Skin-improving agent

Abstract

This skin-improving agent contains the following components (A) to (C). (A) At least one selected from the group consisting of L-cysteine, a derivative thereof and a salt thereof. (B) At least one selected from the group consisting of ascorbic acid, a derivative thereof, and a salt thereof. (C) One or more selected from the group consisting of vitamin B5, vitamin B6, vitamin B2, vitamin E, gamma oryzanol, dong quai and an extract thereof.

Description

Skin improver

[0001] The present invention relates to a skin improving agent.

[0002] When skin is damaged by UV rays or other factors, keratinocytes secrete various cytokines that promote melanin production. These cytokines stimulate melanocytes and promote melanin production. The melanin produced by melanocytes is then passed on to keratinocytes, and its accumulation in the epidermis is known to cause age spots, freckles, and pigmentation due to sunburn or rashes.

[0003] Patent Document 1 (JP Patent Publication No. 8-99859) describes a topical skin preparation containing water-soluble rutin and a tyrosinase activity inhibitor as active ingredients (claim 1), and describes the results of measuring the tyrosinase activity inhibition rate of samples containing specific amounts of water-soluble rutin and a specific amount of a Morus alba extract, a specific amount of a Sophora root extract, a specific amount of an Angelica acutiloba extract, or a specific amount of a hop extract (Table 1).

[0004] Patent Document 2 (JP 2004-10503 A) describes a moisturizing plant extract consisting of a mixture of extracts of Angelica acutiloba, Rehmannia Root, Peony Root, Cnidium Rhizome, Coptis Rhizome, Scutellaria Root, Salicylic Acid Berry, and Phellodendron Bark (Claim 1). It is stated that such moisturizing plant extract has a long-lasting moisturizing effect, and that cosmetics and bath agents containing the extract are effective in preventing, alleviating, or improving dryness, roughness, cracks, chapped skin, dandruff, itching, etc. for skin, and in preventing dryness, dryness, split ends, breakage, and imparting shine to hair (paragraph 0152).

[0005] Furthermore, Patent Document 3 (JP 2012-77044 A) describes an external skin preparation containing phosphorylated sugar calcium as a turnover-promoting component (claim 1).

[0006] Japanese Patent Laid-Open No. 8-99859 Japanese Patent Laid-Open No. 2004-10503 Japanese Patent Laid-Open No. 2012-77044

[0007] The present invention provides a new skin improving agent.

[0008] The present inventors have found that a combination of specific ingredients can provide excellent skin-improving effects.

[0009] According to the present invention, the following skin improving agent is provided. [1] A skin improving agent containing the following components (A) to (C): (A) at least one selected from the group consisting of L-cysteine, derivatives thereof, and salts thereof; (B) at least one selected from the group consisting of ascorbic acid, derivatives thereof, and salts thereof; and (C) one or more selected from the group consisting of vitamin B5s, vitamin B6s, vitamin B2s, vitamin Es, gamma oryzanol, and Angelica acutiloba and extracts thereof. [2] The skin improving agent according to [1], which is a skin whitening agent. [3] The skin improving agent according to [1] or [2], which is an agent for reducing one or more selected from the group consisting of age spots, freckles, and post-inflammatory hyperpigmentation. [4] The skin improving agent according to any one of [1] to [3], which is a melanin production inhibitor.

[0010] According to the present invention, a new skin improving agent can be obtained.

[0011] 1 is a diagram showing the evaluation results of the gene expression level of NOS3. FIG. 2 is a diagram showing the evaluation results of the gene expression level of NOS2. FIG. 3 is a diagram showing the evaluation results of the gene expression level of PTGS1. FIG. 4 is a diagram showing the evaluation results of the gene expression level of EDN2.

[0012] Hereinafter, an embodiment of the present invention will be described. In this embodiment, the composition may contain each component alone or in combination of two or more. In this specification, the term "to" indicating a numerical range means "at least" or "at most," and both end values ​​are included.

[0013] (Skin improving agent) In the present embodiment, the skin improving agent contains the following components (A) to (C): (A) at least one selected from the group consisting of L-cysteine, derivatives thereof, and salts thereof (B) at least one selected from the group consisting of ascorbic acid, derivatives thereof, and salts thereof (C) one or more selected from the group consisting of vitamin B5s, vitamin B6s, vitamin B2s, vitamin Es, gamma oryzanol, and Angelica acutiloba and extracts thereof The skin improving agent is specifically a composition containing the above components (A) to (C).

[0014] In this embodiment, an excellent skin improvement effect can be obtained by using components (A) to (C) in combination. Specifically, it has been newly discovered that using components (A) to (C) in combination suppresses the expression of specific genes related to melanin production or melanocyte stimulating factors in the skin more than when components (A) and (B) are used alone.

[0015] That is, the skin improving agent is preferably an agent for suppressing the expression of at least one gene selected from the group consisting of genes associated with melanin production and melanocyte stimulating factors.

[0016] Specifically, the gene associated with melanin production is one or more genes selected from the group consisting of nitric oxide synthase 2 (NOS2), nitric oxide synthase 3 (NOS3), prostaglandin synthase 1 (PTGS1), and endothelin 2 (EDN2). The skin improving agent is preferably an expression inhibitor of one or more genes selected from the group consisting of NOS2, NOS3, PTGS1, and EDN2.

[0017] Specifically, the gene associated with the melanocyte stimulating factor is one or more genes selected from the group consisting of NOS2, NOS3, PTGS1, and EDN2.

[0018] By suppressing the expression of genes related to melanin production or melanocyte stimulating factors, melanin production in the skin can be suppressed. In this regard, the skin improving agent in this embodiment is preferably a melanin production inhibitor. Furthermore, the skin improving agent in this embodiment may be a melanocyte stimulating factor inhibitor.

[0019] By inhibiting melanin production, for example, it is possible to inhibit melanin retention, thereby providing a whitening effect. The skin improving agent is preferably a whitening agent. Specific examples of the whitening agent include one or more agents selected from the group consisting of age spots, freckles, and post-inflammatory pigmentation reducers.

[0020] (Dosage Form, etc.) The skin improving agent is preferably a pharmaceutical composition. The skin improving agent is also preferably an oral composition. This allows for excellent ease of ingestion.

[0021] The skin improving agent is preferably a solid such as a solid preparation. This can improve the storage stability of the skin improving agent. Furthermore, it can be made easy to take. The dosage form of the solid preparation is, for example, a tablet, granules, pills, powder, gummies, or jellies, and is preferably a tablet. Examples of tablets include plain tablets, plain tablets, sugar-coated tablets, orally disintegrating tablets, film-coated tablets, and chewable tablets. The tablet may be a multilayer tablet formed by compressing two or more layers of powders or granules with different compositions. The film can be given properties such as fast-dissolving, slow-dissolving, gastric-soluble, and enteric-soluble properties depending on the desired composition.

[0022] It is also preferable that the skin improving agent is an external preparation. This allows the skin improving agent to be selectively applied to a desired area. The skin improving agent may be a quasi-drug (such as a medicated cosmetic) or a pharmaceutical, and is preferably a cosmetic, an external skin preparation, or a quasi-drug (such as a medicated cosmetic). In this case, the skin improving agent is applied to the skin, preferably spread on the skin.

[0023] The dosage form of the external preparation may be, for example, a liquid preparation for external use including a liniment or a lotion; a cream; a spray preparation including an aerosol or a pump spray; or a gel. Here, the liniment is specifically a liquid or muddy external preparation that is rubbed into the skin. Furthermore, the lotion is specifically an external preparation in which an active ingredient is dissolved, emulsified, or finely dispersed in an aqueous liquid. Next, the ingredients contained in the skin improving agent will be described.

[0024] (Component (A)) Component (A) is at least one selected from the group consisting of L-cysteine, its derivatives, and salts thereof. Component (A) may also be a hydrate. Component (A) is a known compound and may be obtained either as a commercially available product or by a known method. Specific examples of component (A) include L-cysteine; L-cysteine ​​derivatives such as N-acetyl-L-cysteine, L-homocysteine, L-cysteic acid, L-homocysteic acid, L-cysteinesulfinic acid, S-sulfino-L-cysteine, S-sulfo-L-cysteine, and cystine (a cysteine ​​dimer); and salts of cysteine ​​and its derivatives such as mineral acid salts (e.g., hydrochloride, nitrate, sulfate), alkali metal salts (e.g., sodium salt, potassium salt, calcium salt, magnesium salt), and alkaline earth metal salts. Component (A) is preferably one or more compounds selected from the group consisting of L-cysteine ​​and L-cysteine ​​salts (including hydrates) such as L-cysteine ​​hydrochloride hydrate, and more preferably L-cysteine. This allows the skin improving effect to be obtained more stably. L-cysteine ​​is listed in the 18th Edition of the Japanese Pharmacopoeia. Component (A) is also preferably a solid such as a powder. This allows the production stability of the skin improving agent to be improved.

[0025] The content of component (A) in the skin improving agent is preferably 0.1 mg or more, more preferably 1 mg or more, and even more preferably 10 mg or more, in terms of the content in a single dose of the skin improving agent. This makes it possible to further enhance the skin improving effect. Furthermore, the content of component (A), preferably L-cysteine ​​and a salt thereof, in the skin improving agent is preferably 250 mg or less, more preferably 125 mg or less, and even more preferably 100 mg or less, in terms of the content in a single dose of the skin improving agent. This makes it possible to more efficiently enhance the skin improving effect.

[0026] The content of component (A) in the skin improving agent is preferably 0.1 mg or more, more preferably 1 mg or more, and even more preferably 10 mg or more, per daily application amount. This can further enhance the skin improving effect. Furthermore, the content of component (A) in the skin improving agent is preferably 500 mg or less, more preferably 300 mg or less, and even more preferably 250 mg or less, per daily application amount. This can more efficiently enhance the skin improving effect.

[0027] Here, the amount of the skin improving agent to be applied can be determined, for example, depending on the form of the skin improving agent. The number of times the skin improving agent is applied per day may be, for example, 1 to 10 times, preferably 1 to 5 times, and more preferably 1 to 3 times.

[0028] (Component (B)) Component (B) is at least one selected from the group consisting of ascorbic acid, its derivatives, and salts thereof. Component (B) may also be a hydrate. Component (B) is a known compound, and may be obtained either as a commercially available product or by a known method. Specific examples of component (B) include ascorbic acid; ascorbate salts such as sodium ascorbate, magnesium ascorbate, potassium ascorbate, and calcium ascorbate; monoalkyl or monoalkenyl ascorbate esters such as ascorbate monostearate, ascorbate monopalmitate, and ascorbate monooleate; dialkyl or dialkenyl ascorbate esters such as ascorbate distearate, ascorbate dipalmitate, and ascorbate dioleate; ascorbate tristearate, ascorbate tripartite, and ascorbate dioleate; Examples of suitable ascorbic acid esters include trialkyl or trialkenyl ascorbate esters such as ascorbyl sulfate, sodium ascorbyl sulfate, potassium ascorbyl sulfate, magnesium ascorbyl sulfate, and calcium ascorbyl sulfate; ascorbic acid phosphate esters such as ascorbyl phosphate, sodium ascorbyl phosphate, potassium ascorbyl phosphate, magnesium ascorbyl phosphate, and calcium ascorbyl phosphate; and ascorbic acid glycosides such as ascorbic acid glycoside. Component (B) is preferably one or more compounds selected from the group consisting of ascorbic acid and ascorbic acid salts such as calcium ascorbate and sodium ascorbate, and more preferably ascorbic acid. This allows for more stable skin-improving effects. Ascorbic acid is listed in the 18th Edition of the Japanese Pharmacopoeia. Component (B) is also preferably a solid, such as a powder. This allows for improved manufacturing stability of the skin-improving agent.

[0029] The content of component (B) in the skin improving agent is preferably 0.01 mg or more, more preferably 100 mg or more, and even more preferably 200 mg or more, as the content in a single dose of the skin improving agent. This can further enhance the skin improving effect. In addition, in order to obtain a more significant skin improving effect, it is also preferable that the content of component (B) in a single dose of the skin improving agent is 500 mg or more. In addition, the content of component (B) in the skin improving agent is preferably 6000 mg or less, more preferably 4000 mg or less, and even more preferably 2000 mg or less, as the content in a single dose of the skin improving agent. This can more efficiently enhance the skin improving effect.

[0030] The content of component (B) in the skin improving agent is preferably 0.01 mg or more, more preferably 200 mg or more, and even more preferably 250 mg or more, as the content per daily application amount. This can further enhance the skin improving effect. In addition, in order to obtain a more significant skin improving effect, the content of component (B) in a daily amount of the skin improving agent is also preferably 800 mg or more, and more preferably 1000 mg or more. In addition, the content of component (B) in the skin improving agent may be, for example, 4000 mg or less, and preferably 3500 mg or less, as the content per daily application amount. In addition, in order to obtain a more efficient skin improving effect, the content of component (B) per daily application amount is preferably 3000 mg or less, more preferably 2500 mg or less, and even more preferably 2000 mg or less.

[0031] (Component (C)) Component (C) is one or more selected from the group consisting of vitamin B5, vitamin B6, vitamin B2, vitamin E, gamma oryzanol, and Angelica acutiloba and extracts thereof. Component (C) is preferably a solid such as a powder. This can improve the production stability of the skin improving agent.

[0032] (Vitamin B5) Specific examples of vitamin B5 include pantothenic acid, calcium pantothenate, sodium pantothenate, panthenol, etc. Vitamin B5 may contain one or more compounds selected from this group, and is preferably calcium pantothenate, sodium pantothenate, or panthenol, and more preferably calcium pantothenate. This allows for a more stable skin-improving effect. Calcium pantothenate is listed in the 18th revised Japanese Pharmacopoeia. For example, commercially available products can be used as vitamin B5, including calcium pantothenate.

[0033] The content of vitamin B5 in the skin improving agent is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 5 mg or more, as the content in a single dose of the skin improving agent. This can further enhance the skin improving effect. Furthermore, the content of vitamin B5 in the skin improving agent is preferably 30 mg or less, more preferably 15 mg or less, and even more preferably 12.5 mg or less, as the content in a single dose of the skin improving agent. This can more efficiently enhance the skin improving effect.

[0034] The content of vitamin B5 in the skin improving agent is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 5 mg or more, per daily application amount. This can further enhance the skin improving effect. Furthermore, the content of vitamin B5 in the skin improving agent is preferably 60 mg or less, more preferably 30 mg or less, and even more preferably 25 mg or less, per daily application amount. This can more efficiently enhance the skin improving effect.

[0035] When the skin improving agent contains a combination of L-cysteine, ascorbic acid, and calcium pantothenate, the mass ratio of the amounts of these compounds can be, for example, L-cysteine:ascorbic acid:calcium pantothenate=1-500:1-200:1-300.

[0036] Ratios indicated above and below using ":" are mass ratios of the components in the skin improving agent. In this mass ratio, each component can have a value within a numerical range. For example, if "x:y=1-10:1-15", then x can be 1 or more and 10 or less, and y can be 1 or more and 15 or less, and x:y is 10:1 to 1:15.

[0037] When the skin improving agent contains a combination of components (A), (B), and vitamin B5, the mass ratio of the amount of these components blended, i.e., the mass ratio of the content of vitamin B5 to the total content of components (A) and (B) (vitamins B5 / ((A)+(B))), is preferably 0.002 or more, more preferably 0.005 or more, even more preferably 0.01 or more, and still more preferably 0.015 or more. This can further enhance the skin improving effect. Alternatively, the mass ratio may be, for example, 0.5 or more. Alternatively, the mass ratio (vitamins B5 / ((A)+(B))) is preferably 2 or less, more preferably 1.5 or less, even more preferably 1 or less, and still more preferably 0.75 or less. This can more efficiently enhance the skin improving effect. Alternatively, the mass ratio may be, for example, 0.02 or less.

[0038] (Vitamin B6) Specific examples of vitamin B6 include pyridoxine and its salts (such as hydrochloride), pyridoxal, pyridoxal phosphate ester hydrate, and pyridoxamine. Vitamin B6 may contain one or more compounds selected from this group, and preferably contains pyridoxine and its salts, more preferably pyridoxine salts, and even more preferably pyridoxine hydrochloride. This allows for a more stable skin improvement effect.

[0039] Pyridoxine hydrochloride is listed in the 18th edition of the Japanese Pharmacopoeia. As the vitamin B6 compound including pyridoxine hydrochloride, for example, commercially available products can be used.

[0040] The content of vitamin B6 in the skin improving agent is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 2.5 mg or more, as the content in a single dose of the skin improving agent. This can further enhance the skin improving effect. Furthermore, the content of vitamin B6 in the skin improving agent is preferably 50 mg or less, more preferably 25 mg or less, and even more preferably 10 mg or less, as the content in a single dose of the skin improving agent. This can more efficiently enhance the skin improving effect.

[0041] The content of vitamin B6 in the skin improving agent is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 2.5 mg or more, per daily application amount. This can further enhance the skin improving effect. Furthermore, the content of vitamin B6 in the skin improving agent is preferably 100 mg or less, more preferably 50 mg or less, and even more preferably 25 mg or less, per daily application amount. This can more efficiently enhance the skin improving effect.

[0042] When the skin improving agent contains a combination of L-cysteine, ascorbic acid, and pyridoxine hydrochloride, the mass ratio of the amounts of these compounds can be, for example, L-cysteine:ascorbic acid:pyridoxine hydrochloride=1-500:1-200:1-300.

[0043] When the skin improving agent contains a combination of components (A), (B), and vitamin B6, the mass ratio of the amount of these components blended, i.e., the mass ratio of the content of vitamin B6 to the total content of components (A) and (B) (vitamin B6 / ((A)+(B))), is preferably 0.001 or more, more preferably 0.005 or more, even more preferably 0.01 or more, and still more preferably 0.015 or more. This can further enhance the skin improving effect. Furthermore, the mass ratio (vitamin B6 / ((A)+(B))) is preferably 1.2 or less, more preferably 0.9 or less, even more preferably 0.6 or less, and even more preferably 0.3 or less. This can more efficiently enhance the skin improving effect.

[0044] (Vitamin B2) Specific examples of vitamin B2 include riboflavin and its salts (e.g., hydrochloride), riboflavin butyrate, riboflavin sodium phosphate, and flavin adenine dinucleotide sodium. Vitamin B2 may contain one or more compounds selected from this group, and is preferably at least one selected from the group consisting of riboflavin, riboflavin hydrochloride, and riboflavin butyrate. This allows for a more stable skin-improving effect. Riboflavin is listed in the 18th revised Japanese Pharmacopoeia. For example, commercially available products can be used as vitamin B2, including riboflavin.

[0045] The content of vitamin B2 in the skin improving agent is preferably 0.001 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more, as the content in a single dose of the skin improving agent. This can further enhance the skin improving effect. Furthermore, the content of vitamin B2 in the skin improving agent is preferably 60 mg or less, more preferably 30 mg or less, and even more preferably 15 mg or less, as the content in a single dose of the skin improving agent. This can more efficiently enhance the skin improving effect.

[0046] The content of vitamin B2 in the skin improving agent is preferably 0.001 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more, per daily application amount. This can further enhance the skin improving effect. Furthermore, the content of vitamin B2 in the skin improving agent is preferably 60 mg or less, more preferably 30 mg or less, and even more preferably 15 mg or less, per daily application amount. This can more efficiently enhance the skin improving effect.

[0047] When the skin improving agent contains a combination of L-cysteine, ascorbic acid, and riboflavin, riboflavin butyrate, or riboflavin hydrochloride, the mass ratio of the amounts of these blended can be, for example, L-cysteine:ascorbic acid:riboflavin, riboflavin hydrochloride, or riboflavin butyrate=1-500:1-200:1-300.

[0048] When the skin improving agent contains a combination of components (A), (B), and vitamin B2, the mass ratio of the amount of these components blended, i.e., the mass ratio of the content of vitamin B2 to the total content of components (A) and (B) (vitamin B2 / ((A)+(B))), is preferably 0.001 or more, more preferably 0.0025 or more, even more preferably 0.005 or more, and still more preferably 0.0075 or more. This can further enhance the skin improving effect. The mass ratio may be, for example, 0.1 or more. The mass ratio (vitamin B2 / ((A)+(B))) is preferably 1 or less, more preferably 0.6 or less, even more preferably 0.3 or less, and still more preferably 0.15 or less. This can more efficiently enhance the skin improving effect. The mass ratio may be, for example, 0.01 or less.

[0049] (Vitamin E's) Specific examples of vitamin E's include tocopherols such as α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol, as well as esters and salts thereof. Examples of tocopherol esters include succinate esters, acetate esters, nicotinate esters, and phosphate esters. Examples of salts of tocopherol and tocopherol esters include calcium salts. Vitamin E may be an optical isomer such as a dl-isomer. The vitamin E is preferably one or more compounds selected from the group consisting of those listed in the 18th edition of the Japanese Pharmacopoeia, such as tocopherol, tocopherol succinate calcium, tocopherol acetate, and tocopherol nicotinate; and those listed in the Japanese Pharmacopoeia Non-Drug Standards 2002, such as d-α-tocopherol, d-α-tocopherol acetate, DL-α-tocopherol acetate, and d-α-tocopherol succinate; and synthetic vitamin E compounds such as dl-α-tocopherol succinate, more preferably at least one compound selected from the group consisting of DL-α-tocopherol acetate and d-α-tocopherol succinate. This allows for a more stable skin-improving effect. As the vitamin E, for example, commercially available products can be used.

[0050] The content of vitamin E in the skin improving agent is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more, as the content in a single dose of the skin improving agent. This makes it possible to further enhance the skin improving effect. Furthermore, the content of vitamin E in the skin improving agent is preferably 100 mg or less, more preferably 75 mg or less, and even more preferably 50 mg or less, as the content in a single dose of the skin improving agent. This makes it possible to more efficiently enhance the skin improving effect.

[0051] The content of vitamin E in the skin improving agent is preferably 0.001 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more, per daily application amount. This can further enhance the skin improving effect. Furthermore, the content of vitamin E in the skin improving agent is preferably 200 mg or less, more preferably 150 mg or less, and even more preferably 100 mg or less, per daily application amount. This can more efficiently enhance the skin improving effect.

[0052] When the skin improving agent contains a combination of L-cysteine, ascorbic acid, and DL-α-tocopherol acetate or d-α-tocopherol succinate, the mass ratio of the amounts of these blended can be, for example, L-cysteine:ascorbic acid:DL-α-tocopherol acetate or d-α-tocopherol succinate=1-500:1-200:1-300.

[0053] When the skin improving agent contains a combination of components (A), (B), and vitamin E, the mass ratio of the amount of these blended, i.e., the mass ratio of the content of vitamin E to the total content of components (A) and (B) (vitamin E / ((A)+(B))), is preferably 0.005 or more, more preferably 0.01 or more, even more preferably 0.02 or more, and still more preferably 0.04 or more. This can further enhance the skin improving effect. Alternatively, the mass ratio may be, for example, 1 or more. Alternatively, the mass ratio (vitamin E / ((A)+(B))) is preferably 2.5 or less, more preferably 2 or less, even more preferably 1.5 or less, and still more preferably 1.2 or less. This can more efficiently enhance the skin improving effect. Alternatively, the mass ratio may be, for example, 0.05 or less.

[0054] (Gamma Oryzanol) As gamma oryzanol, for example, commercially available products can be used.

[0055] The content of gamma oryzanol in the skin improving agent, as measured in a single dose of the skin improving agent, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more. This allows for a further enhancement of the skin improving effect. Furthermore, the content of gamma oryzanol in the skin improving agent, as measured in a single dose of the skin improving agent, is preferably 20 mg or less, more preferably 15 mg or less, and even more preferably 10 mg or less. This allows for a more efficient enhancement of the skin improving effect.

[0056] The content of gamma oryzanol in the skin improving agent, as a content per daily application amount, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 5 mg or more. This allows for a further enhancement of the skin improving effect. Furthermore, the content of gamma oryzanol in the skin improving agent, as a content per daily application amount, is preferably 20 mg or less, more preferably 15 mg or less, and even more preferably 10 mg or less. This allows for a more efficient enhancement of the skin improving effect.

[0057] When the skin improving agent contains a combination of L-cysteine, ascorbic acid, and gamma oryzanol, the mass ratio of the amounts of these blended can be, for example, L-cysteine:ascorbic acid:gamma oryzanol=1-500:1-200:1-300.

[0058] When the skin improving agent contains a combination of components (A), (B), and gamma oryzanol, the mass ratio of the amount of these components blended, i.e., the mass ratio of the content of gamma oryzanol to the total content of components (A) and (B) (gamma oryzanol / ((A)+(B))), is preferably 0.001 or more, more preferably 0.0025 or more, even more preferably 0.005 or more, and even more preferably 0.0075 or more. This can further enhance the skin improving effect. Alternatively, the mass ratio may be, for example, 0.2 or more. Alternatively, the mass ratio (gamma oryzanol / ((A)+(B))) is preferably 0.5 or less, more preferably 0.45 or less, even more preferably 0.3 or less, and even more preferably 0.25 or less. This can more efficiently enhance the skin improving effect. Alternatively, the mass ratio may be, for example, 0.01 or less.

[0059] (Angelica acutiloba and its extract) The Angelica acutiloba and its extract specifically include at least one extract of Angelica acutiloba Kitagawa (Angelica acutiloba Kitagawa) and its extract (Angelica acutiloba extract), etc. There are no limitations on the part of the Angelica acutiloba that is the raw material for the extract, and it can be, for example, one or more parts selected from the group consisting of leaves, branches, stems, flowers, fruits and roots, with the roots being preferred.

[0060] The extraction method for obtaining an extract from Angelica sinensis can be, for example, a method in which the raw material is extracted in a solvent. The extraction solvent can include, for example, one or more solvents selected from the group consisting of water; monohydric alcohols having from 1 to 3 carbon atoms, such as methyl alcohol and ethyl alcohol; liquid polyhydric alcohols, such as propylene glycol and 1,3-butylene glycol; lower alkyl esters, such as ethyl acetate; hydrocarbons, such as benzene and hexane; and ethers, such as ethyl ether. Preferably, the extraction solvent includes one or more solvents selected from the group consisting of water and monohydric alcohols having from 1 to 3 carbon atoms. The extraction temperature can be room temperature (25°C). Alternatively, the extraction can be performed by heating below the boiling point of the solvent. After extraction, the extract can be subjected to at least one of filtration and purification, including deodorization and decolorization. The extract can also be diluted or concentrated as appropriate, or dried. Commercially available products, such as Angelica sinensis extract, can also be used as the extract.

[0061] The Angelica acutiloba and its extract are preferably in the form of a solid such as a powder, which can improve the production stability of the skin improving agent. Furthermore, in order to stably obtain the skin improving effect, it is preferable that the Angelica acutiloba and its extract are not enzyme-treated.

[0062] The content of Dong Quai and its extract in a single dose of the skin improving agent is preferably 0.05 mg or more, more preferably 10 mg or more, and even more preferably 100 mg or more, in terms of the amount of the original herbal drug. This allows for a further enhancement of the skin improving effect. Furthermore, the content of Dong Quai and its extract in a single dose of the skin improving agent is preferably 500 mg or less, more preferably 400 mg or less, and even more preferably 300 mg or less, in terms of the amount of the original herbal drug. This allows for a more efficient enhancement of the skin improving effect.

[0063] The amount of Dong Quai and its extract per daily application is preferably 0.1 mg or more, more preferably 20 mg or more, and even more preferably 200 mg or more, in terms of the amount of the crude drug, thereby enabling a more enhanced skin-improving effect. Furthermore, the amount of Dong Quai and its extract per daily application is preferably 1000 mg or less, more preferably 800 mg or less, and even more preferably 600 mg or less, in terms of the amount of the crude drug, thereby enabling a more efficient enhancement of the skin-improving effect.

[0064] When the skin improving agent contains a combination of L-cysteine, ascorbic acid, and Angelica acutiloba, the mass ratio of the amounts of these compounds can be, for example, L-cysteine:ascorbic acid:Angelica acutiloba (equivalent to crude drug) = 1-500:1-200:1-400.

[0065] When the skin improving agent contains a combination of components (A), (B), and Angelica acutiloba and an extract thereof, the mass ratio of the amounts of these components blended, i.e., the mass ratio of the content of Angelica acutiloba and an extract thereof to the total content of components (A) and (B) (Angelica acutiloba (equivalent to the crude drug) / ((A)+(B))), is preferably 0.025 or more, more preferably 0.05 or more, even more preferably 0.1 or more, and even more preferably 0.25 or more. This allows for a more enhanced skin improving effect. Alternatively, the mass ratio may be, for example, 1.5 or more. Alternatively, the mass ratio (Angelica acutiloba (equivalent to the crude drug) / ((A)+(B))) is preferably 5 or less, more preferably 3 or less, even more preferably 2.5 or less, and even more preferably 2 or less. This allows for a more efficient enhancement of the skin improving effect. Alternatively, the mass ratio may be, for example, 0.5 or less.

[0066] Component (C) may contain two or more components in combination, for example, vitamin B2, vitamin B6, vitamin E, and vitamin B5. Component (C) may also contain at least one component selected from the group consisting of gamma oryzanol, and Angelica acutiloba and extracts thereof, in addition to vitamin B2, vitamin B6, vitamin E, and vitamin B5.

[0067] The total content of component (C) in the skin improving agent, as the content in a single dose of the skin improving agent, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more. This makes it possible to further enhance the skin improving effect. Furthermore, the total content of component (C) in the skin improving agent, as the content in a single dose of the skin improving agent, is preferably 1500 mg or less, more preferably 1000 mg or less, and even more preferably 500 mg or less. This makes it possible to more efficiently enhance the skin improving effect.

[0068] The total content of component (C) in the skin improving agent is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more, per daily application amount. This allows the skin improving effect to be further enhanced. Furthermore, the total content of component (C) in the skin improving agent is preferably 1500 mg or less, more preferably 1000 mg or less, and even more preferably 750 mg or less, per daily application amount. This allows the skin improving effect to be more efficiently enhanced.

[0069] The mass ratio ((C) / ((A)+(B))) of the total content of component (C) to the sum of the contents of components (A) and (B) in the skin improving agent is preferably 0.005 or more, more preferably 0.01 or more, even more preferably 0.025 or more, still more preferably 0.05 or more, and is, for example, 2 or less, preferably 1.5 or less, more preferably 0.5 or less, even more preferably 0.25 or less, and still more preferably 0.15 or less. This makes it possible to obtain a more stable skin improving effect.

[0070] (Other Components) The skin improving agent may contain components other than the above-mentioned components. The other components can be selected, for example, from components used in foods or pharmaceuticals. Furthermore, the other components can be selected, for example, depending on the dosage form of the skin improving agent.

[0071] Examples of other ingredients include one or more selected from the group consisting of excipients, binders, disintegrants, disintegration aids, lubricants, stabilizers, surfactants, antioxidants, buffers, pH adjusters, dispersants, solubilizers, fluidizing agents, glossing agents, flavoring agents, sweeteners, refreshing agents, coloring agents, odorants, fragrances, adsorbents, sugar-coating agents, coating agents, suspending agents, antistatic agents, plasticizers, and fragrances.

[0072] Examples of excipients include celluloses such as crystalline cellulose, lactose (lactose hydrate, anhydrous lactose, etc.), refined white sugar, glucose, powdered sugar, fructose, maltose, reduced maltose syrup, powdered cellulose, starch (corn starch, potato starch, etc.), sugar alcohols (mannitol, xylitol, sorbitol, erythritol, etc.), trehalose, inorganic salts, dextran, dextrin, β-cyclodextrin, sucrose fatty acid esters, soybean lecithin, powdered tragacanth, gum arabic, pullulan, kaolin, anhydrous calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate granules, magnesium aluminometasilicate, methylcellulose ... The excipients are one or more selected from the group consisting of cellulose, calcium hydrogen phosphate hydrate, calcium hydrogen phosphate granules, sodium hydrogen phosphate hydrate, potassium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, sodium dihydrogen phosphate, magnesium aluminosilicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, low-substituted hydroxypropyl cellulose, sodium starch glycolate, powdered reduced maltose syrup, carmellose, carmellose calcium, and carmellose sodium, and preferably one or more selected from the group consisting of mannitol, crystalline cellulose, and corn starch. This allows the skin improving agent to maintain a color closer to white when in a solid formulation. The content of the excipient in the skin improving agent is, for example, 0.1% by mass or more, preferably 0.5% by mass or more, more preferably 1% by mass or more, and for example, 70% by mass or less, preferably 50% by mass or less, more preferably 40% by mass or less, based on the total mass of the skin improving agent. This allows for improved moldability.

[0073] Examples of binders include gum arabic, gelatin, pregelatinized starch, alginic acid, sodium alginate, carboxyvinyl polymer, agar, pullulan, dextrin, shellac, sucrose, tragacanth, tragacanth powder, xanthan gum, pectin, sodium polyacrylate, guar gum, corn starch, hydroxyethyl cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, copolyvidone, hypromellose (hypromellose (2208), hypromellose The hydroxybenzoates are one or more selected from the group consisting of hypromellose (2906), hypromellose (2910), etc.), hypromellose acetate succinate, hypromellose phthalate (200731), hypromellose phthalate (220824), povidone (K25), povidone (K30), povidone (K90), polyvinyl alcohol (polyvinyl alcohol (completely saponified), polyvinyl alcohol (partially saponified), etc.), methylcellulose, and magnesium aluminometasilicate.

[0074] The disintegrant is, for example, one or more selected from the group consisting of corn starch, potato starch, partially pregelatinized starch, hydroxypropyl starch, sodium starch glycolate, sodium carboxymethyl starch, low-substituted sodium carboxymethyl starch, carmellose calcium, low-substituted hydroxypropyl cellulose, croscarmellose sodium, crystalline cellulose, powdered cellulose, crospovidone, carmellose sodium, powdered agar, sodium bicarbonate, and carmellose.

[0075] The lubricant is, for example, one or more selected from the group consisting of magnesium stearate, calcium stearate, stearic acid, talc, sucrose fatty acid ester, sodium stearyl fumarate, carnauba wax, glycerin fatty acid ester, calcium stearate, light anhydrous silicic acid, and magnesium aluminometasilicate.

[0076] The flavoring agent is, for example, one or more selected from the group consisting of organic acids such as citric acid, tartaric acid, malic acid, etc.; amino acid salts such as sodium glutamate, sodium aspartate, etc.; ribonucleic acid salts such as sodium 5'-inosinate, sodium 5-guanylate, etc.; and caramel.

[0077] The sweetener may be one or more selected from the group consisting of high-intensity sweeteners such as saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia, Monk fruit, thaumatin, acesulfame potassium, sucralose, sucrose, fructose, glucose, lactose hydrate, anhydrous lactose, maltose, sorbitol, maltitol, mannitol, xylitol, erythritol, glycerol, inositol, reduced maltose syrup, palatinose, coupling sugar, and honey.

[0078] Examples of sugar-coating agents include monosaccharides and disaccharides such as sucrose (white sugar, refined white sugar), fructose, glucose, lactose hydrate, anhydrous lactose, and trehalose, and sugar alcohols such as erythritol, mannitol, sorbitol, xylitol, maltitol, powdered reduced maltose syrup, and reduced lactose. Examples of sugar-coating liquids include gum arabic, powdered gum arabic, ethyl cellulose, carnauba wax, carmellose sodium, stearic acid, polyoxyl 40 stearate, purified gelatin, purified shellac, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, hydroxypropyl cellulose, hypromellose (2208), hypromellose (2906), hypromellose (2910), pullulan, povidone (K25), povidone (K30), povidone (K90), and polyoxyethylene (105) One or more selected from the group consisting of polyoxypropylene (5) glycol, polyvinyl alcohol (partially saponified), macrogol (Macrogol 1500, Macrogol 4000, Macrogol 6000, etc.), mannitol, calcium monohydrogen phosphate, calcium hydrogen phosphate, calcium dihydrogen phosphate, calcium sulfate, calcium lactate, kaolin, titanium oxide, ferric oxide, yellow ferric oxide, black copper iron oxide, sodium chlorophyllin, and copper chlorophyll.

[0079] Examples of coating agents include ethyl acrylate-methyl methacrylate copolymer dispersion, acetylglycerin fatty acid ester, aminoalkyl methacrylate copolymer E, gum arabic, gum arabic powder, ammonioalkyl methacrylate copolymer, ethyl cellulose, ethyl cellulose aqueous dispersion, octyldecyl triglyceride, carnauba wax, carmellose calcium, carmellose sodium, hydrated silicon dioxide, dried aluminum hydroxide gel, dried methacrylic acid copolymer LD, triethyl citrate, glycerin, glycerin fatty acid ester Stearic acid, magnesium silicate, light anhydrous silicic acid, light anhydrous silicic acid-containing hydroxypropyl cellulose, synthetic aluminum silicate, synthetic hydrotalcite, titanium oxide, magnesium oxide, dimethylaminoethyl methacrylate-methyl methacrylate copolymer, sucrose fatty acid ester, aluminum hydroxide gel, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyoxyl 40 stearate, magnesium stearate, purified gelatin, purified shellac, refined sucrose, gelatin, shellac, D-sorbitol cellulose, D-sorbitol solution, talc, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, concentrated glycerin, white shellac, sucrose, paraffin, hydroxypropyl cellulose, hydroxypropyl methylcellulose 2910 / titanium oxide / macrogol mixture, hypromellose (2208), hypromellose (2906), hypromellose (2910), hypromellose acetate succinate, hypromellose phthalate (200731), hypromellose phthalate (220824) , Fumaric acid, stearic acid, polyvinyl acetal diethylaminoacetate, hydroxypropyl methylcellulose 2910 mixture, pullulan, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, polysorbate 80, polyvinyl acetal diethylaminoacetate, polyvinyl alcohol (completely saponified), polyvinyl alcohol (partially saponified), macrogol 300,One or more selected from the group consisting of Macrogol 400, Macrogol 600, Macrogol 1500, Macrogol 1540, Macrogol 4000, Macrogol 6000, Macrogol 6000EP, Macrogol 20000, Macrogol 35000, mannitol, anhydrous citric acid, anhydrous silicic acid hydrate, phthalic anhydride, anhydrous calcium hydrogen phosphate, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, magnesium aluminometasilicate, methyl methacrylate-methacrylic acid-methyl methacrylate copolymer, aluminum monostearate, glycerin monostearate, sorbitan monostearate, sorbitan monolaurate, calcium sulfate, fumaric acid, and DL-malic acid.

[0080] The skin improving agent may further contain a known component exhibiting a whitening effect or a component enhancing the whitening effect other than components (A) to (C). These components include, for example, catechins; hydroquinone and its derivatives (hydroquinone glycosides such as hydroquinone and hydroquinone-β-D-glucose (arbutin)); glucosamine and its derivatives (glucosamine; glucosamine esters such as acetylglucosamine; glucosamine ethers such as glucosamine methyl ether); hinokitiol and its derivatives (hinokitiol; hinokitiol glycosides such as hinokitiol glucoside); azelaic acid, its derivatives, and salts thereof (azelaic acid; azelaic acid monoesters such as azelaic acid monoalkyl esters; azelaic acid diesters such as azelaic acid dialkyl esters); vitamin B3s such as nicotinic acid and nicotinamide; Ubiquinones (coenzyme Q6 (CoQ6), coenzyme Q7 (CoQ7), coenzyme Q8 (CoQ8), coenzyme Q9 (CoQ9), coenzyme Q10 (CoQ10), etc.); carotenoids (carotene, lutein, violaxanthin, spirilloxanthin, spheroidene, etc.); flavones (flavone, apigenin, luteolin, and their glycosides, etc.), isoflavones and their derivatives (isoflavones; isoflavone glycosides, etc.); flavanones and their derivatives (naringenin, eriodictyol, naringin, etc.), flavonols (kaempferol, quercetin, myricetin, and their glycosides, etc.); Glycyrrhizic acid, its derivatives and salts thereof (glycyrrhizic acid; glycyrrhizinate salts such as dipotassium glycyrrhizinate and monoammonium glycyrrhizinate; glycyrrhizic acid alkyl esters such as stearyl glycyrrhizinate; kojic acid, its derivatives and salts thereof (kojic acid; kojic acid monoalkyl esters such as kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, kojic acid monostearate; kojic acid dialkyl esters such as kojic acid dibutyrate, kojic acid dipalmitate, kojic acid distearate, kojic acid dioleate); ellagic acid, its derivatives and salts thereof (ellagic acid; ellagic acid ethers such as ellagic acid tetramethyl ether;ellagic acid acyl derivatives such as ellagic acid tetraacetate and ellagic acid tetrabenzoate, etc.); glutathione, its derivatives and salts thereof (glutathione; S-acylglutathiones such as S-lactoylglutathione; N,S-diacylglutathione diesters such as N,S-dioctanoylglutathione distearyl and N,S-dipalmitoylglutathione dicetyl, etc.); resorcinol and its derivatives (resorcinol; alkylated resorcinols such as 4-n-butylresorcinol, 4-isoamylresorcinol, 4-cyclohexylresorcinol, 5-methylresorcinol, etc.; halogenated resorcinols such as 4-chlororesorcinol and 4-bromoresorcinol, etc.); glycogen;Coix seed, Hamamelis, Saxifraga, Jumbo, Tea, Japanese knotweed, Melissa, Thyme, Artemisia capillaris, Yarrow, St. John's wort, St. John's wort, Peony, Tree peony, Spanish licorice, Daylily, Mulberry, Morus alba, Japanese mulberry, Sophora flava, Uva-ursi, Scutellaria baicalensis, Hariamiji, Hijiki, Artemisia japonica, Rock hyacinth, Dulse, Sargassum serrata (Sargassum serrata), Sargassum nigra, Sargassum fusiformis, Iwahige, Shimozuku, sundew, sundew, lavender, coptis, Job's tears, rock pear, American rock pear, passion flower, kudzu clock, water lemon, passion flower, moon-leaf lotus, snake wisteria, cup-leaf lotus, wild pansy, sweet violet, violet, Japanese violet, Japanese violet, Japanese violet, Japanese violet, white violet, Siberian violet, Nepalese violet, white-flowered violet, Japanese violet Viola japonica, Viola rubra, Viola trifoliata, Ground fruits, Viola chinensis, Viola globosa, Ireizan, Tessen, Cinnamon, Clematis, Eucommia ulmoides, Eucommia japonica, Tree blossom, Asparagus, Ibuki tora no oak, Pea, Star anise, Scutellaria baicalensis, Ononisu, Rubus, Sophora root, Cinnamon, Gokahi, Chinese yew, Hawthorn, Sun pens, White lily, Japanese yew, Soybean, Tea, Molasses, White angelica, Blueberry One or more selected from the group consisting of Chinese laurel, grape seed, flordemanita, hops, octopus, mocca, monk fruit, aloe, althaea, arnica, angelica tree, inchinko, nettle, turmeric, phellodendron bark, chamomile, goldenshrimp, watercress, comfrey, salvia, lithospermum root, perilla, white birch, calendula, elderberry, balsam, soapberry, astragalus, mugwort, eucalyptus, wild rose, ginkgo, aloe vera, Micromelum minutum, Micromelum pubescens, basil, vaquita, sedge, raspberry, kakyo, and extracts thereof; and placenta extract.

[0081] (Manufacturing Method) In the present embodiment, the manufacturing method of the skin improving agent includes, for example, a step of blending components (A) to (C) and, if necessary, other components. The manufacturing method of the skin improving agent can be, for example, manufactured according to the dosage form, and made into a preparation.

[0082] (Packaging) The packaging is a packaging in which a skin improving agent is contained within a packaging container. By forming a packaging, for example, it is possible to improve the convenience of using the skin improving agent. The packaging container can be selected, for example, depending on the dosage form of the skin improving agent. Specific examples of packaging forms include bottle packaging, jar packaging, PTP packaging (Press Through Package), pouch packaging, stick packaging, and SP packaging (Strip Package). The skin improving agent may be temporarily packaged in these packages and then stored airtight. That is, the skin improving agent may be contained in an airtight package. Furthermore, these may be pillow-packaged, or may be stored in a box or the like. Furthermore, for example, in order to suppress moisture absorption, a desiccant or the like may be contained in the packaging container together with the skin improving agent.

[0083] Examples of materials for the packaging container include one or more materials selected from the group consisting of resin materials, metal materials, and inorganic materials such as glass, etc. If necessary, environmentally friendly materials such as recycled plastics, biomass plastics, and biodegradable plastics may be used for part or all of the packaging material, and environmentally friendly containers and packaging may be used.

[0084] Specific examples of film materials that can be used to form the packaging container include resin films such as polypropylene film, polyethylene terephthalate film, and polyethylene film, as well as these resin films to which metal foil such as aluminum foil is attached by vapor deposition, etc. Either a single-layer film or a multi-layer film (for example, a laminate film) may be used.

[0085] The packaging container may be selected depending on the shape of the skin improving agent. For example, when the skin improving agent is a tablet, the packaging container is, for example, a pouch bag, preferably an aluminum pouch bag. The pouch bag may have a zipper function.

[0086] (Skin Improvement Method) In this embodiment, the skin improvement method (excluding medical procedures on humans) includes, for example, applying the skin improving agent of this embodiment to a subject, and more preferably includes administering the skin improving agent of this embodiment to a subject. A specific example of the form of administration is oral administration. In this embodiment, the skin improving agent has the excellent effects described above, and therefore, by administering it to a subject, the skin improvement effect of the subject can be obtained.

[0087] Although the embodiments of the present invention have been described above, these are merely examples of the present invention, and various other configurations can also be adopted.

[0088] The present embodiment will be specifically described below with reference to examples, but the present embodiment is not limited to these examples.

[0089] Test Example 1 In this example, gene expression levels in human epidermal keratinocytes were measured by the following procedure: Human immortalized keratinocyte cell line (HaCat) was cultured in a 6 cm dish at 7.5 × 10 s with Dulbecco's Modified Eagle Medium (Gibco). ５ The cells were seeded at 100 cells / dish. The day after seeding, the medium was removed and replaced with a test solution prepared by diluting each test substance in Dulbecco's Modified Eagle Medium (Gibco), and the cells were cultured for 24 hours. After culturing, the medium was removed and replaced with PBS (Gibco), and the cells were cultured at 7.5 mJ / cm 2 The medium was replaced with each test solution and incubated for 4 hours. RNA was extracted using an RNeasy Mini Kit (QIAGEN), and cDNA was synthesized by reverse transcription using a Verso cDNA Synthesis Kit (Thermo Fisher). The expression levels of various genes (RNA) were then measured by real-time PCR. Measurements were performed three times for each gene in each test example.

[0090] The genes whose expression levels were measured are shown below. The primers used (all manufactured by Thermo Fisher Scientific) are shown in parentheses. Genes related to melanin production and melanocyte stimulation: NOS2 (Hs01075529_m1), NOS3 (Hs01574659_m1), PTGS1 (Hs00377726_m1), EDN2 (Hs00266516_m1).

[0091] The test substances were tested at the following concentrations in the test solution. (A) L-cysteine ​​(manufactured by TCI): 0.2 mg / mL (B) Ascorbic acid (manufactured by TCI): 0.01 mg / mL (C) Angelica acutiloba: dried Angelica acutiloba extract (manufactured by Ogi Pharmaceutical Co., Ltd.), 0.4 mg / mL in terms of the concentration of Angelica acutiloba in terms of the crude drug (C) Riboflavin hydrochloride (manufactured by Sigma): 0.03 mg / mL (C) Pyridoxine hydrochloride (manufactured by Nacalai Tesque): 0.06 mg / mL (C) Calcium pantothenate: D-calcium pantothenate (manufactured by Nacalai Tesque), 0.12 mg / mL (C) DL-α tocopherol acetate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.): 0.25 mg / mL (C) Gamma oryzanol (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.): 0.05 mg / mL Phosphorylated oligosaccharide calcium (manufactured by Glyco Nutrition Foods Co., Ltd.): 1 mg / mL

[0092] The average gene expression levels of NOS3, NOS2, PTGS1, and EDN2 are shown in Table 1 (Control Example 1, Comparative Example 1, Examples 1-1 to 1-4), Table 2 (Control Example 2, Comparative Example 2, Examples 2-1 to 2-4), Table 3 (Control Example 3, Comparative Example 3, Example 3), and Table 4 (Control Example 4, Comparative Example 4, Example 4), respectively. The expression level ratio in the examples listed in each table is the ratio of the expression level of each composition when the expression level of the control example containing components (A) and (B) but not component (C) is set to 1.00. In the tables, "*" indicates a significant difference from the control example in the same table (p<0.05, t-test).

[0093] The criteria for the expression level ratio in each table are as follows: A to C were considered to be acceptable. A: Less than 0.50 B: 0.50 or more and less than 0.65 C: 0.65 or more and 0.80 or less -: More than 0.80

[0094] 1 to 4 are diagrams showing the evaluation results of the control example and the example with respect to the gene expression levels of NOS3, NOS2, PTGS1 and EDN2, respectively.

[0095]

[0096]

[0097]

[0098]

[0099] (Preparation Examples 1 to 13) Tablets were prepared by a conventional method according to the composition shown in Table 5 below (daily dose: 4 tablets).

[0100]

[0101] This application claims priority based on Japanese Patent Application No. 2023-153908, filed September 20, 2023, the disclosure of which is incorporated herein by reference in its entirety.

Claims

1. A skin improving agent containing the following components (A) to (C): (A) at least one selected from the group consisting of L-cysteine, its derivatives and salts thereof, (B) at least one selected from the group consisting of ascorbic acid, its derivatives and salts thereof, and (C) one or more selected from the group consisting of vitamin B5, vitamin B6, vitamin B2, vitamin E, gamma oryzanol, and Angelica sinensis and extracts thereof.

2. The skin improving agent according to claim 1, which is a skin whitening agent.

3. The skin improving agent according to claim 1 or 2, which is an agent for reducing one or more types of pigmentation selected from the group consisting of age spots, freckles and post-inflammatory pigmentation.

4. A skin improving agent according to any one of claims 1 to 3, which is a melanin production inhibitor.

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