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WO2007037295A1 - Prevention ou attenuation des rides au moyen d'un inhibiteur des adam - Google Patents

Prevention ou attenuation des rides au moyen d'un inhibiteur des adam Download PDF

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Publication number
WO2007037295A1
WO2007037295A1 PCT/JP2006/319236 JP2006319236W WO2007037295A1 WO 2007037295 A1 WO2007037295 A1 WO 2007037295A1 JP 2006319236 W JP2006319236 W JP 2006319236W WO 2007037295 A1 WO2007037295 A1 WO 2007037295A1
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WIPO (PCT)
Prior art keywords
acid
group
adam
extract
oil
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2006/319236
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English (en)
Japanese (ja)
Inventor
Takuya Hiruma
Hirotada Fukunishi
Masaru Suetsugu
Yukiko Matsunaga
Michio Shibata
Satoshi Amano
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Shiseido Co Ltd
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Shiseido Co Ltd
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Publication of WO2007037295A1 publication Critical patent/WO2007037295A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/42—Amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a novel ADAM inhibitor and the prevention or improvement of wrinkles using the same.
  • Non-patent Document 2 it has been reported that continuous destruction of the barrier function with unsaturated fatty acids causes epidermal wrinkles.
  • Cosmetics containing moisturizers such as glycerin, sorbitol, and plant juice extract.
  • moisturizers such as glycerin, sorbitol, and plant juice extract.
  • ADAM a disintegrin and metalloprotease
  • MMP matrix metalloprotease
  • HB-EGF heparin-binding EGF3 ⁇ 4 neprin-binding epidermal growth factor.
  • HB-EGF -like growth factor
  • TNF tumor necrosis factor
  • ADAM activity that occurs in skin cells occurs when a signal such as proliferation and separation is transmitted to cells to cause proliferation and thickening of the skin.
  • Non-Patent Document 1 Ninagawa et al., Fragrance Journal; 1992 (11) 29-42
  • Non-Patent Document 2 Jin Masaki Perfume Journal; 2001 Vol.25, No. 1, 34-38
  • Non-patent literature 3 Asakura, M., et al. 2002.Cardiac hypertrophy is inhioited by antagon ismof ADAM 12 processing of HB-EGF: metalloproteinase inhibitors as a new thera py. Nat. Med. 8: 35-40
  • Patent Document 4 Izumi, Y., et al. 1998. A metalloprotease- disintegrin, MDC9 / meltrin -— / ADAM9 and PKC_ are involved in TPA- induced ectodomain shedding of membra ne— anchored heparin— binding EGF— like growth factor. EMBO J. 17: 7260—7272.
  • Non-Patent Document 5 Lemjabbar, H., and C. Basbaum. 2002. Platelet-activating factor rece ptorand ADAM 10 mediate responses to Staphylococcus aureus in epithelial cells. Nat. Med. 8: 41-46
  • Patent Document 6 Sunnarborg, S.W., et al. 2002.Tumor necrosis factor-alpha convertin g enzyme (TACE) regulates epidermal growth factor receptor ligand availability.J. B iol. Chem. 277: 12838-12845
  • Non-Patent Document 7 Yan, Y., K. Shirakabe, and Z. Werb. 2002.
  • the metalloprotease Kuzb anian (ADAM 10) mediates the trans activation of EGF receptor by G protein-coupled receptors. J. Cell Biol. 158 : 221-226.
  • the present invention aims to find a novel compound capable of effectively preventing or improving wrinkles, particularly fine wrinkles, and to use it to more effectively prevent or improve wrinkles. It is what.
  • ADAM a disintegrin and metalloprotease family
  • ADAM-9 and ADAM-17 proteins belonging to the ADAM-9 and ADAM-17
  • ADAMs such as ADAM-9, ADAM-10, and ADAM-17 are present on the skin cell surface, and growth factors such as HB—EGF, Amphiregulin, TNF—a, and TGF—a are released from the cell membrane in the skin. It is an enzyme that is released and activated. Due to skin noria destruction, ADAM is activated or up-regulated in the skin and promotes the release and activation of growth factors such as HB-EGF, resulting in thickening of the epidermis and dermis. This is considered to be one important mechanism of fine wrinkle formation.
  • growth factors such as HB—EGF, Amphiregulin, TNF—a, and TGF—a are released from the cell membrane in the skin. It is an enzyme that is released and activated. Due to skin noria destruction, ADAM is activated or up-regulated in the skin and promotes the release and activation of growth factors such as HB-EGF, resulting in thickening of the epidermis and dermis. This is considered to be one important
  • Fig. 1 shows a schematic diagram illustrating the mechanism for preventing or improving wrinkles by inhibiting AD AM activity in the skin.
  • the ADAM inhibitor of the present invention is characterized by comprising benzohydroxamic acid represented by the following general formula (I) or a salt power thereof.
  • each R is independently an alkyl group having 1 to 18 carbon atoms or a cycloamino group having 3 to 8 carbon atoms.
  • N is an integer of 0-3.
  • R is preferably a hydrogen atom.
  • R is an alkyl group having 1 to 18 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms,
  • R is substituted at the 4-position, and in this case, R is a carbon number of 1 to
  • R is preferably an 18 alkyl group, a cycloalkyl group having 3 to 8 carbon atoms, or an alkoxy group having 1 to 18 carbon atoms, and R is preferably a hydrogen atom.
  • the alkyl group has 1 to 18 carbon atoms, preferably linear or branched, and preferably 1 to 6 carbon atoms.
  • the cycloalkyl group has 3 to 8 carbon atoms, and is preferably a cyclopentyl group, a cyclohexyl group, or a cycloheptyl group.
  • the rhogen atom and the rogen atom are preferably a fluorine atom or a chlorine atom.
  • the alkoxy group is a hydroxyl group substituted with an alkyl having 1 to 18 carbon atoms, preferably a hydroxyl group substituted with an alkyl having 1 to 6 carbon atoms, more preferably
  • the benzyloxy group may have a substituent on the benzene ring, and may be an alkyl group, a cycloalkyl group, a halogen atom, a hydroxyl group, an alkoxy group, a benzyloxy group, an aryloxy group, an amino group, an acylamino group, an aryl group. Etc. may be substituted.
  • the acylamino group is an amino group substituted with an acyl group, and the acyl group is an alkyl group, a cycloalkyl group, a halogen atom, a hydroxyl group, an alkoxy group, a benzyloxy group, an aryloxy group, an amino group, an acylamino group, It may be substituted with a substituent such as aryl group.
  • 4-methoxybenzohydroxamic acid is a tyrosinase inhibitor and has been reported to have a whitening effect by preventing or inhibiting pigment formation (for example, international 1S 4_Methoxybenzohydroxamic acid S SADAM activity can be inhibited, and wrinkles can be prevented or ameliorated! / Was never known.
  • the wrinkle prevention or improvement agent of the present invention is characterized in that it also has the above-mentioned benzohydroxamic acid, which is an ADAM inhibitor, or a salt power thereof.
  • the method for preventing or improving wrinkles of the present invention is characterized by applying the above-mentioned benzohydroxamic acid or a salt thereof, which is an ADAM inhibitor, to the skin.
  • the benzohydroxamic acid of the present invention can suppress an increase in the activity of HB-EGF or the like by inhibiting or suppressing the activity of ADAM in the skin, thereby reducing the thickness of the epidermis and dermis. Suppress to prevent wrinkle formation or improve formed wrinkles.
  • the invention's effect is described above, the benzohydroxamic acid of the present invention.
  • ADAM inhibitor of the present invention By applying the ADAM inhibitor of the present invention to the skin, the activity of ADAM present in the skin such as ADAM-9, ADAM-10, or ADAM-17 is inhibited to reduce sebum, wash the face, etc. Suppresses the growth of growth factors such as HB-EGF in the epidermis and dermis induced by the destruction of the skin barrier caused by various factors, and suppresses thickening of the epidermis and dermis. It is possible to effectively prevent or improve the formation of wrinkles, especially fine lines.
  • FIG. 1 is a schematic diagram illustrating a mechanism for preventing or improving wrinkles by inhibiting ADAM activity in the epidermis.
  • FIG. 2 is a graph showing the wrinkle improving effect of 4-methoxybenzohydroxamic acid in visual judgment.
  • Fig. 3 is a graph showing the wrinkle improvement effect of 4-methoxybenzohydroxamic acid in wrinkle area (%).
  • FIG. 4 is a graph showing the inhibitory effect of 4-methoxybenzohydroxamic acid on TEWL elevation.
  • each R independently represents an alkyl group having 1 to 18 carbon atoms or a cycloamino group having 3 to 8 carbon atoms.
  • N is an integer of 0-3.
  • benzohydroxamic acid of the present invention examples include 4-methoxybenzohydroxamic acid, 4-butylbenzohydroxamic acid, benzohydroxamic acid, 2-hydroxy-3-methylbenzohydroxamic acid, 3- (phenoxycetylamino) Benzohydroxamic acid, 4-cyclohexyl benzohydroxamic acid, 2-chloro-orchid benzohydroxamic acid, 3-methoxybenzohydroxamic acid, 2-methoxybenzohydroxamic acid, 4- clo-benzobenzoxamic acid, 4- (4-Fluorobenzyloxy) -3-isobutylbenzohydroxamic acid, 2-hydroxy-5-methylbenzohydroxamic acid and the like.
  • the benzohydroxamic acid used in the present invention includes a medically acceptable salt form in addition to the free acid.
  • these salts include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, methylamine salts, dimethylamine salts, trimethylamine salts, methylbiperidine salts, and ethanolamine salts.
  • the Powers including, but not limited to, amine salts such as ethanolamine salt, triethanolamine salt, lysine salt, ammonium salt, basic amino acid salt and the like.
  • Benzohydroxamic acid and salts thereof can be produced according to known production methods, and commercially available products can also be used.
  • the benzohydroxamic acid of the present invention or a salt wrinkle preventing or improving agent thereof, preferably used in a skin external preparation preferably used in a skin external preparation.
  • the blending amount of benzohydroxamic acid or a salt thereof in the external preparation for skin varies depending on the use mode, product form, etc., and is not particularly limited. For example, it is preferably 0.001% by mass to 10% based on the total amount of the external preparation for skin. % By mass, more preferably 0.005% by mass to 5% by mass, and still more preferably 0.01% by mass to 1% by mass.
  • “skin external preparation” includes cosmetics, pharmaceuticals, quasi drugs and the like.
  • the dosage form can be any agent such as aqueous solution, solubilization system, emulsification system, oil liquid system, gel system, paste system, ointment system, aerosol system, water oil 2 layer system, water oil powder 3 layer, etc. Includes type. Moreover, what was carry
  • the product form and use of the external preparation for skin are also arbitrary, and for example, it can be used as an external preparation for facial, body, or scalp such as lotion, milky lotion, cream, knock.
  • the external preparation for skin is appropriately formulated with other optional components that are usually used in external preparations for skin such as cosmetics and pharmaceuticals as needed.
  • a skin external preparation can be prepared by blending benzohydroxamic acid or a salt thereof and one or more of the following components.
  • UV absorbers examples include aminobenzoic acid (hereinafter abbreviated as PABA), PABA monoglycerin ester, ⁇ , ⁇ -dipropoxy PABA ethyl ester, ⁇ , ⁇ -diethoxy PABA ethyl ester, ⁇ , ⁇ -dimethyl PABA
  • Benzoic acid UV absorbers such as ethyl ester, ⁇ , ⁇ -dimethyl PABA butyl ester, ⁇ , ⁇ -dimethyl PABA methyl ester, anthracic acid UV absorbers such as homomenthyl-N-acetylethyl anthracate, Rate, menthyl salicylate, homomenthyl salicylate, octyl salicylate, feni Salicylic acid UV absorbers such as rusalicylate, benzyl salicylate, p-isopropanol phenol salicylate, octylcinnamate, ethyl-4-
  • Examples of the ultraviolet light scattering agent include powders of titanium oxide, fine particle titanium oxide, zinc oxide, fine particle zinc oxide, iron oxide, fine particle iron oxide, cerium oxide and the like.
  • UV scattering agents needle-like, spindle-like, spherical and granular powders are usually used. Further, a fine particle powder having a particle size of 0.1 m or less is preferable.
  • Silicone treatment such as methylhydrogen polysiloxane silane coupling agent; metal calcite treatment; perfluoroalkyl phosphate diethanolamine salt hydrofluorination by perfluoroalkyl silane, dextrin fatty acid ester treatment, etc.
  • a treated UV scattering agent is also preferred.
  • liquid fats examples include apogado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, barley germ oil, southern power oil , Castor oil, linseed oil, safflower oil, cottonseed oil, eno oil, soybean oil Peanut oil, tea seed oil, oyster oil, rice bran oil, cinnagiri oil, Japanese kiri oil, jojoba oil, germ oil, triglycerin and the like.
  • solid fat examples include cacao butter, coconut oil, horse fat, hydrogenated coconut oil, palm oil, beef tallow, sheep fat, hardened beef tallow, palm kernel oil, pork tallow, beef bone fat, mollusc kernel oil, hardened And oil, beef leg fat, beeswax and hydrogenated castor oil.
  • waxes include beeswax, candelilla wax, cotton wax, carnauba wax, beveri wax, ibota wax, straw wax, montan wax, nuka wax, lanolin, kapok wax, lanolin acetate, liquid lanolin, sugar cane wax, lanolin fatty acid isopropyl, Examples include hexyl laurate, reduced lanolin, jojoba wax, hard lanolin, shellac wax, POE lanolin alcohol ether, POE lanolin alcohol acetate, POE cholesterol ether, lanolin fatty acid polyethylene glycol, and POE hydrogenated lanolin alcohol ether.
  • hydrocarbon oil examples include liquid paraffin, ozokerite, squalene, pristane, paraffin, ceresin, squalene, petrolatum, microcrystalline wax, polyethylene tuss, and Fischer-Tropsch wax.
  • Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, undecylenic acid, toluic acid, linoleic acid, linolenic acid, eicosapentaenoic acid (EPA), docosa Hexaenoic acid (DHA) and the like can be mentioned.
  • Examples of higher alcohols include linear alcohols (for example, lauryl alcohol, cetino-leanolecanole, stearino-leanoleconore, behenino-leanolecanol, myristino-leanolol, oleyl alcohol, ceto alcohol. Stearyl alcohol, etc.); branched chain alcohols (eg, monostearyl glycerin ether (batyl alcohol), 2-decyltetradecinol, lanolin alcohol, cholesterol, phytosterol, hexyldodecanol, octyl dodecanol, etc.).
  • linear alcohols for example, lauryl alcohol, cetino-leanolecanole, stearino-leanoleconore, behenino-leanolecanol, myristino-leanolol, oleyl alcohol, ceto alcohol. Stearyl alcohol, etc.
  • branched chain alcohols e
  • Synthetic ester oils include isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyldecyl dimethyloctanoate , Cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene di-2-ethylhexanoate Glycol, dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate, diisostearyl malate, glycerin di-2-heptyl decanoate, tri-2-ethylhe
  • silicone oil examples include linear polysiloxanes (for example, dimethylpolysiloxane, methylphenol polysiloxane, diphenylpolysiloxane, etc.); cyclic polysiloxanes (for example, otatamethylcyclotetrasiloxane, decamethyl).
  • linear polysiloxanes for example, dimethylpolysiloxane, methylphenol polysiloxane, diphenylpolysiloxane, etc.
  • cyclic polysiloxanes for example, otatamethylcyclotetrasiloxane, decamethyl
  • moisturizing agents such as polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol; cellulose, hydroxychetinoresenorelose, hydroxypropinoresenorelose, Methinorehydroxypropinore senorelose, methinorescenorelose, canoleboxy methinorescenellose, quince seed, carrageenan, pectin, mannan, curdlan, chondroitin sulfate, starch, galactan, dermatan sulfate, glycogen, gum arabic, to Paran sulfate, hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate, chondroitin, xanthan gum, mucoy Thin sulfate, hydroxyethyl dagam, carb
  • benzohydroxamic acid or a salt thereof is applied to the skin in any form as long as it can be applied to the skin and the object of the present invention can be achieved. It can be applied alone or in combination with other optional ingredients. Moreover, the place of the skin to apply is not limited, and includes any skin on the body surface including the scalp.
  • the method of the present invention is usually used as a cosmetic method.
  • the use of the ADAM inhibitor comprising the benzohydroxamic acid of the present invention or a salt thereof is not limited to the prevention or improvement of wrinkles described above, but can be any use that can exert an effect by inhibiting the activity of ADAM.
  • it can also be used for the treatment or prevention of various diseases that are adversely affected by the proliferation or differentiation of skin cells due to the activity of ADAM.
  • the present invention will be specifically described with reference to examples. However, the present invention is not limited to the following examples.
  • the compounding quantity of a compound is the mass% unless there is particular notice.
  • HB-EGF-AP / HT-1080 Heat-alkaline phosphatase ( ⁇ Using human fibrosarcoma-derived cultured cells (HT-1080) modified so as to forcefully express the fusion protein added with P), a compound having ADAM enzyme inhibitory activity was screened.
  • the full-length HB-EGF molecule is expressed on the cell surface of the cell line HB-EGF-AP / HT-1080 used in the form fused with alkaline phosphatase!
  • the ADAM enzyme on the cell membrane surface is activated and cleaves the HB-EGF molecule. Cleaved free HB-EGF binds alkaline phosphatase, so the alkaline phosphatase activity in the culture supernatant is measured to indirectly increase the ADA M enzyme inhibitory activity of the compound. It can be measured.
  • HB-EGF-AP / HT-080 with the number of cells adjusted to 2.0 ⁇ 10 5 cells / ml was seeded on a 96-well culture microplate at 0.2 ml / well at 37 ° C. It was cultivated. After removing the medium and washing with PBS ( ⁇ ), 0.1 ml / well of the medium containing the test substance was added and incubated at 37 ° C. for 30 minutes for pretreatment.
  • the culture supernatant is removed, and a medium containing the test substance and 60 nM TPA (honorebonole estenole: 12-0—Tetradecanoylphorbo ⁇ acetate; Sigma P8139) is added again at 0.2 ml / well. Treated by incubating for minutes. After completion of the treatment, 0.1 ml of the culture supernatant of each well was transferred to a well of a microplate for alkaline phosphatase activity measurement, and incubated at 65 ° C. for 10 minutes to inactivate the endogenous alfa phosphatase.
  • TPA nonorebonole estenole: 12-0—Tetradecanoylphorbo ⁇ acetate
  • Inhibition rate (%) (A0-AS) / (A0-A100) * 100
  • the benzohydroxamic acid of the present invention showed a high inhibitory effect on HB-EGF release, suggesting that it inhibits ADAM activity.
  • Table 1 shows the release inhibition rate of each benzohydroxamic acid.
  • T EWL Transdermal water transpiration
  • TE WL transepidermal water transpiration
  • TEWL increased to 216% in the vehicle application group, while it remained only 126% increase in the 4-methoxybenzohydroxamic acid application group.
  • Benzohydroxamic acid significantly inhibited the increase in TEWL due to tape stripping.
  • 4-methoxybenzohydroxamic acid inhibits the release of HB-EGF, an epidermal growth factor, by inhibiting activated ADAM, and suppresses the growth and thickening of the skin. It has been suggested that formation can be prevented or improved. Furthermore, it was suggested that 4-methoxybenzohydroxamic acid significantly suppresses the increase in transepidermal water transpiration (TEWL) due to skin destruction, and also has an effect of preventing rough skin.
  • TEWL transepidermal water transpiration
  • phase A Dissolve carboxybulu polymer in a small amount of purified water (phase A). Remaining purified water Add polyethylene glycol 1500, triethanololamine, and 4-methoxybenzohydroxamic acid to heat and dissolve at 70 ° C (aqueous phase). Mix other ingredients, heat and melt and keep at 70 ° C (oil phase). The oil phase was added to the aqueous phase and pre-emulsified, and the A phase was uniformly emulsified with a cake homomixer. After emulsification, the mixture was cooled to 30 ° C. while stirring well to obtain an emulsion.
  • Vitamin E acetate 0.3
  • Methylbenzohydroxamic acid 1.0 0 Posiethylene gutinole 1500 2. 0 Jojoba oil 1. 0 Isostearic acid 0.5 Stearic acid 0.5 Behenic acid 0.5 Tetra-2-ethylhexyl acid pentaerythrit 3. 0
  • Macadamia nut oil 1. 0 Phytosteryl hydroxystearate 0. 05 Lactic acid 0. 05
  • Dimethinorepolysiloxane 1. 0 Stearyl alcohol 1. 8 Behe-Noleanolecanol 1. 6 Glycerin 8.0
  • Cetyl ethylhexanoate 4.0 Polyoxyethylene hydrogenated castor oil 0.5 Self-emulsifying glyceryl monostearate 3.0 Potassium hydroxide 0.15 Sodium hexametaphosphate 2.0 0.05 Trimethylglycine 2.0
  • Dimethylolene polysiloxane 2. 0 Stearyl alcohol 3. 0 Behe-noreno-reconole 2. 0 Glycerin 5.0

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Abstract

L'invention concerne une méthode très efficace de prévention ou d'atténuation des rides. Cette méthode consiste à appliquer sur la peau un inhibiteur d'ADAM comprenant un acide benzohydroxamique représenté par la formule générale (I) suivante.[Formule chimique (I)] (I) (dans cette formule, R1's représente chacun C1-18 alkyle, C3-8cycloalkyle, halogéno, hydroxy, C1-18alkoxy, benzyloxy, amino, ou acylamino; R2 est hydrogène, méthyle ou phényle; et n est un entier compris entre 0 et 3.)
PCT/JP2006/319236 2005-09-29 2006-09-28 Prevention ou attenuation des rides au moyen d'un inhibiteur des adam Ceased WO2007037295A1 (fr)

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JP2005283501 2005-09-29
JP2005-283501 2005-09-29
JP2006-101430 2006-04-03
JP2006101430A JP2007119444A (ja) 2005-09-29 2006-04-03 Ａｄａｍ阻害剤によるしわの防止または改善

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CN101983051B (zh) 2008-03-31 2013-04-24 株式会社资生堂 用于防止或改善皱纹的口服、注射、皮肤外用剂和美容方法
JP2012505441A (ja) 2009-03-24 2012-03-01 株式会社日立製作所 ストレージ装置およびそのデータ制御方法

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WO2003007954A2 (fr) * 2001-07-19 2003-01-30 Pharmacia Corporation Sulfonyl aryl hydroxamates et leur utilisation comme inhibiteurs des metalloproteases matricielles
WO2003089601A2 (fr) * 2002-04-17 2003-10-30 Dynamis Therapeutics, Inc. 3-desoxyglucosone et la peau
EP1364645A1 (fr) * 2002-05-21 2003-11-26 ZAMBONI, Paolo Combination pharmaceutique pout traitment topique avec chelateur de fer, inhibiteur de metalloproteases et facteur XIII
US20040146539A1 (en) * 2003-01-24 2004-07-29 Gupta Shyam K. Topical Nutraceutical Compositions with Selective Body Slimming and Tone Firming Antiaging Benefits
WO2005019162A1 (fr) * 2003-08-26 2005-03-03 Amorepacific Corporation Derives d'acide hydroxamique et leur methode de preparation
WO2006041214A1 (fr) * 2004-10-14 2006-04-20 Shiseido Company, Ltd. Prevention de l'apparition de rides ou diminution des rides par l'emploi d'un inhibiteur de l'activation d'une adam
US20060165641A1 (en) * 2005-01-18 2006-07-27 Kumar Pillai Cosmetic compositions containing combinations of hydroxamate derivatives and antioxidants in a liposomal delivery system

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