CN101160114B - Composition and method for scalp and hair treatment - Google Patents
Composition and method for scalp and hair treatment Download PDFInfo
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- CN101160114B CN101160114B CN200580045568.4A CN200580045568A CN101160114B CN 101160114 B CN101160114 B CN 101160114B CN 200580045568 A CN200580045568 A CN 200580045568A CN 101160114 B CN101160114 B CN 101160114B
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Abstract
Provided is a composition for scalp and hair treatment, comprising a menthol derivative and a prostaglandin compound having two hetero atoms at the 15 position. The composition of the present invention is effective not only for preventing dandruff and itchy scalp but also for preventing or treating hair loss, baldness, or hair thinness.
Description
Technical field
The present invention relates to hair and scalp treatment field.In more detail, the present invention relates to hair and scalp treatment compositions, it can be used as medicine, pastille cosmetics or cosmetic product and provides.The invention still further relates to the method for processing scalp and hair.
Background technology
In this aging society that is full of pressure, the variety of issue that relates to scalp and/or hair increases day by day.For the demand of the scalp of processing those problems and/or hair care product also rapid growth.
Developed the product of many processing scalps and/or hair, comprised that the hair cosmetic composition and the hair growth that are applicable to various hairs and scalp condition promote prescription.For example, developed by the prevention dandruff and the product of scratching where it itches to prevent the hair disappearance.
Usually, the known origin cause of formation that bald, alopecia, hair disappearance, oligotrichosis, the dandruff and scalp are scratched where it itches comprise excessive generation, the lipid peroxide of activation, the sebum of androgen in some organ such as the hair gland generation, hair follicle and stress in sanguimotor minimizing.The undernutrition of folliculus can't grow dense and beautiful hair and may cause oligotrichosis.In addition, sanguimotor minimizing can cause the damaged of undernutrition and waste discharge function in the folliculus.Consider the mechanism about hair disappearance described above, improve the cuticular turnover of scalp, suppress the generation of excess sebum and promote the blood circulation of scalp to be considered to develop for the treatment of the key about the composition of scalp and/or hair problem.
Usually, combine to prepare conventional scalp and hair treatment product by will effectively eliminating or alleviate sick compositions bald or one or more origin causes of formation that hair lacks.For example, vitamin is such as vitamin B and vitamin E; Aminoacid is such as serine and methionine, nicotinic acid, Japanese Herba Swertiae bimaculatae extract; Vasodilation is such as the acetylcholine derivant; Antiinflammatory is such as shikonin (erythrorhizon); Estrogen is such as estradiol; And the skin function factor, as for the manufacture for the treatment of with prevent the cepharathin of the compositions of bald, hair disappearance and/or oligotrichosis.(Japanese Patent Laid publication number H2-48516, H5-255044, H7-206647, H7-277930 and 2001-288047)
An inventor of the present invention has found that having two heteroatomic prostaglandin compounds at 15 has hair growth promotion activity and submitted international application (WO2005/013928 is by being incorporated herein with reference to the disclosure of drawing this application) to.
Summary of the invention
An object of the present invention is to provide the compositions for hair and scalp treatment, it not only effectively prevents the dandruff and scalp to scratch where it itches but also promotes hair growth and/or prevention hair disappearance, and has fabulous stability and safety.Further purpose of the present invention is to provide the scalp of processing the patient who is subjected to scalp and/or the puzzlement of hair problem and/or the method for hair.
The invention provides the compositions for scalp and/or hair treatment, it comprises menthol derivative and has two heteroatomic prostaglandin compounds at 15.
The present invention also provides the scalp of processing the patient who needs said composition and/or the method for hair, comprises the menthol derivative of effective dose and 15 are had two heteroatomic prostaglandin compound topical application to patient's scalp and/or hair.
Detailed Description Of The Invention
The PG chemical compound nomenclature of using in this description and the claim is based on the numbering system of the prostanoic acid of following formula (A) expression.
Formula (A) shows the basic framework of C-20 carbon atom, but the invention is not restricted to have same carbon atoms number purpose skeleton those.In formula (A), begin consisting of the carbon atoms numbered of PG chemical compound basic framework from carboxylic acid (No. 1), the carbon atom towards pentacyclic direction in α-chain will be numbered 2-7, and those atoms are 8-12 in the ring, and those are 13-20 in ω-chain.When the carbon atom number in α-chain reduces, sequentially delete numbering since 2; When the carbon atom number in α-chain increases, with the chemical compound called after at 2 corresponding substituent substituted compounds with alternative carboxyl (C-1).Similarly, when the carbon atom number in ω-chain reduces, sequentially delete numbering since 20; And when the carbon atom number in ω-chain increased, the carbon atom that surpasses 20 was named as substituent group.Except as otherwise noted, the spatial chemistry of chemical compound is identical with the spatial chemistry of above-mentioned formula (A).
Usually, term PGD, PGE and PGF are illustrated respectively in 9 and/or 11 the PG chemical compounds with hydroxyl, except the PG chemical compound that has a hydroxyl at 9 and/or 11, these terms also are included in 9 and/or 11 and have substituent PG chemical compound but in this manual.This compounds is called as 9-dehydroxylation-9-replacement-PG chemical compound or 11-dehydroxylation-11-replacement-PG chemical compound.PG chemical compound with hydrogen substituted hydroxy is called after 9-or 11-dehydroxylation-PG chemical compound simply.
As mentioned above, the nomenclature of PG chemical compound is based on the skeleton of prostanoic acid.Yet, have at chemical compound in the situation of the structure that partly is similar to prostaglandin, can use abbreviation " PG ".Therefore, wherein α-chain namely has 9 carbon atoms by the PG chemical compound of two carbon atom expansions in α-chain, is named as 2-decarboxylation-2-(2-carboxyethyl)-PG chemical compound.Similarly, the PG chemical compound that has 11 carbon atoms in α-chain is named as 2-decarboxylation-2-(4-carboxylic butyl)-PG chemical compound.Further, the PG chemical compound of ω-chain by the expansion of two carbon atoms (that is: have in ω-chain 10 carbon atoms) is named as 20-ethyl-PG chemical compound.Yet these chemical compounds also can be named according to the IUPAC nomenclature.
The example of analog (derivant that comprises replacement) or derivant comprises the esterified PG chemical compound of carboxyl of α-chain end; The chemical compound that α-chain is lengthened out; Its physiologically acceptable salt; Two keys are arranged in the 2-3 position or in the 5-6 position chemical compound of triple bond is arranged, 3,5,6,16,17,18, the chemical compound of 19 and/or 20 substds; Have the low alkyl group of alternative hydroxyl or the chemical compound of hydroxyl (rudimentary) alkyl at 9 and/or 11.
According to the present invention, 3,17,18 and/or 19 preferred substituents comprises the alkyl with 1-4 carbon atom, particularly methyl and ethyl.Preferred substituents at 16 comprises low alkyl group, such as methyl and ethyl, hydroxyl, halogen atom such as chlorine and fluorine, aryloxy group such as fluoroform phenoxy group.Comprise low alkyl group such as methyl and ethyl, hydroxyl, halogen atom such as chlorine and fluorine, aryloxy group such as fluoroform phenoxy group 17 preferred substituents.Comprise saturated or undersaturated low alkyl group such as C1-4 alkyl, lower alkoxy such as C1-4 alkoxyl, low-grade alkoxy alkyl such as C1-4 alkoxy-C 1-4 alkyl 20 preferred substituents.Comprise halogen atom such as chlorine and fluorine 5 preferred substituents.Comprise the oxo group that forms carbonyl 6 preferred substituents.Can be α, β or its mixture 9 and/or 11 spatial chemistry with PGs of hydroxyl, low alkyl group or hydroxyl (rudimentary) alkyl substituent.
Further, above-mentioned analog or derivant can be the chemical compounds that has alkoxyl, cycloalkyl, cycloalkyl oxy, phenoxy group or phenyl at ω-chain end, and wherein this chain is shorter than original PGs.
The preferred prostaglandin compound that the present invention uses is represented by formula (I):
Wherein L, M and N are hydrogen, hydroxyl, halogen, low alkyl group, hydroxyl (rudimentary) alkyl, lower alkanoyloxy or oxo, and wherein L and M have at least one to be the group outside the hydrogen, and five-membered ring can have a two key at least;
A is-CH
3Or-CH
2OH ,-COCH
2OH ,-COOH or its functional derivant;
B is-CH
2-CH
2-,-CH=CH-or-C ≡ C-;
Z
1And Z
2Be oxygen, nitrogen or sulfur;
R
2And R
3Be the optional low alkyl group that replaces, it randomly is joined together to form low-grade alkylidene,
R
1Be saturated or undersaturated bivalent lower or intermediate aliphatic hydrocarbon residue, it is unsubstituted or is replaced by halogen, alkyl, hydroxyl, oxo, aryl or heterocycle group, and at least one carbon atom in the aliphatic hydrocarbon is randomly replaced by oxygen, nitrogen or sulfur; With
Ra is saturated or undersaturated rudimentary or intermediate aliphatic hydrocarbon residue, and it is unsubstituted or is replaced by halogen, oxo, hydroxyl, lower alkoxy, lower alkanoyloxy, ring (rudimentary) alkyl, ring (rudimentary) alkyl oxy, aryl, aryloxy group, heterocyclic radical or heterocyclic oxy group; Lower alkoxy; Lower alkanoyloxy; Ring (rudimentary) alkyl; Ring (rudimentary) alkyl oxy; Aryl; Aryloxy group; Heterocyclic radical; Heterocyclic oxy group.
The preferred prostaglandin compound that the present invention uses is represented by formula (II):
Wherein L and M are hydrogen, hydroxyl, halogen, low alkyl group, hydroxyl (rudimentary) alkyl, lower alkanoyloxy or oxygen, and wherein L and M have at least one to be the group outside the hydrogen, and five-membered ring can have one or more pairs of keys at least;
A is-CH
3Or-CH
2OH ,-COCH
2OH ,-COOH or its functional derivant;
B is-CH
2-CH
2-,-CH=CH-or-C ≡ C-;
Z
1And Z
2Be oxygen, nitrogen or sulfur;
R
2And R
3Be the optional low alkyl group that replaces, it randomly is joined together to form low-grade alkylidene,
X
1And X
2Be hydrogen, low alkyl group or halogen;
R
1Be saturated or undersaturated bivalent lower or intermediate aliphatic hydrocarbon residue, it is unsubstituted or is replaced by halogen, alkyl, hydroxyl, oxo, aryl or heterocycle group; And at least one carbon atom in the aliphatic hydrocarbon is randomly replaced by oxygen, nitrogen or sulfur;
R
4Be singly-bound or low-grade alkylidene; With
R
5Be low alkyl group, lower alkoxy, lower alkanoyloxy, ring (rudimentary) alkyl, ring (rudimentary) alkyl oxy, aryl, aryloxy group, heterocyclic radical or heterocyclic oxy group.
In following formula, R
1And R
aTerm in the definition " undersaturated " is intended to comprise at least one or a plurality of pairs of keys and/or triple bond, the described pair of key and/or triple bond between the carbon atom of main chain and/or side chain isolated ground, exist dividually or continuously.According to common nomenclature, the unsaturated bond between two serial positions points out that by sign the less numbering of two positions represents, the unsaturated bond between two terminal positions represents by the numbering that indicates two positions.
Term " rudimentary or intermediate aliphatic hydrocarbon " refers to have 1-14 carbon atom, the straight or branched alkyl (for side chain, 1-3 carbon atom is preferred) of preferred 1-10, a particularly 1-8 carbon atom.
Term " halogen atom " comprises fluorine, chlorine, bromine and iodine.
Except as otherwise noted, the term " rudimentary " that runs through description is intended to comprise the group with 1-6 carbon atom.
Term " low alkyl group " refers to contain the saturated hydrocarbyl of the straight or branched of 1-6 carbon atom, and comprises, such as methyl, ethyl, propyl group, isopropyl, butyl, isobutyl group, the tert-butyl group, amyl group and hexyl.
Term " low-grade alkylidene " refers to contain the divalent saturated hydrocarbon of the straight or branched of 1-6 carbon atom, and comprises such as methylene, ethylidene, propylidene, isopropylidene, butylidene, isobutylidene, the inferior tert-butyl group, pentylidene and hexylidene.
Term " lower alkoxy " refers to low alkyl group-O-group, and wherein low alkyl group as above defines.
Term " hydroxyl (rudimentary) alkyl " refers to the low alkyl group that replaced by at least one oh group as defined above, for example methylol, 1-ethoxy, 2-ethoxy and 1-methyl isophthalic acid-ethoxy.
Term " low-grade alkane acidyl oxygen base " refers to the group that represented by formula RCO-O-, and wherein RCO-is the acyl group that is formed by the oxidation of low alkyl group as defined above, such as acetyl group.
Term " ring (rudimentary) alkyl " refers to still contain the cyclic group that formed by the cyclisation of low alkyl group as defined above three or more carbon atom, and comprise such as cyclopropyl, cyclobutyl, cyclopenta and cyclohexyl.
Term " ring (rudimentary) alkyl oxy " finger ring (rudimentary) alkyl-O-, its medium ring (rudimentary) alkyl as above defines.
Term " aryl " can comprise aromatic hydrocarbon (group of preferred monocycle) unsubstituted or that replace, such as phenyl, tolyl, xylyl.Substituent example is halogen atom and halogen (rudimentary) alkyl, and wherein halogen atom and low alkyl group as above define.
Term " aryloxy group " refers to the group that represented by formula ArO-, and wherein Ar is aryl as defined above.
Term " heterocyclic group " can comprise Dan Zhisan ring, the heterocyclic group of preferred monocycle, and it is to have optional carbon atom and a 1-4 that replaces, preferred 1-3 is selected from the heteroatomic 5-14 of 1 in nitrogen-atoms, oxygen atom and the sulphur atom or 2 kind unit, preferred 5-10 unit ring.The example of heterocyclic group comprises furyl, thienyl, pyrrole radicals oxazolyl isoxazolyl, thiazolyl, isothiazolyl, imidazole radicals, pyrazolyl, the furazan base, pyranose, pyridine radicals, pyridazinyl, pyrimidine radicals, pyrazinyl, the 2-pyrrolinyl, pyrrolidinyl, the 2-imidazolinyl, the imidazoles base of washing, the 2-pyrazolinyl, pyrazolidinyl, piperidyl, piperazinyl, morpholino, indyl, benzothienyl, quinolyl, isoquinolyl, purine radicals, quinazolyl, carbazyl, acridinyl, phenanthridinyl, benzimidazolyl, the benzimidazoline base, benzothiazolyl, phenothiazinyl.Substituent example in this case comprises low alkyl group that halogen and halogen replace, wherein halogen atom and low alkyl group be as mentioned above.
Term " heterocyclic oxy group group " refers to the group that represented by formula HcO-, and wherein Hc is aforesaid heterocyclic group.
" functional derivatives " of term A comprises salt (preferred pharmaceutically acceptable salt), ether, ester and amide.
" pharmaceutically acceptable salt " that suits comprises the conventional nontoxic salts that uses, for example: the salt that becomes with inorganic base such as alkali metal salt (for example sodium salt and potassium salt), alkali salt (for example calcium salt and magnesium salt), ammonium salt; Or the salt that becomes with organic base, for example: amine salt (for example methylamine salt, dimethylamine salt, cyclohexylamine salt, benzene methanamine salt, piperidinium salt, ethylenediamine salt, ethanolamine salt, diethanolamine salt, triethanolamine salt, three (hydroxyl methylamine) ethane salt, monomethyl-monoethanolamine salt, procaine salt and theophylline salt), alkaline amino acid salt (for example arginine salt and lysinate), tetraalkylammonium salt etc.These salt can prepare by conventional method, for example by corresponding bronsted lowry acids and bases bronsted lowry or standby by salt exchange system.
The example of ether comprises alkyl ether, for example, and lower alkyl ether such as methyl ether, ether, propyl ether, diisopropyl ether, butyl ether, isobutyl ether, tertbutyl ether, amyl ether and 1-cyclopropyl ethylether; With middle rank or senior alkyl ether such as Octyl Ether, diethylhexyl ether, lauryl ether and whale alkyl ether; Unsaturated ethers such as oleyl ether and inferior oil base (linolenyl) ether; Low-grade alkenyl ether such as vinyl Ether, allyl ether; Low-grade alkynyl ether such as acetylene ether and propine ether; Hydroxyl (rudimentary) alkyl ether such as hydroxyethyl ether and hydroxyl isopropyl ether; Lower alkoxy (rudimentary) alkyl ether such as methoxy ether and 1-methoxy ethyl ether; The optional aryl ether that replaces such as diphenyl ether, tosyl ether, 2-methyl-2-phenylpropane base ether, salicyl ether, 3,4-two-anisyl ether and Benzoylamide phenylate; And aryl (rudimentary) alkyl ether such as methyl phenyl ethers anisole, trityl ether and dibenzyl ether.
The example of ester comprises aliphatic ester, and for example: lower alkyl esters such as methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, the tert-butyl ester, pentyl ester and 1-encircle the third ethyl ester; Low-grade alkenyl ester such as vinyl acetate and allyl ester; Low-grade alkynyl ester such as ethynyl ester and propynyl ester; Hydroxyl (rudimentary) Arrcostab such as hydroxy methacrylate; Lower alkoxy (rudimentary) Arrcostab such as methoxymethyl ester and 1-methoxy ethyl ester; With the optional aryl ester that replaces, as, for example: phenyl ester, tolyl ester, tert-butyl group phenyl ester, salicyl ester, 3,4-two-methoxyl group phenyl ester and Benzoylamide phenyl ester; And aryl (rudimentary) Arrcostab such as benzyl esters, trityl ester and benzhydryl ester.
The amide of A refers to the R by formula-CONR ' "; wherein R ' and R " is respectively hydrogen, low alkyl group, aryl, alkyl-or aryl-sulphonyl, low-grade alkenyl and low-grade alkynyl, and comprises for example low alkyl group amide such as methyl nitrosourea, acetamide, dimethylformamide and diethylamide; Aryl amide such as anilid and toluidide; And alkyl-or aryl-sulfonamide such as methylsulfonamides, ethyl sulfonamide and toluenesulfonamide.
The preferred embodiment of L and M comprises hydroxyl and oxo, and especially, M and L are the hydroxyl with 5-ring structure of so-called PGF type.
The preferred embodiment of A is-COOH, its pharmaceutically acceptable salt, ester or amide.
Preferred B is CH
2-CH
2-, so-called 13,14-two Hydrogens.
X
1And X
2Preferred embodiment be fluorine, so-called 16,16-difluoro type.
Preferred R
1For containing 1-10 carbon atom, the hydrocarbyl residue of preferred 6-10 carbon atom.Further, at least one carbon atom in the aliphatic hydrocarbon is randomly replaced by oxygen, nitrogen or sulfur.
For example, R
1Example comprise following radicals:
-CH
2-CH
2-CH
2-CH
2-CH
2-CH
2-，
-CH
2-CH＝CH-CH
2-CH
2-CH
2-，
-CH
2-CH
2-CH
2-CH
2-CH＝CH-，
-CH
2-C≡C-CH
2-CH
2-CH
2-，
-CH
2-CH
2-CH
2-CH
2-O-CH
2-，
-CH
2-CH＝CH-CH
2-O-CH
2-，
-CH
2-C≡C-CH
2-O-CH
2-，
-CH
2-CH
2-CH
2-CH
2-CH
2-CH
2-CH
2-，
-CH
2-CH＝CH-CH
2-CH
2-CH
2-CH
2-，
-CH
2-CH
2-CH
2-CH
2-CH
2-CH＝CH-，
-CH
2-C＝C-CH
2-CH
2-CH
2-CH
2-，
-CH
2-CH
2-CH
2-CH
2-CH
2-CH(CH
3)-CH
2-，
-CH
2-CH
2-CH
2-CH
2-CH(CH
3)-CH
2-，
-CH
2-CH
2-CH
2-CH
2-CH
2-CH
2-CH
2-CH
2-，
-CH
2-CH＝CH-CH
2-CH
2-CH
2-CH
2-CH
2-，
-CH
2-CH
2-CH
2-CH
2-CH
2-CH
2-CH＝CH-
-CH
2-C=C-CH
2-CH
2-CH
2-CH
2-CH
2-, and
-CH
2-CH
2-CH
2-CH
2-CH
2-CH
2-CH(CH
3)-CH
2-。
Preferred Ra contains 1-10 carbon atom, the more preferably hydrocarbon of 1-8 carbon atom.Ra can have one or two side chain that contains a carbon atom.
Preferred Z
1And Z
2Oxygen.
R
2And R
3Preferably be joined together to form C2 or C3 alkylidene.
Above-mentioned formula (I) and (II) and α-and/or the configuration of ω chain can be identical or different with original PGs.But the present invention also comprises the mixture of the chemical compound of chemical compound with archetype configuration and non-archetype configuration.
In the present invention, for example single tautomer, its mixture or optical isomer or its mixture, racemic mixture and other stereoisomer all can be used for same purpose in any isomer.
In the present invention, preferred prostaglandin compound is 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF
2 αIsopropyl ester, 13,14-dihydro-15,15-ethylenedioxy-17-phenyl-18,19,20-three nor-(trinor)-PGF
2 αIsopropyl ester, 13,14-dihydro-15,15-three methylene-dioxies-20-ethyl-PGF
2 αIsopropyl ester, 13,14-dihydro-15,15-dimethoxy-20-ethyl-PGF
2 αIsopropyl ester and 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF
2 αEthyl ester.Especially, preferably use 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF
2 αEthyl ester.
The consumption of prostaglandin compound is can the enough blood circulation facilitations of effective supply and/or scalp bating effect and can not cause that product makes the amount of difficulty in the present composition.Consumption can be 0.0001-10.0wt% (dry weight) according to the gross weight of compositions, preferably, and 0.001-5.0wt%.
The menthol derivative of using in the compounds of this invention can be for example Menthol and dl-menthol of any menthol of using in cosmetics or pharmaceuticals.The commercially available acquisition of menthol derivative or by extract Herba Menthae herbaceous plant (Mentha herbs) for example Mentha arvensis L. syn.M.haplocalyxBrig (peppermint) obtain.Menthol derivative can be used alone or in combination.
The consumption of the menthol derivative in the present composition is can the effective supply antiinflammatory, anti-pachylosis, anti-dandruff, anti-ly scratch where it itches, hair growth promotes and/or the amount of hair disappearance preventive effect.In addition, should determine consumption the upper limit so that compositions disadvantageous sensation can be provided and can not cause that product makes difficulty.
According to the gross weight of compositions, the amount of menthol derivative can be 0.001-5.0wt% in the present composition, is preferably 0.01-3.0wt%.
The present composition may further include the active component that usually joins in conventional scalp and/or the Hiar treatment compositions, only otherwise damage purpose of the present invention.
The example that can add the active component in the compositions of the present invention comprises material Swertia japonica (Swertia japonica) extract for example that can improve blood circulation, the vitamin E or derivatives thereof, the acetylcholine derivant, cepharanthine, carpronium chloride, nicotinic acid and nicotinic acid derivates and minoxidil; Local irritant is capsicum tincture for example, n-nonanoic acid chinese cymbidium amide (vanilamide), Vanillyl pelargonic amide (vanillylamide), Camphora, ginger tincture and benzyl nicotinate; Antiseborrheic is the pyridoxol or derivatives thereof for example, sulfur and vitamin B6; Metabolic improver is photochromic pigment 301 for example, placental protein, biotin, nicotiamide, vitamin B6 and its derivant, biotin, pantothenic acid and its derivant, cepharanthine, single nitroguaiacol, single nitroguaiacol sodium salt, 6-benzyl amidopurin, diisopropylamine dichloroacetate, hinokitol, the pentadecanoic acid monoglyceride, DADA, CTP and SD-35; Anti-inflammatory agent is glycyrrhizic acid for example, enoxolone or derivatives thereof, adenosine or derivatives thereof, Radix Arnebiae (Radix Lithospermi) (lithospermi radix) extract, salicylic acid and its derivant, Octopirox (octopirox), zinc oxide, allantoin, benzalkonium chloride, isopropyl methyl phenol, Camphora, ichthyol, guaiazulene, epsilon, aminocaproic acid, lysozyme chloride and diphhydramine hydrochloride; The 5α-reductase inhibitor is oxendolone and Tamsulosin for example; Wetting agent is glycerol for example, 1,3 butylene glycol, propylene glycol, dipropylene glycol, PEG400, polyethylene glycol 1500, Macrogol 4000, polyethylene glycol 6000, glucamE-10, hyaluronic acid, biological hyaluronic acid, sorbitol solution, erithritol, maltose alcohol, soluble collagen, chondroitin sulfate is by the polysaccharide of Polianthes tuberosa L. (polianthes tuberosa) acquisition, urea, trisaccharide, vitamin C calcium phosphate and carboxylate ketopyrrolidine sodium; Estrogen is estradiol and estrone for example; Aminoacid is serine for example, methionine and tryptophan, and vitamin is vitamin A for example, B2, B12 and D, the pantothenic acid or derivatives thereof, etc.
Usually the plant extract that joins in conventional scalp and/or the Hiar treatment compositions also can add in the compositions of the present invention.The example of plant extract comprises those that are obtained by following plant: Althaea officinalis, Semen Coicis, curled dock, Fructus Capsici, Aloe, slender lobule western snowberry, Radix Artemisia ordosicae, Oryza sativa L., wild pepper, Herba Rosmarini Officinalis, Rhizoma Drynariae (Drynaria fortunei), Flos Caraganae Sinicae, Gentiana lutea, Radix Salviae Miltiorrhizae (Salvia miltiorrhiza), Fructus Luffae, Radix Platycodonis, pinaster, Radix Sophorae Flavescentis (Sophoraflavescens Aiton), A.acutiloba's root, Flos Carthami, Japanese Radix Berberidis Amurensis, Semen Arecae (betel nut), tasmanian blue gum, Spica Prunellae, Caulis Akebiae, Achyrantes root, Radix Bupleuri root, Flos Camelliae Japonicae, Radix Glycyrrhizae (Glycyrrhiza), hop, Flos Chrysanthemi, Radix Polygalae (Polygala senega), Semen Sesami, Fructus Cnidii (Cnidium officinal), Radix Polygoni Multiflori, Radix Puerariae, Rosa maikwai H.Haraflower, Stigma Croci, Herba Rosmarini Officinalis, Radix Rehmanniae, tree mallow, gambir, Herba Cichorii, Hierb Luisa (Lemongrass), Ramulus et folium taxi cuspidatae, Tarragon, Borassus filabellifer, Fructus Foeniculi, common Radix Malvae sylvestris, rose hip, Herba Urticae Cannabinae, payta, kakocha, Radix Polygoni Multiflori, Ageratum houstonianum Miller., Valeriana Fauriei Briq., Guarana, star bud Centaurea cyanus, cantharides, Fruit of Catalpa Ovata G. Don, Flos Inulae, Osmanthus tragranscv.Aurantiacu, Japanese Catnip (Schizonepeta tenuifolia Briq.var japonica Kitagawa), Semen Pharbitidis, geranium thunbergii, cuachalalate, Herba Chelidonii (Chelidonium majus), Kumaseba, Chinese Gallnuts (Galla rhois), Fructus Arctii { Arctii fructus}, cilantro, Japanese Glcditsia Sinensis, the Radix Bupleuri root, cape jasmine fruit, Japanese Fructus Piperis, Paeonia suffruticosa, Semen Plantaginis, terculia foetida, Radix Dichroae root, cedron, toadpoison, Swertia japonica, Cacumen Platycladi, Folium Perillae, Sophora, Radix Et Rhizoma Rhei, matico, Herba Scopariae (Chanca piedra) (Phyllanthus niruri), Flos Caryophylli, bitter tree overground part, Symphytum officinale, Semen Arecae (betel nut), Semen Strychni, Fructus Chaenomelis, Herba Leonuri, Caulis Seu Folium Lespedezae Bicoloris, Herba Equiseti Arvinsis (Regro) (Equisetum arvense), Colophonium, cotton, Cortex Moutan, comfrey (beinwell) (Symphytum officinale L.), Arnica montana, sweet laurustinus (Sweet hydrangea) (Hydrangea macrophylla var.thunbergii), Chinese Cordyceps (Cordycepssinensis), Japan's Herba Rabdosiae glaucocalycis, Fructus Hordei Vulgaris, Fructus Citri junoris, Sargassum, Fructus Cucumidis sativi, Fructus Arctii, Lentinus Edodes, Ransium domesticum, Folium Eriobotryae, grape leaf, european plum, Fructus Luffae, Rosa maikwai H.Hara, Flos Lilii viriduli and Fructus Mali pumilae.
In addition, following material can be joined in the compositions of the present invention, as long as they can not damage effect of the present invention: lactic acid or its Arrcostab; Organic acid is succinic acid for example, malic acid and citric acid; Protease inhibitor is tranamic acid for example; Oil is olive oil for example, squalane, liquid paraffin, isopropyl myristate, higher fatty acids and higher alcohol; Polyhydric alcohol is glycerol and propylene glycol for example; Other for example surfactant is the castor oil hydrogenated ethylene oxide adduct for example, wetting agent, thickening agent, antioxidant, UV absorbent, freshener, spice, pigment, second alcohol and water.
Scalp of the present invention and Hiar treatment compositions can be any forms, need only it and are suitable for the scalp external, for example liquid, emulsion, ointment, emulsifiable paste, gel and aerosol.Compositions of the present invention can prepare with the basic ingredient for the preparation of desired form of routine.The present composition can provide with the form of pharmaceuticals, pastille cosmetics or cosmetics.
Hair of the present invention and scalp care compositions can be used for the treatment of or prevent hair disappearance, bald, alopecia, the dandruff and/or scalp to scratch where it itches.The non-limiting example that is suitable for the disease of said composition comprises treatment or prevention android type diffusibility alopecia and alopecia circumscripta alopecia bald, that mainly observe in the women.
Optionally compositions of the present invention is used or sparged on the scalp.Because the cause of each composition combination, active component effectively percutaneous is absorbed.
Determine the dosage of hair of the present invention and scalp care compositions according to the degree of age of patient and sex and the hair disappearance for the treatment of or oligotrichosis.Consumption can change according to the dosage form of compositions.Usually.For adult male, the amount of the compositions of application is the 0.0001-100mg/day/kg body weight, and the amount of the prostaglandin compound of preferably using is the 0.001-10mg/day/kg body weight.Can be with this consumption to provide for 2-4 time divided dose every day.
Synthetic example 1
13,14-dihydro-15,15-three methylene-dioxies-20-ethyl-PGF
2 αIsopropyl ester (5)
Add the p-toluenesulfonic acid of 1,3-PD (0.92ml, 12.73mmol) and catalytic amount in the solution of the chemical compound 1 (510.0mg, 1.273mmol) in toluene (10.2ml) and with mixture heating 17 hours under refluxing.After this, will react maintenance and leave standstill, until it is cooled to room temperature, wash with saturated sodium bicarbonate aqueous solution and sodium-chloride water solution.With organic facies with dried over mgso and reduction vaporization.(Merck 7734, hexane: ethyl acetate=3: 2) obtain chemical compound with the residue purification by silica gel column chromatography
2(581.3mg).
With the chemical compound 2 (580.0mg in toluene (11.6ml), 1.265mmol) solution be cooled to-78 ℃, dropwise to wherein adding 1.5M-DIBAH (in the toluene, 2.95ml, 4.427mmol) and with mixture stirring 1 hour, then in the gained mixture, dropwise add methanol (1.79ml).To wherein adding saturated Rochelle's salt solution (100ml) and with mixture strong stirring 30 minutes.Use ethyl acetate extraction gained mixture, and with saturated salt water washing organic layer, use magnesium sulfate to carry out drying and reduction vaporization.By silica gel column chromatography with residue purification (Merck7734, hexane: ethyl acetate=1: 9-0: 10) obtain chemical compound
3(275.2mg, by
1Productive rate be 61.4%).
0 ℃, be added in the 1M-potassium tert-butoxide among the THF (6.07ml, 6.07mmol) in (4-carboxylic butyl) tri-phenyl-phosphorus bromide (1.346g, the 3.038mmol) dispersion liquid in THF (6ml).To react stirring in room temperature and then be cooled to-20 ℃ in 1 hour.To wherein being added in the chemical compound 3 among the THF (7ml) and stirring 2 hours at-20-0 ℃.In reaction, add icy water, remove THF by reduction vaporization.In concentrated residue, dropwise add ice-cold 1N aqueous hydrochloric acid solution solution is adjusted to pH 4 at 0 ℃.
Use ethyl acetate extraction solution and use saturated sodium-chloride water solution washing organic layer, use dried over mgso and reduction vaporization.Add ether in the residue and stirring at room 17 hours, then use diatomite filtration.Reduction vaporization filtrate obtains chemical compound
4Crude product.
At 45 ℃ toward the chemical compound in acetonitrile (7.6ml)
4(0.7594mmol) add DBU (0.45ml, 3.038mmol), isopropyl iodide compound (0.30ml, 3.038mmol) also stirred 4 hours.The reduction vaporization reactant mixture.Add water and use ethyl acetate extraction toward residue.Use saturated sodium-chloride water solution washing organic layer, use dried over mgso and reduction vaporization.(Merck 9385, hexane: ethyl acetate=2: 3) the purification residue obtains the product (yield by 3 is 72.1%) of 727.2mg expectation via silica gel column chromatography.(carboxylic acid 259.0mg) is further purified and obtains chemical compound by separating HPLC thus obtained chemical compound 4
5(isopropyl ester, 240.3mg, the yield of HPLC purification are 92.8%).
Chemical compound
5 1H-NMR composes (200MHz, CDCl
3): δ 5.57-5.14 (2H, m), 5.01 (1H, sept, J=6.2Hz), 4.17 (1H, bs), 3.97 (1H, bs), 4.00-3.78 (4H, m), (2.76 1H, d, J=6.2Hz), 2.29 (2H, t, J=7.5Hz), 2.44-2.06 (5H, m), 1.88 (2H, bt), 1.93-1.18 (22H, m), 1.23 (6H, d, J=6.2Hz), 0.89 (3H, t, J=6.8Hz)
Synthetic example 2
13,14-dihydro-15,15-dimethoxy-20-ethyl-PGF
2 αIsopropyl ester (10)
To chemical compound
1P-toluene sulfate, original acid A ester (2.19ml, 20.02mmol) and the anhydrous magnesium sulfate (1.20g, 10.01mmol) of the methanol of (797.8mg, 2.002mmol) (2.4ml) solution adding catalytic amount and reflux 4 hours.The cooling reaction also adds sodium bicarbonate, and use diatomite filtration.Reduction vaporization filtrate and with residue (Merck 7734g, hexane: ethyl acetate=3: 2) purification obtains chemical compound via silica gel column chromatography
7(884.3mg, yield 98.9%).
With chemical compound
7The toluene of (767.5mg, 1.719mmol) (15.4ml) solution is cooled to-78 ℃, dropwise to wherein adding 1.5M-DIBAH (in the toluene, 4.0ml, 6.016mmol) and mixture being stirred 1 hour.Then in reaction, dropwise add methanol and reaction is heated to room temperature.To wherein adding saturated Rochelle's salt solution (150ml) and with mixture strong stirring 30 minutes.Use ethyl acetate extraction gained mixture, and with saturated salt water washing organic layer, use magnesium sulfate to carry out drying and reduction vaporization.(Merck9385, hexane: ethyl acetate=1: 9) purification obtains chemical compound via silica gel chromatography with residue
8(415.8mg, yield 70.2%).
0 ℃, be added in the 1M-potassium tert-butoxide among the THF (5.64ml, 5.64mmol) in (4-carboxylic butyl) tri-phenyl-phosphorus bromide (1.250g, the 2.819mmol) dispersion liquid in THF.To react stirring in room temperature and then be cooled to-20 ℃ in 1 hour.To the chemical compound that wherein dropwise is added among the THF (4ml)
8(242.8mg, 0.7048mmol) also stirred 2 hours at-20-0 ℃.In reaction, add icy water, remove THF by reduction vaporization.In residue, dropwise add ice-cold 1N aqueous hydrochloric acid solution solution is adjusted to pH 5 at 0 ℃.Use ethyl acetate extraction solution and use saturated sodium-chloride water solution washing organic layer, use dried over mgso and reduction vaporization.Add ether and stirring at room 17 hours, then use diatomite filtration toward residue.Reduction vaporization filtrate obtains chemical compound
9Crude product (carboxylic acid).
At 45 ℃ of past chemical compounds
9Add DBU (0.42ml, 2.819mmol), isopropyl iodide compound (0.28ml, 2.819mmol) in acetonitrile (0.7048mmol) (7ml) solution and mixture was stirred 16 hours.The reduction vaporization reactant mixture.Add water and use ethyl acetate extraction toward residue.Use saturated sodium-chloride water solution washing organic layer, use dried over mgso and reduction vaporization.(Merck 9385, hexane: ethyl acetate=1: 2) purification obtains chemical compound via silica gel chromatographic column with residue
10(268.0mg is obtained from
8Yield be 80.8%).
Chemical compound with above upper acquisition
10(altogether 370mg) is further purified the chemical compound that obtains purification by separating HPLC
10(341.9mg, the yield of HPLC purification are 92.4%).
Chemical compound 10
1H-NMR composes (200MHz, CDCl
3): δ 5.54-5.13 (2H, m), 5.00 (1H, sept, J=6.2Hz), (4.18 1H, bs), 3.95 (1H, bs), 3.16 (6H, s), 2.66 (1H, d, J=6.4Hz), 2.29 (2H, t, J=7.3Hz), 2.48-2.06 (5H, m), 1.89 (2H, bt), 1.79-1.17 (20H, m), 1.23 (6H, d, J=6.2Hz), 0.89 (3H, t, J=6.8Hz)
Synthetic example 3
13,14-dihydro-15,15-ethylenedioxy-17-phenyl-18,19,20-three nor--PGF
2 αIsopropyl ester (12)
With the method identical with synthetic example by chemical compound
11The preparation chemical compound
12
Chemical compound
11 1H-NMR composes (200MHz, CDCl
3): δ 8.04-7.93 (2H, m), 7.63-7.38 (3H, m), 7.35-7.11 (5H, m), 5.21-5.03 (2H, m), 2.98-2.24 (HH, m), 2.12-1.98 (1H, m), 1.80-1.50 (2H, m)
Chemical compound
12 1H-NMR composes (200MHz, CDCl
3): δ 7.35-7.12 (5H, m), 5.56-5.35 (2H, m), 5.00 (1H, sept, J=6.2Hz), 4.15 (1H, bs), 3.96 (4H, s), 3.92 (1H, bs), 3.18 (1H, bd), (2.86 1H, bd), 2.75-2.63 (2H, m), (2.28 2H, t, J=7.3Hz), 2.46-1.15 (17H, m), 1.22 (6H, d, J=6.2Hz)
Synthetic example 4
13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF
2 αEthyl ester (15)
At 0 ℃ of sodium hydrate aqueous solution (24.49ml) that adds 8N in the solution of the chemical compound 13 (9.18g, 19.59mmol) in methanol (91.8ml).Reactant mixture was at room temperature stirred 3 hours, then at 0 ℃ of hcl acidifying that uses 6N.Use ethyl acetate (100ml+50ml) extraction mixture.Use saturated sodium-chloride water solution (100ml * 2) washing organic layer, carry out drying at anhydrous magnesium sulfate.The vapourisation under reduced pressure extract obtains to be the crude acid 14 of grease.
In the solution of the crude acid 14 in acetonitrile (60ml) and 1,8-diazabicyclo (5,4,0) 11 carbon-7 alkene (11.72ml), dropwise add iodoethane (6.27ml) at 0 ℃.Reactant mixture was stirred 17 hours 45, then be cooled to room temperature, evaporation.Add entry (100ml) to residue.Use ethyl acetate (100ml * 2) extraction mixture.Use 0.1N hydrochloric acid, saturated sodium bicarbonate aqueous solution (100ml) and saturated sodium-chloride water solution (100ml) to wash organic layer.Dry extract and evaporation on anhydrous magnesium sulfate.With residue by twice silica gel column chromatography purification (Merck 7734,220g, hexane: ethyl acetate=2: 3 ,-＞BW-300,210g, hexane: 2-propanol=6: 1) obtain ethyl ester into colorless oil
15(8.60g, 18.92mmol are 96.6% by 13 productive rates).
Chemical compound 15
1H-NMR is (at CDCl
3Middle 200MHz, TMS=0ppm): δ 5.58-5.29 (2H, m), 4.15 (1H, brs), 4.13 (2H, q, J=7.1Hz), (3.97 1H, brs), 3.94 (4H, s), 2.80-2.70 (IH, br), (2.49-2.36 IH, m), 2.32 (2H, t, J=7.4Hz), 2.36-2.15 (4H, m), 1.90-1.83 (2H, m), 1,83-1.12 (20H, m), (1.26 3H, t, J=7.1Hz), (0.88 3H, t, J=6.5Hz).
Embodiment
Will be by explaining in more detail the present invention with embodiment.But those embodiment should not be used for limiting the scope of the invention.
Ingredients listed prepares scalp and hair treatment washing liquid and effect that its prevention dandruff and scalp are scratched where it itches is assessed in the use table 1.In following examples, except as otherwise noted, the consumption of composition is expressed as the percetage by weight (dry weight) based on composition total weight.
1) preparation of washing liquid
With ammonium glycyrrhizinate, nicotiamide, 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF2 α ethyl ester (below, be called " PG compd A "), DL-alpha-tocopherol acetate, MENTHOL and spice are added to and obtain pure composition in the ethanol.With lactic acid, sodium lactate, dipropylene glycol, polyoxyethylene hydrogenated Oleum Ricini and pigment are added to and obtain water composition in the pure water.Pure composition and water composition are mixed, and stirring and filtration obtain test composition.Embodiment 2,4,6,7 and 8 is comparing embodiment
Table 1
| Embodiment | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
| The PG compd A | 0.1 | 0.1 | 0.01 | 0.01 | 0.001 | 0.001 | - | - |
| MENTHOL | 0.2 | - | 0.2 | - | 0.2 | - | 0.2 | - |
| Ammonium glycyrrhizinate | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 |
| The POE castor oil hydrogenated | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
| Nicotiamide | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
| DL-alpha-tocopherol acetate | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
| Pigment | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
| Spice | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
| Lactic acid | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
| Sodium lactate | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount | In right amount |
| Ethanol | 70.0 | 70.0 | 70.0 | 70.0 | 70.0 | 70.0 | 70.0 | 70.0 |
| Pure water | Aequum | Aequum | Aequum | Aequum | Aequum | Aequum | Aequum | Aequum |
| Dipropylene glycol | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 | 2.0 |
| Scalp is scratched where it itches | 0 | 0.6 | 0 | 0.6 | 0 | 0.8 | 0.2 | 0.8 |
| The dandruff | 0 | 0.4 | 0 | 0.4 | 0 | 0.4 | 0.2 | 0.6 |
| Use sensation | 4.4 | 3.0 | 4.2 | 3.0 | 4.2 | 2.8 | 3.8 | 2.0 |
(2) the prevention dandruff and scalp is scratched where it itches and the assessment of result of use.
Complaint have the dandruff and scalp scratch overworked male accept to use embodiment 1-8 compositions processing and assessed the prevention dandruff and effect that scalp is scratched where it itches.Also assessed result of use.This research uses every group of 5 people to carry out.
The 2-3ml compositions is applied to each tester's scalp, one day twice one totally month.The tester once washs his hair with the shampoo that does not contain the medicine composition every day during this period.When the treatment phase finishes, collect tester's the dandruff and measure the protein content of the dandruff by adsorbent equipment.The amount of the dandruff is assessed and average mark is listed in table 1 according to following listed evaluation criteria.In addition, according to following listed evaluation criteria, the tester has assessed scratching overworked and use sensation on the scalp.Average mark is listed in table 1.
Evaluation criteria
I) scalp is scratched where it itches
3: itch very much
2: medium overworked
1: some is itched
0: itch hardly
Ii) amount of the dandruff
3: a lot of dandruffs
2: the dandruff of moderate
1: some dandruffs
0: almost do not have the dandruff
Iii) use sensation
Everyone feels to assess and mark to the use of compositions according to following listed standard, and average mark is listed in table 1.
5: very good
4: good
3: medium
2: bad
1: very bad
(3) natural on-off cycles of hair growth promotes test (mouse hair restores test)
Test according to the people such as Ogawa (Normal and Abnormal EpidermalDifferentiation, M.Seiji and I.A.Barstein edit, Todai Shuppan-kai publishes, by with reference to this list of references is incorporated herein).Use male C3H mouse (60 days large).The hair of every mouse back is cut off, and size is about 2 * 4cm.From second day, test composition is applied to prunes the zone once a day.At the 18th day, assessment was marked with respect to total ratio of building observed hair regeneration zone, zone and according to following listed standard.Each test composition is used 3 mices and list meansigma methods in table 2.
Evaluation criteria
0: do not observe hair regeneration
1: less than 10% pruning regional observation to hair regeneration
2: the pruning regional observation about 30% is to hair regeneration
3: the pruning regional observation about 50% is to hair regeneration
4: greater than 80% pruning regional observation to hair regeneration
In table 2, list the result
Table 2
| The compositions of using | The 18th day |
| Contrast (75% ethanol) | 0 |
| Embodiment 3 | 2.3 |
| Embodiment 4 | 1.7 |
| Embodiment 7 | 0 |
| Embodiment 8 | 0 |
(4) in the compositions 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF
2 αThe stability of ethyl ester (PG compd A)
With the compositions of embodiment 1 and 2 room temperature storage 2 months.After this, from every kind of compositions, weigh up about 5g and Accurate Measurement weight.The hot benzene of mark (octanophene) obtains test solution in the 5ml to wherein accurately adding.Be injected into 2 microlitre test solutions in the liquid-phase chromatographic column and measure the stability of PG compd A.Read the ratio (PG compd A/hot benzene) of the peak area of PG chemical compound and the hot benzene of interior mark by chromatogram.Determined the weight of PG compd A in part by weight (PG compd A/hot benzene) and the calculation composition by the peak area ratio according to previously prepared standard curve.Simultaneously, as above identical chemical compound was stored 2 months at 0 ℃.After this, as above measure the weight of PG compd A in the compositions with same method.To calculate in the described chemical compound of room temperature storage and the ratio of 0 ℃ of storage compound as 100% in the weight of the PG of 0 ℃ of storage compd A.
Measuring condition
LC system: LC-2010C (Shimadzu Corporation, Kyoto, Japan)
Detector: ultraviolet spectrometer
Wavelength: 254nm
Post: CAPCELL PAK C18 MGII (S-3) (Shiseido Co., Ltd, Tokyo, Japan)
Operative temperature: 40 ℃
Mobile phase: the phosphate of dilution and the mixed solvent of acetonitrile
Flow velocity: regulate so that the retention time of PG compd A is about 16 minutes.
In table 3, list the result
Table 3
| Embodiment | PG compd A (%) |
| 3 | 99.2 |
| 4 | 99.0 |
Preparation embodiment
Embodiment is as follows in preparation:
Preparation embodiment 1
Target and the effect of preparation:
The prevention dandruff and scalp are scratched where it itches.The sensation of pleasant is provided
Table 4
| Composition | Wt％ |
| The PG compd A | 0.05 |
| Ethanol | 60 |
| Dipropylene glycol | 2 |
| The POE castor oil hydrogenated | 0.5 |
| Lactic acid | In right amount |
| Sodium lactate solution | In right amount |
| Ammonium glycyrrhizinate | 0.1 |
| Nicotiamide | 0.1 |
| DL-alpha-tocopherol acetate | 0.1 |
| MENTHOL | 0.2 |
| Pigment | In right amount |
| Pure water | Aequum |
| Spice | In right amount |
[0191]
Preparation embodiment 2
Target and the effect of preparation:
The prevention dandruff and scalp are scratched overworked.The sensation of pleasant is provided
Table 5
| Composition | Wt％ |
| The PG compd A | 0.05 |
| Ethanol | 75 |
| Polyethylene glycol oxide polyoxypropylene myristyl myristyl ether | 1 |
| Lactic acid | In right amount |
| Sodium lactate solution | In right amount |
| panthenylethyl ether | 0.01 |
| Benzyl nicotinate | 0.1 |
| Nicotiamide | 0.2 |
| DL-alpha-tocopherol acetate | 0.05 |
| MENTHOL | 1 |
| Pigment | In right amount |
| Pure water | Aequum |
| Spice | In right amount |
Preparation embodiment 3
Target and the effect of preparation:
The prevention dandruff and scalp are scratched where it itches.The sensation of pleasant is provided
Table 6
| Composition | Wt％ |
| The PG compd A | 0.05 |
| Methyl polysiloxane | 2 |
| Ethanol | 7 |
| Polyethylene glycol oxide polyoxypropylene decyl myristyl ether | 1 |
| Talcum | 5 |
| Lactic acid | In right amount |
| Sodium lactate solution | In right amount |
| Benzyl nicotinate | 0.05 |
| Nicotiamide | 0.05 |
| DL-alpha-tocopherol acetate | 0.2 |
| MENTHOL | 0.3 |
| Pigment | In right amount |
| Pure water | Aequum |
Preparation embodiment 4
Target and the effect of preparation:
The prevention dandruff and scalp are scratched where it itches.The prevention hair lacks, and the sensation of pleasant is provided
Table 7
| Composition | Wt％ |
| The PG compd A | 0.05 |
| Ethanol | 80 |
| Isooctadecanol | 2 |
| 1,3 butylene glycol | 3 |
| The POE castor oil hydrogenated | 1 |
| Sodium lauryl sulphate | 0.3 |
| The DL-malic acid | In right amount |
| β-enoxolone | 0.2 |
| panthenylethyl ether | 0.1 |
| Benzyl nicotinate | 0.1 |
| Nicotiamide | 0.1 |
| DL-alpha-tocopherol acetate | 0.5 |
| Decyl myristyl dimethyl methyl amine oxide aqueous solution (20%) | 5 |
| MENTHOL | 1 |
Preparation embodiment 5
Target and the effect of preparation:
The prevention dandruff and scalp are scratched where it itches.Sensation for pleasant.The prevention hair becomes ash.
Table 8
| Composition | Wt％ |
| The PG compd A | 0.05 |
| Ethanol | 70 |
| Isooctadecanol | 1 |
| The Trigryceryl-2-ethylhexoate | 1 |
| Lactic acid | In right amount |
| Sodium lactate solution | In right amount |
| The Swertia japonica extract is stuck with paste | 0.2 |
| β-enoxolone | 0.5 |
| panthenylethyl ether | 0.5 |
| Benzyl nicotinate | 0.02 |
| Nicotiamide | 0.1 |
| DL-alpha-tocopherol acetate | 0.1 |
| MENTHOL | 0.5 |
| The Pericarpium Zanthoxyli fruit extract | 10 |
| Pure water | Aequum |
| Spice | In right amount |
Claims (4)
1. scalp and/or Hiar treatment compositions comprise:
MENTHOL or D/L menthol; With
By the prostaglandin compound with following formula (II) expression
Wherein L and M are hydroxyl;
A is-COOH or its salt or C
1-C
6Arrcostab;
B is-CH
2-CH
2-;
Z
1And Z
2Be oxygen;
R
2And R
3Be C
1-C
6Alkyl, perhaps R
2And R
3Be joined together to form C
1-C
6Alkylidene;
R
1For comprising the hydrocarbon of 6-10 carbon atom;
X
1And X
2Be hydrogen, C
1-C
6Alkyl or halogen;
R
4Be singly-bound or C
1-C
6Alkylidene; With
R
5Be C
1-C
6Alkyl.
2. compositions as claimed in claim 1, wherein:
R
1For comprising the hydrocarbon of 6 carbon atoms;
R
2And R
3Be joined together to form C
1-C
6Alkylidene;
X
1And X
2Be hydrogen; With
R
4Be C
1-C
6Alkylidene.
3. compositions as claimed in claim 2, wherein:
R
1For-CH
2-CH=CH-CH
2-CH
2-CH
2-.
4. compositions as claimed in claim 1, wherein said prostaglandin compound is 13,14-dihydro-15,15-ethylenedioxy-20-ethyl-PGF
2 αEthyl ester.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63984504P | 2004-12-29 | 2004-12-29 | |
| US60/639,845 | 2004-12-29 | ||
| JP034763/2005 | 2005-02-10 | ||
| JP2005034763 | 2005-02-10 | ||
| PCT/JP2005/024276 WO2006070942A1 (en) | 2004-12-29 | 2005-12-28 | Composition and method for scalp and hair treatment |
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| CN101160114A CN101160114A (en) | 2008-04-09 |
| CN101160114B true CN101160114B (en) | 2013-02-06 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101889971A (en) * | 2010-08-03 | 2010-11-24 | 程远迪 | Health-care hair beautifying and conditioning agent |
| WO2012176792A1 (en) * | 2011-06-21 | 2012-12-27 | 株式会社アールテック・ウエノ | Pharmaceutical composition for inflammatory diseases, allergic diseases and autoimmune diseases |
| KR102102578B1 (en) * | 2019-06-26 | 2020-04-21 | 코스맥스 주식회사 | Cosmetic composition for strengthening hair bulb comprising mixture of 18β-Glycyrrhetic acid, D-panthenol and Menthol as effective component |
| US11357809B2 (en) * | 2019-08-14 | 2022-06-14 | Ge Nutrients, Inc. | Herbal preparation for stimulation of hair growth, control of hair fall, dandruff and infections thereof using Ageratum spp |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0308135B1 (en) * | 1987-09-18 | 1992-11-19 | R-Tech Ueno Ltd. | Ocular hypotensive agents |
| US6262105B1 (en) * | 1997-02-04 | 2001-07-17 | Murray A. Johnstone | Method of enhancing hair growth |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0308135B1 (en) * | 1987-09-18 | 1992-11-19 | R-Tech Ueno Ltd. | Ocular hypotensive agents |
| US6262105B1 (en) * | 1997-02-04 | 2001-07-17 | Murray A. Johnstone | Method of enhancing hair growth |
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| CN101160114A (en) | 2008-04-09 |
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