JP2022037274A - Hair growth promoter - Google Patents

Abstract

To provide a new hair growth promoter and a new VEGF production promoter.SOLUTION: The present invention discloses a hair growth promoter and a VEGF production promoter each containing proteoglycan. The proteoglycan has a molecular weight of, preferably, 100 kDa or more and 800 kDa or less. The proteoglycan is preferably derived from nasal cartilage of salmon. The hair growth promoter is preferably an oral agent or a topical agent.SELECTED DRAWING: Figure 1

Description

The present invention relates to a hair growth promoter and a VEGF production promoter.

Recently, many people are suffering from hair loss symptoms such as hair loss and thinning hair, and hair growth agents that promote hair growth, anti-hair loss agents that prevent hair loss, and the like have been developed. Patent Document 1 discloses a hair growth-promoting agent that promotes the production of vascular endothelial growth factor (VEGF) and contains an egg yolk protein hydrolyzate as an active ingredient.

International Publication No. 2016/068338

However, conventional hair growth stimulants are not sufficient to meet the demands of consumers. An object of the present invention is to provide a new hair growth promoter and VEGF production promoter.

The present invention provides the hair growth promoters and VEGF production promoters exemplified below.
[1] A hair growth promoter containing proteoglycan.
[2] The hair growth-promoting agent according to [1], wherein the molecular weight of proteoglycan is 100 kDa or more and 800 kDa or less.
[3] The hair growth-promoting agent according to [1] or [2], wherein the proteoglycan contains chondroitin sulfate as a component.
[4] The hair growth-promoting agent according to any one of [1] to [3], wherein the proteoglycan is derived from salmon nasal cartilage.
[5] A hair growth-promoting agent containing proteoglycan extracted from salmon nasal cartilage using acetic acid.
[6] The hair growth-promoting agent according to any one of [1] to [5], which is an oral preparation.
[7] The hair growth-promoting agent according to [6], which is a health functional food, a dietary supplement or a supplement.
[8] The hair growth-promoting agent according to any one of [1] to [5], which is an external preparation.
[9] A vascular endothelial growth factor (VEGF) production promoter containing proteoglycan.
[10] The VEGF production-promoting agent according to [9], which promotes VEGF production in dermal papilla cells.
[11] A hair growth promoting set containing an oral preparation containing proteoglycan and an external preparation containing proteoglycan.

According to the present invention, a new hair growth-promoting agent and a VEGF production-promoting agent can be provided.

It is a graph which shows the time-dependent change of the mouse coat regeneration rate in Experiment 1. It is a photograph which shows the state of the hair on the back of a mouse in Experiment 1. It is a graph which shows the VEGF production amount in Experiment 2.

[Hair growth promoter]
The hair growth stimulant according to the present invention contains proteoglycan. Proteoglycan has hair growth promoting, hair growth promoting, hair growth promoting, hair loss suppressing action and the like. The hair growth-promoting agent according to the present invention can also be referred to as a hair-growth promoting agent, a hair-nourishing agent, and an anti-hair-removing agent. The hair growth-promoting agent according to the present invention can promote the development of hair of an ingested, administered or applied subject, and can prevent and reduce thinning hair and hair loss.

(Proteoglycan)
Proteoglycan is a glycoprotein consisting of a core protein and glycosaminoglycan (acidic mucopolysaccharide) bound to it. Proteoglycans are present in the skin, cartilage, bone, blood vessel walls and the like as the main components of the extracellular matrix.

As the proteoglycan, for example, those purified from the cartilage of aquatic organisms such as salmon, sharks, rays and whales can be used. In addition to fish-derived cartilage tissues such as salmon, mollusc-derived cartilage tissues such as squid and octopus, bird-derived cartilage tissues such as chickens, and mammalian-derived cartilage tissues such as cows and whales can also be used. From the viewpoint of availability of raw materials and ease of extraction operation, it is preferable to use proteoglycan derived from salmon nasal cartilage. As a raw material, for example, a head discharged when salmon (mainly white salmon) caught on the coast of Aomori Prefecture or the coast of Hokkaido is processed as various processed products can be used.

Examples of the glycosaminoglycan constituting the proteoglycan include chondroitin sulfate and keratan sulfate. Proteoglycans preferably contain chondroitin sulfate as a component. Proteoglycans containing chondroitin sulfate as glycosaminoglycans can be stably obtained from salmon nasal cartilage. The proteoglycan may be a mixture of a plurality of proteoglycans having different types and molecular weights.

The molecular weight of proteoglycan is preferably 100 kDa or more and 800 kDa or less, more preferably 600 kDa or less, and further preferably 400 kDa or less. The molecular weight of proteoglycans can vary depending on the extraction and purification method. A proteoglycan having such a molecular weight can be obtained with high purity by, for example, the production method described later.

The method for purifying proteoglycan is not particularly limited, and for example, a method for extracting proteoglycan using acetic acid described in JP-A-2002-69097 and JP-A-2019-123692 can be adopted. This method is a method of eluting crude proteoglycan from salmon nasal cartilage using acetic acid as an extraction solvent, removing impurities, and then concentrating the crude proteoglycan. Concentration may be performed by dialysis. Specifically, as a method for purifying proteoglycan, crude proteoglycan is eluted from minced salmon nasal cartilage using acetic acid as an elution solvent, and then the obtained eluate is filtered and centrifuged, and the supernatant is used. A step of dissolving a semi-solid precipitate containing crude proteoglycan obtained by adding salt-saturated ethanol and centrifuging in acetic acid and then dialyzing may be included. According to this purification method, proteoglycans that are efficient and safe can be obtained without using harmful reagents. According to this purification method, proteoglycan having a molecular weight of about 100 to 800 kDa can be obtained with high purity from salmon nasal cartilage.

The acetic acid used may be any of food and industrial use, and may be appropriately selected depending on the purpose of use of the obtained proteoglycan. The concentration of the acetic acid solution is, for example, 0.01 to 20% by mass, preferably 0.1 to 10% by mass, and more preferably 4.0 to 5.0% by mass.

Elution of crude proteoglycan into acetic acid is carried out, for example, at 20-40 ° C. By elution in such a temperature range, proteoglycan can be efficiently extracted as a glycoprotein complex without causing decomposition of proteoglycan.

Extraction is preferably performed under the condition that the entire cartilage surface is in fluid contact with the extraction solvent, and the flow rate of the extraction solvent at this time is, for example, 0.04 to 10.0 cm / sec, preferably 0.04 to 5.0 cm / sec. sec. This flow is not limited to horizontal circular motion with a stirrer or mixer, but also vertical direction by a method such as circulating liquid, and unidirectional flow such as flowing liquid from one side to the other on the cartilage. It does not matter, but it is possible to improve the extraction efficiency by constantly flowing the liquid. As the crude proteoglycan eluate, a lipid component that may be mixed may be adsorbed and removed by using powdered cellulose and / or an oil absorbing mat or the like.

The proteoglycan obtained from the eluate after removing the lipid may be solid-liquid separated by a separation membrane or the like having an appropriate molecular weight cut-off, and the extract may be recovered. In this operation, if a separation membrane of 50,000 or more is used, low molecular weight impurities (collagen, etc.) can be removed from the liquid phase, and the purity of proteoglycan can be increased. It is preferable to use a separation membrane of 100,000 or more. Further, the obtained fractionation liquid may be made into a solid substance by using a vacuum freeze-dryer. It may be dried with a spray dryer to obtain a powdery solid content.

As an example of the method for purifying proteoglycan, salmon nasal cartilage is immersed in 4 mass% acetic acid at 4 ° C. for 48 hours and stirred to obtain an extract of proteoglycan. The extract may be filtered through a stainless steel mesh (150 μm) to remove insoluble material. Further, the filtered solution may be centrifuged (4 ° C., 10000 rpm, 20 minutes) with a centrifuge. A semi-solid proteoglycan can be obtained by adding 3 times the amount of saturated ethanol to the obtained supernatant and centrifuging again (4 ° C., 10000 rpm, 20 minutes). This semi-solid proteoglycan can be dissolved again by immersing it in 4% by mass acetic acid and dialyzed against a cellulose ester membrane dialysis tube having an exclusion limit molecular weight of 100,000 to obtain high-purity proteoglycan.

As another example of the method for purifying proteoglycan, salmon nasal cartilage is put into 5 mass% acetic acid and extracted at a temperature of 5, 20, 30 or 40 ° C. for 72 hours to obtain an extract of proteoglycan. The extract may be filtered through a stainless steel mesh (150 μm) to remove insoluble material. Next, after adsorbing the oil in the upper layer with an oil absorbing mat (manufactured by Maeda Kosen Co., Ltd., trade name "oil adsorption sheet SP-1300N (DX)", powdered cellulose (manufactured by Nippon Paper Industries Co., Ltd., trade name "KC Flock W") -400G ") may be added, and the mixture may be stirred for 30 minutes and then filtered. The filtrate can be sufficiently dialyzed with a cellulose ester membrane dialysis tube having a molecular weight of 100,000, and the obtained solution can be freeze-dried to obtain proteoglycan.

As another method for purifying proteoglycan, the method described in JP-A-2009-173702 can also be preferably adopted. In this method, for example, frozen aquatic animal tissue is crushed, water having a temperature of 0 to 20 ° C. and a pH of 4.8 to 7 is added to float the lipid, and the precipitate is collected by centrifugation, and the precipitate is dried into fine powder. To become. An organic solvent such as ethanol can be added to the obtained dry fine powder to further remove the lipid remaining in the precipitate. According to this method, it is possible to obtain proteoglycan suitable for use in foods, beverages, cosmetics, etc., without causing decomposition of proteoglycan in the tissue and having less offensive odor.

It is not necessary to use highly purified proteoglycans in order to incorporate proteoglycans into the compositions of the present invention, for example, crudely purified proteoglycans containing other components that do not adversely affect the action of proteoglycans (eg, salmon). Extracts from raw materials such as cartilage) may be used. The content of proteoglycan in the crude product (extract) of proteoglycan is, for example, 20.0% by mass or more, preferably 50.0% by mass or more.

The salmon nasal cartilage-derived proteoglycan was stable in a heating test at 120 ° C. for up to 1 hour. In addition, salmon nasal cartilage-derived proteoglycan was stable in the pH range of 2.0-10. Therefore, salmon cartilage-derived proteoglycan is stable even when processed into oral and external preparations, and is excellent in processability.

It has been found that salmon nasal cartilage-derived proteoglycans are significantly more absorbed in the intestinal tract than chondroitin 4-sulfate and chondroitin 6-sulfate.

The hair growth stimulant can be expected to improve additive or synergistic effects when used in combination with other active ingredients used for promoting hair growth. Other active ingredients used to promote hair growth include minoxidil, finasteride and the like.

(Form of hair growth stimulant)
The hair growth-promoting agent according to the present invention can be administered to mammals as an oral preparation or an external preparation.

Oral preparations may be foods, pharmaceuticals or quasi-drugs. Foods include beverages or feeds. Foods include special-purpose foods, foods with health claims (foods for specified health use, foods with nutritional claims, foods with functional claims), dietary supplements, and supplements. Pharmaceuticals include veterinary drugs, therapeutic agents or preventive agents.

Examples of foods include dairy products such as cheese, prepared milk powder, ice cream and yogurt, confectionery such as chocolate, cookies, biscuits, candy, Japanese confectionery, rice confectionery, cakes, pies and puddings, and wheat flour products such as bread and noodles. , Rice products such as miscellaneous cooking and rice, seasonings such as soy sauce, miso, mayonnaise, and dressing. The food may be a processed fishery product, a processed agricultural product, or a processed livestock product.

Examples of the beverage include tea, coffee, milk, milk beverage, fruit juice beverage, juice, lactic acid beverage, soft beverage, nutritional drink, beauty drink and the like.

The food may be a food additive such as a liquid, a paste, a powder, a flake, or a granule. Food additives also include beverage additives. The food additive can be produced according to a general method for producing a food additive.

Foods can contain various additives depending on their type. Examples of the additive include sweeteners. Examples of the sweetener include glucose, fructose, sucrose, maltose, sorbitol, stebioside, rubusoside, corn syrup, lactose, maltitol and the like.

Other additives include citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, magnesium stearate, calcium stearate. , Hydroxypropyl cellulose and other cellulose derivatives, crystalline cellulose, silicon dioxide, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, Arabic gum, carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, Examples thereof include calcium pantothenate, fatty acids, calcium salts, pigments, fragrances, preservatives and the like.

The dosage form of the oral preparation is not particularly limited, and the tablet, capsule, granule, powder, fine granule, chewable tablet, pill, troche, sublingual tablet, ointment, cream, emulsion, suspension, jelly. Agents, syrups, liquids and the like can be mentioned.

The blending amount of proteoglycan in the oral preparation may be, for example, 0.1% by mass to 50% by mass, 1% by mass to 30% by mass, or 2% by mass to 20% by mass.

The intake of oral preparations can be widely adjusted according to the sex, age, body weight, and the severity of symptoms of the subject, but in general, the daily intake of proteoglycan is 1 mg or more and 100 mg or less. It is preferable to make it. Oral preparations may be taken once a day or in several divided doses.

Oral preparations include non-toxic excipients, binders, lubricants, disintegrants, preservatives, isotonic agents, stabilizers, dispersants, antioxidants, colorants, flavoring agents, buffers. It can be carried out by a known method using additives such as a pH adjuster and a thickening agent. Non-toxic additives contained in these preparations include, for example, starch, gelatin, glucose, dextrin, hyaluronic acid, lactose, fructose, maltose, magnesium carbonate, silicon dioxide, talc, magnesium stearate, calcium stearate, methyl cellulose, and the like. Examples thereof include carboxymethyl cellulose, crystalline cellulose, gum arabic, polyethylene glycol, propylene glycol, petrolatam, glycerin, ethanol, syrup, sodium chloride, sodium sulfite, sodium phosphate, citric acid, polyvinylpyrrolidone, water, shelac, carnauba wax and the like. In order to reinforce or enhance the usefulness of the present invention, the pharmaceutical product may contain other components, drugs and the like.

The external preparation may be a drug, a quasi drug or a cosmetic product. External preparations can be applied or applied directly to the skin (scalp, etc.), for example, liquids, creams, emulsions, lotions, ointments, gels, aerosols, packs, microneedle patches, hair tonics, hair liquids. , Hair gel, hair cream, treatment, hair spray, aerosol mousse, shampoo, conditioner and the like.

The blending amount of proteoglycan in the external preparation may be, for example, 0.001 to 20.0% by mass, 0.01 to 15.0% by mass or 0.05 to 10.0% by mass.

The external preparation can be formulated by mixing proteoglycan with a base or carrier usually used for pharmaceuticals, quasi-drugs or cosmetics according to a conventional method. As the base or carrier, fats and oils such as coconut oil, olive oil, rice bran oil, shea butter; hydrocarbons such as vaseline and liquid paraffin; waxes such as jojoba oil, miuro, candelilla wax and lanolin; cetanol and cetostearyl. Higher alcohols such as alcohol, stearyl alcohol, behenyl alcohol, octyldodecanol, isostearyl alcohol, phytosterol, cholesterol; silicones such as dimethicone, cyclic silicone, modified silicone; cellulose derivatives such as ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose; polyvinyl Pyrrolidone; carrageenan; polyvinyl butyrate; polyethylene glycol; dioxane; butylene glycol adipate polyester; diisopropyl adipate, isopropyl myristate, octyldodecyl myristate, isopropyl palmitate, cetyl palmitate, isononyl isononanoate, tetra2-ethylhexanoic acid Esters such as pentaerythlit; polysaccharides such as dextrin and maltodextrin; vinyl polymers such as carboxyvinyl polymers and alkyl-modified carboxyvinyl polymers; lower alcohols such as ethanol and isopropanol; propylene glycol, 1,3-butylene glycol , Polyhydric alcohols such as glycerin, polyethylene glycol; glycol ethers such as diethylene glycol monoethyl ether; water. These can be used alone or in combination of two or more, and the amount used thereof is appropriately selected from a range known to those skilled in the art.

The external preparation includes known additives such as surfactants, stabilizers, antioxidants, colorants, dispersants, chelating agents, pH regulators, preservatives, and thickening agents as long as the effects of the present invention are not impaired. Agents, irritation reducing agents, fragrances, UV absorbers, moisturizers, vasodilators and the like can be added. These additives can be used alone or in combination of two or more.

Examples of the surfactant include sorbitan such as sorbitan monoisostearate, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, penta-2-ethylhexyl acid diglycerol sorbitan, and tetra-2-ethylhexyl acid diglycerol sorbitan. Fatty acid esters; propylene glycol fatty acid esters such as propylene glycol monostearate; polyoxyethylene cured castor oil 40 (HCO-40), polyoxyethylene cured castor oil 50 (HCO-50), polyoxyethylene cured castor oil 60 (HCO-60), cured castor oil derivatives such as polyoxyethylene cured castor oil 80; polyoxyethylene monolaurate (20) sorbitan (polysorbate 20), polyoxyethylene monostearate (20) sorbitan (polysorbate 60), Polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene monooleate (20) sorbitan (polysorbate 80) and polyoxyethylene (20) sorbitan isostearate; polyoxyethylene monococonut oil fatty acid glyceryl; glycerin alkyl ether; alkyl glucoside; Polyoxyalkylene alkyl ethers such as polyoxyethylene cetyl ether; amines such as stearylamine and oleylamine can be mentioned.

Examples of the stabilizer include sodium polyacrylate, dibutylhydroxytoluene, and butylhydroxyanisole.

Examples of the antioxidant include dibutylhydroxytoluene, sodium pyrosulfite, sodium edetate, butylhydroxyanisole, sorbic acid, sodium sulfite, ascorbic acid, erythorbic acid, and L-cysteine hydrochloride.

Examples of the colorant include inorganic pigments and natural pigments.

Examples of the dispersant include sodium pyrophosphate, sodium hexametaphosphate, polyvinyl alcohol, polyvinylpyrrolidone, methyl vinyl ether / maleic anhydride crosslinked copolymer, and organic acids.

Examples of the chelating agent include EDTA / 2 sodium salt and citric acid.

Examples of the pH adjuster include inorganic acids such as hydrochloric acid and sulfuric acid; organic acids such as lactic acid, sodium lactate, citric acid, sodium citrate, succinic acid and sodium succinate; and inorganic bases such as potassium hydroxide and sodium hydroxide. Examples thereof include organic bases such as triethanolamine, diisopropanolamine and triisopropanolamine.

Examples of the preservative include benzoic acid, sodium benzoate, dehydroacetic acid, sodium dehydroacetate, parabens, and phenoxyethanol.

Examples of the thickener include cellulose-based thickeners such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose and carboxyethyl cellulose, guar gum, pectin, purulan, gelatin and locust bean gum. Carrageenan, agar, xanthan gum, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, alkyl methacrylate copolymer, polyethylene glycol, bentonite, alginic acid, propylene glycol alginate, macrogol, hyaluronic acid, sodium hyaluronate, (hydroxyacrylate) Ethyl / acryloyldimethyltaurine Na) polymers, (acryloyldimethyltaurine ammonium / vinylpyrrolidone) polymers can be mentioned.

Examples of the irritation reducing agent include licorice extract, sodium alginate, gum arabic, polyvinylpyrrolidone, licorice extract and sodium alginate.

Examples of the ultraviolet absorber include ethyl paraaminobenzoate, ethylhexyl paradimethylaminobenzoate, amyl salicylate and its derivatives, 2-ethylhexyl paramethoxycinnamate, octyl silicate, oxybenzon, 2,4-dihydroxybenzophenone, 2-hydroxy-4. -Methoxybenzophenone-5-sulfonate, 4-tershally butyl-4-methoxybenzoylmethane, 2- (2-hydroxy-5-methylphenyl) benzotriazole, urocanic acid, ethyl urocanate, aloe extract can be mentioned. ..

Examples of the moisturizer include glycerin, propylene glycol, dipropylene glycol, 1,3-butylene glycol, polyethylene glycol, sorbitol, xylitol, sodium pyrrolidone carboxylate, trehalose and other saccharides, and mucopolysaccharides (eg, sodium hyaluronate, heparin). ), Elastin, collagen, NMF-related substances, lactic acid, urea, higher fatty acid octyldodecyl, seaweed extract, silane root (white and) extract, various amino acids and their derivatives.

Examples of the vasodilator include carpronium chloride, benzyl nicotinate, Swertia japonica extract, minoxidil, Panax ginseng extract, and tincture.

The hair growth-promoting agent according to the present invention is expected to be able to obtain a higher hair growth-promoting effect by using an oral agent and an external preparation in combination. One embodiment of the present invention may be a hair growth promoting set containing an oral preparation containing proteoglycan and an external preparation containing proteoglycan.

[VEGF production promoter]
The VEGF production promoter according to the present invention contains proteoglycan. The VEGF production promoter preferably promotes VEGF production in dermal papilla cells. It is considered that hair growth is promoted when proteoglycan activates dermal papilla cells and promotes VEGF production of dermal papilla cells.

Examples of proteoglycans include the above-mentioned proteoglycans. The VEGF production promoter can be an oral preparation or an external preparation. The VEGF production promoter may further contain the other components described above.

Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

[Experiment 1: Animal test]
The hair growth promoting effect of proteoglycan was evaluated using mice. As the mouse, SPF C3H / HeN Slc (male) handled by Nippon SLC Co., Ltd. was used. Individuals were randomly assigned so that the average body weight of each test group was as even as possible. The breeding conditions for the mice were 5 mice per cage, a room temperature of 25 ° C., and a 12-hour cycle of light and dark. Before the start of the test, the feed was MF feed for mice, rats and hamsters (Oriental yeast), and the drinking water was public tap water.

After purchasing 6-week-old mice, they were pre-reared for 1 week and acclimatized to the test environment. The back coat of 7-week-old mice was shaved with a safety razor. The test was started 3 days after shaving. Specifically, in the proteoglycan intake group, a feed obtained by mixing salmon nasal cartilage-derived proteoglycan (manufactured by Ichimaru Falcos Co., Ltd., molecular weight peak of about 450 kDa) and a normal feed (MF feed) in the amount shown in Table 1 was used as a negative control. The group was fed a normal diet (MF diet) orally. The shaved part on the back surface was photographed over time, and the total area of the shaved part and the area of the hair regeneration part were quantified from the photographed image using image analysis software. The ratio of the area of the hair regeneration portion to the total area of the shaved portion was calculated as the hair regeneration rate, and the presence or absence of the hair growth promoting effect was determined.

The time course of the mouse coat regeneration rate of the negative control group and the proteoglycan ingestion group is shown in FIG. FIG. 2 shows the appearance of the hair on the back of the mouse on the 24th day after the start of the test in the negative control group and the proteoglycan ingestion group. In mice fed with proteoglycan orally, hair regrowth was promoted, and a statistically significant difference was observed in the hair regrowth rate.

[Experiment 2: Cell test]
The amount of VEGF produced was measured using dermal papilla cells. Human dermal papilla cells (HFDPC, Cell Applications, Inc.) in the logarithmic growth phase are prepared in a dermal papilla cell growth medium (PCGM, Cell Applications, Inc.) to 3 × 10 ⁴ cells / ml, and 1 ml is 24- It was subcultured in a well plate (coloren-coated) and precultured.

After confirming the growth of cells by microscopic observation, the total amount of the culture medium was exchanged. At this time, salmon nasal cartilage-derived proteoglycan (manufactured by Ichimaru Falcos Co., Ltd., molecular weight peak of about 450 kDa) was dissolved in the culture solution so as to have a final concentration of 250 μg / ml. After incubation for 2 days, the VEGF concentration in the culture medium was measured using a Human VEGF ELISA kit (R & D SYSTEMS).

The results are shown in FIG. It was confirmed that the addition of proteoglycan significantly increased the amount of VEGF secreted from the dermal papilla cells into the culture medium.

This test system is recognized as a primary evaluation method for searching for external components in hair growth and hair growth. In the existing drug minoxidil, Lachgar S. et al. et al. , Br J Dermatol. The experiment described in 1998, Mar; 138 (3): 407-11 is the basis for the mechanism of action as an external preparation. Therefore, the proteoglycan whose VEGF production promoting effect was confirmed in this test can also be used as an external hair restorer.

Claims (11)

Hair growth promoter containing proteoglycan. The hair growth-promoting agent according to claim 1, wherein the proteoglycan has a molecular weight of 100 kDa or more and 800 kDa or less. The hair growth-promoting agent according to claim 1 or 2, wherein the proteoglycan contains chondroitin sulfate as a component. The hair growth-promoting agent according to any one of claims 1 to 3, wherein the proteoglycan is derived from salmon nasal cartilage. A hair growth-promoting agent containing proteoglycan extracted from salmon nasal cartilage using acetic acid. The hair growth-promoting agent according to any one of claims 1 to 5, which is an oral preparation. The hair growth-promoting agent according to claim 6, which is a health functional food, a dietary supplement or a supplement. The hair growth-promoting agent according to any one of claims 1 to 5, which is an external preparation. A vascular endothelial growth factor (VEGF) production promoter containing proteoglycan. The VEGF production promoter according to claim 9, which promotes VEGF production of dermal papilla cells. Hair growth promoting set containing an oral preparation containing proteoglycan and an external preparation containing proteoglycan.

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