Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
  • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
  • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
  • A61K31/5685—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone having an oxo group in position 17, e.g. androsterone
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/63—Steroids; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/04—Antipruritics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/08—Anti-ageing preparations

Definitions

• the present invention relates to the use of 7-hydroxylated steroids for the preparation of cosmetic or dermatological compositions for preventing and / or treating the cutaneous effects of aging and of the action of ultraviolet radiation.
• DHEA and its sulfate derivative (S-DHEA) circulate in significant quantities in adult men, but its level decreases with age (Orentreich & coll., J " . Clin. Endocr. Me tab. 5_9_: 551-555 , 1984). It has thus been proposed, for example in the French patent application published under the number 2 729 854 or the corresponding European patent application published under the number 723 775, to use S-DHEA in a cosmetic composition . for topical application for the treatment of certain signs of aging multiple effects of DHEA have been reported, but some oppose processes and diseases associated with aging (Watson et al, Drug aging S 9:.. 274-291 , 1996).
• DHEA and the production of its 7-hydroxyl derivatives decrease with age while that of glucocorticoids does not vary.
• the intake of hormonal steroids in the skin is therefore modified with a predominance of glucocorticoids, the promoting effects of skin aging are known.
• European patent application published under the number 415 766 describes the use of retinoid agents to combat skin atrophy by an antiglucocorticoid mechanism. However, there is no structural relationship between the retinoids (vitamin A and its derivatives) and steroids. European patent application published under number 189 738 describes the use of dehydroepiandrosterone (DHEA) and its ester derivatives to treat dry skin, but these compounds are different from the steroids which are the subject of the present invention.
• DHEA dehydroepiandrosterone
• DHEA sulfate in cosmetic and dermatological compositions and suggests the addition in these compositions of steroid hormones other than DHEA sulfate, such as androgens, estrogens , progestagens.
• these steroids are devoid of hormonal action, and their use is intended only to offset the undesirable hormonal effects of DHEA and DHEA sulfate.
• DHEA sulfate has no structural relationship with the steroids which are the subject of the present invention.
• the invention therefore relates to the use, in a cosmetic or dermatological composition with topical application intended to prevent or treat the manifestations of skin aging and / or the effects of UV irradiation on the skin, of a compound 7 ⁇ or 7 ⁇ substituted with DHEA or PREG, reduced or not in position 5, and therefore corresponding to the formula: R-
• R ⁇ is chosen from: a hydrogen atom, the organic acid ester functions from 1 to 24 carbon atoms, sulfuric ester or phosphoric ester, or carbon ether from 1 to 24 carbon atoms comprising zero or more atoms nitrogen, ethers of carbohydrates of 3 to 100 carbon atoms and their derivatives, including those with or without one or more nitrogen atoms.
• R2 is chosen from: a hydrogen atom or a fatty acid ester function of 1 to 24 carbon atoms.
• the compounds of the invention are substituted 7 ⁇ or 7 ⁇ derivatives of DHEA or of PREG and more particularly still 7 ⁇ or 7 ⁇ -hydroxylated derivatives reduced or not in position 5.
• a group of preferred compounds of the invention are the 7 ⁇ -hydroxylated derivatives, that is to say those in which the oxygen carried in position 7 is axial (7 ⁇ ) and the substituent R2 is hydrogen.
• Ri is a palmitate, an oleate or a ferulate, and in particular 3 ⁇ -palmitoyl-7 ⁇ -hydroxy-DHEA, 3 ⁇ -oleyl-7 ⁇ -hydroxy-DHEA and 3 ⁇ -feruloyl-7 ⁇ -hydroxy-DHEA.
• compositions of the invention can comprise one or more steroid derivatives according to the invention, as well as other compounds known for their cosmetic or dermatological property such as hormones, and, of course, the adjuvants or vehicles conventionally used in these areas.
• a steroid derivative of the invention for the use of a steroid derivative of the invention in a cosmetic composition intended to compensate, treat and / or prevent the cutaneous effects of aging and / or the effects of UV irradiation on the skin, said derivative is administered to a dose of between 0.05 and 10 mg per application and per day and preferably between 0.05 and 5 mg per application and per day.
• the effect of restoring or preventing skin aging in people of a certain age as well as protective effects against UV is applicable for any treatment aimed at restoring skin tone, firming the skin and erasing wrinkles.
• the derivatives of the invention can be used in very various galenical forms for their percutaneous administration. They may be forms resulting from the addition to the derivatives of the invention of compounds acceptable in cosmetics and making it possible to produce creams, pastes, gels, lotions, "water in oil” or “emulsions". oil in water "as well as forms composed of liposomes of single or mixed micelles or other penetration promoters such as lysophospholipids, cyclodextrins, polyethylene glycol, surfactants, alcohols, fatty acids, vegetable oils. This list is not exhaustive and any other presentation known to man can be envisaged as soon as it is adapted to the steroid derivatives of the invention which have the characteristic of being both water-soluble and liposoluble.
• the cosmetic or dermatological compositions of the invention can be in the form of creams, lotions, gels and ointments or any other form generally used for topical applications.
• Example 1 Ef f of 3 ⁇ , l - di hydr o xy - 5 - androstene- 17 -one (7 ⁇ -hvdroxy-DHEA) and 3 ⁇ , 7 ⁇ -dihvdroxy- 5 ⁇ - andros tane- 17 - one (7 ⁇ -hvdroxy- ISOA) on cellular apoptosis induced by glucocorticoids.
• the thymus of 4-week-old C57BL / 6 mice is taken. The culture of the thymocytes is carried out for 6 hours in RPMI 1640 medium and in the presence or in the absence of the steroid tested.
• Apoptosis (DNA fragmentation) is measured by flow cytometry after labeling with propidium iodide.
• the apoptotic phenomenon is controlled by electrophoresis of the DNA revealed by ethidium bromide according to the conventional technique (observation of scales of 200 base pairs). The results reported in Table I below were obtained:
• mice Their effect at 10 M is greater than that of their precursor steroid (DHEA or dehydroepiandrosterone or 3 ⁇ -hydroxy-5-androstene-17-one).
• Example 2 Effects of 3 ⁇ , 7 ⁇ -dihvdroxy-5 - androstene- 17 -one (7 -hvdroxy-DHEA) on the viability of human keratinocytes in culture.
• Any value greater than 100 indicates a product promoting cell viability.
• Example 3 Effects of 3 ⁇ , 7 ⁇ -dihvdroxy-5-androstene-17-one (7 -hvdroxy-DHEA) on the proliferation of human fibroblasts in culture.
• the cultures of human fibroblasts (32-year-old woman) are seeded in 24-well plates at a rate of 50,000 cells / well in the standard culture medium (DMEM, gentamycin, amphotericin B, penicillin, L-glutamine, 10% FCS). The tests are carried out on 4 series of 3 wells. After 24 h, the fibroblasts adhere to the support and 3 series are treated with 7 ⁇ -hydroxy-DHEA at concentrations of 10 M, 5.10 M and 10 M. The fourth series contains only the vector (ethanol). The media are renewed daily, and at 96 h (72 h of contact of the 7-hydroxy-DHEA under test), the fibroblasts are counted on a Malassez cell in the presence of trypan blue. The results of the effects on the proliferation of fibroblasts are reported in Table III below.
• Keratinocytes from a healthy donor are cultured up to the subconfluent stage in a specific medium (KGM) for the proliferation of keratinocytes.
• KGM specific medium
• the suspensions obtained are distributed in triplicate in 4 series, 3 of which are irradiated for 30 min with a lamp emitting UVA in order to activate the production of free radicals.
• one contains the vitamins C + E (0.7%) and serves as a protective reference, one contains the 7 ⁇ -hydroxy-DHEA

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Dermatology (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Medicinal Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Gerontology & Geriatric Medicine (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Birds (AREA)
• Steroid Compounds (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Cosmetics (AREA)

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Cited By (12)

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Citations (5)

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• 1997
  • 1997-03-10 FR FR9702811A patent/FR2760362B1/fr not_active Expired - Fee Related
• 1998
  • 1998-03-06 EP EP98913857A patent/EP0973524B1/fr not_active Expired - Lifetime
  • 1998-03-06 ES ES98913857T patent/ES2183341T3/es not_active Expired - Lifetime
  • 1998-03-06 AU AU68402/98A patent/AU6840298A/en not_active Abandoned
  • 1998-03-06 JP JP53928198A patent/JP2001515488A/ja not_active Ceased
  • 1998-03-06 WO PCT/FR1998/000457 patent/WO1998040074A1/fr not_active Ceased
  • 1998-03-06 DE DE69807454T patent/DE69807454T2/de not_active Expired - Fee Related
  • 1998-03-06 US US09/380,870 patent/US6407084B2/en not_active Expired - Fee Related
• 2002
  • 2002-05-02 US US10/136,941 patent/US6620803B2/en not_active Expired - Fee Related

Patent Citations (6)

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