JP2008007476A - Hair-growing and restoring agent composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a hair-growing and restoring agent composition which is excellent in a hair-growing and restoring effect and can resist to employment over a long period. <P>SOLUTION: This hair-growing and restoring agent composition comprises (A) an apoptosis induction promotion protein-inhibiting substance, (B) a hydroxypyridone derivative, and (C) an ester compound having a hydroxy group in the molecule. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a hair restorer composition, and in particular, to a hair restorer composition that enhances the hair restore effect of an inhibitor of apoptosis induction promoting protein.

  For humans, hair greatly affects the appearance and occupies a very important position in beauty. In addition, there is still no accurate treatment for alopecia, which is a source of deep concern for people with alopecia or its tendency. Although alopecia is congenital and acquired, there are many unclear points although many studies have been conducted on the cause and mechanism of alopecia areata. Therefore, the present condition is that a great number of hair-growth nourishing agents developed frantically are on the market.

  As the above-mentioned hair restoring agent, various hair restoration agents for hair restoration containing various chemicals have been provided so far. For example, a composition comprising a compound such as vitamin E, alloxazine, pyridine N-oxide, adenosine 3 ′, 5′-cyclic monophosphate (see, for example, Patent Documents 1 to 3), Yokuinin, Ginkgo biloba, Kashu, etc. The composition (for example, refer patent documents 4-6) formed by mix | blending herbal medicine extract of this is provided. In addition, vitamin E compounds and assembly extracts that have an effect of improving blood circulation, cysteine and methionine as amino acids that serve as nutritional supplements, and female hormone agents such as estradiol and ethinylestradiol are provided. ing. Furthermore, hair cosmetics for hair growth nourishing in which these active ingredients are made to correspond to various causes of hair loss and are appropriately combined have been developed and used for the prevention and / or treatment of alopecia. Such a conventional hair cosmetic for hair growth is effective for improving dandruff and kayumi and preventing hair loss and promoting hair growth and hair growth. However, the effect varies greatly between individuals, and the effect is not sufficient. For this reason, there are still no products that can produce satisfactory results.

  On the other hand, recently, a hair loss inhibitor / hair nourishing agent using a caspase inhibitor that inhibits the apoptosis phenomenon has been proposed (see, for example, Patent Documents 7 and 8). However, the hair loss suppressing and hair nourishing agents described in Patent Documents 7 and 8 contain a caspase inhibitor as an active ingredient, and this caspase inhibitor has an action of directly inhibiting the apoptosis phenomenon. This apoptotic phenomenon is essentially an important action for maintaining the homeostasis of the living body, and is not limited to the hair part, but the action extends to the entire living body. Therefore, the inhibition of the apoptosis phenomenon itself using a hair loss inhibitor / hair nourishing agent containing the above caspase inhibitor suppresses the apoptosis phenomenon involved in the metabolic balance of the whole organism, and may cause side effects on the organism. There is. Moreover, in the hair-growth nourishing agents provided so far, extracts such as the above-mentioned various compounds and herbal medicines have been applied, but there are practically no significant effects. Moreover, even if it has a certain effect, there is a drawback that continuous use is difficult, such as skin irritation and side effects.

JP-A 64-56608 JP-A-1-261321 JP-A-2-204406 Japanese Patent Publication No. 1-13451 JP-A-2-48512 JP-A-2-48514 JP 2002-87937 A JP 2002-87938 A

  The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a hair-restoring agent composition that is excellent in hair-restoration effect and can withstand use for a long period of time.

  As a result of intensive studies to achieve the above-mentioned object, the present inventor has examined the gene expression comparison in the hair papilla cells at the hair loss site of the hair loss person and the corresponding hair loss person, and the hair papilla cells at the hair loss site of the hair loss person and Compared with the dermal papilla cells of the corresponding site of non-hairless persons, the group of factors with increased gene expression and the group of factors with decreased gene expression were clarified. Furthermore, from detailed examination of these factors, the genes that are particularly expressed in hair loss individuals are those that encode proteins involved in promoting apoptosis induction, and conversely the genes that are down-regulated It has been clarified that many proteins encode proteins involved in the suppression of apoptosis induction.

  The present inventor paid attention to the protein involved in the promotion of apoptosis induction (hereinafter referred to as apoptosis induction promoting protein), and by using a substance that inhibits this protein (hereinafter referred to as an inhibitor of apoptosis induction promoting protein), the apoptosis phenomenon It was found that the period until reaching the regression phase was prolonged, the hair growth effect could be promoted, the effect appeared earlier and there were no side effects.

  Based on the above findings, as a result of various searches for inhibitors of apoptosis induction promoting proteins, several components were found. Further, when (B) a hydroxypyridone derivative is used in combination with these components, the inhibitory effect of the apoptosis induction promoting protein can be promoted, and the hair growth effect can be expressed more quickly. Furthermore, (C) the hydroxy group in the molecule When used in combination with an ester compound having the above, an effect of allowing an inhibitor of apoptosis induction protein and (B) a hydroxypyridone derivative to permeate into the vicinity of the hair papilla cells is remarkably exhibited, and a hair-growth nourishing agent comprising these ingredients The composition has been found to exhibit an excellent hair-restoring effect, and has led to the present invention.

Therefore, the present invention provides [1]. (A) an inhibitor of apoptosis induction promoting protein;
(B) a hydroxypyridone derivative;
(C) a hair-growth hair nourishing agent composition comprising an ester compound having a hydroxy group in the molecule,
[2]. Furthermore, (D) the hair-restoring agent composition according to [1], comprising a polyhydric alcohol and / or an ester compound of a monohydric alcohol and an aliphatic monocarboxylic acid.

  ADVANTAGE OF THE INVENTION According to this invention, the hair-restoration agent composition which is excellent in the hair-restoration effect and can endure use for a long term can be provided.

  The component (A) of the present invention is an inhibitor of apoptosis induction promoting protein, and can be used alone or in combination of two or more. The inhibitor of the apoptosis induction promoting protein is not particularly limited as long as it does not cause a problem in safety. Examples of such inhibitory substances include natural product extracts and synthetic compounds.

  Examples of the inhibitory substances include cynosidaceae, genus walrus (Ailanthus altissima), Kumonetsusho (Anemone Altaica), liquor flower (Buddleia davidii), legumes, renge Astragalus sinicus, phytocollage (fermented extract from pea (soybean)), deuterium (Bisohofia javanica), citrus (Citrus reticulata), Guangxi segisgisg Euphorbiaceae, Fura genus Asaku (Hura crepitans), Kajime genus Echonia (Ecklonia maxima), Darus eyes, Darus Dalmus (Palmaria palmata), Pterocera sp. ), Giraffe (Irideaea sp.), Dragosa (Pterocladiella tenuis), fullcellaria (Furcellaria umbilicalis), willow mok (Sargassum coreumum), and two species selected from the species Nemastus decipei Or extracts of seaweed and the like. Among these, extracts of cinnamon, phytocollage (derived from pea (soybean)), asaku, echronia, dallus, and okasa are preferred.

  The plant or seaweed used for the extraction of the above plant or seaweed extract is not particularly limited in its application part, but from the viewpoint of exerting its effectiveness, asaku is made of wood, echronia, dulls, okusa, tsutsuregusa, tochaka, It is preferable to use the whole plant or seaweed for Calophyllus, Okinawa Mozuku, Echinocera, Dragusa, Fruceraria, Willow Mok, and Mozuku. The “wood” means the woody part of the stem of a woody plant.

  As the plant-derived material and plant extract, commercially available products or those obtained by known extraction methods can be used. Examples of the solvent used in the extraction method (hereinafter referred to as “extraction solvent”) include water; alcohols such as methanol, ethanol, propanol, and butanol; polyhydric alcohols such as propylene glycol and butylene glycol, and the like. Can be used alone or as a mixed solvent of two or more.

  Various conditions in the extraction method are not particularly limited, but the ratio of the extraction raw material to the extraction solvent is usually in a range of about 1: 2 to 1:50 extraction raw material: extraction solvent = 1: 50 by mass ratio. preferable. The extraction temperature is preferably in the range of 5 to 80 ° C., and is preferably performed by immersing or stirring in the extraction solvent for 1 hour to 1 week. The extraction pH is not particularly limited as long as it is not extremely acidic or alkaline.

  When the extraction solvent is a non-toxic solvent such as water, ethanol, water / ethanol (hydrous ethanol) or the like, the extract may be used as it is as a hair growth agent or as a diluent. Moreover, the said extract may be used as a concentrated extract, and may be made into a dry powder by freeze drying or the like, or may be prepared in a paste form. When other solvents are used, it is preferable to distill the solvent and dilute the dried portion with a non-toxic solvent.

  The blending amount of the component (A) varies depending on the product form and frequency of use and cannot be specified unconditionally, but is usually preferably 0.001 to 5% by mass, more preferably as an extract with respect to the hair restoration agent composition. 0.01 to 1% by mass. In this range, a hair-restoring effect can be obtained, and if the blending amount is too large, the effect may reach a peak or a problem may occur in terms of the stability of the preparation.

  The hydroxypyridone derivative of the component (B) of the present invention is a 1-hydroxy-2-pyridone compound represented by the following general formula (1). These can be used individually by 1 type or in combination of 2 or more types.

（式中、Ｒ¹は、水素原子、１〜１７個の炭素原子を有するアルキル基、２〜１７個の炭素原子を有するアルケニル基、５〜８個の炭素原子を有するシクロアルキル基、７〜９個の炭素原子を有するビシクロアルキル基、シクロアルキル基が５〜８個の炭素原子を有し、かつアルキル基が１〜４個の炭素原子を有するシクロアルキル−アルキル基（但し、シクロアルキル基は、その水素原子の一部が１〜４個の炭素原子を有するアルキル基によって置換されていてもよい）、６〜１４個の炭素原子を有するアリール基、アリール基が６〜１４個の炭素原子を有し、かつアルキル基が１〜４個の炭素原子を有するアラルキル基、アリール基が６〜１４個の炭素原子を有し、かつアルケニル基が２〜４個の炭素原子を有するアリールアルケニル基、アリール基が６〜１４個の炭素原子を有し、かつアルキル基がそれぞれ１〜４個の炭素原子を有するアリールオキシアルキル基もしくはアリールメルカプトアルキル基、ベンズヒドリル基、アルキル基が１〜４個の炭素原子を有するフェニルスルフォニルアルキル基、フリル基又はアルケニル基が２〜４個の炭素原子を有するフリルアルケニル基を示す。但し、上述のアリール基は、その水素原子の一部が１〜４個の炭素原子を有するアルキル基、１〜４個の炭素原子を有するアルコキシ基、ニトロ基、シアノ基又はハロゲン原子によって置換されていてもよい。Ｒ²は、水素原子、１〜４個の炭素原子を有するアルキル基、２〜４個の炭素原子を有するアルケニル基、２〜４個の炭素原子を有するアルキニル基、ハロゲン原子、フェニル基又はベンジル基を示す。Ｘ⁺は、有機塩基、アルカリ金属イオン、アンモニウムイオン又は２〜４価の陽イオンを示す。）

Wherein R ¹ is a hydrogen atom, an alkyl group having 1 to 17 carbon atoms, an alkenyl group having 2 to 17 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms, 7 to A bicycloalkyl group having 9 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms and an alkyl group having 1 to 4 carbon atoms (provided that the cycloalkyl group Is optionally substituted by an alkyl group having 1 to 4 carbon atoms), an aryl group having 6 to 14 carbon atoms, or an aryl group having 6 to 14 carbon atoms. An aralkyl group having an atom and an alkyl group having 1 to 4 carbon atoms, an aryl group having 6 to 14 carbon atoms, and an alkenyl group having 2 to 4 carbon atoms Base An aryloxyalkyl group or an arylmercaptoalkyl group, a benzhydryl group, an alkyl group having 1 to 4 carbon atoms in which the aryl group has 6 to 14 carbon atoms and the alkyl group has 1 to 4 carbon atoms each A phenylsulfonylalkyl group having an atom, a furyl group or an alkenyl group represents a furylalkenyl group having 2 to 4 carbon atoms, provided that the above-mentioned aryl group has a carbon atom part of which has 1 to 4 carbon atoms. Optionally substituted by an alkyl group having an atom, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a cyano group or a halogen atom R ² has a hydrogen atom, 1 to 4 carbon atoms Alkyl groups, alkenyl groups having 2 to 4 carbon atoms, alkynyl groups having 2 to 4 carbon atoms, halogen atoms, phenyl groups .X ⁺ is showing a benzyl group shows an organic base, an alkali metal ion, an ammonium ion or a divalent to tetravalent cations.)

Specific examples of the compound represented by the general formula (1) include the following compounds and salts thereof.
1-hydroxy-2-pyridone, 1-hydroxy-4-methyl-2-pyridone, 1-hydroxy-6-methyl-2-pyridone, 1-hydroxy-4,6-dimethyl-2-pyridone, 1-hydroxy- 4-methyl-6-heptyl-2-pyridone, 1-hydroxy-4-methyl-6- (1-ethylpentyl) -2-pyridone, 1-hydroxy-4-methyl-6- (2,4,4- Trimethylpentyl) -2-pyridone, 1-hydroxy-4-methyl-6-undecyl-2-pyridone, 1-hydroxy-4-methyl-6-propenyl-2-pyridone, 1-hydroxy-4-methyl-6 Octenyl-2-pyridone, 1-hydroxy-4-methyl-6- (2,2-dibutyl-vinyl) -2-pyridone, 1-hydroxy-4-methyl-6- (cyclohexe Ridene-methyl) -2-pyridone, 1-hydroxy-4-methyl-6-cyclohexyl-2-pyridone, 1-hydroxy-4-methyl-6- (methyl-cyclohexyl) -2-pyridone, 1-hydroxy-4 -Methyl-6- (2-bicyclo [2,2,1] heptyl) -2-pyridone, 1-hydroxy-4-methyl-6- [2- (dimethylcyclohexyl) -propyl] -2-pyridone, 1- Hydroxy-4-methyl-6- (4-methyl-phenyl) -2-pyridone, 1-hydroxy-4-methyl-6- (3-methyl-phenyl) -2-pyridone, 1-hydroxy-4-methyl- 6- (4-tert-butyl-phenyl) -2-pyridone, 1-hydroxy-4-methyl-6- (3-methyl-4-chloro-phenyl) -2-pyridone, 1-hydroxy 4-methyl-6- (3,5-dichloro-phenyl) -2-pyridone, 1-hydroxy-4-methyl-6- (3-bromo-4-chloro-phenyl) -2-pyridone, 1-hydroxy- 4-methyl-6- (4-methoxystyryl) -2-pyridone, 1-hydroxy-4-methyl-6- [1- (4-nitrophenoxy) -butyl] -2-pyridone, 1-hydroxy-4- Methyl-6- (4-cyanophenoxymethyl) -2-pyridone, 1-hydroxy-4-methyl-6- (phenylsulfonylmethyl) -2-pyridone, 1-hydroxy-4-methyl-6- [1- ( 4-chlorophenylsulfonyl) -butyl] -2-pyridone, 1-hydroxy-4-methyl-6-benzyl-2-pyridone, 1-hydroxy-4-methyl-6- (2,4-dimethylben Dil) -2-pyridone, 1-hydroxy-4-methyl-6- (tert-butyl-benzyl) -2-pyridone, 1-hydroxy-4-methyl-6- (2-chloro-benzyl) -2-pyridone 1-hydroxy-4-methyl-6- (4-chlorobenzyl) -2-pyridone, 1-hydroxy-4-methyl-6- (2,5-dichloro-benzyl) -2-pyridone, 1-hydroxy- 4-methyl-6- (4-bromo-benzyl) -2-pyridone, 1-hydroxy-4-methyl-6- (phenoxymethyl) -2-pyridone, 1-hydroxy-4-methyl-6- (3- Methylphenoxy-methyl) -2-pyridone, 1-hydroxy-4-methyl-6- (4-secondary phenphenoxy-methyl) -2-pyridone, 1-hydroxy-4-methyl-6- (2,4,4) 5-to Chlorophenoxy-methyl) -2-pyridone, 1-hydroxy-4-methyl-6- (4-bromophenoxy-methyl) -2-pyridone, 1-hydroxy-4-methyl-6- (4-chlorophenylmercapto- Methyl) -2-pyridone, 1-hydroxy-4-methyl-6- (4-methylphenylmercapto-methyl) -2-pyridone, 1-hydroxy-4-methyl-6- (2-naphthyl) -2-pyridone 1-hydroxy-4-methyl-6-benzhydryl-2-pyridone, 1-hydroxy-4-methyl-6-furyl-2-pyridone, 1-hydroxy-4-methyl-6- (furylvinyl) -2- Pyridone, 1-hydroxy-4-methyl-6-styryl-2-pyridone, 1-hydroxy-4-methyl-6- (phenylbutadienyl) -2-pyridone Down, 1-hydroxy-4-phenyl-6-methyl-2-pyridone, mention may be made of 1-hydroxy-4,6-diphenyl-2-pyridone and the like.

  The said compound is used as a salt, for example, can be used conveniently as a salt with an organic amine. Specifically, for example, ethanolamine, diethanolamine, N-ethylethanolamine, N-methyl-diethanolamine, triethanolamine, diethylamino-ethanol, 2-amino-2-methyl-n-propanol, dimethylaminopropanol, 2-amino 2-methyl-propanediol, tri-isopropanolamine, ethylenediamine, hexamethylenediamine, morpholine, piperidine, cyclohexylamine, tributylamine, dodecylamine, N, N-dimethyl-dodecylamine, stearylamine, oleylamine, benzylamine, di Benzylamine, N-ethylbenzylamine, dimethylstearylamine, N-methyl-morpholine, N-methylpiperazine, 4-methylcyclohexylamine, N- Dorokishiechiru - morpholine, and the like.

  The hydroxypyridone compound used in the present invention may be a salt with an inorganic ion, for example, an alkali metal salt such as sodium salt or potassium salt, an alkaline earth metal such as ammonium salt, magnesium salt or calcium salt. A salt or the like can be used. Furthermore, salts with divalent to tetravalent cations such as zinc salts, aluminum salts and zirconium salts can also be used.

  Examples of the 1-hydroxy-2-pyridone compound of the general formula (1) include piroctone olamine represented by the following formula (2) [alias: 1-hydroxy-4-methyl-6- (2,4,4). -Trimethylpentyl) -2 (1H) -pyridone monoethanolamine salt] (trade name “Octopirox”, manufactured by Clariant) or cyclopyrox olamine represented by the following formula (3) [alias: 1- Hydroxy-4-methyl-6-cyclohexyl-2 (1H) -pyridone monoethanolamine salt (trade name “Cyclopyrox”, manufactured by Hoechst) is preferably used.

  (B) Although the compounding quantity of a component can be adjusted suitably, 0.01-5 mass% is preferable with respect to the hair-restoring hair nourishing agent composition, More preferably, it is 0.1-3 mass%. In this range, the hair-growth effect can be obtained. If the blending amount is too large, no further effect is exhibited and the stability may be adversely affected.

  (C) component of this invention is an ester compound which has a hydroxyl group in a molecule | numerator, and can be used individually by 1 type or in combination of 2 or more types. As the penetration enhancers (A) and (B), ester compounds having a hydroxy group exhibit particularly remarkable effects.

  Examples of the ester compound having a hydroxy group in the molecule include a hydroxy acid ester that is an ester compound of a hydroxy acid and an alcohol, and a polyhydric alcohol ester that is an ester compound of a polyhydric alcohol and a carboxylic acid, Examples thereof include ester compounds having a hydroxyl group.

  In the ester compound having a hydroxy group composed of a hydroxy acid and an alcohol, as the hydroxy acid, hydroxyisobutyric acid, hydroxyisocaproic acid, hydroxy-n-caproic acid, hydroxyisocaprylic acid, hydroxy-n-caprylic acid, Examples include hydroxy-n-capric acid, hydroxystearic acid, malic acid, citric acid, tartaric acid, glycolic acid, and lactic acid. Of the hydroxy acids, glycolic acid, lactic acid, malic acid, and citric acid are particularly preferable.

In the ester compound having a hydroxy group composed of a hydroxy acid and an alcohol, specific examples of the alcohol include hexanol, heptanol, octanol, 2-ethylhexanol, decanol, undecanol, dodecanol, tridecyl alcohol, myristyl. C ₆ -C ₃₂ aliphatic alcohols such as alcohol, pentadecyl alcohol, cetyl alcohol, heptadecyl alcohol, stearyl alcohol, nonadecane alcohol, 1-methylheptyl alcohol, 2-methylheptyl alcohol, 1-butylhexyl alcohol, 2 -Methyl-5-ethylheptyl alcohol, 2,3,6-trimethylheptyl alcohol, 6-ethyldecyl alcohol, 7-methyltetradecyl alcohol, 7-ethylhexyl Decyl alcohol, 7,12-dimethyloctadecyl alcohol, octyldodecyl alcohol, 8,11-dimethyloctadecyl alcohol, 7,10-dimethyl-7-ethylhexadecyl alcohol, 9,10-dioctyloctadecyl alcohol, 8,9-di Aliphatic alcohols having C ₁ -C ₂₂ side chains such as nonylhexadecyl alcohol, unsaturated alcohols such as oleyl alcohol, linoleyl alcohol and linoleic alcohol, alicyclic alcohols such as cyclohexanol, cholesterols, benzyl Examples thereof include aromatic alcohols such as alcohol.

  On the other hand, in the ester compound having a hydroxy group composed of a polyhydric alcohol and a carboxylic acid, examples of the polyhydric alcohol include a divalent hydroxyl compound, a trivalent hydroxyl compound, a tetravalent hydroxyl compound, and the like. Examples of the divalent hydroxyl compound include ethylene glycol, diethylene glycol, triethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, dipropylene glycol, polypropylene glycol, 1,4-butanediol, 2,2- Butanediol, hexanediol, pentanediol, hexanediol, 2-methyl-1,3-propanediol, 3-methyl-1,5-heptanediol, cyclohexanediol, heptanediol, octanediol, nonanediol, decanediol, isopreneglycol , Butylene glycol, neopentyl glycol and the like. Examples of the trivalent hydroxyl compound include glycerin and trimethylolpropane, examples of the tetravalent hydroxyl compound include pentaerythritol, and examples of other polyvalent hydroxy compounds include various sugars.

In the ester compound having a hydroxy group composed of a polyhydric alcohol and a carboxylic acid, examples of the carboxylic acid include various carboxylic acids such as a monocarboxylic acid and a polyvalent carboxylic acid. Examples of monocarboxylic acids include C _1-32 saturated monocarboxylic acids such as acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, pivalic acid, lauric acid, myristic acid, and palmitic acid, acrylic acid, methacrylic acid, and olein. Aliphatic monocarboxylic acids such as unsaturated monocarboxylic acids such as acid, linolenic acid, linoleic acid, crotonic acid and isocrotonic acid, alicyclic monocarboxylic acids such as cyclobutanecarboxylic acid and cyclohexanecarboxylic acid, and aromatics such as benzoic acid A monocarboxylic acid etc. are mentioned. Examples of the polyvalent carboxylic acid include saturated polyvalent carboxylic acids having 2 to 32 carbon atoms such as oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, and sebacic acid, maleic acid, maleic anhydride, fumaric acid, Aliphatic polycarboxylic acids such as unsaturated polycarboxylic acids such as itaconic acid, alicyclic polycarboxylic acids such as cyclobutanedicarboxylic acid and cyclohexanedicarboxylic acid, aromatic polycarboxylic acids such as phthalic acid and isophthalic acid, etc. Is mentioned.
A polyhydric alcohol ester which is an ester compound of a polyhydric alcohol and a carboxylic acid, and the ester compound having a hydroxyl group in the molecule must have at least a monovalent hydroxy group remaining. There are no restrictions on the synthesis method.

  There is no restriction | limiting in the property of the ester compound which has a hydroxyl group in a molecule | numerator, Although a solid thing, a paste-like thing, and a liquid thing are used at 25 degreeC, A liquid thing is used suitably. In addition, a liquid thing is a thing whose viscosity measured with the BH type | mold viscosity meter (6 rpm, No. 4 rotor use) is 10 Pa * s or less at 25 degreeC.

  Specifically, propylene glycol monooctanoate, propylene glycol monodecanoate, polypropylene glycol succinate, isopropyl citrate, triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, triethylhexyl citrate, octyldodecyl citrate Acetyltributyl citrate, neopentyl glycol 2-ethylhexanoate, neopentyl glycol decanoate, isostearyl lactate, octyl dodecyl lactate, octyl lactate, cetyl lactate, myristyl lactate, lauryl lactate, isostearyl malate, diiso Stearyl etc. are mentioned.

  (C) Although the compounding quantity of a component can be adjusted suitably, 0.01-20 mass% is preferable with respect to the hair-restoring hair nourishing agent composition, More preferably, it is 0.1-10 mass%. In this range, a hair-growth effect can be obtained. Even if it exceeds 20% by mass, no further effect is usually exhibited, and stickiness and other feelings of use may be adversely affected.

  It is preferable to further blend (D) an ester compound of a polyhydric alcohol and / or a monohydric alcohol with an aliphatic monocarboxylic acid in the hair growth agent composition of the present invention. These can be used individually by 1 type or in combination of 2 or more types.

  Examples of the polyhydric alcohol include ethylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, 1,3-butylene glycol, pentanediol, glycerin, polyglycerin, sorbitol, mannitol, trehalose and the like. Of these, propylene glycol, dipropylene glycol, polyethylene glycol, glycerin, and polyglycerin are preferable among the polyhydric alcohols. More preferred are propylene glycol and polyethylene glycol.

  The range of the preferable average molecular weight of polyethylene glycol (the average molecular weight test method of polyethylene glycol 200 listed in the cosmetic raw material standard is applied mutatis mutandis) is 190 to 1,050, more preferably 280 to 630. Specifically, polyethylene glycol 200 (average molecular weight 190-210), 300 (average molecular weight 280-320), 400 (average molecular weight 380-420), 600 (average molecular weight 570-630), 1000 based on cosmetic raw material standards (950 to 1,050) is preferable, and 300 to 600 is more preferable. If the average molecular weight is greater than 1,050, the intended effect may not be obtained.

  Examples of ester compounds of monohydric alcohols and aliphatic monocarboxylic acids include isostearyl laurate, hexyl laurate, methyl myristate, ethyl myristate, butyl myristate, cetyl myristate, myristyl myristate, isopropyl myristate, myristine Isostearyl acid, isocetyl myristate, isotridecyl myristate, octyldodecyl myristate, decyl myristate, butyl myristate, isobutyl myristate, methyl palmitate, ethyl palmitate, isopropyl palmitate, isostearyl palmitate, cetyl palmitate, Butyl palmitate, isobutyl palmitate, octyl palmitate, octyl isopalmitate, ethyl stearate, butyl stearate, steer Phosphate Bacillus, stearyl stearate, octyl stearate, isocetyl stearate, isopropyl isostearate, ethyl oleate, decyl oleate, oleyl oleate, octyldodecyl oleate, ethyl linoleate, and isopropyl linoleate and the like.

  Although the compounding quantity of (D) component can be adjusted suitably, 0.01-15 mass% is preferable with respect to the hair-restoring hair nourishing agent composition, More preferably, it is 0.1-10 mass%. In this range, a hair-growth effect can be obtained, and even if it exceeds 15% by mass, there is usually no difference in the effect.

  Moreover, in the hair growth agent composition of this invention, according to the intended purpose, arbitrary components other than the above can be used individually by 1 type or in combination of 2 or more types as appropriate. Examples of such components include purified water, ethanol, surfactants, celluloses, fats and oils, hydrocarbon oils, ester oils other than the components (C) and (D), higher fatty acids, higher alcohols, glyceride oils, Polymer resins, powders, colorants, organic acids, antibacterial / preservatives, fragrances, UV absorbers, vitamins, amino acids, basic nucleic acids or derivatives thereof, keratolytic agents, moisturizers, medicinal ingredients, etc. be able to. In addition, these compounding quantities are the ranges which do not impair the effect of this invention.

  Examples of the surfactant include commonly used anionic surfactants, nonionic surfactants, cationic surfactants, and amphoteric surfactants. Specifically, as anionic surfactants, Alkyl sulfate, polyoxyethylene alkyl ether sulfate, alkyl benzene sulfonate, α-olefin sulfonate, fatty acid salt, α-sulfo fatty acid salt, ether carboxylate, alkyl phosphate, polyoxyethylene alkyl ether Examples thereof include phosphates, dialkyl sulfosuccinic acid ester salts, sulfosuccinic acid alkyl salts, alkenyl succinic acid salts, N-acyl amino acid salts, N-acyl methyl taurate salts, and the like. Examples of the counter ion (cation) of these anionic surfactants include alkali metal ions, alkaline earth metal ions, alkanolamine ions, and ammonium ions.

  Examples of the cationic surfactant include alkyltrimethylammonium salts, dialkyldimethylammonium salts, alkylammonium salts, benzalkonium salts, benzethonium salts, pyridinium salts, imidazolinium salts, and the like. Examples of counter ions (anions) of these cationic surfactants include halogen ions.

  Examples of amphoteric surfactants include alkyl carboxy betaines, alkyl sulfo betaines, alkyl hydroxy sulfo betaines, alkyl amide betaines, imidazolinium betaines, and the like.

  Nonionic surfactants include polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkylphenyl ether, fatty acid polyglycerin ester, fatty acid sucrose ester, fatty acid alkanolamide, alkylamine oxide, amidoamine Examples include oxides.

  Examples of celluloses include hydroxymethylcellulose, hydroxypropylcellulose, and hydroxypropylmethylcellulose.

  Examples of the fats and oils include avocado oil, linseed oil, almond oil, ibotarou, eno oil, olive oil, cacao butter, kapok wax, kayak oil, carnauba wax, liver oil, candelilla wax, beef tallow, bovine tallow, beef bone fat, and cured beef tallow , Kyounin oil, whale wax, hydrogenated oil, wheat germ oil, sesame oil, rice germ oil, rice bran oil, sugar cane wax, sasanqua oil, safflower oil, shea butter, cinnamon oil, cinnamon oil, jojo barr, shellac wax, turtle oil, Soybean oil, tea seed oil, camellia oil, evening primrose oil, corn oil, lard, rapeseed oil, Japanese kiri oil, nukarou, germ oil, horse fat, persic oil, palm oil, palm kernel oil, castor oil, hydrogenated castor oil , Castor oil fatty acid methyl ester, sunflower oil, grape oil, bayberry wax, jojoba oil, macadamia nut oil, beeswax, mink , Cottonseed oil, cotton wax, owl, owl kernel oil, montan wax, coconut oil, hydrogenated coconut oil, tricoconut oil fatty acid glyceride, sheep oil, peanut oil, lanolin, liquid lanolin, reduced lanolin, lanolin alcohol, hard lanolin, lanolin acetate, lanolin Examples include fatty acid isopropyl, hexyl laurate, POE lanolin alcohol ether, POE lanolin alcohol acetate, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, egg yolk oil and the like.

  Examples of the hydrocarbon oil include ozokerite, squalane, squalene, ceresin, paraffin, paraffin wax, liquid paraffin, pristane, polyisobutylene, microcrystalline wax, petrolatum and the like.

  As higher fatty acids, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), isostearic acid , 12-hydroxystearic acid and the like.

  As higher alcohols, lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, behenyl alcohol, hexadecyl alcohol, oleyl alcohol, isostearyl alcohol, hexyl decanol, octyldodecanol, cetostearyl alcohol, 2-decyltetradecinol, Examples include cholesterol, phytosterol, POE cholesterol ether, monostearyl glycerin ether (batyl alcohol), monooleyl glyceryl ether (ceracyl alcohol), and the like.

  Examples of the glyceride oil include acetoglyceryl, glyceryl triisooctanoate, glyceryl triisostearate, glyceryl triisopalmitate, glyceryl monostearate, glyceryl di-2-heptylundecanoate, glyceryl trimyristate, and diglyceryl myristate. Is mentioned.

  Examples of the polymer resin include amphoteric, cationic, anionic and nonionic polymers.

  Examples of powders and colorants are those used in normal cosmetics, such as the shape (spherical, rod-like, needle-like, plate-like, indeterminate, scale-like, spindle-like) and particle diameter ( Regardless of the type of smoke, fine particles, pigment grade, etc.) and particle structure (porous, non-porous, etc.), any of them can be used, for example, inorganic powder, organic powder, surfactant metal salt powder Bodies, colored pigments, pearl pigments, metal powder pigments, natural dyes, etc., specifically, inorganic powders include pigment grade titanium oxide, zirconium oxide, pigment grade zinc oxide, cerium oxide, magnesium oxide, sulfuric acid Barium, calcium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, talc, mica, kaolin, sericite, muscovite, synthetic mica, phlogopite, saucite, biotite, lithia mica, silicic acid, anhydrous silicic acid, silicic acid Arminius , Magnesium silicate, aluminum magnesium silicate, calcium silicate, barium silicate, strontium silicate, metal tungstate, hydroxyapatite, vermiculite, hydrite, bentonite, montmorillonite, hectorite, zeolite, ceramic powder, dicalcium phosphate , Alumina, aluminum hydroxide, boron nitride, boron nitride, silica, fine particle titanium oxide, fine particle zinc oxide, fine particle cerium oxide, etc., and organic powders include polyamide powder, polyester powder, polyethylene powder, polypropylene powder, polystyrene Powder, polyurethane powder, benzoguanamine powder, polymethylbenzoguanamine powder, polytetrafluoroethylene powder, Limethyl methacrylate powder, cellulose, silk powder, nylon powder, 12 nylon, 6 nylon, silicone powder, silicone rubber powder, silicone elastomer spherical powder, styrene / acrylic acid copolymer, divinylbenzene / styrene copolymer, vinyl resin , Urea resin, phenol resin, fluorine resin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, microcrystalline fiber powder, starch powder, lauroyl lysine and the like.

  Surfactant metal salt powder (metal soap) includes zinc stearate, aluminum stearate, calcium stearate, magnesium stearate, zinc myristate, magnesium myristate, zinc cetyl phosphate, calcium cetyl phosphate, zinc sodium cetyl phosphate, etc. Can be mentioned. As colored pigments, inorganic red pigments such as iron oxide, iron hydroxide and iron titanate, inorganic brown pigments such as γ-iron oxide, inorganic yellow pigments such as yellow iron oxide and loess, black iron oxide, carbon black, etc. Lake inorganic black pigments, inorganic purple pigments such as manganese violet and cobalt violet, inorganic green pigments such as chromium hydroxide, chromium oxide, cobalt oxide and cobalt titanate, inorganic blue pigments such as bitumen and ultramarine blue, and tar dyes And a synthetic resin powder obtained by compounding these powders. Examples of pearl pigments include titanium oxide coated mica, titanium oxide coated mica, bismuth oxychloride, titanium oxide coated bismuth oxychloride, titanium oxide coated talc, fish scale foil, titanium oxide coated colored mica, and metal powder pigments (tar pigments). Red 3, Red 104, Red 106, Red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 227, Red 228, Red 230, Red 401, Red 505, Yellow 4, Yellow 5, Yellow 202, Yellow 203, Yellow 204, Yellow 401, Blue 1, Blue 2, Blue 201, Blue 404, Green 3 Green 201, Green 204, Green 205, Orange 201, Orange 203, Orange 204, Orange 206, Orange 207, and the like. Examples of natural pigments include powders selected from carminic acid, laccaic acid, calsamine, bradylin, crocin and the like. These powders can be used as long as they do not interfere with the effects of the present invention, and powders treated with general oils, silicone oils, fluorine compounds, surfactants, and the like. For example, fluorine compound treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, polyacrylic acid treatment, metal soap treatment, amino acid treatment, inorganic compound treatment The surface treatment may or may not be performed in advance by plasma treatment, mechanochemical treatment or the like, and these may be used alone or in combination of two or more.

  Examples of the organic acid include alkyl sulfuric acid, alkyl phosphoric acid, monocarboxylic acid, dicarboxylic acid, hydroxycarboxylic acid, polycarboxylic acid, and acidic amino acid. Among these, carboxylic acid is preferable, and in particular, dicarboxylic acid, hydroxycarboxylic acid, malonic acid, succinic acid, glutaric acid, adipic acid, maleic acid, fumaric acid, phthalic acid, L-glutamic acid, L-aspartic acid and the like can be mentioned, L-glutamic acid is particularly preferable. Hydroxycarboxylic acids include glycolic acid, lactic acid, hydroxyacrylic acid, oxybutyric acid (especially α-oxybutyric acid), glyceric acid, malic acid, tartaric acid, formic acid such as citric acid, acetic acid, citric acid, lactic acid, glycolic acid, benzoic acid Examples of inorganic acids include phosphoric acid, hydrochloric acid, sulfuric acid and the like.

  Antibacterial and preservatives include aminoethyl sulfonic acid, benzoic acid, sodium benzoate, benzyl benzoate, anthracite, liquid phenol, ethanol, sodium edetate, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, and dry sodium sulfate , Kanten, dl-camphor, strong sump leather N (trade name: Saneigen F.F.I.), citric acid, sodium citrate, chlorocresol, chlorobutanol, gentisic acid ethanolamide, salicylic acid, sodium salicylate, Dibutylhydroxytoluene, 2,6-di-t-butyl-4-methylphenol, cecept (trade name: manufactured by Seiwa Kasei Co., Ltd.), sorbic acid, potassium sorbate, nitrogen, thymol, dehydroacetic acid, sodium dehydroacetate, 2 -Naphtho , Hinokitiol, sucrose, honey, isobutyl paraoxybenzoate, isopropyl paraoxybenzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate, propyl paraoxybenzoate, methyl paraoxybenzoate, paraformaldehyde, phenylethyl alcohol, phenol, proxel GXL Name: manufactured by Zeneca), benzyl alcohol, boric acid, borax, d-borneol, l-menthol, eucalyptus oil, oxyquinoline sulfate, isopropylmethylphenol, undecylenic acid monoethanolamide, distearyldimethylammonium chloride, stearyldimethyl chloride Benzylammonium, stearyltrimethylammonium chloride, alkyldiaminoethylglycine hydrochloride, chlorhexidine hydrochloride (gluconic acid), Rutophenylphenol, cresol, chloramine T, chlorxylenol, chlorphenesin, alkyl isoquinolinium bromide solution, domifene bromide, thianthol, trichlorocarbanilide, parachlorophenol, halocarban, 2- (2-hydroxy- 5-methylphenyl) benzotriazole, hexachlorophene, resorcin, phenoxyethanol and the like.

  As the fragrance and the fragrance composition used in the hair growth agent composition of the present invention, the fragrance ingredients described in JP-A-2003-300111 [0021] to [0035], and the like, and further for the fragrance described in the same [0050] A solvent etc. are mentioned. In addition, a fragrance | flavor composition means the mixture which consists of a fragrance | flavor component, a solvent, a fragrance | flavor stabilizer, etc. Although the fragrance | flavor solvent is mix | blended 0.1-99 mass% in a fragrance | flavor composition, Preferably 1-50 mass% is mix | blended. Examples of the perfume stabilizer include dibutylhydroxytoluene, butylhydroxyanisole, vitamin E and its derivatives, catechin compounds, flavonoid compounds, polyphenol compounds and the like, and dibutylhydroxytoluene is preferable. The compounding quantity of a fragrance | flavor stabilizer is 0.0001-10 mass% normally in a fragrance | flavor composition, and 0.001-5 mass% is preferable. The blending amount of the fragrance composition is 0.005 to 40% by mass, preferably 0.01 to 10% by mass in the hair-growth hair nourishing agent composition.

  Examples of the ultraviolet absorber include octyl methoxycinnamate (Neoheliopan AV), oxybenzone, urocanic acid and the like.

  Vitamins include vitamin A, vitamin B group, vitamin C, vitamin D, vitamin E, vitamin F, vitamin K, vitamin P, vitamin U, carnitine, ferulic acid, γ-oryzanol, α-lipoic acid, orotic acid and Examples thereof include derivatives thereof.

  Examples of amino acids include arginine, glycine, alanine, serine, proline, leucine, isoleucine, valine, threonine, phenylalanine / tryptophan, cysteine, aspartic acid, glutamic acid, lysine, histidine, 2-pyrrolidone-5-carboxylic acid, etc. Can do. Among these, one or more selected from arginine, glycine, alanine, serine, glutamic acid, proline, leucine, and isoleucine are preferable. About the said amino acid, use can be made of L-form or DL-form, acid type or alkali metal salt (sodium salt etc.), alkaline earth metal salt (magnesium salt etc.), inorganic acid salt (hydrochloride etc.) and the like.

  The basic nucleic acid is not particularly limited as long as it is deoxyribonucleic acid or a base constituting ribonucleic acid. Specifically, as purine bases, as purine, adenine, guanine, and pyrimidine bases, pyrimidine, pyrazine, pyridazine, cytosine, thymine , Uracil. The derivative of the basic nucleic acid is not particularly limited as long as it is a substance derived from a purine base or a pyrimidine base, but a sugar residue, a phosphate group, a sulfonate group, a carboxyl group, an amino group, a quaternary ammonium group, Examples thereof include guanidino group, hydroxyl group, polyoxyalkylene group, polyol group, alkyl group, fluoroalkyl group, betaine group, and amine oxide group.

  Examples of the keratolytic agent include salicylic acid and resorcin.

  Medicinal components include β-glycyrrhetinic acid, cephalanthin, sempri extract, hinokitiol, iodinated garlic extract, biotin, allantoin, pyridoxine hydrochloride, dl-α-tocopherol, dl-α-tocopherol acetate, trans-3,4'- Vitamins such as dimethyl-3-hydroxyflavanone, pentadecanoic acid glyceride, nicotinic acid, nicotinamide, calcium D-pantothenate, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, estradiol, ethinylestradiol, capronium chloride, diphenhydramine hydrochloride , Photosensitizer 301, camphor, nonyl acid vanillylamide, nonanoic acid vanillylamide, mononitroguaiacol, γ-aminobutyric acid, seaweed extract other than component (A), assembly X , Plant extracts such as aloe extract, ginkgo biloba extract, oxon extract, auxin, hypericum extract, cantalis tincture, clara extract, ginseng tincture, duke extract, eucalyptus extract, and caterpillar extract, bovine hematin, Examples include animal-derived extracts such as placenta extract, 10-hydroxy-Δ2-desanoic acid, hydrocortisone, and the like.

  Examples of the application field of the hair-restoring agent composition of the present invention include various external preparations (including preparations used for animals) in general. Specifically, capsules, powders, granules, solids, liquids, gels, ointments, or foams (1) pharmaceuticals, (2) quasi drugs, (3) topical or systemic (4) Medicinal and / or cosmetic preparations applied to the scalp and hair (eg shampoos, rinses, treatments, permanent liquids, hair dyes, hair preparations, hair styling agents, hair growth / Hair nourishing etc.).

  The hair-growth nourishing composition of the present invention can be used for external use in the form of a uniform solution, lotion, gel or the like according to a conventional method. Further, the hair-growth nourishing composition of the present invention can take the form of an aerosol. In that case, in addition to the above components, lower alcohols such as n-propyl alcohol or isopropyl alcohol, butane, propane, isobutane, liquefied petroleum Gas, combustible gas, such as dimethyl ether, compressed gas, such as nitrogen gas, oxygen gas, carbon dioxide gas, nitrous oxide gas, can be contained.

  The hair restorer composition of the present invention can be obtained based on a conventional method by mixing the above essential components, optional components, and the remaining solvent (ethanol, water).

  EXAMPLES Hereinafter, although a test example, an Example, and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. In the following examples, unless otherwise specified, “%” in the composition represents mass%.

[Test Examples 1 to 21]
The plant-derived materials and plants shown in Table 1 as test samples were extracted with 70% ethanol and seaweed with water, and the resulting extract was dried to obtain a solid. This solid was dissolved in ethanol to a concentration of 100 mg / mL. The extract thus prepared was added to keratinocytes previously cultured at 20,000 cells / well so that the final concentration was 100 μg / mL. At the same time, apoptosis induction promoting protein (Neurotrophin-4, hereinafter referred to as “NT-4”) was added to the well so that the final concentration was 1 ng / mL. After 24 hours, the apoptosis induction rate was measured using the TUNEL method. The apoptosis induction rate was determined by staining the cells causing apoptosis using a TUNEL staining kit “TACS _™ 2 TdT DAB” (manufactured by TREVIGEN) and determining the ratio thereof. As a result of the apoptosis induction inhibition test, the induction inhibition rate (%) was calculated with the addition of NT-4 alone as the apoptosis induction rate of 100%, and the results were shown by the following criteria.
<Standard>
◎: Suppressed by 80% or more compared to the case of adding only NT-4 ○: Suppressed by 50% or more and less than 80% compared to the case of adding only NT-4 ×: Suppressed by less than 50% compared to the case of adding only NT-4

  Table 1 shows the results of the apoptosis induction suppression test. As shown in Table 1, the extract was found to suppress the induction of apoptosis. In particular, it was revealed that apoptosis induction was excellent in scab, asaku, echronia, dallus, and geek. Therefore, it was confirmed that the extract was an inhibitor of apoptosis induction promoting protein.

[Comparative Test Example 1]
Ethanol was added to keratinocytes previously cultured at 20,000 cells / well to a final concentration of 0.1%. At the same time, apoptosis induction promoting protein (NT-4) was added to the well so that the final concentration was 1 ng / mL. Apoptosis induction rate was determined in the same manner as in the above test example. As a result, the action of the apoptosis induction promoting protein was not suppressed, and apoptosis was induced.

[Examples 1 to 15 and Comparative Examples 1 to 4]
Plant-derived materials and plants shown in Tables 2 to 4 were extracted with 70% ethanol, seaweed was extracted with water, and the resulting extract was dried to obtain a solid. This solid was dissolved in ethanol to a concentration of 0.1% and used as an extract. On the other hand, commercially available extracts were used as they were. Using these extracts, hair growth nourishing compositions having the compositions shown in Tables 2 to 4 were prepared in a conventional manner. The hair growth agent composition was adjusted to pH 6.0 with citric acid (pH adjuster). Using this hair growth agent composition, an inhibition test of apoptosis induction by an apoptosis induction promoting protein and a hair growth test in mice were performed. The results are also shown in the table.

Apoptosis induction suppression test The test sample was added to keratinocytes previously cultured at 20,000 cells / well so that the final concentration was 0.1%. At the same time, apoptosis induction promoting protein NT-4 was added to the well so that the final concentration was 1 ng / mL. After 24 hours, the apoptosis induction rate was measured using the TUNEL method. The apoptosis induction rate was determined by staining the cells causing apoptosis using a TUNEL staining kit “TACS _™ 2 TdT DAB” (manufactured by TREVIGEN) and determining the ratio thereof. The result of the apoptosis induction suppression test was expressed as an induction suppression rate (%) with the addition of NT-4 alone as an apoptosis induction rate of 100%. In addition, the standard of the inhibitory effect of apoptosis induction by the apoptosis induction promoting protein is shown below.
<Criteria>
80% or more suppression compared to the case of adding only NT-4: 60% or more but less than 80% compared to the case of adding only effective NT-4: 40% or more but less than 60% compared to the case of adding only effective NT-4 Suppression: Slightly less than 40% compared to the case of adding only effective NT-4: Ineffective

Hair growth test in mice The back of 49-day-old C3H / Heslc mice in the rest period of the hair cycle was depilated using an electric clipper and an electric shaver, and subjected to experiments as 10 mice per group. The test sample was applied to the back part from which hair was removed from the next day after hair removal, 0.1 mL each, once a day. The hair growth effect of each test sample was determined by measuring the hair growth area of the mouse hair removal back and determining the number of days when the hair growth area relative to the hair removal area was 50%. Similarly, the number of days in which the hair growth area with respect to the area where hair was removed when ethanol alone was applied was 50% was examined, the number of days for promoting hair growth was calculated based on the following formula, and the average value of 10 animals was shown.
Hair growth promotion days = (days on which the hair growth area of ethanol application is 50%) − (days on which the hair growth area of test sample application is 50%)
The standard of hair growth effect is shown in the following standard.
<Standard>
Hair growth promotion days 7 days or more: Great effect
3 days or more and less than 7 days: Valid
0 days or more and less than 3 days: Invalid

  Examples of the hair-growth nourishing composition of the present invention are shown below. In addition, the hair-restoring agent composition of each following Example was prepared according to the usual method of each dosage form according to each composition.

[Example 16]
(Hair restorer)
Composition%
Asaku extract 1.0
Piroctone Olamine 0.5
Triethylhexyl citrate 5.0
Propylene glycol monooctanoate 1.0
Ethyl oleate 2.0
Polyethylene glycol 400 1.0
Monopentadecanoic acid glyceride 3.0
Tocopherol acetate 0.1
Coleus-Forskori root extract 0.5
Glycerin 1.0
Palm oil fatty acid sorbitan 1.0
Sucrose myristic acid ester 1.0
Decaglyceryl myristate 1.0
Lauryldimethylaminoacetic acid betaine 0.5
Amphoteric polymer * 1 0.2
Succinic acid 0.1
Fragrance * 2 0.5
Purified water 0.3
99% ethanol remaining
Total 100.0
* 1: N-methacryloyloxyethyl-N, N-dimethylammonium / α-N-methylcarboxybetaine / alkyl methacrylate copolymer * 2: Composition A in Table 2 of JP-A-2003-113019

[Example 17]
(Hair growth lotion)
Composition%
Okinawa Mozuku Extract 1.0
Phyto Collage Extract 1.0
Piroctone Olamine 0.3
Propylene glycol monostearate 0.5
Polyethylene glycol 400 0.1
Butyl myristate 0.1
D-pantothenyl alcohol 2.0
Nicotinamide 1.0
β-glycyrrhetinic acid 0.5
Isopropylmethylphenol 0.5
Assembly extract 0.1
POE (40) hydrogenated castor oil 0.5
POE (30) tetrasorbate sorbit 0.1
Sorbitan monopalmitate 0.5
Coleus-Forskori root extract 0.5
l-Menthol (synthesis) 0.1
Hinokitiol 0.3
Methylparapen 0.1
Citric acid 0.05
Fragrance * 3 0.3
Purified water 10.0
99% ethanol remaining
Total 100.0
* 3: B composition in Table 2 described in JP2003-113019 (hair growth spray)

[Example 18]
(Hair growth spray)
Composition%
Asaku extract 0.5
Piroctone Olamine 0.5
Octyldodecyl lactate 2.0
Polyethylene glycol 300 0.5
Isopropyl myristate 2.0
Monopentadecanoic acid glyceride 2.0
Tocopherol acetate 0.5
β-glycyrrhetinic acid 0.5
Isopropylmethylphenol 0.5
Amphoteric polymer * 1 0.2
Succinic acid 0.3
Sucrose myristic acid ester 0.5
Sorbitan monolaurate 0.5
Decaglyceryl myristate 0.5
Glycerin 0.05
l-Menthol (synthesis) 0.3
Purified water 0.3
Fragrance * 4 0.5
99% ethanol remaining
Total 100.0
(Filling liquid for dilution)
Stock solution 70.0
Dimethyl ether 30.0
Total 100.0
* 1: N-methacryloyloxyethyl-N, N-dimethylammonium / α-N-methylcarboxybetaine / alkyl methacrylate copolymer * 4: C composition in Table 2 of JP-A No. 2003-113019

[Example 19]
(Hair growth hair spray)
Composition%
Okinawa Mozuku Extract 1.0
Dulse extract 0.5
Phytocollage extract 0.5
Ciclopirox olamine 0.2
Propylene glycol octoate 0.05
Polyethylene glycol 600 3.0
Isopropyl myristate 0.1
Pantothenyl ethyl ether 1.0
Salicylic acid 0.5
Nicotinamide 0.05
β-glycyrrhetinic acid 0.05
POE (40) hydrogenated castor oil 0.5
POE (40) tetraoleate sorbit 0.3
Enmeso Extract 1.0
Citric acid 0.1
l-Menthol (synthesis) 0.5
Perfume * 5 Appropriate amount
Purified water 30.0
99% ethanol remaining
Total 100.0
(Filling liquid for dilution)
Stock solution 80.0
Dimethyl ether 20.0
Total 100.0

* 5: D composition in Table 2 of JP2003-1113019

[Example 20]
(Hair growth tonic)
Composition%
Asaku extract 0.5
Piroctone Olamine 0.5
POE (2) oleyl ether 1.0
Octyldodecyl lactate 1.0
Polyethylene glycol 200 0.1
Ethyl oleate 5.0
Monopentadecanoic acid glyceride 5.0
D-pantothenyl alcohol 0.4
β-glycyrrhetinic acid 0.1
Tocopherol acetate 0.1
Coleus-Forskori root extract 0.5
Propylene glycol monooctanoate 0.8
Sucrose myristic acid ester 0.3
Amphoteric polymer * 1 0.1
Succinic acid 0.1
Fragrance * 6 0.5
99% ethanol remaining
Total 100.0
(Filling liquid for dilution)
Stock solution 80.0
LPG 20.0
Total 100.0
* 1: N-methacryloyloxyethyl-N, N-dimethylammonium / α-N-methylcarboxybetaine / alkyl methacrylate copolymer * 6: E composition in Table 2 described in JP-A No. 2003-113019

  When the hair-growing compositions of various dosage forms in Examples 16 to 20 were evaluated in the same manner as in the above-described Examples, all showed a high inhibitory effect on apoptosis induction by the apoptosis induction promoting protein and an excellent hair-growth effect.

  The raw materials used in Examples and Comparative Examples are shown below.

Claims (2)

(A) an inhibitor of apoptosis induction promoting protein;
(B) a hydroxypyridone derivative;
(C) A hair-growth nourishing composition comprising an ester compound having a hydroxy group in the molecule. Furthermore, the hair-growth nourishing composition of Claim 1 formed by mix | blending the ester compound of (D) polyhydric alcohol and / or monohydric alcohol, and aliphatic monocarboxylic acid.