Expression promoters, cosmetic methods, and compositions for preventing graying hair.

Abstract

To provide a novel gene expression promoter that promotes the expression of melanin-related genes, and to provide a cosmetic method using said gene expression promoter. [Solution] An expression promoter for the MLPH gene, MYO5A gene, DCT gene, or TYRP1 gene, comprising melon extract, and a beauty method using the expression promoter.

Description

Technical Field

[0001] The present invention relates to an expression promoter, a beauty method, and a composition for preventing gray hair.

Background Art

[0002] Melanin is present in hair and skin and plays a role in preventing damage to living tissues by ultraviolet rays. Melanin is also a colored pigment and is involved in the color tone of hair and skin.

[0003] Conventionally, research has been conducted to prevent the occurrence of gray hair and improve the color tone of hair by promoting the production of melanin and increasing the amount of melanin in newly produced hair from hair follicles. In addition, research has also been conducted to improve the skin color tone for the purpose of skin tanning by promoting the production of melanin by melanin-producing cells present in the epidermis.

[0004] As an example of such research, an agent having an excellent melanocyte activating action that can be used as a gray hair preventing agent or a tanning agent by exerting a cyclic AMP inducing action and a tyrosinase activity promoting action in melanocytes by a melanocyte activator containing a plant extract of the genus Nekoshita of the Asteraceae family has been proposed (Patent Document 1).

[0005] On the other hand, focusing on the mechanism of melanin production in vivo, techniques for promoting melanin production by promoting the expression of genes related to melanin production in melanin-producing cells such as melanocytes have been studied. For example, in Patent Document 2, an extract of kudzu root, etc., enhances the gene expression related to hair melanin synthesis, melanosome formation, and melanosome transport, and a preventive and improving agent for hair color tone change that exhibits a preventive and improving effect on hair color tone change has been proposed. In addition, in Patent Document 3, an expression promoter for a melanin synthesis gene and / or a melanin transport gene containing one or more selected from a cinchona extract, a yokukinin extract, and a wild thyme extract has been proposed.

Prior Art Documents

[0006] [Patent Document 1] Japanese Patent Publication No. 2002-114700 [Patent Document 2] Japanese Patent Publication No. 2019-38790 [Patent Document 3] Japanese Patent Publication No. 2022-47195 [Overview of the project] [Problems that the invention aims to solve]

[0007] While conventional techniques for promoting melanin production exist, such as those described in Patent Documents 1-3, further proposals are needed.

[0008] In view of the above circumstances, the present invention aims to provide a novel gene expression promoter that promotes the expression of melanin-related genes, and a cosmetic method using said gene expression promoter. Another object of the present invention is to provide a novel cosmetic method and a novel anti-gray hair composition. [Means for solving the problem]

[0009] Based on the above-mentioned problems, the inventors diligently investigated components that can promote the expression of melanin-related genes in melanocytes. As a result, the inventors obtained new findings that the expression of MLPH, MYO5A, DCT, and TYRP1 genes in melanocytes can be promoted when using melon extract. They also obtained another new finding that the expression of MLPH gene in melanocytes can be promoted when using zinc. Based on these findings, they discovered that melon extract can be used as an expression promoter for MLPH, MYO5A, DCT, or TYRP1 genes, and that zinc can be used as an expression promoter for MLPH gene.

[0010] The present invention includes the following inventions [1] to [7].

[0011] [1] The gene expression promoters include melon extract and are gene expression promoters for the MLPH gene, MYO5A gene, DCT gene, or TYRP1 gene.

[0012] The expression promoter [2] is the expression promoter [1], which contains zinc and is an expression promoter for the MYO5A gene.

[0013] [3] The expression promoter is a zinc-containing MLPH gene expression promoter.

[0014] The expression promoter [4] is one of the expression promoters [1] to [3] and is for the purpose of preventing graying hair.

[0015] The beauty treatment described in [5] uses one of the expression promoters selected from [1] to [4].

[0016] The anti-gray hair composition [6] contains the expression promoters [1] to [4] as active ingredients.

[0017] The beauty method described in [7] uses the anti-gray hair composition described in [6]. [Effects of the Invention]

[0018] According to the present invention, novel expression promoters for the MLPH gene, MYO5A gene, DCT gene, or TYRP1 gene can be provided. Furthermore, cosmetic methods using these expression promoters can be provided.

[0019] Furthermore, the anti-gray hair composition according to the present invention can provide a new anti-gray hair composition. Additionally, a beauty method using this anti-gray hair composition can be provided. [Modes for carrying out the invention]

[0020] The present invention will be described below based on embodiments of the present invention (hereinafter referred to as "this embodiment").

[0021] <(1) Expression promoter> The expression promoter according to this embodiment includes the expression promoters shown in the following (1-1) and (1-2). (1-1) An expression promoter for the MLPH gene, MYO5A gene, DCT gene, or TYRP1 gene containing a melon extract (hereinafter sometimes referred to as "the expression promoter of the first embodiment"). (1-2) An expression promoter for the MLPH gene containing zinc (hereinafter sometimes referred to as "the expression promoter of the second embodiment").

[0022] <(1-1) Expression promoter of the first embodiment> The expression promoter of the first embodiment is an expression promoter for the MLPH gene, MYO5A gene, DCT gene, or TYRP1 gene containing a melon extract. According to the expression promoter of the first embodiment, the expression of the MLPH gene, MYO5A gene, DCT gene, or TYRP1 gene can be promoted. Therefore, the expression promoter of the first embodiment may be one or more expression promoters selected from the MLPH gene, MYO5A gene, DCT gene, and TYRP1 gene. In the following description, the MLPH gene, MYO5A gene, DCT gene, and TYRP1 gene may be collectively referred to as "MLPH gene etc.".

[0023] The expression promoter of the first embodiment can further improve the function of melanin transport or synthesis in melanocytes present in the hair root or skin by promoting the expression of the MLPH gene etc. Thereby, the expression promoter of the first embodiment can increase the amount of melanin in the hair or skin in melanocytes, and a gray hair suppressing effect can be expected.

[0024] (MLPH gene) The MLPH gene is a gene encoding melanophilin. Melanophilin is an effector protein of the Rab protein that transports melanin in melanocytes and contributes to the promotion of melanosome transport.

[0025] (MYO5A gene) The MYO5A gene encodes myosin Va. Myosin Va is an actin-dependent motor protein. It is an effector protein of the Rab protein, which transports melanin within melanocytes, and contributes to the promotion of melanosome transport.

[0026] In melanocytes located in the hair follicle, increased expression of the MLPH gene or MYO5A gene leads to an increase in melanophilin or myosin Va, thereby promoting melanosome transport in melanocytes. This increased melanosome transport is thought to increase the amount of melanin supplied to the hair shaft, contributing to a decrease in hair brightness.

[0027] Furthermore, if the expression levels of the MLPH gene or MYO5A gene increase in melanocytes present in the skin, melanophilin or myosin Va increases, thereby promoting melanosome transport in melanocytes. This promotion of melanosome transport is thought to increase the amount of melanin supplied to the skin, contributing to a decrease in skin brightness.

[0028] The expression promoter of the first embodiment promotes the expression of the MLPH gene or the MYO5A gene, thereby promoting the transport of melanosomes in melanocytes and increasing the amount of melanin supplied to the hair shaft. Therefore, it is believed that the expression promoter of the first embodiment contributes to a decrease in hair brightness by increasing the amount of melanin, and can suppress changes in hair color and the occurrence of gray hair. Similarly, it is believed that the expression promoter of the first embodiment promotes the transport of melanosomes in skin melanocytes and contributes to a decrease in skin brightness.

[0029] (DCT gene) The DCT gene is the gene that encodes dopachrome tautomerase. Dopachrome tautomerase is an enzyme involved in melanin pigment production in cells.

[0030] (TYRP1 gene) The TYRP1 gene encodes tyrosinase-related protein 1, which plays a role in supporting the activity of tyrosinase. Tyrosinase is an enzyme involved in melanin pigment production in cells. Tyrosinase-related protein 1 supports the activity of tyrosinase and is involved in melanin pigment production.

[0031] In melanocytes located in the hair follicles, increased expression of the DCT gene or TYRP1 gene leads to an increase in dopachrome tautomerase or tyrosinase-related protein 1, which promotes melanin production within the cells. This increase is thought to stimulate melanin production in melanocytes, increasing the amount of melanin supplied to the hair shaft and thus contributing to a decrease in hair brightness.

[0032] Furthermore, if the expression level of the DCT gene or TYRP1 gene increases in melanocytes present in the skin, the amount of dopachrome tautomerase or tyrosinase-related protein 1, which promotes melanin pigment production within cells, increases, thereby promoting melanin pigment production in melanocytes. This promotion of melanin pigment production increases the amount of melanin supplied to the skin, and is therefore thought to contribute to a decrease in skin brightness.

[0033] The expression promoter of the first embodiment enhances the function of melanin synthesis in melanocytes in the hair follicles by promoting the expression of the DCT gene or the TYRP1 gene, thereby increasing the amount of melanin. Therefore, it is believed that the expression promoter of the first embodiment can suppress changes in hair color and the occurrence of gray hair by contributing to a decrease in hair brightness due to the increase in the amount of melanin. Similarly, it is believed that the expression promoter of the first embodiment enhances the function of melanin synthesis in melanocytes in the skin, thereby contributing to a decrease in skin brightness.

[0034] (Melon extract) The melon extract relating to the expression promoter of the first embodiment is an extract obtained from a melon (scientific name: Cucumis melo) belonging to the genus Cucumis of the family Cucurbitaceae. The type of melon (variety, cultivar, subspecies, etc.) is not particularly limited as long as it is a melon of the genus Cucumis of the family Cucurbitaceae, but examples include canterp melon, muskmelon, and oriental melon. Examples of extraction parts include the fruit, placenta, pericarp, seeds, and roots. The melon extract may also be obtained by extracting from the juice of the melon.

[0035] The above extracts include extracts obtained from melons of the Cucurbitaceae family, genus Cucumis, using an extraction solvent, and processed products of the extract (e.g., diluted, concentrated, or dried extracts). The extraction method can be any known method used for plant extracts. The extraction temperature can be set appropriately depending on the extraction solvent used; for example, it can be set arbitrarily within the range of -4°C to 100°C. Examples of extraction solvents include water, organic solvents, or mixtures thereof. Examples of organic solvents include lower aliphatic alcohols with 1 to 5 carbon atoms, such as methanol, ethanol, and isopropyl alcohol; and polyhydric alcohols with 2 to 5 carbon atoms, such as 1,3-butylene glycol, propylene glycol, and glycerin. When using organic solvents, one or more types may be used.

[0036] The melon extract related to the expression promoter of the first embodiment may be obtained using the extraction method described above, or a commercially available product may be used.

[0037] Examples of melon extracts include melon fruit concentrate, melon fruit extract, melon seed extract, melon root extract, melon peel water extract, melon peel / seed water extract, melon juice, and melon fruit water.

[0038] (Amount of melon extract included) The amount of melon extract used in the expression promoter of the first embodiment (excluding the extraction solvent or dilution solvent if the melon extract contains them; the same applies to the amount of melon extract used hereinafter) is not particularly limited and can be set as appropriate.

[0039] (Amount of melon extract to be taken orally) When the expression promoter of the first embodiment is taken orally, the amount of melon extract in the expression promoter of the first embodiment should be such that, for example, the daily intake of melon extract for an adult is 0.5 mg or more. From the viewpoint of further promoting the expression of the MLPH gene, etc., an amount of 1 mg or more is preferred, and an amount of 2 mg or more is more preferred.

[0040] When the expression promoter of the first embodiment is taken orally, the amount of melon extract in the expression promoter of the first embodiment should be such that the daily intake of melon extract for an adult is, for example, 200 mg or less. From the viewpoint of cost reduction, an amount of 100 mg or less is preferred, and an amount of 50 mg or less is more preferred.

[0041] When the expression promoter of the first embodiment is taken orally, the range of the amount of melon extract in the expression promoter of the first embodiment should be such that the daily intake of melon extract for an adult is, for example, 0.5 mg to 200 mg. From the above viewpoint, an amount of 1 mg to 100 mg is preferred, and an amount of 2 mg to 50 mg is more preferred.

[0042] (Amount of melon extract to be included when used externally) When the expression promoter of the first embodiment is used externally, the amount of melon extract in the expression promoter of the first embodiment is, for example, 0.01% by mass or more, but from the viewpoint of further promoting the expression of the MLPH gene, etc., 0.1% by mass or more is preferred, and 0.5% by mass or more is more preferred.

[0043] When the expression promoter of the first embodiment is used externally, the amount of melon extract in the expression promoter of the first embodiment is not particularly limited, but for example, it is 30% by mass or less.

[0044] When the expression promoter of the first embodiment is used externally, the range of the amount of melon extract in the expression promoter of the first embodiment is, for example, 0.01% by mass or more and 30% by mass or less, but from the above viewpoint, 0.1% by mass or more and 30% by mass or less is preferred, and 0.5% by mass or more and 30% by mass or less is more preferred.

[0045] The expression promoter of the first embodiment may contain other components besides melon extract, or it may not contain any other components. For example, the expression promoter of the first embodiment may consist solely of melon extract.

[0046] (optional ingredient) The expression promoter of the first embodiment may contain other components in addition to melon extract. Examples of such other components include zinc, surfactants, alcohols, polyhydric alcohols, sugar alcohols, sugars, ester oils, fats and oils, fatty acids, hydrocarbons, waxes, silicones, polymer compounds, amino acids, plant and animal extracts (excluding melon extract), microbial-derived products, inorganic compounds, fragrances, preservatives, metal ion chelating agents, ultraviolet absorbers, and water.

[0047] (zinc) The expression promoter of the first embodiment may contain zinc. The expression promoter of the first embodiment is preferably zinc-containing from the viewpoint of being excellent at promoting the expression of the MYO5A gene. The expression promoter of the first embodiment may, for example, consist of melon extract and zinc.

[0048] As zinc, for example, zinc (Zn) may be used, or a zinc salt may be used. As a zinc salt, for example, an organic acid salt or organic acid salt of zinc may be used. Examples of zinc salts include (silver / zinc / ammonium) zeolite, DNA zinc, PCA zinc, ascorbyl phosphate (Mg / zinc), zinc ascorbate, aspartic acid (zinc / Mg), zinc aspartate, acetylmethionine zinc, adenosine triphosphate zinc, undecylenol hydrolyzed wheat protein zinc, zinc undecylenate, zinc ethylhexanoate, carboxydecyltrisiloxane zinc, zinc citrate, zinc glycine, zinc glycyrrhetinate, zinc gluconate, (ammonium / silver / zinc / Al) silicate, coco-alkyl sulfate zinc, coceth sulfate zinc, Saccharomyces / zinc culture, zinc salicylate, zinc stearate, cetyl phosphate (zinc / Examples include sodium taurate (Na / zinc), taurine dithiooctanamide (Na / zinc), zinc palmitate, palmitoyl nonapeptide-14 zinc, zinc picolinate, bis(methylpalmitoyl aspartate) zinc, histidine dithiooctanamide (Na / zinc), pyrithione zinc, phenolsulfonate zinc, hexapeptide-11 zinc, zinc myristate, zinc laurate, lauroyl aspartate zinc, zinc ricinoleate, hydrolyzed collagen zinc, hydrolyzed hyaluronic acid zinc, oxide (Al / zinc), oxide (Al / zinc / cerium), oxide (Al / zinc / iron), zinc acetate, zinc carbonate, zinc lactate, Lactobacillus / (milk / Ca / phosphorus / Mg / zinc) ferment product, and zinc sulfate. The zinc salt used in the expression promoter of the first embodiment may be appropriately selected depending on whether it is taken orally or applied topically.

[0049] (Zinc content) The amount of zinc in the expression promoter of the first embodiment (if zinc is included as a zinc salt, the amount converted to zinc; the same applies to the amount of zinc hereinafter) is not particularly limited and can be set as appropriate.

[0050] (Zinc content when taken orally) When the expression promoter of the first embodiment is taken orally, the amount of zinc in the expression promoter of the first embodiment should be such that the daily intake of zinc for an adult is, for example, 1 mg or more. From the viewpoint of further promoting the expression of the MYO5A gene, an amount of 2 mg or more is preferred, and an amount of 3 mg or more is more preferred.

[0051] When the expression promoter of the first embodiment is taken orally, the amount of zinc in the expression promoter of the first embodiment should be such that the daily intake of zinc for an adult is, for example, 15 mg or less. From the viewpoint of preventing excessive zinc intake, an amount of 13 mg or less is preferred, and an amount of 12 mg or less is more preferred.

[0052] When the expression promoter of the first embodiment is taken orally, the amount of zinc in the expression promoter of the first embodiment should be such that the daily intake of zinc for an adult is, for example, 1 mg to 15 mg. From the above viewpoint, an amount of 2 mg to 13 mg is preferred, and an amount of 3 mg to 12 mg is more preferred.

[0053] (Zinc content when used externally) When the expression promoter of the first embodiment is used externally, the amount of zinc in the expression promoter of the first embodiment is, for example, 0.005% by mass or more, but from the viewpoint of further promoting the expression of the MYO5A gene, 0.01% by mass or more is preferred, and 0.05% by mass or more is more preferred.

[0054] When the expression promoter of the first embodiment is used externally, the amount of zinc in the expression promoter of the first embodiment is, for example, 5% by mass or less.

[0055] When the expression promoter of the first embodiment is used externally, the range of zinc content in the expression promoter of the first embodiment is, for example, 0.005% by mass or more and 5% by mass or less, but from the above viewpoint, 0.01% by mass or more and 5% by mass or less is preferred, and 0.05% by mass or more and 5% by mass or less is more preferred.

[0056] (Application) The expression promoter of the first embodiment may be used, for example, as an oral composition such as a supplement, or as a topical composition such as a cosmetic.

[0057] [Oral composition] The expression promoter of the first embodiment may be, for example, an oral composition. The oral composition may also be used as, for example, a pharmaceutical, quasi-drug, or food (including general food, nutritional functional food, functional food, food for specified health uses, and supplement).

[0058] The expression promoter of the first embodiment may be used as a food when used as an oral composition. Examples of food products include supplements, dairy products, beverages, frozen desserts, ice cream, confectionery, seasonings, creams, jellies, jams, syrups, processed foods, processed meat products, retort foods, and frozen foods.

[0059] The expression promoter of the first embodiment may be, for example, a supplement for supplementing melon extract.

[0060] When the expression promoter of the first embodiment is an oral composition, examples of its dosage form include tablets, granules, fine granules, powders, capsules, soft capsules, pills, liquids, syrups, beverages, jellies, syrups, dry syrups, tablets, chewables, lozenges, effervescent tablets, drops, suspensions, and orally disintegrating tablets.

[0061] [External composition] The expression promoter of the first embodiment may be, for example, a topical composition. In this specification, "topical composition" means a substance used externally on external parts of the human body (hair, skin (including scalp), etc.) by methods such as application or patching.

[0062] When the expression promoter of the first embodiment is used as an external composition, it may be, for example, a cosmetic (a composition for treating the human body for the purpose of beautification, cleansing, protection, or deodorization). The cosmetic may be classified as a pharmaceutical, quasi-drug, or cosmetic.

[0063] Examples of cosmetics include hair cosmetics, scalp cosmetics, and skin cosmetics other than scalp cosmetics.

[0064] If the expression promoter of the first embodiment is a cosmetic, its form can be appropriately selected, for example, liquid, emulsion, cream, wax, solid, foam, or mist.

[0065] (Hair cosmetic product) The expression promoter of the first embodiment may be, for example, a hair cosmetic. Examples of hair cosmetics include hair care cosmetics (e.g., shampoo, hair treatment, styling and hair treatment, a component of a multi-component hair treatment, hair treatment for pre-perm treatment, hair treatment for post-perm treatment, hair treatment for pre-hair coloring, hair treatment for post-hair coloring, hair treatment for pre-bleaching, hair treatment for post-bleaching, etc.), hair styling cosmetics (e.g., hair styling agents), hair dyes (including gray hair dyes), hair colorants (including gray hair dyes), and hair nourishing or hair growth cosmetics (e.g., hair nourishing agents, hair growth agents). The hair treatment may be a leave-in hair treatment or a rinse-off hair treatment.

[0066] (Scalp cosmetic) The expression promoter of the first embodiment may be, for example, a scalp cosmetic. Examples of scalp cosmetics include scalp treatments (e.g., leave-in scalp treatments, rinse-off scalp treatments, and components of multi-component scalp treatments).

[0067] (Skin cosmetics other than scalp cosmetics) The expression promoter of the first embodiment may be, for example, a skin cosmetic other than a scalp cosmetic. Examples of skin cosmetics other than scalp cosmetics include serums, lotions, creams, packs, or masks other than those for the scalp.

[0068] Furthermore, the expression promoter of the first embodiment may, for example, be a hair cosmetic and a scalp cosmetic, a scalp cosmetic and a skin cosmetic other than a scalp cosmetic, or a hair cosmetic, a scalp cosmetic and a skin cosmetic other than a scalp cosmetic.

[0069] (For preventing gray hair) The expression promoter of the first embodiment may also be for anti-gray hair use. For anti-gray hair use, for example, it may be used to suppress gray hair that increases due to aging or environmental changes. "For anti-gray hair use" means use to suppress the occurrence of gray hair in the hair (including use for gray hair prevention and use for gray hair improvement) (the same applies in the following description). The "use to suppress the occurrence of gray hair in the hair" may also mean use to suppress the occurrence of gray hair in scalp hair.

[0070] In the case of the expression promoter of the first embodiment, if it is an oral composition or scalp cosmetic for anti-graying hair, for example, it can be in the form of a product in which the oral composition or scalp cosmetic for anti-graying hair (such as an anti-graying food, pharmaceutical, quasi-drug, or cosmetic) is indicated on the packaging, brochure, instruction manual, or other explanatory materials that it is used for anti-graying hair and that it has efficacy and effects on gray hair.

[0071] When the expression promoter of the first embodiment is used as a scalp cosmetic for preventing graying of hair, examples of its product form include scalp care agents for preventing graying of hair (such as scalp shampoos, scalp rubbings, conditioners, and treatments).

[0072] (Manufacturing method) The method for producing the expression promoter of the first embodiment is not particularly limited and can be produced by employing a known manufacturing method depending on the dosage form.

[0073] (How to use) The method of using the expression promoter of the first embodiment is not particularly limited and may be set as appropriate depending on the target of application, product form, dosage form, etc.

[0074] <(1-2) Expression promoter of the second embodiment> The expression promoter of the second embodiment is an MLPH gene expression promoter containing zinc. According to the expression promoter of the second embodiment, the expression of the MLPH gene can be promoted. The MLPH gene is as described above in the description of the expression promoter of the first embodiment.

[0075] The expression promoter of the second embodiment can further improve the function of melanin transport in melanocytes present in hair follicles or skin by promoting the expression of the MLPH gene. As a result, the expression promoter of the second embodiment can increase the amount of melanin in hair or skin, and is expected to have a gray hair suppression effect.

[0076] (zinc) The zinc in the expression promoter of the second embodiment is the same as the zinc described above in the expression promoter of the first embodiment. Therefore, the zinc used can be the same as that described in the expression promoter of the first embodiment.

[0077] (Zinc content) The amount of zinc in the expression promoter of the second embodiment is not particularly limited and can be set as appropriate.

[0078] (Zinc content when taken orally) When the expression promoter of the second embodiment is taken orally, the amount of zinc in the expression promoter of the second embodiment should be such that, for example, the daily intake of zinc for an adult is 1 mg or more. From the viewpoint of further promoting the expression of the MLPH gene, an amount of 2 mg or more is preferred, and an amount of 3 mg or more is more preferred.

[0079] When the expression promoter of the second embodiment is taken orally, the amount of melon extract in the expression promoter of the second embodiment should be such that the daily zinc intake for an adult is, for example, 15 mg or less. From the viewpoint of preventing excessive zinc intake, an amount of 13 mg or less is preferred, and an amount of 12 mg or less is more preferred.

[0080] When the expression promoter of the second embodiment is taken orally, the amount of zinc in the expression promoter of the second embodiment may be set to an amount that is, for example, 1 mg to 15 mg of the daily zinc intake for adults. From the above viewpoint, an amount of 2 mg to 13 mg is preferred, and an amount of 3 mg to 12 mg is more preferred.

[0081] (Zinc content when used externally) When the expression promoter of the second embodiment is used externally, the amount of zinc in the expression promoter of the second embodiment is, for example, 0.005% by mass or more, but from the viewpoint of further promoting the expression of the MLPH gene, 0.01% by mass or more is preferred, and 0.05% by mass or more is more preferred.

[0082] When the expression promoter of the second embodiment is used externally, the amount of zinc in the expression promoter of the second embodiment is, for example, 5% by mass or less.

[0083] When the expression promoter of the second embodiment is used externally, the range of zinc content in the expression promoter of the second embodiment is, for example, 0.005% by mass or more and 5% by mass or less, but from the above viewpoint, 0.01% by mass or more and 5% by mass or less is preferred, and 0.05% by mass or more and 5% by mass or less is more preferred.

[0084] (optional ingredient) The expression promoter of the second embodiment may contain other components besides zinc. Examples of such other components include melon extract and the components described in the expression promoter of the first embodiment (excluding zinc).

[0085] The expression promoter of the second embodiment may contain other components in addition to zinc, or it may not contain any other components. For example, the expression promoter of the second embodiment may consist solely of zinc.

[0086] The "uses," "manufacturing method," and "method of use" for the expression promoter of the second embodiment are the same as those for the expression promoter of the first embodiment, and are therefore omitted.

[0087] <(3) Beauty method> The cosmetic method of this embodiment can employ known cosmetic methods, except for using the expression promoter of the first embodiment or the expression promoter of the second embodiment described above (hereinafter, the expression promoter of the first embodiment and the expression promoter of the second embodiment are collectively referred to as "expression promoter, etc."). It should be noted that the cosmetic method of this embodiment is for cosmetic purposes only and excludes medical procedures (such as methods of surgery, treatment, or diagnosis of humans).

[0088] The beauty method of this embodiment may also involve orally ingesting a hair growth promoter or the like. The method of oral ingestion may be appropriate depending on the dosage form of the hair growth promoter or the like. For example, the method of oral ingestion may be an orally ingestion method for anti-graying hair.

[0089] The beauty method of this embodiment may also be a method of applying a hair growth promoter, etc., to the scalp or other skin. The method of applying to the scalp or other skin may be a method of bringing the hair growth promoter, etc., into contact with the scalp or other skin by means of application, spraying, etc. The above method of applying to the scalp or other skin may be, for example, a method of applying to the scalp for anti-gray hair treatment.

[0090] <(4) Composition for preventing graying hair> The anti-gray hair composition of this embodiment contains a hair growth promoter and the like as active ingredients. Since the hair growth promoter and the like function as active ingredients for anti-gray hair in the anti-gray hair composition of this embodiment, an anti-gray hair effect can be expected.

[0091] When the anti-gray hair composition of this embodiment is used as an oral composition or scalp cosmetic for anti-gray hair, it can be in a product form in which the efficacy and effects of anti-gray hair, such as those due to the expression promoter, are displayed on the packaging, brochures, instructions, and other explanatory materials.

[0092] The amount of the expression promoter and other active ingredients included in the anti-gray hair composition of this embodiment may be set appropriately according to the dosage form of the anti-gray hair composition. If the expression promoter and other ingredients included in the anti-gray hair composition include melon extract, the amount of melon extract included in the anti-gray hair composition may be the same as that of the expression promoter in the first embodiment. Also, if the expression promoter and other ingredients included in the anti-gray hair composition include zinc, the amount of zinc included in the anti-gray hair composition may be the same as that of the expression promoter in the first embodiment.

[0093] The anti-gray hair composition of this embodiment can be the same as the "oral composition or scalp cosmetic for anti-gray hair" described in the expression promoter of the first embodiment.

[0094] Furthermore, the anti-gray hair composition of this embodiment may contain other components (for example, optional components mentioned in the expression promoter of the first embodiment) in addition to the expression promoter.

[0095] <(5) Beauty methods using anti-gray hair compositions> The beauty method using the anti-gray hair composition of this embodiment can employ any known beauty method other than using the anti-gray hair composition of this embodiment. It should be noted that the beauty method using the anti-gray hair composition of this embodiment is for cosmetic purposes only and excludes medical procedures (such as surgery, treatment, or diagnosis of humans).

[0096] The beauty method using the anti-gray hair composition of this embodiment may also involve orally ingesting the anti-gray hair composition of this embodiment. The method of oral ingestion may be appropriate depending on the dosage form of the anti-gray hair composition.

[0097] The beauty method of this embodiment may also be a method of applying the anti-gray hair composition of this embodiment to the scalp or other skin. The method of applying to the scalp or other skin may be a method of bringing the anti-gray hair composition of this embodiment into contact with the scalp or other skin by means of application, spraying, etc. [Examples]

[0098] The present invention will be described in detail below based on examples, but the present invention should not be interpreted as being limited based on the description of these examples.

[0099] (evaluation) The relative expression levels of genes were evaluated using the following test samples 1-3.

[0100] (Test sample 1) Test sample 1 containing melon fruit extract was prepared using the following method.

[0101] A solution was prepared by adding 400 mg of BIONOV's product name SOD B HOLIMEL S (containing melon fruit extract (derived from Cantabile melon), shellac, and maltodextrin) and 3600 μL of ethanol to a centrifuge tube (capacity 15 mL). Subsequently, the solution was subjected to sonication for 30 seconds (instrument name: ULTRAONIC HOMOGENIZER VP-050 TAITEC, transducer normal output 10-40 W, oscillation frequency range 19.5-20.5 kHz, output setting 65%. The same conditions apply to the sonication described below.) followed by centrifugation (instrument name: KUBOTA Hybrid High-Speed ​​Refrigerated Centrifuge 6200, 750 × g, 3 min, 20°C. The same conditions apply to the centrifugation described below.) to remove the supernatant containing ethanol and obtain the residue settled at the bottom of the centrifuge tube. Next, 3600 μL of dimethyl sulfoxide was added to the centrifuge tube to dissolve the residue, and after sonication for 30 seconds, further centrifugation was performed to remove the supernatant containing dimethyl sulfoxide and obtain the residue settled at the bottom of the centrifuge tube. Then, 3600 μL of purified water was added to the centrifuge tube to dissolve the residue, and after sonication for 30 seconds, further centrifugation was performed to obtain the supernatant. This supernatant was designated as test sample 1 (sample containing melon fruit extract).

[0102] (Test samples 2-3) Test sample 2: "Zinc gluconate" manufactured by Fuso Chemical Industries Co., Ltd. Test sample 3: "Cassis Polyphenol" Product name: Meiji Cassis Polyphenol (AC10) Manufactured by Meiji Food Materia Co., Ltd.

[0103] 1. Evaluation of the relative expression level of the MLPH gene The relative expression levels of the MLPH gene were evaluated according to the following procedures [1] to [4-1].

[0104] [1] A culture medium prepared by mixing standard human epidermal melanocyte culture medium (Gibco) with human melanocyte growth supplement (Gibco) to a concentration of 1% by mass, to which normal human epidermal melanocyte cells were inoculated at a rate of 1.0 × 10⁻⁶. 5The cells were adjusted to a concentration of cells / mL, and 0.5 mL was seeded per well in a 24-well plate. The cells were then incubated at 37°C under 5% CO2 for 24 hours. [2-1] 24 hours after the start of culture, test samples 1-3 were added to the culture medium in each well. The amounts of test samples 1-3 added were such that their ppm concentrations in the culture medium were as follows. Test sample 1: 100 ppm (Example 1), 1000 ppm (Example 2) Test sample 2: 1 ppm (Example 3), 5 ppm (Example 4) Test sample 3: 100 ppm (Comparative example 1) Furthermore, as a control for each test sample, purified water was added to the culture medium in separate wells to a concentration of 0.1% by mass. After adding each test sample, it was incubated at 37°C under 5% CO2 for 24 hours. [3] 24 hours after adding each test sample, each well was washed with D-PBS(-), and total RNA was extracted from each cell using the Rneasy Plus Mini Kit (QIAGEN) according to its protocol. [4-1] The extracted total RNA was reverse transcribed into cDNA using the GoScript Reverse Transcription System (Promega). The Ct values ​​of the MLPH gene and β-Actin gene were measured using real-time PCR (Roche LightCycler96) with each of the obtained cDNAs. The β-Actin gene, a housekeeping gene, was used as the internal standard.

[0105] The primers used for measuring the relative expression levels of genes by real-time PCR as described above were as follows: Primers used to measure the relative expression level of the MLPH gene Sequence IDs 15 and 16 described in paragraph 0074 of Japanese Patent Publication No. 2022-47195 Primers used to measure the relative expression level of the β-Actin gene Sequence IDs 17 and 18 described in paragraph 0074 of Japanese Patent Publication No. 2022-47195

[0106] (Examples 1-4, Comparative Example 1) In the above evaluation, the sample with 100 ppm of test sample 1 added was designated as "Example 1," the sample with 1000 ppm of test sample 1 added as "Example 2," the sample with 1 ppm of test sample 2 added as "Example 3," the sample with 5 ppm of test sample 2 added as "Example 4," and the sample with 100 ppm of test sample 3 added as "Comparative Example 1." The relative expression level of the MLPH gene (hereinafter sometimes abbreviated as "relative expression level of the MLPH gene") in Examples 1 to 4 and Comparative Example 1, with the control set to 1, was calculated using the following formula.

[0107] Relative expression level = 2 -(ΔCq(samp.)-ΔCq(cont.ave.)) Here, in the above calculation formula, "ΔCq(samp.)" is the value obtained by subtracting the Ct value of the β-Actin gene from the Ct value of the MLPH gene in each sample (Examples 1-4, Comparative Example 1) to which one of the test samples (MLPH gene Ct value - β-Actin gene Ct value) was added (for each sample to which the "MLPH gene Ct value" - "β-Actin gene Ct value" was added), and "ΔCq(cont.ave.)" is the average value (N=5) obtained by subtracting the Ct value of the β-Actin gene from the Ct value of the MLPH gene in the sample to which the control (purified water) was added (for the control to which the "MLPH gene Ct value" - "β-Actin gene Ct value" was added).

[0108] Note that the "relative expression level of the MLPH gene" listed in Table 1 represents the average value calculated from the relative expression levels of the MLPH gene obtained from the number of tests (N) shown in Table 1. A relative expression level of the MLPH gene exceeding 1 indicates that the expression level of the MLPH gene in the test sample is relatively higher compared to the control.

[0109] (Evaluation results) Table 1 shows the results of the evaluation of the relative expression levels of the MLPH gene.

[0110] [Table 1]

[0111] As shown in Table 1, the relative expression level of the MLPH gene increased in all cases where the expression promoters in Examples 1 to 4 were added to the cells. Conversely, the relative expression level of the MLPH gene decreased when Comparative Example 1 was added to the cells. From these results, it can be understood that expression promoters containing melon extract or zinc can promote the expression of the MLPH gene.

[0112] 2. Evaluation of the relative expression levels of the MYO5A gene, DCT gene, and TYRP1 gene. The relative expression levels of the MYO5A, DCT, and TYRP1 genes were evaluated in the same manner as the evaluation of the relative expression levels of the MLPH gene, except that the procedures [2-1] and [4-1] described above for evaluating the relative expression levels of the MLPH gene were changed to the procedures [2-2] and [4-2] shown below, respectively. [2-2] 24 hours after the start of culture, test sample 1, test sample 2, and test samples 1 and 2 were added to the culture medium in each well. Each test sample was added so that its ppm concentration in the culture medium was as shown below. Test sample 1: 100 ppm (Example 1) Test sample 2: 5 ppm (Reference example 1) Test samples 1 and 2: Test sample 1 at 100 ppm and test sample 2 at 5 ppm (Example 5) Furthermore, as a control for each test sample, purified water was added to the culture medium in separate wells to a concentration of 0.1% by mass. After adding each test sample, it was incubated at 37°C under 5% CO2 for 24 hours. [4-2] The extracted total RNA was reverse transcribed into cDNA using the GoScript Reverse Transcription System (Promega). The Ct values ​​of the MYO5A gene, DCT gene, TYRP1 gene, and β-Actin gene were measured using real-time PCR (Roche LightCycler96) with each of the obtained cDNAs. The β-Actin gene, a housekeeping gene, was used as the internal standard.

[0113] The primers used to measure the relative expression levels of each gene by real-time PCR as described above are as follows. Furthermore, the primers used for the β-Actin gene were the same as those used to evaluate the relative expression level of the MLPH gene. Primers used to measure the relative expression level of the MYO5A gene Sequence IDs 13 and 14 described in paragraph 0074 of Japanese Patent Publication No. 2022-47195 Primers used to measure the relative expression level of the DCT gene Sequence IDs 3 and 4 described in paragraph 0074 of Japanese Patent Publication No. 2022-47195 Primers used to measure the relative expression level of the TYRP1 gene Sequence IDs 5 and 6 described in paragraph 0074 of Japanese Patent Publication No. 2022-47195

[0114] (Examples 1, 5, Reference Example 1) In the above evaluation, the sample with 100 ppm of test sample 1 added was designated as "Example 1," the sample with 5 ppm of test sample 2 added was designated as "Reference Example 1," and the sample with 100 ppm of test sample 1 and 5 ppm of test sample 2 was designated as "Example 5." The relative expression levels of the MYO5A gene, DCT gene, and TYRP1 gene, respectively, with the control set to 1, were then determined for Examples 1, 5, and Reference Example 1 as follows. (Hereafter, these will be abbreviated as "relative expression level of the MYO5A gene," "relative expression level of the DCT gene," and "relative expression level of the TYRP1 gene," respectively.)

[0115] Relative expression levels of the MYO5A gene, DCT gene, or TYRP1 gene: From the formula used for calculating the relative expression level of the MLPH gene as described above, "ΔCq(samp.)" was calculated as the value obtained by subtracting the Ct value of the β-Actin gene from the Ct value of the MYO5A gene, DCT gene, or TYRP1 gene in each test sample (Examples 1, 5, and Reference Example 1) that was added ("Ct value of the MYO5A gene, DCT gene, or TYRP1 gene" - "Ct value of the β-Actin gene" in each test sample addition). "ΔCq(cont.ave.)" was calculated as the average value (N=5) of the value obtained by subtracting the Ct value of the β-Actin gene from the Ct value of the MYO5A gene, DCT gene, or TYRP1 gene in the control (purified water) that was added ("Ct value of the MYO5A gene, DCT gene, or TYRP1 gene" - "Ct value of the β-Actin gene" in the control addition).

[0116] The "relative expression levels of the MYO5A, DCT, and TYRP1 genes" listed in Table 2 represent the average values ​​calculated from the relative expression levels of the MYO5A, DCT, and TYRP1 genes obtained from the number of tests (N) shown in Table 2. A relative expression level of MYO5A, DCT, or TYRP1 exceeding 1 indicates that the expression levels of these genes in the test sample are relatively higher compared to the control.

[0117] (Evaluation results) Table 2 shows the evaluation results of the relative expression levels of the MYO5A gene, DCT gene, and TYRP1 gene.

[0118] [Table 2]

[0119] As shown in Table 2, the relative expression levels of the MYO5A, DCT, and TYRP1 genes increased when the expression promoters of Examples 1 and 5 were added to cells, respectively. Conversely, the relative expression levels of the MYO5A, DCT, and TYRP1 genes decreased when Reference Example 1 was added to cells. Furthermore, the expression promoter of Example 5 increased the relative expression level of the MYO5A gene more significantly than the expression promoter of Example 1. These results indicate that expression promoters containing melon extract can promote the expression of the MYO5A, DCT, and TYRP1 genes, and that expression promoters containing melon extract and zinc can further promote the expression of the MYO5A gene.

[0120] 3. Evaluation of the relative expression levels of the TYR gene and the Rab27A gene. The relative expression levels of the TYR gene and Rab27A gene were evaluated in the same manner as the evaluation of the relative expression levels of the MLPH gene, except that the procedures [2-1] and [4-1] described above for evaluating the relative expression levels of the MLPH gene were changed to the procedures [2-3] and [4-3] shown below, respectively. [2-3] 24 hours after the start of culture, test sample 1, test sample 2, and test samples 1 and 2 were added to the culture medium in each well. Each test sample was added so that its ppm concentration in the culture medium was as shown below. Test sample 1: 100 ppm (Reference example 2) Test sample 2: 5 ppm (Reference example 1) Test samples 1 and 2: Test sample 1 at 100 ppm, test sample 2 at 5 ppm (Reference Example 3) Furthermore, as a control for each test sample, purified water was added to the culture medium in separate wells to a concentration of 0.1% by mass. After adding each test sample, it was incubated at 37°C under 5% CO2 for 24 hours. [4-3] The extracted total RNA was reverse transcribed into cDNA using the GoScript Reverse Transcription System (Promega). The Ct values ​​of the TYR gene, Rab27A gene, and β-Actin gene were measured using real-time PCR (LightCycler96, Roche) with each of the obtained cDNAs. The β-Actin gene, a housekeeping gene, was used as an internal standard.

[0121] The primers used to measure the relative expression levels of each gene by real-time PCR as described above are as follows. Furthermore, the primers used for the β-Actin gene were the same as those used to evaluate the relative expression level of the MLPH gene. • Primers used to measure the relative expression level of the TYR gene Sequence IDs 1 and 2 described in paragraph 0074 of Japanese Patent Publication No. 2022-47195 • Primers used to measure the relative expression level of the Rab27A gene Sequence IDs 11 and 12 described in paragraph 0074 of Japanese Patent Publication No. 2022-47195

[0122] (Reference examples 1~3) In the above evaluation, the sample with 100 ppm of test sample 1 added was designated as "Reference Example 2," the sample with 5 ppm of test sample 2 added was designated as "Reference Example 1," and the sample with 100 ppm of test sample 1 and 5 ppm of test sample 2 added was designated as "Reference Example 3." The relative expression levels of the TYR gene and Rab27A gene (hereinafter sometimes abbreviated as "relative expression level of the TYR gene" and "relative expression level of the Rab27A gene," respectively) in Reference Examples 1 to 3, with the control set to 1, were then determined as follows.

[0123] Relative expression levels of the TYR gene and Rab27A gene: Using the formula described above for the relative expression level of the MLPH gene, "ΔCq(samp.)" is calculated as the value obtained by subtracting the Ct value of the β-Actin gene from the Ct value of the TYR gene or Rab27A gene in each test sample (Reference Examples 1-3) to which one of the test samples (Reference Examples 1-3) was added ("Ct value of the TYR gene or Rab27A gene" - "Ct value of the β-Actin gene" in each test sample addition), and "ΔCq(cont.ave.)" is calculated as the average value (N=5) of the value obtained by subtracting the Ct value of the β-Actin gene from the Ct value of the TYR gene or Rab27A gene in the control (purified water) to which the control ("Ct value of the TYR gene or Rab27A gene" - "Ct value of the β-Actin gene" in the control addition).

[0124] The "relative expression levels of the TYR gene and Rab27A gene" listed in Table 3 represent the average values ​​calculated from the relative expression levels of the TYR gene and Rab27A gene obtained from the number of tests (N) shown in Table 3. A relative expression level of TYR gene or Rab27A gene exceeding 1 indicates that the expression levels of the TYR gene and Rab27A gene in the test product are relatively increased compared to the control.

[0125] The TYR and Rab27A genes used in this expression level evaluation are genes that encode proteins involved in melanin synthesis in cells and melanin transport in melanocytes, respectively. • TYR gene: A gene that codes for tyrosinase. Tyrosinase is involved in melanin pigment production in cells. • Rab27A gene: The gene that codes for Rab27A. Rab27A is a type of small GTPase that plays a role in transporting melanosomes in melanocytes.

[0126] (Evaluation results) Table 3 shows the results of the evaluation of the relative expression levels of the TYR gene and the Rab27A gene.

[0127] [Table 3]

[0128] As shown in Table 3, when Reference Examples 1-3 were added to cells, the relative expression levels of the TYR gene and the Rab27A gene decreased, with the exception of the relative expression level of the Rab27A gene in Reference Example 2.

[0129] Considering the results shown in Tables 1-3, it can be seen that melon extract and zinc can promote the expression of specific genes, such as the MLPH gene, which are involved in melanin synthesis and melanin transport.

[0130] <Example prescription> The following are examples of formulations for MLPH gene expression promoters. Examples A1-A3 are oral formulations, and examples B1-B4 are topical formulations. These formulations may also be used for anti-graying purposes.

[0131] (Prescription example A1: Oral composition (tablets)) Melon fruit concentrate 10mg Zinc gluconate 10mg Vitamin B2 1 mg Vitamin B6 1 mg Crystalline cellulose 100mg Hydroxypropylcellulose 5mg Dextrin 50mg Silicon dioxide 10mg Appropriate amount of citric acid Magnesium stearate 10mg

[0132] (Formulation example A2: Oral composition (hard capsule)) The contents (1) listed below are filled into commercially available HPMC capsules, and hard capsules are manufactured by a conventional method. ·Contents (1) Melon fruit concentrate 10mg Zinc gluconate 10mg Vitamin B2 1 mg Vitamin B6 1 mg Starch 100mg Silicon dioxide 30mg Appropriate amount of citric acid Magnesium stearate 10mg

[0133] (Formulation example A3: Oral composition (beverage)) Melon fruit concentrate 10mg Zinc gluconate 10mg Vitamin B2 1 mg Vitamin B6 1 mg Vitamin C 10mg Glucose-fructose syrup 50mg Fragrance 1mg Purified water 100mg

[0134] (Formulation Example B1: External Composition (Hair Shampoo or Body Cleanser)) Melon fruit extract 0.5% by mass Zinc gluconate 0.5% by mass Sodium laureth sulfate 12% by mass Cocamidopropyl betaine 3% by mass Polyquaternium-10 0.1% by mass Methylparaben 0.2% by mass Amount of citric acid that results in a pH of 4 Fragrance 0.1% by mass Purified water: an amount that makes up 100% by mass.

[0135] (Formulation example B2: Topical composition (hair cream)) Melon fruit extract 0.5% by mass Zinc gluconate 0.5% by mass Stearyltrimonium chloride 2% by mass Cetanol 3% by mass Stearyl alcohol 3% by mass Olive oil 2% by mass Dimethicone 2% by mass Phenoxyethanol 0.2% by mass Glycerin 3% by mass Amount of citric acid that results in a pH of 4 Fragrance 0.1% by mass Purified water: an amount that makes up 100% by mass.

[0136] (Formulation example B3: Topical composition (liquid for hair or liquid for skin)) Melon fruit extract 0.5% by mass Zinc gluconate 0.5% by mass PEG-60 Hydrogenated Castor Oil 0.5% by mass Methylparaben 0.2% by mass Glycerin 3% by mass Amount of citric acid that results in a pH of 4 Fragrance 0.1% by mass Purified water: an amount that makes up 100% by mass.

[0137] (Formulation example B4: Topical composition (hair gel or skin gel)) Melon fruit extract 0.5% by mass Zinc gluconate 0.5% by mass Carbomer 0.5% by mass Hydroxyethylcellulose 0.1% by mass Sodium hydroxide 0.1% by mass Glycerin 3% by mass PEG-60 Hydrogenated Castor Oil 0.2% by mass Methylparaben 0.1% by mass Amount of citric acid that results in a pH of 4 Fragrance 0.1% by mass Purified water: an amount that makes up 100% by mass.

Claims

1. Contains melon extract, An expression enhancer for the MLPH gene, MYO5A gene, DCT gene, or TYRP1 gene.

2. The expression promoter according to claim 1, which contains zinc and is an expression promoter for the MYO5A gene.

3. Contains zinc An MLPH gene expression promoter.

4. An expression promoter according to any one of claims 1 to 3, for use in preventing graying hair.

5. A cosmetic method using the expression promoter described in any one of claims 1 to 3.

6. A composition for preventing graying hair, comprising the expression promoter described in any one of claims 1 to 3 as an active ingredient.

7. A beauty method using the anti-gray hair composition described in claim 6.

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