Composition for promoting hair growth

Abstract

To provide a composition for promoting expression of placental growth factor, a composition for promoting hair growth, a composition for complementing hair-growing action of a minoxidil-containing composition and a composition for promoting expression of sulfotransferase 1A1 gene.SOLUTION: There is prepared a composition for promoting expression of placental growth factor which comprises (A) pantothenic acid, a derivative of pantothenic acid or a salt thereof, (B) pyridoxine, a derivative of pyridoxine or a salt thereof and (C) tocopherol, a derivative of tocopherol or a salt thereof. Further, there are prepared: a composition for promoting hair growth comprising the components (A) to (C); and a composition for complementing hair-growing action of a minoxidil-containing composition comprising the components (A) to (C). Furthermore, there is prepared a composition for promoting expression of sulfotransferase 1A1 gene which comprises (A) pantothenic acid, a derivative of pantothenic acid or a salt thereof or (B) pyridoxine, a derivative of pyridoxine or a salt thereof.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition for promoting hair growth. [Background technology]

[0002] Hair grows and falls out in a certain cycle, and is controlled by various factors secreted from hair papilla cells, outer root sheath cells, etc. Known such factors include hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), GLI transcription factor, Wnt protein, etc. (Non-Patent Documents 1 and 2).

[0003] Here, Patent Document 1 discloses that taurine extends the hair growth phase and is therefore excellent in promoting hair growth.

[0004] Patent Document 2 discloses that rice extract promotes the production of hepatocyte growth factor and is therefore highly effective in promoting hair growth.

[0005] Patent Document 3 discloses that bamboo shoot extract activates hair papilla cells and promotes the production of vascular endothelial growth factor and fibroblast growth factor, and thus has excellent hair growth promoting effects. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] JP 2002-097116 A [Patent Document 2] JP 2004-099503 A [Patent Document 3] JP 2013-180999 A [Non-patent literature]

[0007] [Non-Patent Document 1] Karoline Krause and Kerstin Foitzik (2006) Biology of the Hair Follicle:The Basics. Seminars in Cutaneous Medicine and Surgery 25(1):2-10. [Non-Patent Document 2] Rishikaysh et. al.,(2014) Signaling Involved in Hair Follicle Morphogenesis and Development. Int. J. Mol. Sci.15:1647-1670. Summary of the Invention [Problem to be solved by the invention]

[0008] An objective of the present invention is to provide a composition for promoting hair growth, a composition for promoting the expression of placental growth factor, and the like. [Means for solving the problem]

[0009] As a result of intensive research by the present inventors to solve the above problems, (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; (B) pyridoxine, a derivative of pyridoxine, or a salt thereof; and (C) It was found that tocopherol, a tocopherol derivative, or a salt thereof has a hair growth effect, and the present invention was completed based on this finding.

[0010] In particular, the present inventors have found that a composition containing pantothenic acid, a pantothenic acid derivative, or a salt thereof; pyridoxine, a pyridoxine derivative, or a salt thereof; and tocopherol, a tocopherol derivative, or a salt thereof is useful for increasing the strength of hair roots and the thickness of hair, or for increasing the length of hair, and have completed the present invention.The present inventors have also found that in particular pantothenic acid, a pantothenic acid derivative, or a salt thereof acts on hair papilla cells to promote the expression of placenta growth factor, and have completed the present invention.

[0011] That is, the present invention provides a composition for promoting expression of placenta growth factor, a composition for promoting hair growth, and a composition for complementing the hair growth effect of a minoxidil-containing composition, as described below.

[0012] Section 1. (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; (B) pyridoxine, a derivative of pyridoxine, or a salt thereof; and (C) Tocopherol, a derivative of tocopherol, or a salt thereof A composition for promoting the expression of placenta growth factor, comprising one or more members selected from the group consisting of: Section 2. (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; (B) pyridoxine, a derivative of pyridoxine, or a salt thereof; and (C) Tocopherol, a derivative of tocopherol, or a salt thereof A composition for promoting hair growth comprising as an active ingredient. Section 3. Item 2. A hair growth promoting composition according to Item 1, wherein the hair growth promotion is prevention or prevention of the progression of symptoms such as loss of hair elasticity and strength, loss of volume, loss of volume, or thinning. Section 4. Item 3. The hair growth promoting composition according to any one of items 1 and 2, wherein the hair growth promotion is to elongate hair after hair growth, to thicken hair after hair growth, or to make hair after hair growth less likely to fall out. Section 5. 4. The hair growth promoting composition according to any one of items 1 to 3, wherein the mass ratio of the components (A), (B) and (C) is 1:0.05:0.08. Section 6. (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; (B) pyridoxine, a derivative of pyridoxine, or a salt thereof; and (C) Tocopherol, a derivative of tocopherol, or a salt thereof A composition for complementing the hair growth effect of a minoxidil-containing composition. Section 7. (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; or (B) pyridoxine, a derivative of pyridoxine, or a salt thereof; A composition for promoting expression of the sulfotransferase 1A1 gene, comprising: Section 8. (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; or (B) pyridoxine, a derivative of pyridoxine, or a salt thereof; 1. A composition for promoting the in vivo conversion of minoxidil to minoxidil sulfate, comprising: Effect of the Invention

[0013] According to the present invention, an excellent composition for promoting the expression of placenta growth factor can be provided. Furthermore, the present invention can provide an excellent composition for promoting expression of the sulfotransferase 1A1 gene. [Brief description of the drawings]

[0014] [Figure 1] FIG. 1 is a graph showing the results of evaluating PGF gene expression when hair papilla cells were subjected to pantothenyl ethyl ether treatment. [Diagram 2] FIG. 2 is a graph showing the results of evaluating PGF gene expression when dermal papilla cells were subjected to pyridoxine hydrochloride treatment. [Diagram 3] FIG. 3 is a graph showing the results of evaluating PGF gene expression when hair papilla cells were subjected to tocopherol acetate treatment. [Figure 4] FIG. 4 is a graph showing the amount of whisker growth when the whisker organs of mice were treated with pantothenyl ethyl ether, pyridoxine hydrochloride, or tocopherol acetate alone. [Diagram 5] FIG. 5 is a graph showing the amount of whisker growth when the whisker organ of a mouse was treated with pantothenyl ethyl ether, pyridoxine hydrochloride, and tocopherol acetate. [Figure 6]FIG. 6 is a graph showing the results of evaluating PGF gene expression in hair papilla cells when mouse whisker organs were treated with pantothenyl ethyl ether, pyridoxine hydrochloride, and tocopherol acetate. [Figure 7] FIG. 7 is a graph showing the results of evaluating the expression of sulfotransferase 1A1 gene when human hair follicle keratinocytes were subjected to pantothenyl ethyl ether treatment. [Figure 8] FIG. 8 is a graph showing the results of evaluating the expression of sulfotransferase 1A1 gene when human hair follicle keratinocytes were treated with pyridoxine hydrochloride. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] In this specification, the term "hair growth" includes an action that favorably promotes the growth and development of hair. In particular, it includes the prevention or prophylaxis of the progression of symptoms such as a decrease in the firmness and strength of hair and eyelashes, a decrease in the amount and volume of hair on the top of the head or other parts, or thinning of hair, as well as the elongation of hair after growth, the thickening of hair after growth, or the prevention of hair loss after growth. Such an action is also useful, for example, in suppressing undesirable hair wavyness.

[0016] Hair means any hair that grows on the body of an animal, including a human, and means any body hair, such as hair (head hair), eyebrows, eyelashes, moustache, beard, chest hair, back hair, etc., and mainly means hair, eyebrows, or eyelashes.

[0017] In this specification, "containing as an active ingredient" means clearly indicating that the effect of the present invention is exhibited by, for example, the action of component (A), component (B), or component (C), or a combination of components (A) to (C), or further, the action of the combined use with other components. The active ingredient is not directly related to whether or not it is labeled as an active ingredient on the label of the actual product.

[0018] As used herein, "w / v%" means g / 100ml. "v / v%" means ml / 100ml.

[0019] Placental growth factor (PlGF) is a cytokine that belongs to the vascular endothelial growth factor (VEGF) family and binds to VEGF receptor-1. It specifically binds to Flt-1. It is commonly abbreviated as PIGF, but in this specification, "placenta growth factor" and "PGF" are used interchangeably.

[0020] [Composition for promoting expression of placental growth factor] The present invention relates to (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; (B) pyridoxine, a derivative of pyridoxine, or a salt thereof; and (C) Tocopherol, a derivative of tocopherol, or a salt thereof The present invention relates to a composition for promoting the expression of a placenta growth factor, comprising one or more members selected from the group consisting of:

[0021] ((A) Pantothenic acid, a derivative of pantothenic acid, or a salt thereof) The (A) pantothenic acid, a pantothenic acid derivative, or a salt thereof used in the present invention is not particularly limited as long as it is used in the fields of pharmaceuticals, quasi-drugs, or cosmetics. The component (A) is not limited, but is preferably selected from the group consisting of pantothenic acid, calcium pantothenate, pantothenyl alcohol (panthenol), D-panthesine, D-pantethine, coenzyme A, and pantothenyl ethyl ether. These components may be used alone or in combination of two or more.

[0022] In the composition for promoting expression of placenta growth factor of the present invention, the content of component (A) relative to the total amount of the composition is appropriately set depending on the balance with other components. From the viewpoint of exerting the effects of the present invention, the content of component (A) relative to the total amount of the composition is preferably 0.1 to 5 w / v%, more preferably 0.3 to 3 w / v%, and even more preferably 0.5 to 2 w / v%.

[0023] ((B) Pyridoxine, pyridoxine derivatives, or salts thereof) The pyridoxine, pyridoxine derivatives, or salts thereof (B) used in the present invention are not particularly limited as long as they are used in the fields of pharmaceuticals, quasi-drugs, or cosmetics. Examples of pyridoxine or pyridoxine derivatives include pyridoxine, pyridoxal, and pyridoxamine. Examples of their salts include, but are not limited to, hydrochloride, sulfate, nitrate, hydrobromide, and phosphate. As the (B) component, pyridoxine hydrochloride is particularly preferred. These components can be used alone or in combination of two or more.

[0024] In the composition for promoting expression of placenta growth factor of the present invention, the content of component (B) relative to the total amount of the composition is appropriately set depending on the balance with other components. From the viewpoint of exerting the effects of the present invention, the content of component (B) relative to the total amount of the composition is preferably 0.001 to 1 w / v%, more preferably 0.005 to 0.5 w / v%, and even more preferably 0.01 to 0.1 w / v%.

[0025] The mass ratio of the (A) component to the (B) component is not particularly limited, but is preferably 0.001 to 1 part by mass of the (B) component per 1 part by mass of the (A) component, more preferably 0.005 to 0.5 parts by mass, and even more preferably 0.01 to 0.1 parts by mass.

[0026] ((C) Tocopherol, a derivative of tocopherol, or a salt thereof) The (C) tocopherol, tocopherol derivative, or salt thereof used in the present invention is not particularly limited as long as it is used in the fields of pharmaceuticals, quasi-drugs, or cosmetics. Although not limited, any of α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol can be used as the tocopherol. In terms of exhibiting the effects of the present invention remarkably, α-tocopherol is preferred. Examples of tocopherol derivatives include organic acid esters of tocopherol such as tocopherol acetate, tocopherol nicotinate, tocopherol succinate, and tocopherol linoleate. As the (C) component, it is preferable to use an organic acid ester of tocopherol, and tocopherol acetate is particularly preferred. These components can be used alone or in combination of two or more.

[0027] In the composition for promoting expression of placenta growth factor of the present invention, the content of component (C) relative to the total amount of the composition is appropriately set depending on the balance with other components. From the viewpoint of exerting the effects of the present invention, the content of component (C) relative to the total amount of the composition is preferably 0.001 to 1 w / v%, more preferably 0.005 to 0.5 w / v%, and even more preferably 0.01 to 0.1 w / v%.

[0028] The mass ratio of the (A) component to the (C) component is not particularly limited, but is preferably 0.001 to 1 part by mass of the (C) component per 1 part by mass of the (A) component, more preferably 0.005 to 0.5 parts by mass, and even more preferably 0.01 to 0.1 parts by mass.

[0029] Furthermore, the mass ratio of the (A), (B), and (C) components is not particularly limited, but is preferably 0.001 to 1 part by mass of the (B) component and 0.001 to 1 part by mass of the (C) component per 1 part by mass of the (A) component, more preferably 0.005 to 0.5 parts by mass of the (B) component and 0.005 to 0.5 parts by mass of the (C) component, even more preferably 0.01 to 0.1 parts by mass of the (B) component and 0.01 to 0.1 parts by mass of the (C) component, and most preferably the mass ratio of the (A), (B), and (C) components is 1:0.05:0.08.

[0030] (Base / Carrier) In the present invention, the composition for promoting placental growth factor expression may contain, in addition to the components (A), (B), and (C), a pharma- ceutical or physiologically acceptable base or carrier for topical preparations, quasi-drugs, or cosmetics, within a range that does not impair the effects of the present invention.

[0031] Such bases or carriers include hydrocarbons such as water, ethanol, liquid paraffin, squalane, petrolatum, gelling hydrocarbons (such as Plastibase), ozokerite, a-olefin oligomers, and light liquid paraffin; silicone oils such as methyl polysiloxane, highly polymerized methyl polysiloxane, cyclic silicone, alkyl modified silicone, amino modified silicone, polyether modified silicone, polyglycerin modified silicone, silicone / alkyl chain co-modified polyether modified silicone, silicone / alkyl chain co-modified polyglycerin modified silicone, polyether modified branched silicone, polyglycerin modified branched silicone, acrylic silicone, phenyl modified silicone, and silicone resin; oils and fats such as coconut oil, olive oil, rice bran oil, and shea butter; waxes such as jojoba oil, meu wax, candelilla wax, and lanolin; cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, octyl dodeca higher alcohols such as ethanol, isostearyl alcohol, phytosterol, and cholesterol; cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose; polyvinylpyrrolidone; carrageenan; polyvinyl butyrate; polyethylene glycol; dioxane; butylene glycol adipate polyester; esters such as isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, and pentaerythritol tetra 2-ethylhexanoate; polysaccharides such as dextrin and maltodextrin; vinyl polymers such as carboxyvinyl polymers and alkyl-modified carboxyvinyl polymers; lower (carbon number 1-4) alcohols such as methanol, propanol, isopropyl alcohol, butanol, isobutyl alcohol, sec-butyl alcohol, test-butyl alcohol, etc.;and glycol ethers such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol monopropyl ether, diethylene glycol monobutyl ether, propylene glycol monoethyl ether, propylene glycol monopropyl ether, dipropylene glycol monoethyl ether, and dipropylene glycol monopropyl ether; and polyols such as glycerin, diglycerin, polyglycerin, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, sorbitol, mannitol, trehalose, erythritol, and xylitol. The base or carrier may be used alone or in combination of two or more.

[0032] (Additives) In the present invention, the composition for promoting expression of placenta growth factor may contain pharma- ceutical or physiologically acceptable additives for topical drugs, quasi-drugs, and cosmetics. Examples of such additives include antioxidants, surfactants, thickeners, preservatives, pH adjusters, stabilizers, irritation reducers, preservatives, colorants, fragrances, and dissolution aids. Examples of surfactants include anionic surfactants, cationic surfactants, amphoteric surfactants, and nonionic surfactants.

[0033] Examples of anionic surfactants include carboxylic acid-based anionic surfactants, sulfonic acid-based anionic surfactants, phosphoric acid-based anionic surfactants, amino acid-based anionic surfactants, and protein hydrolysate-based anionic surfactants. Examples of carboxylic acid-based anionic surfactants include fatty acid salts, ether carboxylates, and amide ether carboxylates. Examples of fatty acid salts include salts of C8 to C22 fatty acids, and specifically include salts of caprylic acid, pelargonic acid, capric acid, lauric acid, myristic acid, pentadecylic acid, palmitic acid, palmitoleic acid, margaric acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, arachidic acid, and behenic acid. Examples of ether carboxylates include salts of polyoxyethylene alkyl ether carboxylates, polyoxyethylene cocoyl ether carboxylates, polyoxyethylene lauryl ether carboxylates, and polyoxyethylene myristyl ether carboxylates.Examples of sulfonic acid anionic surfactants include alkyl sulfates (C8 to C22 alkyl sulfates such as lauryl sulfate), alkyl sulfonates (C8 to C22 alkyl sulfonates such as lauryl sulfonate), alkyloxyalkyl sulfonates (alkyloxy C8 to C22 alkyl sulfonates), alkylaryl sulfates (C8 to C22 alkylaryl sulfates such as lauryl phenyl sulfate), alkylbenzene sulfonates (C8 to C22 alkylbenzene sulfonates such as lauryl benzene sulfonate), alkyl polyoxyethylene sulfates, glyceryl sulfates, acyl alkyl taurine salts (C8 to C22 alkyl alkyl taurine salts such as cocoyl methyl taurine salts), and the like. Examples of the phosphate-based anionic surfactant include monoalkyl phosphate, polyoxyethylene alkyl ether phosphate, polyoxyethylene polyoxypropylene alkyl ether phosphate, etc. Examples of the phosphate-based anionic surfactant include monoalkyl phosphate, polyoxyethylene alkyl ether phosphate, polyoxyethylene polyoxypropylene alkyl ether phosphate, etc. Examples of the phosphate-based anionic surfactant include monoalkyl phosphate, polyoxyethylene alkyl ether phosphate, polyoxyethylene polyoxypropylene alkyl ether phosphate, etc.Examples of amino acid-based anionic surfactants include acyl glutamate (C8-C22 alkanoyl glutamate such as cocoyl glutamate), acyl glycine salt (C8-C22 alkanoyl glycine salt such as cocoyl glycine salt), acylalanine salt (C8-C22 alkanoyl alanine salt such as cocoyl alanine salt), acyl alkyl alanine salt (C8-C22 alkanoyl alkyl alanine salt such as lauroyl methyl alanine salt), acylaspartate (C8-C22 alkanoyl aspartate such as lauroyl aspartate), monoalkyl phosphate (C8-C22 alkyl phosphate, etc.), acyl sarcosine salt (C8-C22 alkanoyl sarcosine salt such as cocoyl sarcosine salt), etc. Examples of protein hydrolyzate-based anionic surfactants include alkyl hydrolyzed collagen salt, coconut oil fatty acid hydrolyzed collagen salt, alkyl hydrolyzed silk salt, etc.

[0034] Examples of the cationic surfactant include alkyl trimethyl ammonium salts, dialkyl dimethyl ammonium salts, alkyl benzyl dimethyl ammonium salts, etc. Examples of the salts of these include hydrochlorides and sulfates.

[0035] Examples of amphoteric surfactants include carbobetaine, sulfobetaine, imidazolinium betaine, amidobetaine, etc. Specific examples include fatty acid amidopropyl betaine, hydroxypropyl sulfobetaine, desalted secondary imidazolinium betaine, etc.

[0036] Examples of nonionic surfactants include amine oxides, glycerin fatty acid esters, sorbitan fatty acid esters, alkyl polyglucosides, sucrose fatty acid esters, alkyl sugar amides, polyglycerin fatty acid esters, polyoxyalkylene alkyl ethers, fatty acid alkanolamides, polyoxyalkylene hydrogenated castor oil, alkyl monoglyceryl ethers, etc. Specific examples include lauryl dimethylamine oxide, lauric acid diethanolamide, myristyl dimethylamine oxide, myristic acid monoethanolamide, myristic acid dinoethanolamide, isostearic acid monoglyceride, lauric acid monoethanolamide, oleic acid monoglyceride, sorbitan monolaurate, sorbitan monooleate, sorbitan sesquioleate, sorbitan monoisostearate, sorbitan trioleate, alkyl polyglucosides, coconut oil fatty acid monoethanolamide, coconut oil fatty acid diethanolamide, etc. The additives may be used alone or in combination of two or more.

[0037] (Pharmacologically active ingredients / biologically active ingredients) In the present invention, the composition for promoting expression of placenta growth factor can contain pharmacologically active or physiologically active ingredients for topical pharmaceuticals, quasi-drugs, and cosmetics other than the active ingredient. Examples of such ingredients include blood circulation promoting ingredients, angiogenesis promoting factors, moisturizing ingredients, anti-inflammatory ingredients, antibacterial ingredients, organic acids, vitamins other than the active ingredient, peptides or derivatives thereof, amino acids or derivatives thereof, cell activating ingredients, anti-aging ingredients, keratin softening or keratin dissolving ingredients, skin whitening ingredients, astringent ingredients, vasodilating ingredients, antihistamine ingredients, antioxidant ingredients, metabolic activators, and cooling agents. In addition, it can also contain hair growth ingredients such as minoxidil, carpronium chloride, adenosine, t-flavanone, ethinyl estradiol, 6-benzylaminopurine, glycyrrhetinic acid, cepharanthine, nicotinamide, carrot extract, and Swertia japonica extract, and preferably includes minoxidil, carpronium chloride, adenosine, t-flavanone, and ethinyl estradiol. The pharmacologically active ingredient or physiologically active ingredient can be used alone or in combination of two or more.

[0038] (pH) In the present invention, the pH of the composition for promoting expression of placenta growth factor is not particularly limited, and is preferably about 4.0 to 8.0, about 4.0 to 7.5, about 4.0 to 7.0, about 5.0 to 8.0, about 5.0 to 7.5, about 5.0 to 7.0, about 6.0 to 8.0, about 6.0 to 7.5, or about 6.0 to 7.0.

[0039] Within the above range, irritation to the scalp due to high pH can be avoided. The pH can be adjusted using a pH adjuster such as an inorganic acid such as phosphoric acid, hydrochloric acid, or sulfuric acid, or an organic acid such as lactic acid, sodium lactate, citric acid, sodium citrate, malic acid, sodium malate, succinic acid, sodium succinate, tartaric acid, sodium tartrate, gluconic acid, or sodium gluconate, etc. If necessary, the pH can be adjusted using a pH adjuster such as an organic base such as triethanolamine, diisopropanolamine, or triisopropanolamine, or an inorganic base such as potassium hydroxide or sodium hydroxide. The pH adjusters can be used alone or in combination of two or more.

[0040] (Application) The composition for promoting the expression of placental growth factor of the present invention is preferably prepared as a product for hair regeneration, a product for hair regeneration, a product for hair growth, a product for hair care, a product for hair loss prevention, etc. Among these, the use of the composition for promoting the expression of placenta growth factor of the present invention is particularly preferably a cosmetic product for the scalp and hair. (e.g. scalp lotion, scalp cream, shampoo, hair conditioner, hair treatment, hair essence, hair mist, hair tonic), skin care cosmetics Examples of the cosmetic product include cosmetic products (e.g., lotion, cream, facial cream, facial lotion, milky lotion, pack, liquid facial cleanser, soap, eyelash serum), and makeup cosmetics (e.g., eyeliner, eyebrow), and most preferred are scalp lotion, scalp cream, shampoo, hair conditioner, hair treatment, hair essence, hair tonic, eyelash serum, eyeliner, and eyebrow, but are not limited to these.

[0041] Thus, the dosage form of the composition for promoting expression of placental growth factor of the present invention is not particularly limited, and examples thereof include liquids, suspensions, emulsions, creams, gels, liniments, lotions, and aerosols. In addition, when the composition contains water to an extent that the (A), (B), and (C) components can be dissolved, it can be made into an ointment. Among them, liquids, suspensions, emulsions, lotions, and aerosols are preferred, and liquids, lotions, and aerosols are more preferred. When the composition for promoting expression of placental growth factor of the present invention contains an oily base and an aqueous base, such as creams, emulsions, and sometimes ointments and aerosols, the dosage form may be W / O type or O / W type, but O / W type is preferred in terms of good usability. The preparation can be produced by mixing the components according to or in accordance with the General Provisions of the 17th Revised Japanese Pharmacopoeia.

[0042] (container) In the present invention, the container in which the composition for promoting expression of placenta growth factor is filled is not particularly limited, and may be any container that can be used as a container for topical pharmaceutical preparations, quasi-drugs, or cosmetics. Examples of such container materials include containers in which a part or all, preferably all, of the surface that comes into contact with the composition for promoting placental growth factor expression is made of at least one material selected from the group consisting of polyolefins, acrylic acid resins, terephthalic acid esters, 2,6-naphthalenedicarboxylic acid esters, polycarbonates, polymethylterpenes, fluororesins, polyvinyl chloride, polyamides, ABS resins, AS resins, polyacetals, modified polyphenylene ethers, polyarylates, polysulfones, polyimides, cellulose acetate, aluminum, and glass.

[0043] (How to use) In the present invention, the method of using the composition for promoting expression of placenta growth factor varies depending on the condition of the hair, scalp, age, sex, etc. of the subject of use, but may be, for example, as follows. That is, an appropriate amount (eg, about 0.5 to 2 g, or 0.5 to 2 ml) may be applied to the skin (eg, scalp) several times a day (eg, about 1 to 5 times, preferably 1 to 3 times). The composition may be applied to the skin (e.g., scalp) so that the daily usage amount of the (A) component, the (B) component, and the (C) component is, for example, about 1 to 20 mg, 5 to 100 mg, and 10 to 50 mg. The application method may be painting or spraying, etc., depending on the dosage form. The application period may be, for example, about 7 days or more. Furthermore, the composition may be applied until the effect of the present invention is sufficiently obtained, for example, within 6 months, at least within 4 months.

[0044] [Hair growth promoting composition] The present invention also provides (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; (B) pyridoxine, a derivative of pyridoxine, or a salt thereof; and (C) Tocopherol, a derivative of tocopherol, or a salt thereof The present invention relates to a composition for promoting hair growth, comprising the above-mentioned compound as an active ingredient.

[0045] In the hair growth-promoting composition, the definitions and amounts of components (A), (B), and (C), as well as the base, carrier, additives, pharmacologically active ingredients, physiologically active ingredients, pH, method of use, etc., used in combination with each other are similar to those explained in the section on the composition for promoting placental growth factor expression.

[0046] [Composition for complementing the hair growth effect of a minoxidil-containing composition] The present invention also provides (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; (B) pyridoxine, a derivative of pyridoxine, or a salt thereof; and (C) Tocopherol, a derivative of tocopherol, or a salt thereof and a composition for complementing the hair growth effect of a minoxidil-containing composition. In such a composition, the definitions and amounts of components (A), (B), and (C), the base, carrier, additive, pharmacologically active ingredient, physiologically active ingredient, pH, method of use, etc., used in combination are the same as those described for the composition for promoting placental growth factor expression.

[0047] [Composition for promoting expression of sulfotransferase 1A1 gene] The present invention also provides (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; or (B) A composition for promoting expression of the sulfotransferase 1A1 gene, comprising pyridoxine, a pyridoxine derivative, or a salt thereof. The definition and amount of the components (B), the base, carrier, additive, pharmacologically active ingredient, physiologically active ingredient, pH, method of use, etc. used in combination shall be in accordance with the contents explained in the section on the composition for promoting placental growth factor expression.

[0048] [Composition for promoting the conversion of minoxidil to minoxidil sulfate in vivo] The present invention also provides (A) pantothenic acid, a derivative of pantothenic acid, or a salt thereof; or The present invention relates to a composition for promoting the conversion of minoxidil to minoxidil sulfate in vivo, which contains (B) pyridoxine, a derivative of pyridoxine, or a salt thereof. Since minoxidil is believed to act by being converted to "minoxidil sulfate" by "sulfotransferase" present in the body, such a substance capable of promoting the sulfation of minoxidil can fully bring out the action of minoxidil. In such a composition, the definitions and amounts of the components (A) and (B), the base, carrier, additive, pharmacologically active ingredient, physiologically active ingredient, pH, method of use, etc., used in combination are as described in the section on the composition for promoting placental growth factor expression. EXAMPLES

[0049] Next, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples.

[0050] In order to investigate the effects of pantothenyl ethyl ether, pyridoxine hydrochloride, or tocopherol acetate on hair growth from multiple viewpoints, the following tests were carried out. In the following tests, cells were cultured in a CO2 (5%) incubator.

[0051] The gene expression levels shown as the results of the test examples are corrected values, and in Test Example 1, β-actin (ACTB) was used as the housekeeping gene.

[0052] <Test 1: Evaluation of PGF gene expression> (1) Verification of the effects of pantothenyl ethyl ether Total RNA was extracted from hair papilla cells and the expression level of the PGF gene was analyzed according to the following procedure.

[0053] Human hair dermal papilla cells (HFDPC) (manufactured by Toyobo Co., Ltd.) suspended in DMEM containing 10% FBS were added at 4 × 10 4 The cells were seeded on a collagen-coated 24-well plate at 1.5 cells / well and cultured at 37°C for 48 hours. After confirming by microscopic observation that there were no problems with cell growth, a solution prepared with 0.1% FBS-containing DMEM was added to the cells so that the final concentrations of pantothenyl ethyl ether were 0.03, 0.1, and 0.3 v / v%. After culturing at 37°C for 24 hours, the cells were harvested and the gene expression level of PGF was measured by real-time PCR. Evaluation was performed with n=3. As a control, a sample without pantothenyl ethyl ether was used.

[0054] (2) Verification of the effects of pyridoxine hydrochloride or tocopherol acetate Similarly, PGF gene expression was evaluated using pyridoxine hydrochloride at final concentrations of 0.01, 0.03, or 0.1 w / v%, or tocopherol acetate at final concentrations of 0.01, 0.03 v / v, or 0.1 v / v, instead of pantothenyl ethyl ether.

[0055] These results are shown in Figures 1 to 3. As is clear from Figure 1, it was found that pantothenyl ethyl ether acts on dermal papilla cells and enhances PGF gene expression in a concentration-dependent manner. Similarly, as shown in Figures 2 and 3, it was found that pyridoxine hydrochloride and tocopherol acetate also act on dermal papilla cells and enhance PGF gene expression in a concentration-dependent manner.

[0056] <Test 2: Evaluation using mouse whisker organ culture> Mouse whisker organ culture was performed according to the following procedure: Nine-day-old mice (B6C3F1) were used for evaluation.

[0057] Specifically, first, whisker hair follicles were isolated on the 0th day of organ culture and photographed under a microscope. Then, the hair follicles were cultured in 10% FBS-containing RPMI1640 medium containing 0.3 w / v% pantothenyl ethyl ether, 0.015 w / v% pyridoxine hydrochloride, or 0.024 w / v% tocopherol acetate in a 24-well plate. After 3 days from the start of culture, the hair follicles were photographed again, the whisker length was measured, and the length extended during the 3-day culture was calculated. Evaluation was performed with n=9. As a control, only 10% FBS-containing RPMI1640 medium without any added components was used. The results are shown in Figure 4.

[0058] Similarly, hair follicles were cultured in 10% FBS-RPMI1640 medium containing 0.3 w / v% pantothenyl ethyl ether, 0.015 w / v% pyridoxine hydrochloride, and 0.024 w / v% tocopherol acetate in a 24-well plate, and the length of the hair follicles extended over 3 days of culture was calculated. After 24 hours of organ culture, hair papilla tissue was isolated from the hair follicles, and total RNA was extracted from the hair papilla cells to analyze the expression level of the PGF gene. The results are shown in Figures 5 and 6, respectively.

[0059] As shown in FIG. 4, when pantothenyl ethyl ether, pyridoxine hydrochloride, or tocopherol acetate was used alone, the mouse whisker organ did not elongate significantly.

[0060] On the other hand, when the three components of pantothenyl ethyl ether, pyridoxine hydrochloride, and tocopherol acetate were combined, mouse whisker organs were significantly elongated, as shown in Figure 5. Furthermore, when the three components were administered in combination, PGF gene expression was enhanced in hair papilla cells, as shown in Figure 6.

[0061] These results indicate that the combination of the three components, pantothenyl ethyl ether, pyridoxine hydrochloride, and tocopherol acetate, enhances the production of PGF and promotes hair elongation.

[0062] <Test 3: Evaluation of sulfotransferase (SULT) 1A1 gene expression> (1) Verification of the effects of pantothenyl ethyl ether Total RNA was extracted from human hair follicle keratinocytes and the expression level of the SULT1A1 gene was analyzed according to the following procedure.

[0063] Human hair follicle keratinocytes (HHFK) (ScienCell Research Laboratories, Inc., product number 2440) suspended in keratinocyte medium (ScienCell Research Laboratories, Inc., product number 2101NZ) were added at 5 × 10 4The cells were seeded on a 24-well plate at 1000 cells / well and cultured at 37°C for 48 hours. After confirming that there was no problem with cell growth by microscopic observation, a solution prepared with Defined Keratinocyte-SFM (Thermo Fisher Scientific; product number 10744019) was added to the cells so that the final concentration of pantothenyl ethyl ether was 0.03, 0.1, or 0.3 v / v%. After culturing at 37°C for 24 hours, the cells were collected and the gene expression level of SULT1A1 was measured by real-time PCR. Evaluation was performed with n=3. As a control, a solution without pantothenyl ethyl ether was used. The results are shown in Figure 7.

[0064] (2) Verification of the effects of pyridoxine hydrochloride Similarly, SULT1A1 gene expression was evaluated using pyridoxine hydrochloride at final concentrations of 0.01, 0.03, and 0.1 w / v% instead of pantothenyl ethyl ether. The results are shown in FIG.

[0065] As shown in Figure 7, pantothenyl ethyl ether acts on human hair follicle keratinocytes and enhances SULT1A1 gene expression in a concentration-dependent manner. Similarly, as shown in Figure 8, pyridoxine hydrochloride also acts on human hair follicle keratinocytes and enhances SULT1A1 gene expression in a concentration-dependent manner. These results suggest that pantothenyl ethyl ether and pyridoxine hydrochloride have the effect of promoting the conversion of minoxidil to minoxidil sulfate in vivo.

[0066] [Formulation example] Formulation examples are shown in the following Tables 1 and 2. The values ​​indicating the contents in the formulation examples are all w / v %.

[0067] [Table 1]

[0068] [Table 2]

Claims

[Claim 1] The invention described in this specification.

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