| 摘要 |
#CMT# #/CMT# Cosmetic use of at least one 1-[(1H-pyrazol-4-yl)carbonyl] heterocyclic compounds (I) and their salts and/or solvates in a cosmetic care and/ or make-up composition for human keratin fibers, to induce and/or stimulate their growth, reduce their loss and/or increase their density. #CMT# : #/CMT# Cosmetic use of at least one 1-[(1H-pyrazol-4-yl)carbonyl] heterocyclic compounds of formula (I) and their salts and/or solvates in a cosmetic care and/ or make-up composition for human keratin fibers, to induce and/or stimulate their growth, reduce their loss and/or increase their density. R 1phenyl or 1-3C alkyl; R 2phenyl or 1-3C alkyl (both substituted by 1-3C alkoxy (preferably methoxy) or one or more halo); and NR 3R 45-7 a heterocycle containing 5-7 atoms, or two heteroatoms comprising N and/or O, and additional nitrogen atom substituted by 1-3C alkyl, preferably piperidine, piperazine, morpholine or azepine. Independent claims are included for: (1) a method of cosmetic care of hair and/or scalp of humans, to improve their condition and/or appearance, comprising applying the cosmetic composition; leaving the composition in contact with the hair and/or scalp; and rinsing the hair and/or scalp, where the composition comprises (I); (2) a process of cosmetic care and/or make-up of the human eyelashes, regarding to improve their condition and or their appearance, comprising applying mascara composition to eyelashes and/or eyelids, where the composition comprises (I); (3) compositions for care and/or make-up of keratin fibers, preferably eyelashes, comprising (I) in a medium, and at least an additional active agent for the growth of the human keratin fibers, limiting hair falls and/or increasing the hair density; and (4) 1-[(1H-piperidin-4-yl)carbonyl] heterocyclic derivatives of formula (Ia) and 1-[(1H-piperazine-4-yl)carbonyl]heterocyclic derivatives of formula (Ib) and their salts or solvates. #CMT#[Image]#/CMT# #CMT#[Image]#/CMT# #CMT#ACTIVITY : #/CMT# Endocrine-Gen. #CMT#MECHANISM OF ACTION : #/CMT# 15-Hydroxy prostaglandin dehydrogenase (15-PGDH) inhibitor. The ability of (I) to inhibit 15-PGDH was tested. The result showed that 1-[(1,5-diphenyl-1H-pyrazol-4-yl)carbonyl]piperidine exhibited an IC 5 0value of 5 nM. #CMT#USE : #/CMT# (I) are useful in a cosmetic composition for human hair care, and to treat alopecia, preferably androgenic alopecia. (I) are useful in a cosmetic composition for the care and make-up of the eyelashes to the human; and to induce and/or stimulate the sprout of the eyelashes and increase their density. (I) are useful for the preparation of a composition to treat the disorders related to the presence of 15-hydroxy prostaglandin dehydrogenase type 1. (I) are useful in a cosmetic care and/or make-up composition for human keratin fibers, to induce and/or stimulate their growth, reduce their loss and/or increase their density, where the human keratin fibers are hair, eyebrows, eyelashes, beard hairs or mustache. (I) are useful as hair cream, hair lotion, shampoo, after-shampoo, hair mascara or eyelash, and as mascara composition. (I) are useful in the method of cosmetic care of hair and/or scalp of humans to improve the condition and appearance of the hair (all claimed). #CMT#ADVANTAGE : #/CMT# The composition: maintains good condition of hair and/or avoids natural hair fall; and is non-toxic. (I) have improved solubility. #CMT#PHARMACEUTICALS : #/CMT# Preferred Composition: The composition contains other ingredients comprising solvents, thickeners and gelling aqueous phase or oily phase, dyes soluble in the medium of the composition, fillers, pigments, antioxidants, conservatives, perfumes, electrolytes, neutralizing agents, polymer film, UV blocker, pharmaceutical and cosmetic active compound (I) and their mixtures. The composition further comprises another active agents comprising proteins, protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts, hydroxy acids, retinol derivatives, tocopherol derivatives, essential fatty acids, ceramides, essential oils, salicylic acid and its derivatives, hydroxy acid esters, and/or phospholipids. Preferred Components: (I) are present at 10 -> 3>to 10 wt.%, preferably 10 -> 2>to 10 wt.%. The additional active agent is: aminexil, 6-0-[(9Z,12Z)-octadeca-9,12-dienoyl]hexapyranose, benzalkonium chloride, benzethonium chloride, phenol, estradiol, chlorpheniramine maleate, chlorophylline derivative, cholesterol, cysteine, methionine, menthol, peppermint oil, calcium pantothenate, panthenol, resorcinol, protein kinase C activators, glycosidase inhibitors, glycosaminoglycanase inhibitors, pyroglutamic acid esters, hexosaccharidic or acylhexosaccharidic acids, aryl substituted ethylenes, N-acyl amino-acids, flavonoids, derivatives and analogues of ascomycin, histamine antagonists, saponin, proteoglycanase inhibitor, estrogen agonists and antagonists, pseudoterines, cytokines and growth factor promoters, interleukin-1 (IL-1) or IL-6 inhibitors, IL-10 promoters, TNF inhibitors, benzophenones, hydantoin and retinoic acid; the vitamins such as vitamin D, analogous of vitamin B12, the pantothenol; triterpenes; antipruriginous agents such as thenaldine, trimeprazine or cyproheptadine; antiparasitic agents, preferably metronidazole, crotamiton, or pyrethroids; calcium antagonists such as cinnarizine, diltiazem, nimodipine, verapamil, alverine or nifedipine; hormones comprising estriol or its analogous, thyroxine and its salt or progesterone; FP receptor agonist (receptor to the prostaglandins of the type F) such as the latanoprost, (5E)-7-{(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenyl-pentyl]cyclopentyl}hept-5-enoic acid, bimatoprost, travoprost, unoprostone or butaprost; O-acyl derivatives obtained by partial or total esterification of vitamin F by glucose; pyridine-dicarboxylate derivatives or their salts; and/or 15-hydroxy prostaglandin dehydrogenase inhibitor, preferably aminexil, FP receptor agonists, prostaglandins and their derivatives and vasodilators, O-acyl derivatives obtained by partial or total esterification of vitamin F by glucose, minoxidil, latanoprost, (5E)-7-{(1R,2R,3R,5S)-3,5-dihydroxy-2-[(3R)-3-hydroxy-5-phenyl-pentyl]cyclopentyl}hept-5-enoic acid, travoprost, unoprostone or butaprost; and/or diethyl pyridine-2,4-dicarboxylate. #CMT#ADMINISTRATION : #/CMT# Administration of (I) is topical in the form of aqueous, alcoholic or aqueous-alcoholic solution or suspension (all claimed). Administration of (I) is oral (0.1-300 mg per day, preferably 5-10 mg). #CMT#SPECIFIC COMPOUNDS : #/CMT# The use of 8 compounds (I) is specifically claimed e.g. 1-[(5-ethyl-1-phenyl-1H-pyrazol-yl)carbonyl]piperidine of formula (Ia), 1-[(1,5-diphenyl-1 H-pyrazol-4-yl)carbonyl]piperidine, 1-{[1-phenyl-5-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}piperidine, 1-[(1,5-diphenyl-1H-pyrazol-4-yl)carbonyl]azepane and 1,5-diphenyl-4-(pyrrolidin-1-ylcarbonyl)-1 H-pyrazole. #CMT#[Image]#/CMT#. |
