Classifications

• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
  • A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
  • A23L33/12—Fatty acids or derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/88—Liliopsida (monocotyledons)
  • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
  • A61K8/9783—Angiosperms [Magnoliophyta]
  • A61K8/9794—Liliopsida [monocotyledons]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q7/00—Preparations for affecting hair growth

Definitions

• the present invention relates to a hair growth agent.
• VEGF Vascular endothelial growth factor
• IGF-1 insulin-like growth factor
• Treatment drugs for androgenetic alopecia include dutasteride and finasteride, which inhibit 5 ⁇ -reductase, but they have serious side effects such as decreased sexual function and liver dysfunction, and their use is contraindicated, especially in pregnant women. ing.
• there has been increasing interest in natural product-derived alternatives that have less risk For example, it has been shown that phytic acid and inositol derived from natural products have the effect of promoting hair growth (Patent Documents 1 and 2). Furthermore, it has been shown that an extract of yacon has an antihair loss effect by inhibiting 5 ⁇ -reductase (Patent Document 3).
• An object of the present invention is to provide a novel hair growth agent derived from natural products.
• the present invention includes the following inventions in order to solve the above problems.
• a hair growth agent containing a rice bran-derived ingredient mixture [2] The hair growth agent according to [1] above, wherein the rice bran-derived component mixture is selected from the following (1) to (4): (1) Water-soluble rice bran components (2) Esters of plant sterols and fatty acids and/or esters of triterpene alcohols and fatty acids (3) Rice bran oil unsaponifiables concentrate (4) Rice containing 20% by mass or more of ⁇ -oryzanol Oil [3] The hair growth agent according to [2] above, wherein the above (1) contains phytic acid and inositol.
• a pharmaceutical product comprising the hair restorer according to [1] above.
• a cosmetic product comprising the hair growth agent according to [1] above.
• Dermal papilla cell proliferation promoter containing a rice bran-derived ingredient mixture [10] Dermal papilla cell proliferation promoter containing a rice bran-derived ingredient mixture. [11] A vascular endothelial growth factor production promoter containing a rice bran-derived component mixture. [12] An insulin-like growth factor-1 production promoter containing a rice bran-derived component mixture. [13] Type 2 5 ⁇ -reductase production inhibitor containing a rice bran-derived component mixture.
• a novel hair growth agent derived from natural products can be provided.
• the hair restorer of the present invention can be used as a pharmaceutical, cosmetic, or food/beverage product.
• FIG. 1 is a diagram showing the relative gene expression level of the VEGF gene in human primary dermal papilla cells treated with RSE, RTN, or RICEO relative to the negative control.
• Figure 2 is a diagram showing the relative gene expression level of IGF-1 gene by RSE and RICEO treatment with respect to negative control in human primary dermal papilla cells.
• FIG. 3 is a diagram showing the relative gene expression level of the 5 ⁇ -R2 gene by GX-N or RTN treatment with respect to the negative control in human prostate cancer cells.
• FIG. 4 is a diagram showing the cell proliferation rate of human primary dermal papilla cells treated with RICEO compared to a negative control.
• FIG. 5 is a diagram showing the relative gene expression level of the VEGF gene in human primary dermal papilla cells treated with PA, IN or IN/PA mix compared to the negative control.
• the present invention provides a hair growth agent containing a rice bran-derived ingredient mixture as an active ingredient.
• the rice bran-derived ingredient mixture in the hair growth agent of the present invention is not particularly limited as long as it is a mixture containing two or more types of ingredients obtained using rice bran as a raw material.
• the rice bran-derived component mixture contains, for example, 20% by mass or more of a water-soluble rice bran component, an ester of a plant sterol and a fatty acid and/or an ester of a triterpene alcohol and a fatty acid, a concentrate of rice bran oil unsaponifiables, and ⁇ -oryzanol. Rice oil, combinations thereof, etc. are included.
• the water-soluble rice bran component is not particularly limited as long as it is a mixture of water-soluble components obtained from rice bran.
• Water-soluble rice bran components include phytic acid, inositol, minerals (potassium, magnesium, potassium, sodium, iron, zinc, copper, selenium, etc.), dietary fiber, protein, water-soluble vitamins (vitamin B group, etc.), etc. .
• the water-soluble rice bran component preferably contains phytic acid and inositol, more preferably contains more phytic acid than inositol, contains 15% by mass to 45% by mass of phytic acid, and contains inositol.
• the content is 5% by mass or more and 20% by mass or less, and it is particularly preferable that the content of phytic acid is 20% by mass or more and 40% by mass or less, and the content of inositol is 7% by mass or more and 15% by mass or less.
• the water-soluble rice bran component may be dissolved in an aqueous solution, or may be in the form of powder or the like by drying.
• the water-soluble rice bran component may be a water-soluble rice bran component extracted from rice bran using a known method, or may be a commercially available water-soluble rice bran component.
• the method for obtaining water-soluble rice bran components from rice bran is not particularly limited, and for example, one of the organic acids contained in rice bran, acetic acid, oxalic acid, tartaric acid, phosphoric acid, lactic acid, butyric acid, citric acid, succinic acid, etc. Examples include a method of extraction with two or more types of acids, a method described in JP-A-2002-20307, and the like.
• RICEO-EX (trade name) manufactured by Tsukino Foods Co., Ltd.
• RICEO-EX contains about 30% by mass of phytic acid and about 10% by mass of inositol.
• composition of the water-soluble rice bran component is not limited, as an example, in 100g, carbohydrate: 30.0g, potassium: 5.3g, magnesium: 2.7g, calcium: 121mg, sodium: 30.9mg, Iron: 19.1 mg, zinc: 13.2 mg, copper: 0.4 mg, vitamin B 1 : 7.2 mg, vitamin B 2 : 0.6 mg, vitamin B 6 : 10.2 mg, dietary fiber: 11.2 g, protein : 8.2g, phytic acid: 27.8g, and inositol: 11.0g.
• the ester of a plant sterol and a fatty acid and/or the ester of a triterpene alcohol and a fatty acid is not particularly limited as long as it is a mixture containing a sterol ester obtained from rice bran, and any mixture containing an ester of a plant sterol and a fatty acid may be used. It may contain an ester of a triterpene alcohol and a fatty acid, or a mixture thereof.
• Sterol refers to a compound having a hydroxyl group at the 3-position among compounds (steroids) having a cyclopentanoperhydrophenanthrene skeleton (sterane skeleton). Sterols are generally widely distributed in the animal and plant kingdom in the form of free forms, ester forms, glycosides, etc., and are also important constituents of biological membranes.
• the ester of a plant sterol and a fatty acid and/or the ester of a triterpene alcohol and a fatty acid contained in the hair growth agent of the present invention is an ester type sterol with a fatty acid.
• the sterol may be an unsaturated compound having 27 to 30 carbon atoms and having one double bond at the 5/6 position, 7/8 position, 8/9 position or other position, It may also be a saturated compound obtained by hydrogenation.
• plant sterols that are abundant in plants include ⁇ -sitosterol, stigmasterol, campesterol, and the like.
• Triterpene alcohol is a sterol with 30 carbon atoms, and is a component abundantly contained in rice bran or rice oil.
• the ester of plant sterol and fatty acid and the ester of triterpene alcohol and fatty acid have the formula (A): R'CO-OH (A) [In the formula, R'CO is a straight chain fatty acyl group having 14 to 22 carbon atoms and 0 to 3 double bonds. ] It can be derived from the carboxylic acid represented by Examples of the carboxylic acid represented by formula (A) include myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, and behenic acid.
• the ester of a plant sterol and a fatty acid and/or the ester of a triterpene alcohol and a fatty acid may be a sterol ester purified from rice bran using a known method, or a commercially available sterol ester.
• the method for obtaining sterol esters from rice bran is not particularly limited, and for example, a method in which by-products such as soup stock and deodorized scum produced in the process of producing rice oil from rice bran are used as raw materials, and extracted and purified with a solvent such as acetone or hexene.
• the method described in Examples include a method of esterifying at least one species using an enzyme that esterifies non-specifically or specifically.
• examples of commercially available sterol esters include Rice sterol ester (trade name) manufactured by Tsukino Foods Co., Ltd.
• the rice bran oil unsaponifiables concentrate is not particularly limited as long as it is a concentrate of unsaponifiables obtained from rice bran, and is a rice bran oil deodorizing distillate that is a by-product in the deodorizing process in the process of refining rice bran to rice oil. It may also be a concentrate of unsaponifiables obtained by neutralizing and removing fatty acids from substances.
• the rice bran oil unsaponifiables concentrate contains vitamin E (tocopherols, tocotrienols, etc.), sterols (phytosterols, triterpene alcohols, fatty acid esters thereof, etc.), squalene, and the like.
• the plant sterols and triterpene alcohols included in the sterols include those similar to those exemplified as sterols in the esters of plant sterols and fatty acids and/or esters of triterpene alcohols and fatty acids in the present invention.
• the total content of fatty acid esters of plant sterols and/or fatty acid esters of triterpene alcohols in the rice bran oil unsaponifiables concentrate may be 3% by mass or more and 70% by mass or less, and 5% by mass or more and 60% by mass or less. It may be.
• the content of plant sterols in the rice bran oil unsaponifiable matter concentrate may be 5% by mass or more and 20% by mass or less.
• the content of tocopherol in the rice bran oil unsaponifiable matter concentrate may be 1% by mass or more and 5% by mass or less.
• the content of tocotrienols in the rice bran oil unsaponifiables concentrate may be 1% by mass or more and 5% by mass or less.
• the squalene content in the rice bran oil unsaponifiables concentrate may be 1% by mass or more and 10% by mass or less.
• the rice bran oil unsaponifiables concentrate may be a concentrate of unsaponifiables obtained in the process of extracting and refining oil from rice bran using a known method, and commercially available rice bran oil unsaponifiables concentrate It may be.
• the method for obtaining rice bran oil unsaponifiables concentrate from rice bran is not particularly limited. For example, after producing rice bran oil using a known production method, the fatty acids contained in large amounts are extracted using the deodorized scum obtained in the deodorization process. Examples include a method of producing a fat-soluble rice bran oil unsaponifiable concentrate by deoxidizing the rice bran oil with a necessary minimum amount of alkali, a method described in JP-A No.
• rice bran oil unsaponifiable concentrates examples include Rice Trienol (trade name) manufactured by Tsukino Foods Co., Ltd., and the like.
• the composition of the rice bran oil unsaponifiables concentrate is not limited, as an example, the acid value is 0.8 mg KOH/g, and in 100 g, squalene: 5.8 g, plant sterol: 10.1 g, triterpene Examples include those containing 5.2 g of alcohol, 3.7 g of tocopherol, 3.0 g of tocotrienol, and 10.0 g of fatty acid ester of plant sterol and fatty acid ester of triterpene alcohol.
• the rice oil containing 20% by mass or more of ⁇ -oryzanol is not particularly limited as long as it contains 20% by mass or more of ⁇ -oryzanol in the ⁇ -oryzanol-containing rice oil.
• the ⁇ -oryzanol content of the ⁇ -oryzanol-containing rice oil is preferably 25% by mass or more, more preferably 30% by mass or more, and the upper limit of the ⁇ -oryzanol content of the ⁇ -oryzanol-containing rice oil is particularly It is not limited, and may be, for example, 60% by mass.
• the ⁇ -oryzanol-containing rice oil may be ⁇ -oryzanol-containing rice germ oil.
• the ⁇ -oryzanol-containing rice oil may be rice oil to which ⁇ -oryzanol is not added externally.
• the method for producing such ⁇ -oryzanol-containing rice oil is not particularly limited, but it can be produced, for example, by the method described in International Publication No. 2012/063794. Specifically, (A) a step of obtaining a processed fat and oil having an oil layer and a soapstock layer containing a ⁇ -oryzanol salt, and (B) adding an acid to the processed fat and oil obtained in (A).
• a production method including a step of transferring ⁇ -oryzanol from the soapstock layer to the oil layer and recovering fats and oils with increased ⁇ -oryzanol content may be used. By using this production method, rice oil containing about 60% by mass of ⁇ -oryzanol can be produced.
• the ⁇ -oryzanol-containing rice oil may be a commercially available ⁇ -oryzanol-containing rice oil.
• Examples of commercially available rice oil containing ⁇ -oryzanol include rice germ oil GX-N (trade name) manufactured by Tsukino Foods Co., Ltd.
• Rice germ oil GX-N contains about 30% by mass of ⁇ -oryzanol in rice germ oil GX-N.
• the ⁇ -oryzanol content in rice oil can be measured by a known method. For example, this can be done by the following method. However, the method is not limited to this method.
• rice oil containing ⁇ -oryzanol contains ferulic acid, sterols, wax, glucoside ceramide, tocopherol (vitamin E), tocotrienol, etc., which are components contained in common rice oil. It may be something that is currently in use.
• the ⁇ -oryzanol-containing rice oil may be one that can be used as an edible fat or oil.
• the edible oil is not particularly limited as long as it contains ⁇ -oryzanol-containing rice oil, and may be a blended oil that is a mixture of ⁇ -oryzanol-containing rice oil and other edible oils.
• Examples of edible oils and fats other than rice oil containing ⁇ -oryzanol include palm oil, rapeseed oil, soybean oil, sesame oil, corn oil, cottonseed oil, coconut oil, olive oil, coconut oil, safflower oil, sunflower oil, almond oil, and cashew oil.
• the blended oil may be a mixture of two or more kinds of ⁇ -oryzanol-containing rice oil and other edible fats and oils.
• the present invention provides a hair growth agent containing purified inositol and purified phytic acid.
• Inositol and phytic acid in the hair growth agent of the present invention may contain purified inositol and purified phytic acid, respectively.
• “Purified inositol” means inositol obtained from a mixture containing inositol through a purification process to increase the purity of inositol.
• “Purified inositol” may be a powder product.
• “Purified phytic acid” means phytic acid obtained from a mixture containing phytic acid through a purification process to increase the purity of phytic acid.
• “Purified phytic acid” may be a liquid product or a powder product.
• Purified inositol and purified phytic acid may be extracted and purified by known methods using the same biological species as raw materials, or may be extracted and purified by known methods using different biological species as raw materials.
• the inositol and/or phytic acid may be purified from artificially synthesized inositol and/or phytic acid.
• the biological species that can be used as raw materials for purified inositol are not particularly limited as long as they contain inositol in their bodies, and examples include grain bran such as rice bran, legumes such as soybeans, fruits, nuts, etc. Examples include plants, meat, and fish meat.
• the biological species that can be used as raw materials for purified phytic acid are not particularly limited as long as they contain phytic acid in their bodies, and include, for example, grains such as rice bran, legumes such as soybeans, and the like.
• the blending ratio of inositol and phytic acid in the hair growth agent of the present invention is not particularly limited, but may be, for example, 1:2 or more and 1:9 or less in mass ratio, or 1:2.5 or more and 1:1 in mass ratio. It is preferably 5 or less.
• the rice bran-derived ingredient mixture and the mixture of purified inositol and purified phytic acid contained in the hair growth agent of the present invention have hair growth, hair growth, hair nourishment, hair loss inhibiting effects, etc. Therefore, it can be suitably used as an active ingredient as a hair growth agent, hair growth agent, hair tonic, or hair loss inhibitor.
• the hair growth agent of the present invention can be referred to as a hair growth agent, a hair growth agent, or a hair loss inhibitor.
• the rice bran-derived component mixture contained in the hair growth agent of the present invention is a component that can also be used for food, so it is highly safe for living organisms and can be continuously used or ingested over a long period of time. Since the rice bran-derived ingredient mixture contained in the hair growth agent of the present invention contains a plurality of rice bran-derived ingredients, the rice bran-derived ingredients can exhibit excellent hair growth effects due to additive or synergistic effects. It is thought that it can be done. The same applies to a mixture of purified inositol and purified phytic acid.
• the hair growth agent of the present invention is characterized by having a hair growth effect.
• the fact that the hair growth agent of the present invention has a hair growth effect can be confirmed by, for example, treating dermal papilla cells with the hair growth agent of the present invention and measuring the cell proliferation rate of the dermal papilla cells, protein expression of vascular endothelial growth factor (VEGF), etc. measuring the amount or VEGF gene expression level, measuring the protein expression level of insulin-like growth factor (IGF-1) or the IGF-1 gene expression level, and treating prostate cancer cells with the hair growth agent of the present invention. This can be confirmed by measuring the protein expression level of type 2 5 ⁇ -reductase (5 ⁇ -R2) or the 5 ⁇ -R2 gene expression level in prostate cancer cells.
• VEGF vascular endothelial growth factor
• the cell proliferation rate of dermal papilla cells can be measured, for example, using a commercially available cell proliferation measurement kit on the treated cell culture solution.
• the protein expression level of VEGF, IGF-1 or 5 ⁇ -R2 can be determined by extracting proteins from treated dermal papilla cells or prostate cancer cells and using known techniques such as SDS-PAGE, Western blotting, ELISA, and immunoprecipitation. It can be measured using a method.
• the gene expression levels of VEGF, IGF-1, or 5 ⁇ -R2 can be determined, for example, by extracting nucleic acids from treated dermal papilla cells or prostate cancer cells and using known methods such as RT-PCR, quantitative PCR, and microarray. It can be measured using
• the content of the rice bran-derived component mixture and the mixture of purified inositol and purified phytic acid in the hair growth agent of the present invention is not particularly limited as long as the hair growth effect is exerted.
• the total content of purified inositol and purified phytic acid may be, for example, 0.01 (wt/v)% or more and 80 (wt/v)% or less based on the entire hair growth agent. , 0.05 (wt/v)% or more and 50 (wt/v)% or less, or 0.1 (wt/v)% or more and 30 (wt/v)% or less.
• the subjects to which the hair growth agent of the present invention can be administered are not particularly limited as long as they are animals, such as humans, non-human mammals (cows, horses, pigs, sheep, goats, llamas, alpacas, camels, rabbits, mink, foxes). , domestic animals such as chinchillas, geese, and ducks, and pet animals such as dogs and cats).
• the frequency of use or intake of the hair growth agent of the present invention is not particularly limited, and examples include once or more a day, 1 to 5 times a day, etc.
• the period of use or intake of the hair growth agent of the present invention is not particularly limited, and may be, for example, 4 weeks or more, 8 weeks or more, or 12 weeks or more.
• the dosage form of the hair growth agent of the present invention is not particularly limited, and includes, for example, a low-viscosity liquid, a liquid such as a lotion, a suspension, an emulsion, a gel, a paste, a cream, a foam, a sheet, an ointment, and a powder.
• a liquid such as a lotion, a suspension, an emulsion, a gel, a paste, a cream, a foam, a sheet, an ointment, and a powder.
• the present invention provides pharmaceuticals, cosmetics, or food and drink products.
• the pharmaceutical products, cosmetics, or food and drink products of the present invention may be those containing the hair restorer of the present invention.
• the pharmaceutical, cosmetic, or food/beverage product of the present invention can be used in the same dosage form as the hair growth agent described above.
• the food or drink of the present invention may be, for example, a health food, a functional food, a food for specified health uses, a supplement, a food for the sick, or the like.
• the form of the food and drink is not particularly limited, and may be, for example, a processed form such as a natural liquid food, a semi-digested nutritional food, an ingredient nutritional food, or a drink, including tea drinks, soft drinks, carbonated drinks, and nutritional drinks.
• beverages such as fruit drinks and lactic acid drinks
• noodles such as soba, udon, Chinese noodles, and instant noodles
• sweets and breads such as candies, candies, gum, chocolate, snack foods, biscuits, jellies, jams, creams, baked goods, and bread.
• Processed marine and livestock foods such as kamaboko, ham, and sausages, dairy products such as processed milk and fermented milk, fats and oils and processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings, sauces, It may also be seasonings such as sauce, retort pouch foods such as curry, stew, rice bowls, porridge, rice porridge, etc., frozen desserts such as ice cream, sherbet, shaved ice, etc.
• dairy products such as processed milk and fermented milk
• fats and oils and processed foods such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings, sauces
• seasonings such as sauce, retort pouch foods such as curry, stew, rice bowls, porridge, rice porridge, etc.
• frozen desserts such as ice cream, sherbet, shaved ice, etc.
• the pharmaceutical products, cosmetics, or food and drink products of the present invention may contain pharmaceutically or physiologically acceptable components in addition to the hair restorer of the present invention.
• Pharmaceutically or physiologically acceptable ingredients are not particularly limited, and include water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, plant extracts, vitamins, and water-soluble Polymers, surfactants, alcohols, polyhydric alcohols, etc. can be used.
• the pharmaceuticals, cosmetics, or food/beverage products of the present invention may contain known additives used in compositions of pharmaceuticals, quasi-drugs, cosmetics, food/beverage products, etc., such as antioxidants, thickeners, etc., as necessary.
• additives used in compositions of pharmaceuticals, quasi-drugs, cosmetics, food/beverage products, etc., such as antioxidants, thickeners, etc., as necessary.
• Preservatives, pH adjusters, stabilizers, irritation reducers, preservatives, colorants, fragrances, and the like can be added.
• the additives can be used alone or in combination of two or more.
• the pharmaceuticals, cosmetics, or food and drink products of the present invention may further contain other active ingredients used to promote hair growth or to promote hair growth.
• Other active ingredients can be used alone or in combination of two or more.
• Other active ingredients include, for example, minoxidil and finasteride.
• the present invention includes a dermal papilla cell proliferation promoter, a vascular endothelial growth factor production promoter, an insulin-like growth factor-1 production promoter, a type 2 5 ⁇ -reductase production inhibitor, etc., which contain a rice bran-derived component mixture. .
• the present invention also includes a dermal papilla cell proliferation promoter, a vascular endothelial growth factor production promoter, an insulin-like growth factor-1 production promoter, etc., which contain a mixture of purified inositol and purified phytic acid. included.
• the present invention includes a method for promoting hair growth, which comprises administering an effective amount of the hair growth agent of the present invention to an animal in need of hair growth.
• the animal is not particularly limited, and may be, for example, a human, a non-human mammal, or the like. Mammals other than humans include, but are not limited to, cows, horses, pigs, sheep, goats, llamas, alpacas, camels, rabbits, minks, foxes, chinchillas, geese, ducks, dogs, cats, and the like.
• Rice bran-derived component mixture [Example 1: Confirmation of hair-related gene expression level] [Test materials and methods] 1 Rice bran-derived component mixture, control sample, reagent, and solvent 1.1 Rice bran-derived component mixture The following four types were used as the rice bran-derived component mixture. ⁇ RICEO-EX (product name, manufactured by Tsukino Foods Co., Ltd.) ⁇ Rice sterol ester (product name, manufactured by Tsukino Foods Co., Ltd.) ⁇ Lytrienol (product name, manufactured by Tsukino Foods Co., Ltd.) ⁇ Rice germ oil GX-N (product name, manufactured by Tsukino Foods Co., Ltd.)
• Control Samples The following two types were used as control samples. ⁇ Phytic acid (product name, manufactured by Tsukino Foods Co., Ltd.) ⁇ Inositol (product name, manufactured by Tsukino Foods Co., Ltd.)
• the concentration was adjusted according to the intended use, and a medium containing RICEO, phytic acid, and inositol at the desired concentration was prepared. Note that 1% FBS culture medium was used as a negative control for the medium containing RICEO, phytic acid, and inositol.
• a medium containing RSE, RTN, and GX-N at a concentration of 0.1%, 0.01%, or 1/100 of their serial dilutions was obtained.
• a negative control for the medium containing RSE, RTN, and GX-N a medium prepared by adding 50 ⁇ L of DMSO to 4.95 mL of 1% FBS culture medium was used.
• test subjects were human primary dermal papilla cells (HFDPC) and human prostate cancer cells (Lymph Node Carcinoma of the Prostate: LNCaP). While maintaining sterile conditions under a cabinet, the cells of interest stored in a vial in liquid nitrogen were thawed and seeded in a 10 cm culture dish (Violamo). 10 mL of 10% FBS culture medium was used. Thereafter, all cell handling operations were performed under the cabinet after sterilization with ethanol and flame sterilization. The cells were cultured for 3 days at 37° C. in a 5% CO 2 atmosphere using a CO 2 incubator (PHC).
• PLC CO 2 incubator
• the supernatant of the cultured cells was aspirated using a suction pump (Hitech).
• Cells were washed by dropping 5 mL of autoclaved Dulbecco's PBS(-) onto the dish using a 10 mL disposable pipette (Biolamo). The solution was then removed using a suction pump.
• 0.5 mL of trypsin/EDTA solution was added to the dish using a micropipette (Thermo Scientific), and the dish was left standing for 2 minutes.
• Cells were suspended by continuous suction and discharge operations using a micropipette, and 5 mL of 10% FBS culture medium was added using a disposable pipette to stop the reaction.
• the solution after the reaction was stopped was transferred to a 15 mL plastic tube (Bio Lamo Co., Ltd.), and centrifuged at 1200 rpm for 5 minutes at room temperature using a bucket type centrifuge (Tomy Seiko Co., Ltd.) to accumulate cells.
• the solution was removed using a suction pump, and 10 mL of 10% FBS culture medium was added using a new disposable pipette to suspend the cells.
• Cell numbers were counted using a fully automatic cell counter (Bio-Rad). Specifically, 30 ⁇ L each of trypan blue and cell suspension supplied with the device were mixed, the mixed solution was added to two locations on a dedicated counting slide, and the added portion was inserted into the device to perform measurement. The dilution rate was calculated from the obtained concentration, and a cell suspension of 1.0 ⁇ 10 5 cells/mL was prepared.
• the cells of interest were seeded in a 24-well culture plate (Bio Lamo) at 1.0 x 10 5 cells/well. The cells were cultured overnight at 37° C. in a 5% CO 2 atmosphere in a CO 2 incubator.
• RICEO-containing medium 0.01%, 0.1%, 0.5%)
• RSE-containing medium 0.01%, 0.1%)
• RTN-containing medium 0.01%, 0.1%)
• FBS culture medium negative control
• Centrifugation was performed at 12,000 ⁇ g for 15 minutes at room temperature using a high-speed microcentrifuge. The supernatant was removed by decantation, and the opening of the 1.5 mL tube was placed against a Kimtowel (Nippon Paper Crecia Co., Ltd.) for several seconds to remove drips. 500 ⁇ L of 75% ethanol solution was added and mixed by inversion. Centrifugation was performed at 12,000 ⁇ g for 5 minutes at room temperature using a high-speed microcentrifuge. The supernatant was removed by decantation, and the mouth of the tube was placed on a Kimtowel for a few seconds to remove drips, and then 500 ⁇ L of 75% ethanol was added once again and mixed by inversion.
• RNA synthesis was performed using the extracted RNA as a template.
• PrimeScript RT Reagent kit (Takara Bio Inc.) was used for cDNA synthesis.
• An enzymatic method was performed to convert the entire sequence starting from the complementary site of the primer and oligo-dT primer into DNA.
• Each extracted RNA was appropriately diluted with RNase-free distilled water to form a solution of 50 ⁇ g/ ⁇ L.
• a mixed solution was prepared in a 1.5 mL tube at the following doses. ⁇ 5 ⁇ PrimeScript Buffer (for Real Time) 26 ⁇ L ⁇ Oligo dT Primer 50 ⁇ M 6.5 ⁇ L ⁇ Random 6 mers 100 ⁇ M 6.5 ⁇ L ⁇ RNase free distilled water 84.5 ⁇ L Finally, add the following on ice. ⁇ PrimeScript RT Enzyme Mix I 6.5 ⁇ L 26 reactions total 130 ⁇ L
• PCR tubes (Thermo Fisher Scientific) were prepared on a cooled rack, and 5 ⁇ L of the above mixture was added to each tube. 5 ⁇ L each of the 50 ⁇ g/ ⁇ L RNA solution was spotted on the lid of the 8 consecutive PCR tubes to which the mixture had been added. After closing the lid and mixing the solution by inversion or tapping, the solution was collected on the bottom of the tube using a swing-type plate centrifuge (Kubota Seisakusho Co., Ltd.). After performing a reverse transcription reaction using a thermal cycler (Applied Biosystems) according to the following program, the reaction solution was diluted by adding 50 ⁇ L of distilled water. I) 37°C 15 minutes II) 85°C 5 seconds III) 4°C Keep warm
• RT-qPCR Real-time quantitative PCR
• the Cyber Green method was performed using PowerUp SYBR Green Master Mix (Applied Biosystems). The primers were designed with the following sequences based on previous literature (Kim J, Kim M, Yun JG and Hwang J (2017), Pekmezci E, Turkoglu M (2017), and Nakamura T, Yamamura H (2016)). Purchased from Thermo Fisher Scientific.
• Figure 1 shows the relative expression of the vascular endothelial growth factor (VEGF) gene in HFDPC treated with each concentration of RSE, RTN, or RICEO, when the gene expression level of human primary dermal papilla cells (HFDPC) in the negative control is set to 1. Shows gene expression level. A significant difference was determined at p ⁇ 0.05. In RSE, it was confirmed that VEGF gene expression level increased approximately twice as much as in the negative control when treated with 0.1%, and in RTN, it was confirmed that the amount of VEGF gene expression increased approximately twice as much as in the negative control when treated with 0.01% and 0.1%, respectively. A 3-fold or approximately 6-fold increase in VEGF gene expression was confirmed, and in RICEO, an approximately 17-fold increase in VEGF gene expression compared to the negative control was confirmed with 0.5% treatment.
• VEGF vascular endothelial growth factor
• 0.5% RICEO actually corresponds to about 0.15% phytic acid + about 0.05% inositol, but with 0.5% RICEO treatment, 0.15% phytic acid + about 0.05% inositol. It was confirmed that the effect of promoting VEGF gene expression was significantly higher than that of treatment with 5% phytic acid or 0.5% inositol alone. From this, RSE, RTN, and RICEO show superior hair growth effects compared to phytic acid or inositol alone. In particular, RICEO has a synergistic effect with other rice bran-derived ingredients, including phytic acid and inositol. , it was suggested that it exerts a remarkable hair growth effect.
• Figure 2 shows the relative gene expression level of the insulin-like growth factor (IGF-1) gene in HFDPC treated with each concentration of RSE or RICEO, when the gene expression level of HFDPC in the negative control is set to 1. A significant difference was determined at p ⁇ 0.05.
• RSE insulin-like growth factor
• Figure 3 shows the type 2 5 ⁇ -reductase (5 ⁇ -R2) gene in LNCaP treated with GX-N or RTN at each concentration, when the gene expression level of human prostate cancer cells (LNCaP) in the negative control is set to 1.
• the relative gene expression level is shown. A significant difference was determined at p ⁇ 0.05.
• GX-N it was confirmed that the 5 ⁇ -R2 gene expression level decreased by about 0.85 times and about 0.75 times compared to the negative control when treated with 0.01% and 0.1%, respectively, and in RTN, With 0.1% treatment, it was confirmed that the expression level of 5 ⁇ -R2 gene was reduced by about 0.7 times compared to the negative control.
• Example 2 Confirmation of dermal papilla cell proliferation rate
• a cell suspension of 1.0 ⁇ 10 5 cells/mL was prepared in the same manner as in Example 1, except that the cells used were human primary dermal papilla cells (HFDPC).
• the obtained cell suspension was seeded in a 96-well culture plate (Bio Lamo) at a density of 1.0 x 10 4 cells/well, and incubated at 37°C in a 5% CO 2 atmosphere in a CO 2 incubator. Cultured late. Add 0.1 mL of 0.005%, 0.01%, 0.05%, 0.1% RICEO-containing medium or 1% FBS culture medium (negative control) per well, and incubate at 37°C in a CO2 incubator.
• RICEO-containing medium was mixed with phytic acid-containing medium (0.016%, 0.06%, 0.25%, 1%) or inositol-containing medium (0.016%, 0.06%, 0.25%, 1%).
• Culture was carried out in the same manner except for changing to
• FIG. 4 shows the cell proliferation rate when HFDPC was treated with RICEO at various concentrations. A significant difference was determined at p ⁇ 0.05. The number of cells increased significantly when treated with 0.01%, 0.05% and 0.1% RICEO, and in particular, treatment with 0.1% RICEO showed significant cell proliferation of approximately 150-160%. was confirmed.
• Example 3 Verification of the effect of a mixture of inositol and phytic acid on VEGF gene expression level
• Test material The following two types of purified inositol and purified phytic acid were used.
• ⁇ Phytic acid product name, manufactured by Tsukino Foods Co., Ltd.
• Inositol product name, manufactured by Tsukino Foods Co., Ltd.
• HFDPC human primary dermal papilla cells
• phytic acid-containing medium (0.1%, 0.5%)
• inositol-containing medium (0.1%, 0.5%)
• IN/PA mixture-containing medium Cell culture and VEGF gene expression level were carried out in the same manner as in Example 1, except that 1 mL of 0.05%, 0.1%, 0.5%) or 1% FBS culture medium (negative control) was added per well. An analysis was performed.
• Figure 5 shows that when the gene expression level of human primary dermal papilla cells (HFDPC) in the negative control is set to 1, phytic acid (PA), inositol (IN), or a mixture of inositol and phytic acid (IN/PA) at various concentrations
• the relative gene expression level of the vascular endothelial growth factor (VEGF) gene in HFDPC treated with (mix) is shown. A significant difference was determined at p ⁇ 0.05. When treated with 0.1% and 0.5% phytic acid or inositol, respectively, no significant change in VEGF gene expression was observed with 0.1% treatment, and negative with 0.5% treatment. It was confirmed that the expression level of the VEGF gene increased approximately twice as compared to the control.
• PA phytic acid
• IN inositol
• I/PA a mixture of inositol and phytic acid
• inositol With inositol, no significant change in VEGF gene expression was observed with 0.1% treatment, and an approximately 1.5-fold increase in VEGF gene expression was confirmed with 0.5% treatment compared to the negative control.
• the amount of VEGF gene expression was about 2.5 times and about 4 times higher at lower treatment concentrations of 0.05% and 0.1% than treatment with phytic acid or inositol alone, respectively. An increase was confirmed.

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