3.3-O-(2-succinylaminocarbonyl)-7-oxo-dehydroepi an alkyloxycarbonyl group (ROCO) with the exception androsterone; of the CHOCO group; 3.3-O-(2-glutarylaminocarbonyl)-7-oxo-dehydroepi an alkylaminocarbonyl group (R'NHCO) wherein the androsterone; alkyl moiety is necessarily Substituted with one or more of the groups selected from among -OR" and/or -SR' 3.3-O-(ascorbyl phosphate)-7-oxo-dehydroepiandroster and/or -COOR" and/or -NR'R' and/or halogen and/or One, Sulfate and/or phosphate and/or glycoside and/or aryl and/or heterocycle, Said heterocycle being an indole, a 3.3-O-(ascorbyl sulfate)-7-oxo-dehydroepiandrosterone; pyrimidine, a piperidine, a morpholine, a pyran, a 3.3-O-(1-butyldiphenylsilyl)-7-oxo-dehydroepiandroster furan, a piperazine, or a pyridine. one; and 16. A 7-oxo-DHEA compound selected from the group consisting of: 3.3-O-(trimethylsilyl)-7-oxo-dehydroepiandrosterone. 3f3-O-pentanoyl-7-OXO-dehydroepiandrosterone; 18. A process for synthesizing the 3.3-O-alkylcarbonyl-7- OXO-DHEA compound as defined by claim 16, comprising 3.3-O-hexanoyl-7-oxo-dehydroepiandrosterone; introducing 7-OXO-DHEA into a polar aprotic Solvent, add 3 B-O-octanoyl-7-oxo-dehydroepiandrosterone; ing an organic base and an acid chloride thereto and then, 3f3-O-nonanoyl-7-OXO-dehydroepiandrosterone; after reaction of Same, the residue obtained is then recrys tallized or purified. 3f3-O-decanoyl-7-OXO-dehydroepiandrosterone; 19. A process for synthesizing the 33-O-alkyl-carbonyl 3.3-O-myristoyl-7-oxo-dehydroepiandrosterone; 7-oxo-DHEA compounds as defined by claims 16 or 17, comprising adding a carbonyldiimidazole dissolved in a 3.3-O-arachidoyl-7-oxo-dehydroepiandrosterone; polar aprotic Solvent to carboxylic acid dissolved in the 3f3-O-docOSanoyl-7-OXO-dehydroepiandrosterone; Same Solvent, and then, to the Solution Stirred without 3f3-O-lignoceroyl-7-OXO-dehydroepiandrosterone; heating, adding 7-OXO-DHEA dissolved in the Same Solvent, Stirring the mixture under cold conditions and then at room 3.3-O-oleoyl-7-oxo-dehydroepiandrosterone; temperature and then, after reaction of Same, the residue is 3.3-O-linoleoyl-7-oxo-dehydroepiandrosterone; then purified. 20. A process for synthesizing the 3 B-O-alkyl-7-oxo 3.3-O-linolenoyl-7-oxo-dehydroepiandrosterone; DHEA compounds as defined by claims 16 or 17, compris 3.3-O-petroselinoyl-7-oxo-dehydroepiandrosterone; ing introducing 7-OXO-DHEA into a polar aprotic Solvent 3.3-O-methyl-7-oxo-dehydroepiandrosterone; and then adding an alkali metal hydride under cold condi tions, Stirring the reaction medium and then, after adding an 3.3-O-ethyl-7-oxo-dehydroepiandrosterone; alkyl halide, maintaining the reaction medium at room 3.3-O-carboxymethyl-7-oxo-dehydroepiandrosterone; temperature, and, after reaction, the residue obtained is then recrystallized or purified. 3f3-O-glucosyl-7-OXO-dehydroepiandrosterone; 21. A process for synthesizing the 7-keto-DHEA carbam 3B-O-(2-tetrahydrofuranyl)-7-oxo-dehydroepiandroster ates as defined by claims 16 or 17, comprising introducing One, 7-OXO-DHEA into an anhydrous aprotic Solvent, heating the reaction medium after addition, under inert atmosphere, of 3B-O-(trifluoroacetyl)-7-oxo-dehydroepiandrosterone; an isocyanate and an organic base, and, after reaction 3B-O-(4-cyclopentylbutanoyl)-7-oxo-dehydroepiandros thereof, the residue obtained is then recrystallized or puri terone; and fied. 3B-O-(3,4-dihydroxybenzoyl)-7-oxo-dehydroepiandros 22. A topically applicable cosmetic/therapeutic composi terOne. tion Suited for treating an adverse condition/affliction of a 17. A 7-oxo-DHEA compound selected from the group keratinous Substrate/material to improve the appearance consisting of: thereof, comprising (1) an appearance-enhancing effective amount of at least one 7-oxo-DHEA compound having the 3f3-O-7-OXO-dehydroepiandrosterone glycinate; structural formula (I): US 2003/0054021 A1 Mar. 20, 2003 18

proliferation of fibroblasts and keratinocytes and/or kerati nocyte differentiation, muscle relaxants, compounds for (I) reducing irritation of neurogenic origin, antimicrobial Me agents, tensioning agents, anti-pollution agents, and/or free radical Scavengers. 24. The topically applicable cosmetic/therapeutic compo Sition as defined by claim 22, further comprising an effective amount of at least one optionally coated inorganic pigment and/or at least one UV-Screening agent Selected from among: O (a) a benzophenone derivative; (b) a triazine derivative; in which R is a Saturated or unsaturated, linear or branched, or cyclic C-C alkyl radical optionally containing one or (c) benzene-1,4-bis(3-methylidene-10-camphorsulfonic more hetero atoms and optionally Substituted with one or acid), optionally in partially or totally neutralized State; more substituents selected from among -OR" and/or -SR' (d) a Salicylic acid derivative; and/or -COOR" and/or -NR'R' and/or halogen and/or Sulfate and/or phosphate and/or aryl and/or heterocycle; an (e) a cinnamic acid derivative; alkylcarbonyl radical, with the exception of the CHCO (f) a liquid B.f3'-diphenylacrylate derivative; radical, the C-C alkyl moiety of which is Saturated or unsaturated, linear or branched, or cyclic, and optionally (g) a p-aminobenzoic acid derivative; Substituted with one or more Substituents selected from (h) 4-methylbenzylidenecamphor; among -OR" and/or -SR' and/or -COOR" and/or (i) 2-phenylbenzimidazole-5-Sulfonic acid; -NR'R' and/or halogen and/or sulfate and/or phosphate and/or aryland/or heterocycle; an arylcarbonyl radical, or an (i) a 1,3,5-triazine derivative; arylalkylcarbonyl radical, optionally Substituted with one or (k) a plant extract which comprises an extract of ROS more of the Substituents -OR" and/or -SR' and/or COOR marinus Officinalis, LeOntopodium alpinum and/or and/or -NR'R' and/or halogen and/or aryl and/or hetero LeOntopodium Stracheyi, and/or cycle; a group O=P(OH)OR'; a group (O)SOR"; a trialkyl silyl radical (SiR') in which the 3 groups R' may be identical (l) a benzotriazole Silicone having the formula: or different; an alkyloxycarbonyl group (ROCO); an alky laminocarbonyl group (R'NHCO); wherein R' is a hydrogen atom, a Saturated or unsaturated, linear or branched, or CH CH CH cyclic C-C alkyl radical, which may optionally contain HC-Si-O-Si-O-Si-CH. one or more hetero atoms, optionally functionalized with one or more of the groups -OR", -COOR", halogen, CH CH -NR"R", or with an aryl group, optionally functionalized HC with one or more of the groups -OR", -COOR", halogen or -NR"R"; and R" is a hydrogen atom or a saturated or HO unsaturated, linear or branched or cyclic alkyl radical; with eN the proviso that, in each of the groups -NR'R' and N -NR"R", the Substituents R' and R", respectively, are S- M identical or different, formulated into a (2) topically appli N cable, physiologically acceptable vehicle, diluent or carrier CH therefor. 23. The topically applicable cosmetic/therapeutic compo Sition as defined by claim 22, further comprising an effective 25. The topically applicable cosmetic/therapeutic compo amount of at least one other active agent compound Selected sition as defined by claim 22, comprising from 0.00001% to from among descquamating agents, moisturizers, depigment 10% by weight of said at least one 7-oxo-DHEA compound. ing or propigmenting agents, anti-glycation agents, NO 26. The topically applicable cosmetic/therapeutic compo Synthase inhibitors, 5C.-reductase inhibitors, lysyl and/or sition as defined by claim 22, comprising from 0.001% to prolyl hydroxylase inhibitors, agents for Stimulating the 5% by weight of said at least one 7-oxo-DHEA compound. Synthesis of dermal or epidermal macromolecules or for preventing their degradation, agents for Stimulating the k k k k k