Skin improving agent

Abstract

A skin-improving agent containing the following components (A)-(C). (A) at least one substance selected from the group consisting of L-cysteine, derivatives thereof, and salts thereof; (B) at least one substance selected from ascorbic acid, derivatives thereof, and salts thereof; and (C) one or more than two selected from the group consisting of vitamin B5, vitamin B6, vitamin B2, vitamin E, gamma-oryzanol, angelica sinensis and an extract thereof.

Description

Technical Field

[0001] This invention relates to skin improvers. Background Technology

[0002] When skin is damaged by ultraviolet rays or other factors, keratinocytes secrete various cytokines that promote melanin production. These cytokines stimulate melanocytes, promoting melanin production. Subsequently, it is known that the melanin produced by melanocytes is transferred to keratinocytes, and the melanin accumulates in the epidermis, leading to spots, freckles, sunburn, and pigmentation caused by inflammation.

[0003] Patent document 1 (Japanese Patent Publication No. Hei 8-99859) describes a topical skin preparation containing water-soluble rutin and a tyrosinase activity inhibitor as active ingredients (claim 1), and also describes the results of tyrosinase activity inhibition rate determination of a sample containing a specific amount of water-soluble rutin and mulberry bark extract, sophora flavescens extract, angelica extract or hops extract (Table 1).

[0004] Patent document 2 (Japanese Patent Publication No. 2004-10503) describes a moisturizing plant extract composed of an extract of a mixture of Angelica sinensis, Rehmannia glutinosa, Paeonia lactiflora, Ligusticum chuanxiong, Coptis chinensis, Scutellaria baicalensis, Gardenia jasminoides, and Phellodendron chinense (claim 1). The moisturizing plant extract is described as having a long-lasting moisturizing effect. Cosmetics and bath products containing the extract can prevent, alleviate, or improve symptoms such as dryness, roughness, cracking, frostbite, dandruff, and itching of the skin, and can prevent, alleviate, or improve problems such as dryness, frizz, split ends, breakage, and shine of the hair (paragraph 0152).

[0005] In addition, Patent Document 3 (Japanese Patent Publication No. 2012-77044) discloses a topical skin agent containing calcium phosphate as a cell cycle promoting ingredient (claim 1).

[0006] Existing technical documents

[0007] Patent documents

[0008] Patent Document 1: Japanese Patent Application Publication No. 8-99859

[0009] Patent Document 2: Japanese Patent Application Publication No. 2004-10503

[0010] Patent Document 3: Japanese Patent Application Publication No. 2012-77044 Summary of the Invention

[0011] The subject of this invention is to provide a novel skin-improving agent.

[0012] The inventors have discovered that excellent skin-improving effects can be achieved by combining specific ingredients.

[0013] According to the present invention, the following skin improvers can be provided.

[0014] [1] A skin improver containing the following ingredients (A) to (C).

[0015] (A) At least one selected from L-cysteine, its derivatives and their salts.

[0016] (B) Selected from at least one of ascorbic acid, its derivatives and their salts.

[0017] (C) Selected from one or more of vitamin B5, vitamin B6, vitamin B2, vitamin E, γ-oryzanol, and Angelica sinensis and its extracts.

[0018] [2] The skin improver described in [1] is a whitening agent.

[0019] [3] The skin improver according to [1] or [2] is one or more of the reducers selected from spots, freckles and post-inflammatory hyperpigmentation.

[0020] [4] The skin improver according to any one of [1] to [3] is a melanin production inhibitor.

[0021] According to the present invention, a novel skin improver can be obtained. Attached Figure Description

[0022] Figure 1 A graph showing the evaluation results of NOS3 gene expression levels.

[0023] Figure 2 A graph showing the evaluation results of NOS2 gene expression levels.

[0024] Figure 3 A graph showing the evaluation results of PTGS1 gene expression levels.

[0025] Figure 4 A graph showing the evaluation results of EDN2 gene expression levels. Detailed Implementation

[0026] The following describes embodiments of the present invention. In these embodiments, the composition may contain each component individually, or a combination of two or more components.

[0027] In this specification, when “~” is used to indicate a numerical range, it means above and below, and includes the values ​​at both ends.

[0028] (Skin improver)

[0029] In this embodiment, the skin improver contains the following ingredients (A) to (C).

[0030] (A) At least one selected from L-cysteine, its derivatives and their salts.

[0031] (B) At least one selected from ascorbic acid, its derivatives or their salts.

[0032] (C) Selected from one or more of vitamin B5, vitamin B6, vitamin B2, vitamin E, γ-oryzanol, and Angelica sinensis and its extracts.

[0033] The skin improver is specifically a composition containing the above-mentioned ingredients (A) to (C).

[0034] In this embodiment, by using ingredients (A) to (C) in combination, excellent skin improvement effects can be obtained.

[0035] Specifically, the new findings show that by using ingredients (A) to (C) in combination, compared to using ingredients (A) and (B) alone, the expression of specific genes related to melanin production or melanocyte-stimulating factors in the skin can be inhibited.

[0036] That is, the skin improver is preferably an expression inhibitor selected from at least one of the genes related to melanin production and melanocyte stimulating factors.

[0037] Specifically, the genes related to melanin production are selected from one or more genes chosen from nitric oxide synthase 2 (NOS2), nitric oxide synthase 3 (NOS3), prostaglandin synthase 1 (PTGS1), and endothelin 2 (EDN2). Furthermore, the skin-improving agent is preferably an expression inhibitor selected from one or more genes chosen from NOS2, NOS3, PTGS1, and EDN2.

[0038] The genes related to melanocyte stimulating factors are specifically selected from one or more genes among NOS2, NOS3, PTGS1, and EDN2.

[0039] Melanin production in the skin can be inhibited by suppressing the expression of genes related to melanin production or melanocyte-stimulating factors.

[0040] In this regard, the skin improver of this embodiment is preferably a melanin production inhibitor. Alternatively, the skin improver of this embodiment may also be a melanocyte-stimulating factor inhibitor.

[0041] By inhibiting melanin production, melanin retention can be suppressed, thus providing a whitening effect. Furthermore, the skin improver is preferably a whitening agent.

[0042] As a whitening agent, specifically, one or more reducing agents selected from spots, freckles, and post-inflammatory hyperpigmentation can be cited.

[0043] (Dosage form, etc.)

[0044] Skin improvers are preferably pharmaceutical compositions.

[0045] Furthermore, the skin-improving agent is preferably an oral composition. This results in a composition with excellent ease of ingestion.

[0046] Skin improvers are preferably solid formulations or other solid preparations. This improves the storage stability of the skin improver. Furthermore, compositions with excellent ease of ingestion are obtained.

[0047] Solid dosage forms can be, for example, tablets, granules, pills, powders, gummies, or jellies, with tablets being preferred. Examples of tablets include bare tablets, uncoated tablets, sugar-coated tablets, orally disintegrating tablets, film-coated tablets, or chewable tablets. Tablets can be multilayer tablets formed by compressing two or more layers of powders or granules with different compositions. The coating can impart properties such as rapid solubility, slow solubility, gastric solubility, and enteric solubility, depending on the desired composition.

[0048] Furthermore, the skin improver is preferably a topical agent. This allows for selective application of the skin improver to the desired area. The skin improver can be a quasi-medical product (such as a medicated cosmetic) or a pharmaceutical product, preferably a cosmetic, a topical skin agent, or a quasi-medical product (such as a medicated cosmetic).

[0049] At this time, the skin improver is suitable for the skin, preferably applied topically.

[0050] Examples of dosage forms for external use include: topical liquids containing liniments and lotions; creams; sprays including topical aerosols and pump-action sprays; or gels. Specifically, liniments are liquid or mud-like topical liquids applied to the skin through rubbing. Lotions, specifically, are topical liquids in which the active ingredient is dissolved, emulsified, or finely dispersed in an aqueous liquid.

[0051] Next, we will explain the ingredients contained in the skin improver.

[0052] (ingredient (A))

[0053] Component (A) is at least one selected from L-cysteine, its derivatives, and their salts. Additionally, component (A) may be a hydrate. Component (A) is a known compound, and as a method of obtaining it, it may be obtained from commercially available products or manufactured according to known methods.

[0054] Specific examples of component (A) include: L-cysteine; L-cysteine ​​derivatives such as N-acetyl-L-cysteine, L-homocysteine, L-cysteine, L-homocysteine, L-cysteine ​​sulfinic acid, S-sulfinyl-L-cysteine, S-sulfonyl-L-cysteine, cystine (a dimer of cysteine); and salts of cysteine ​​and its derivatives such as hydrochloride, nitrate, sulfate, sodium salt, potassium salt, calcium salt, magnesium salt, alkaline metal salt, and alkaline earth metal salt.

[0055] Component (A) is preferably one or more compounds selected from L-cysteine; and L-cysteine ​​hydrochloride hydrate and other L-cysteine ​​salts (including hydrates), more preferably L-cysteine. This allows for a more stable skin-improving effect.

[0056] L-cysteine ​​is listed in the 18th revised Japanese Pharmacopoeia.

[0057] In addition, component (A) is preferably a solid such as a powder. This improves the manufacturing stability of the skin improver.

[0058] The content of ingredient (A) in the skin improver, based on the content in a single dose of the skin improver, is preferably 0.1 mg or more, more preferably 1 mg or more, and even more preferably 10 mg or more. This further enhances the skin improver effect.

[0059] Furthermore, the content of ingredient (A) in the skin improver, preferably L-cysteine ​​and its salt, is preferably 250 mg or less, more preferably 125 mg or less, and even more preferably 100 mg or less, based on the content in a single dose of the skin improver. This allows for a more efficient improvement in skin condition.

[0060] The content of ingredient (A) in the skin improver, based on a daily recommended dose, is preferably 0.1 mg or more, more preferably 1 mg or more, and even more preferably 10 mg or more. This further enhances the skin-improving effect.

[0061] Furthermore, the content of ingredient (A) in the skin improver, based on a daily recommended dose, is preferably 500 mg or less, more preferably 300 mg or less, and even more preferably 250 mg or less. This allows for a more efficient improvement in skin condition.

[0062] Here, the appropriate dosage of the skin improver can be set according to the form of the skin improver.

[0063] In addition, the skin improver can be applied 1 to 10 times a day, preferably 1 to 5 times, and more preferably 1 to 3 times.

[0064] (Component (B))

[0065] Component (B) is selected from at least one of ascorbic acid, its derivatives, and their salts. Additionally, component (B) may be a hydrate. Component (B) is a known compound, and as a method of obtaining it, it may be obtained from commercially available products or manufactured according to known methods.

[0066] Specific examples of component (B) include: ascorbic acid; ascorbates such as sodium ascorbate, magnesium ascorbate, potassium ascorbate, and calcium ascorbate; monoalkyl or monoalkenyl esters of ascorbic acid such as monostearate, monopalmitate, and monooleate; dialkyl or diene esters of ascorbic acid such as diester, diester, and diester; and tristearate of ascorbic acid. Ascorbic acid trialkyl or trienyl esters such as ascorbic acid palmitate triester and ascorbic acid oleate triester; ascorbic acid sulfates such as ascorbic acid sulfate, sodium ascorbic acid sulfate, potassium ascorbic acid sulfate, magnesium ascorbic acid sulfate, and calcium ascorbic acid sulfate; ascorbic acid phosphates such as ascorbic acid phosphate, sodium ascorbic acid phosphate, potassium ascorbic acid phosphate, magnesium ascorbic acid phosphate, and calcium ascorbic acid phosphate; and ascorbic acid glycosides such as ascorbic acid glycosides.

[0067] Component (B) is preferably selected from ascorbic acid; and one or more compounds selected from ascorbate salts such as calcium ascorbate and sodium ascorbate, more preferably ascorbic acid. This allows for a more stable skin-improving effect.

[0068] Ascorbic acid is listed in the 18th revised Japanese Pharmacopoeia.

[0069] In addition, component (B) is preferably a solid such as a powder. This improves the manufacturing stability of the skin improver.

[0070] The content of ingredient (B) in the skin improver, based on the content in a single dose of the skin improver, is preferably 0.01 mg or more, more preferably 100 mg or more, and even more preferably 200 mg or more. This further enhances the skin improver effect. Furthermore, for a more significant skin improver effect, the content of ingredient (B) in a single dose of the skin improver is also preferably 500 mg or more.

[0071] Furthermore, the content of ingredient (B) in the skin improver, based on the content in a single dose of the skin improver, is preferably 6000 mg or less, more preferably 4000 mg or less, and even more preferably 2000 mg or less. This allows for a more efficient improvement in skin condition.

[0072] The content of ingredient (B) in the skin improver, based on a daily recommended dose, is preferably 0.01 mg or more, more preferably 200 mg or more, and even more preferably 250 mg or more. This further enhances the skin-improving effect. Furthermore, for a more significant skin-improving effect, the content of ingredient (B) in the daily recommended dose of the skin improver is preferably 800 mg or more, and more preferably 1000 mg or more.

[0073] Furthermore, the content of ingredient (B) in the skin improver, based on the daily recommended dose, may be, for example, 4000 mg or less, preferably 3500 mg or less. Additionally, to more efficiently achieve the skin improver effect, the daily recommended dose of ingredient (B) is preferably 3000 mg or less, more preferably 2500 mg or less, and even more preferably 2000 mg or less.

[0074] (Component (C))

[0075] Component (C) is selected from one or more of vitamins B5, B6, B2, E, γ-oryzanol, and Angelica sinensis and its extracts.

[0076] Component (C) is preferably a solid such as a powder. This improves the manufacturing stability of the skin improver.

[0077] (Vitamin B5)

[0078] Specifically, examples of vitamin B5 compounds include pantothenic acid, calcium pantothenate, sodium pantothenate, and panthenol. A vitamin B5 compound only needs to contain one or more compounds selected from these compounds, preferably calcium pantothenate, sodium pantothenate, or panthenol, and more preferably calcium pantothenate. This allows for a more stable skin-improving effect.

[0079] Calcium pantothenate is listed in the 18th revised Japanese Pharmacopoeia. As a vitamin B5 complex containing calcium pantothenate, commercially available products can be used, for example.

[0080] The content of vitamin B5 in the skin improver, based on the content in a single dose of the skin improver, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 5 mg or more. This further enhances the skin improver effect.

[0081] Furthermore, the content of vitamin B5 in the skin improver, based on the content in a single dose of the skin improver, is preferably 30 mg or less, more preferably 15 mg or less, and even more preferably 12.5 mg or less. This allows for a more efficient improvement in skin condition.

[0082] The vitamin B5 content in the skin improver, based on a daily recommended dose, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 5 mg or more. This further enhances the skin-improving effect.

[0083] Furthermore, the vitamin B5 content in the skin improver, based on a daily recommended intake, is preferably 60 mg or less, more preferably 30 mg or less, and even more preferably 25 mg or less. This allows for a more efficient improvement in skin condition.

[0084] When a skin improver contains a combination of L-cysteine, ascorbic acid, and calcium pantothenate, the mass ratio of their combined amounts can be, for example, L-cysteine: ascorbic acid: calcium pantothenate = 1-500: 1-200: 1-300.

[0085] The ratios indicated by ":" above and below are the mass ratios of the ingredients in the skin improver. Within these mass ratios, each ingredient can take values ​​within a range. For example, when "x:y = 1~10:1~15", x can be greater than 1 and less than 10, and y can be greater than 1 and less than 15, resulting in a x:y ratio of 10:1 to 1:15.

[0086] When the skin-improving agent contains a combination of ingredients (A), (B), and vitamin B5, the mass ratio of their combined amounts, i.e., the mass ratio of the total content of vitamin B5 to the total content of ingredients (A) and (B) (vitamin B5 / ((A)+(B)))), is preferably 0.002 or more, more preferably 0.005 or more, further preferably 0.01 or more, and even more preferably 0.015 or more. This further enhances the skin-improving effect. Alternatively, the above mass ratio may be 0.5 or more.

[0087] Furthermore, the aforementioned mass ratio (vitamin B5 / ((A)+(B))) is preferably 2 or less, more preferably 1.5 or less, even more preferably 1 or less, and even more preferably 0.75 or less. This allows for a more efficient improvement in skin condition. Alternatively, the aforementioned mass ratio may be, for example, 0.02 or less.

[0088] (Vitamin B6)

[0089] Specifically, examples of vitamin B6 derivatives include pyridoxine and its salts (such as hydrochloride), pyridoxal, pyridoxal phosphate hydrate, and pyridoxamine. Vitamin B6 derivatives only need to contain one or more compounds selected from these, preferably pyridoxine and its salts, more preferably pyridoxine salts, and even more preferably pyridoxine hydrochloride. This allows for a more stable skin-improving effect.

[0090] Pyridoxine hydrochloride is listed in the 18th revised Japanese Pharmacopoeia. As a vitamin B6 derivative including pyridoxine hydrochloride, commercially available products may be used, for example.

[0091] The vitamin B6 content in the skin improver, based on the content in a single dose of the skin improver, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 2.5 mg or more. This further enhances the skin-improving effect.

[0092] Furthermore, the vitamin B6 content in the skin improver, based on the content in a single dose of the skin improver, is preferably 50 mg or less, more preferably 25 mg or less, and even more preferably 10 mg or less. This allows for a more efficient improvement in skin condition.

[0093] Furthermore, the vitamin B6 content in the skin improver, based on a daily recommended intake, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 2.5 mg or more. This further enhances the skin-improving effect.

[0094] Furthermore, the content of vitamin B6 in the skin improver, based on a daily recommended dose, is preferably 100 mg or less, more preferably 50 mg or less, and even more preferably 25 mg or less. This allows for a more efficient improvement in skin condition.

[0095] When a skin improver contains a combination of L-cysteine, ascorbic acid, and pyridoxine hydrochloride, the mass ratio of their combined amounts can be, for example, L-cysteine:ascorbic acid:pyridoxine hydrochloride = 1-500:1-200:1-300.

[0096] When the skin-improving agent contains a combination of ingredients (A), (B), and vitamin B6, the mass ratio of their combined amounts, i.e., the mass ratio of the total content of vitamin B6 to the total content of ingredients (A) and (B) (vitamin B6 / ((A)+(B)))), is preferably 0.001 or more, more preferably 0.005 or more, further preferably 0.01 or more, and even more preferably 0.015 or more. This further enhances the skin-improving effect.

[0097] Furthermore, the aforementioned 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 still more preferably 0.3 or less. This allows for a more efficient improvement in skin condition.

[0098] (Vitamin B2)

[0099] Specifically, examples of vitamin B2 include riboflavin and its salts (such as hydrochloride), riboflavin butyrate, sodium riboflavin phosphate, and sodium flavin adenine dinucleotide. Vitamin B2 only needs to contain one or more compounds selected from these, preferably at least one selected from riboflavin, riboflavin hydrochloride, and riboflavin butyrate. This allows for a more stable skin-improving effect.

[0100] Riboflavin is listed in the 18th revised Japanese Pharmacopoeia. As a vitamin B2 group containing riboflavin, commercially available products can be used, for example.

[0101] The content of vitamin B2 in the skin improver, based on the content in a single dose of the skin improver, is preferably 0.001 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more. This further enhances the skin-improving effect.

[0102] Furthermore, the vitamin B2 content in the skin improver, based on the content in a single dose, is preferably 60 mg or less, more preferably 30 mg or less, and even more preferably 15 mg or less. This allows for a more efficient improvement in skin condition.

[0103] The vitamin B2 content in the skin improver, based on a daily recommended dose, is preferably 0.001 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more. This further enhances the skin-improving effect.

[0104] Furthermore, the vitamin B2 content in the skin improver, based on a daily recommended dose, is preferably 60 mg or less, more preferably 30 mg or less, and even more preferably 15 mg or less. This allows for a more efficient improvement in skin condition.

[0105] When a skin improver contains a combination of L-cysteine, ascorbic acid, and riboflavin, riboflavin butyrate, or riboflavin hydrochloride, the mass ratio of their combined amounts may be, for example, L-cysteine:ascorbic acid:riboflavin, riboflavin hydrochloride, or riboflavin butyrate = 1–500: 1–200: 1–300.

[0106] When the skin-improving agent contains a combination of ingredients (A), (B), and vitamin B2, the mass ratio of their combined amounts, i.e., the mass ratio of the total content of vitamin B2 to the total content of ingredients (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 even more preferably 0.0075 or more. This further enhances the skin-improving effect. Alternatively, the aforementioned mass ratio may also be 0.1 or more.

[0107] Furthermore, the aforementioned 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 allows for more efficient improvement in skin condition. Alternatively, the aforementioned mass ratio may also be, for example, 0.01 or less.

[0108] (Vitamin E)

[0109] Specifically, examples of vitamin E include tocopherols such as α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol, their esters, and their salts.

[0110] Examples of tocopherol esters include succinate, acetate, nicotinic acid ester, and phosphate ester. Additionally, examples of salts of tocopherols and tocopherol esters include calcium salts. Vitamin E derivatives can be optical isomers such as dl isomers.

[0111] The preferred vitamin E compounds are those specified in the 18th revised Japanese Pharmacopoeia formula, such as tocopherol, calcium tocopherol succinate, tocopherol acetate, and tocopherol nicotinate; as well as those specified in the Japanese Pharmacopoeia formula for pharmaceutical products under specification 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, they are at least one compound selected from DL-α-tocopherol acetate and d-α-tocopherol succinate. This allows for a more stable skin-improving effect.

[0112] As a form of vitamin E, commercially available products can be used, for example.

[0113] The vitamin E content in the skin improver, based on the content in a single dose of the skin improver, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more. This further enhances the skin-improving effect.

[0114] Furthermore, the vitamin E content in the skin improver, based on the content in a single dose of the skin improver, is preferably 100 mg or less, more preferably 75 mg or less, and even more preferably 50 mg or less. This allows for a more efficient improvement in skin condition.

[0115] The vitamin E content in the skin improver, based on a daily recommended dose, is preferably 0.001 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more. This further enhances the skin-improving effect.

[0116] Furthermore, the vitamin E content in the skin improver, based on a daily recommended dose, is preferably 200 mg or less, more preferably 150 mg or less, and even more preferably 100 mg or less. This allows for a more efficient improvement in skin condition.

[0117] When a skin improver contains a combination of L-cysteine, ascorbic acid, and DL-α-tocopherol acetate or d-α-tocopherol succinate, the mass ratio of their combined amounts can be, for example, L-cysteine:ascorbic acid:DL-α-tocopherol acetate or d-α-tocopherol succinate = 1-500:1-200:1-300.

[0118] When the skin-improving agent contains a combination of ingredients (A), (B), and vitamin E, the mass ratio of their combined amounts, i.e., the mass ratio of the total content of vitamin E to the total content of ingredients (A) and (B) (vitamin E / ((A)+(B)))), is preferably 0.005 or more, more preferably 0.01 or more, further preferably 0.02 or more, and even more preferably 0.04 or more. This further enhances the skin-improving effect. Alternatively, the aforementioned mass ratio may also be 1 or more.

[0119] Furthermore, the aforementioned 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 even more preferably 1.2 or less. This allows for a more efficient improvement in skin condition. Alternatively, the aforementioned mass ratio may also be, for example, 0.05 or less.

[0120] (γ-oryzanol)

[0121] As gamma-oryzanol, commercially available products can be used, for example.

[0122] The content of γ-oryzanol in the skin improver, based on the content in a single dose of the skin improver, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more. This further enhances the skin improver effect.

[0123] Furthermore, the content of γ-oryzanol in the skin improver, based on the content in a single dose of the skin improver, 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 improvement in skin condition.

[0124] The content of γ-oryzanol in the skin improver, based on the recommended daily dose, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 5 mg or more. This further enhances the skin-improving effect.

[0125] Furthermore, the content of γ-oryzanol in the skin improver, based on a daily recommended dose, 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 improvement in skin condition.

[0126] When a skin improver contains a combination of L-cysteine, ascorbic acid, and γ-oryzanol, the mass ratio of their combined amounts can be, for example, L-cysteine:ascorbic acid:γ-oryzanol = 1-500:1-200:1-300.

[0127] When the skin-improving agent contains a combination of ingredients (A), (B), and γ-oryzanol, the mass ratio of their combined amounts, i.e., the mass ratio of the total content of γ-oryzanol to the total content of ingredients (A) and (B) (γ-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 further enhances the skin-improving effect. Alternatively, the aforementioned mass ratio may also be 0.2 or more.

[0128] Furthermore, the aforementioned mass ratio (γ-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 allows for a more efficient improvement in skin condition. Alternatively, the aforementioned mass ratio may also be, for example, 0.01 or less.

[0129] (Angelica sinensis and its extracts)

[0130] Specifically, it refers to at least one of the following: Angelica acutiloba Kitagawa and its extract (Angelica extract).

[0131] There are no restrictions on the parts of Angelica sinensis used as raw materials for the extract. For example, it can be selected from one or more of the following: leaves, branches, stems, flowers, fruits, and roots, with roots being preferred.

[0132] Extraction methods for obtaining extracts from Angelica sinensis can include solvent extraction. Extraction solvents can be selected from one or more of the following: water; monohydric alcohols with 1 to 3 carbon atoms, such as methanol and ethanol; liquid polyols such as propylene glycol and 1,3-butanediol; lower alkyl esters such as ethyl acetate; hydrocarbons such as benzene and hexane; and ethers such as ethyl ether. Preferably, the solvent contains one or more of the following: water and monohydric alcohols with 1 to 3 carbon atoms. The extraction temperature can be room temperature (25°C). Alternatively, extraction can be performed by heating to, for example, below the boiling point of the solvent.

[0133] After extraction, at least one of the following can be performed: filtration and purification, such as deodorization and decolorization. Additionally, the extract can be appropriately diluted or concentrated, or dried, depending on the circumstances.

[0134] Alternatively, commercially available products such as angelica extract can be used as extracts.

[0135] Angelica sinensis and its extracts are preferably in solid form, such as powder. This improves the manufacturing stability of the skin-improving agent. Furthermore, to ensure a stable skin-improving effect, Angelica sinensis and its extracts are preferably non-enzymatically treated.

[0136] The content of Angelica sinensis and its extract in a single dose of the skin-improving agent, calculated based on the amount of the raw herb, is preferably 0.05 mg or more, more preferably 10 mg or more, and even more preferably 100 mg or more. This further enhances the skin-improving effect.

[0137] Furthermore, the content of Angelica sinensis and its extract in a single dose of the skin-improving agent, calculated based on the amount of the raw herb, is preferably 500 mg or less, more preferably 400 mg or less, and even more preferably 300 mg or less. This allows for a more efficient improvement in skin-improving effects.

[0138] The daily recommended dosage of Angelica sinensis and its extract, calculated based on the amount of the raw herb, is preferably 0.1 mg or more, more preferably 20 mg or more, and even more preferably 200 mg or more. This can further enhance the skin-improving effect.

[0139] Furthermore, the daily recommended dosage of Angelica sinensis and its extract, calculated based on the amount of the raw herb, is preferably less than 1000 mg, more preferably less than 800 mg, and even more preferably less than 600 mg. This allows for a more efficient improvement in skin condition.

[0140] When a skin improver contains a combination of L-cysteine, ascorbic acid, and angelica, the mass ratio of their combined amounts can be, for example, L-cysteine: ascorbic acid: angelica (converted amount from raw herb) = 1~500: 1~200: 1~400.

[0141] When the skin-improving agent contains a combination of ingredients (A), (B), and Angelica sinensis and its extract, the mass ratio of their combined amounts, i.e., the mass ratio of the total content of Angelica sinensis and its extract to the total content of ingredients (A) and (B) (Angelica sinensis (converted amount from raw herb) / ((A) + (B))), is preferably 0.025 or more, more preferably 0.05 or more, further preferably 0.1 or more, and even more preferably 0.25 or more. This further enhances the skin-improving effect. Alternatively, the aforementioned mass ratio may also be 1.5 or more.

[0142] Furthermore, the aforementioned mass ratio (Angelica sinensis (converted amount of raw herb) / ((A) + (B))) is preferably 5 or less, more preferably 3 or less, further preferably 2.5 or less, and even more preferably 2 or less. This allows for a more efficient improvement in skin condition. Alternatively, the aforementioned mass ratio may also be, for example, 0.5 or less.

[0143] Component (C) may contain two or more components, for example, it may contain vitamin B2, vitamin B6, vitamin E and vitamin B5. In addition, component (C) may contain vitamin B2, vitamin B6, vitamin E and vitamin B5, and further contain at least one selected from γ-oryzanol and angelica and its extracts.

[0144] The total content of ingredient (C) in the skin improver, based on the content in a single dose of the skin improver, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more. This further enhances the skin improver effect.

[0145] Furthermore, the total content of ingredient (C) in the skin improver, based on the content in a single dose of the skin improver, is preferably 1500 mg or less, more preferably 1000 mg or less, and even more preferably 500 mg or less. This allows for a more efficient improvement in skin condition.

[0146] The total content of ingredient (C) in the skin improver, based on a daily recommended dose, is preferably 0.01 mg or more, more preferably 0.1 mg or more, and even more preferably 1 mg or more. This further enhances the skin-improving effect.

[0147] Furthermore, the total content of ingredient (C) in the skin improver, based on a daily recommended dose, is preferably 1500 mg or less, more preferably 1000 mg or less, and even more preferably 750 mg or less. This allows for a more efficient improvement in skin condition.

[0148] The mass ratio of the total content of ingredient (C) to the total content of ingredients (A) and (B) in the skin improver ((C) / ((A)+(B)))) is preferably 0.005 or more, more preferably 0.01 or more, further preferably 0.025 or more, even more preferably 0.05 or more, and for example, 2 or less, preferably 1.5 or less, more preferably 0.5 or less, even more preferably 0.25 or less, and even more preferably 0.15 or less. This allows for a more stable skin improvement effect.

[0149] (Other ingredients)

[0150] Skin improvers may contain ingredients other than those mentioned above. These other ingredients may be selected, for example, from those used in food or pharmaceutical products. Additionally, other ingredients may be selected based on, for example, the dosage form of the skin improver.

[0151] Other ingredients include, for example, one or more of the following: excipients, binders, disintegrants, disintegration aids, lubricants, stabilizers, surfactants, antioxidants, buffers, pH adjusters, dispersants, solubilizers, high-efficiency water-reducing agents, gloss agents, flavoring agents, sweeteners, cooling agents, coloring agents, odor-correcting agents, fragrances, adsorbents, sugar coating agents, coating agents, suspending agents, antistatic agents, plasticizers, and aromatizers.

[0152] Excipients include, for example, celluloses such as crystalline cellulose, lactose (lactose hydrate, anhydrous lactose, etc.), purified 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, astragalus gum powder, gum arabic, pullulan, kaolin, anhydrous calcium hydrogen phosphate, and anhydrous phosphorus. The product contains one or more of the following: calcium hydrogen phosphate granules, magnesium aluminum metasilicate, methylcellulose, calcium hydrogen phosphate hydrate, calcium hydrogen phosphate granules, sodium hydrogen phosphate hydrate, potassium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, sodium dihydrogen phosphate, magnesium aluminum silicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, low-substituted hydroxypropyl cellulose, sodium starch glycolate, powdered reduced maltose syrup, carboxymethyl cellulose, calcium carboxymethyl cellulose, and sodium carboxymethyl cellulose, preferably containing one or more of the following: mannitol, crystalline cellulose, and corn starch. This allows the skin improver to maintain a color closer to white when it is a solid formulation.

[0153] The content of excipients in the skin improver is, for example, 0.1% by mass or more, preferably 0.5% by mass or more, more preferably 1% by mass, and for example, 70% by mass or less, preferably 50% by mass or less, more preferably 40% by mass or less. This improves moldability.

[0154] The binder is selected from gum arabic, gelatin, α-starch, alginic acid, sodium alginate, carboxyvinyl polymer, agar, pullulan, dextrin, shellac, sucrose, astragalus gum, astragalus gum powder, xanthan gum, pectin, sodium polyacrylate, guar gum, corn starch, hydroxyethyl cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, copovidone, hydroxypropyl methylcellulose (hydroxypropyl methylcellulose (2208), hydroxypropyl methylcellulose (2906), hydroxypropyl methylcellulose (2910), etc.), hydroxypropyl methylcellulose ethyl succinate, hydroxypropyl methylcellulose phthalate (200731), hydroxypropyl methylcellulose phthalate (220824), povidone (K25), povidone (K30), povidone (K90), polyvinyl alcohol (polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified), etc.), methylcellulose, and magnesium aluminum metasilicate, or one or more of these.

[0155] The disintegrant may be one or more selected from corn starch, potato starch, partially α-substituted starch, hydroxypropyl starch, sodium starch glycolate, sodium carboxymethyl starch, sodium carboxymethyl starch with low degree of substitution, calcium carboxymethyl cellulose, hydroxypropyl cellulose with low degree of substitution, croscarmellose sodium carboxymethyl cellulose, crystalline cellulose, powdered cellulose, croscarmellose, sodium carboxymethyl cellulose, agar powder, sodium bicarbonate, and carboxymethyl cellulose.

[0156] The lubricant is, for example, one or more selected from magnesium stearate, calcium stearate, stearic acid, talc, sucrose fatty acid ester, sodium stearyl fumarate, carnauba wax, glyceryl fatty acid ester, calcium stearate, light anhydrous silicate, and magnesium aluminum metasilicate.

[0157] Flavoring agents may be one or more of the following: organic acids such as citric acid, tartaric acid, and malic acid; amino acid salts such as monosodium glutamate and monosodium aspartate; ribonucleates such as sodium 5'-inosinate and sodium 5-guanylate; and caramel.

[0158] Sweeteners may be one or more selected from high-sweetness sweeteners such as sodium saccharin, dipotassium glycyrrhizate, aspartame, stevia, monk fruit, sematrandez, potassium acesulfame potassium, sucralose, sucrose, fructose, glucose, lactose hydrate, anhydrous lactose, maltose, sorbitol, maltitol, mannitol, xylitol, erythritol, glycerol, inositol, reduced maltose syrup, isomaltulose, conjugated sugars, and honey.

[0159] Examples of sugar coating agents include monosaccharides or disaccharides such as sucrose (white sugar, purified 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. Additionally, the coating solution may contain ingredients selected from gum arabic, gum arabic powder, ethyl cellulose, carnauba wax, sodium carboxymethyl cellulose, stearic acid, polyoxyethylene 40 stearate, purified gelatin, purified shellac, gelatin, shellac, talc, precipitated calcium carbonate, white shellac, hydroxypropyl cellulose, hydroxypropyl methylcellulose (2208), hydroxypropyl methylcellulose (2906), hydroxypropyl methylcellulose (2910), pullulan, and povidone (K25). One or more of the following: povidone (K30), povidone (K90), polyoxyethylene (105), polyoxypropylene (5) glycol, polyvinyl alcohol (partially saponified), polyethylene glycol (polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, etc.), mannitol, dicalcium phosphate, calcium hydrogen phosphate, calcium dihydrogen phosphate, calcium sulfate, calcium lactate, kaolin, titanium dioxide, iron oxide, yellow iron oxide, black copper ferrous oxide, sodium chlorophyll, and copper chlorophyll.

[0160] Coating agents, for example, are selected from the following: ethyl acrylate-methyl methacrylate copolymer dispersion, acetylated glycerol fatty acid ester, aminoalkyl acrylate copolymer E, gum arabic, gum arabic powder, ammonium alkyl acrylate copolymer, ethyl cellulose, ethyl cellulose aqueous dispersion, octyldecyl triglyceride, carnauba wax, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, hydrated silica, dried aluminum hydroxide gel, dried methacrylate copolymer LD, triethyl citrate, glycerol, glycerol fatty acid ester, magnesium silicate, light anhydrous silica, hydroxypropyl cellulose containing light anhydrous silica, synthetic aluminum silicate, synthetic hydrotalcite, titanium dioxide, magnesium oxide, and dimethylaminoethyl acrylate. Methyl methacrylate copolymer, sucrose fatty acid ester, aluminum hydroxide gel, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyoxyethylene 40 stearate, magnesium stearate, purified gelatin, purified shellac, purified white sugar, gelatin, shellac, D-sorbitol, D-sorbitol liquid, talc, calcium carbonate, magnesium carbonate, precipitated calcium carbonate, low-substituted hydroxypropyl cellulose, concentrated glycerol, white shellac, white sugar, paraffin wax, hydroxypropyl cellulose, hydroxypropyl methylcellulose 2910·titanium oxide·polyethylene glycol mixture, hydroxypropyl methylcellulose (2208), hydroxypropyl methylcellulose (2906), hydroxypropyl methylcellulose (2910), hydroxypropyl methylcellulose ethyl succinate, hydroxypropyl methylcellulose phthalate (200731), hydroxypropyl methylcellulose phthalate (220824), fumaric acid·stearic acid·polyvinylaldehyde diethylaminoethyl ester. Hydroxypropyl methylcellulose 2910 mixture, pullulan, polyoxyethylene 40 hydrogenated castor oil, polyoxyethylene 60 hydrogenated castor oil, polyoxyethylene (105)polyoxypropylene (5) glycol, polyoxyethylene (160)polyoxypropylene (30) glycol, polysorbate 80, polyvinyl aldehyde diethylaminoethyl ester, polyvinyl alcohol (fully saponified), polyvinyl alcohol (partially saponified), polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 4000, polyethylene glycol 60 00, one or more of the following: polyethylene glycol 6000EP, polyethylene glycol 20000, polyethylene glycol 35000, mannitol, anhydrous citric acid, hydrated anhydrous silica, anhydrous phthalic acid, anhydrous calcium hydrogen phosphate, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, magnesium aluminum metasilicate, methyl methacrylate-methacrylic acid-methyl methacrylate copolymer, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, calcium sulfate, fumaric acid, and DL-malic acid.

[0161] In addition, skin improvers may further contain known whitening ingredients or ingredients that enhance whitening effects, other than ingredients (A) to (C). These ingredients may, for example, be selected from: catechins;

[0162] Hydroquinone and its derivatives (hydroquinone, hydroquinone-β-D-glucose (arbutin), and other hydroquinone glycosides, etc.);

[0163] Glucosamine and its derivatives (glucosamine; glucosamine esters such as acetylglucosamine; glucosamine ethers such as glucosamine methyl ether, etc.);

[0164] Juniper alcohol and its derivatives (juniper alcohol; juniper glycosides, etc.);

[0165] Azelaic acid, its derivatives and their salts (azelaic acid; azelaic acid monoalkyl esters and other azelaic acid monoesters; azelaic acid dialkyl esters and other azelaic acid diesters, etc.);

[0166] Niacin, nicotinamide, and other B3 vitamins;

[0167] ubiquinones (coenzyme Q6 (CoQ6), coenzyme Q7 (CoQ7), coenzyme Q8 (CoQ8), coenzyme Q9 (CoQ9), coenzyme Q10 (CoQ10), etc.);

[0168] Carotenoids (carotene, lutein, spirulinaxanthin, spirulinaxanthin, globularene, etc.);

[0169] Flavonoids (flavonoids, apigenin, luteolin and their glycosides, etc.), isoflavones and their derivatives (isoflavones; isoflavone glycosides, etc.);

[0170] Flavonoids and their derivatives (naringenin, sennaol, naringin, etc.), flavonols (kaempferol, quercetin, myricetin and its glycosides, etc.);

[0171] Glycyrrhizic acid, its derivatives and their salts (glycyrrhizic acid; glycyrrhizates such as dipotassium glycyrrhizate and monoammonium glycyrrhizate, and alkyl glycyrrhizate esters such as stearyl glycyrrhizate, etc.);

[0172] Kojic acid, its derivatives and their salts (kojic acid; kojic acid monobutyl ester, kojic acid monooctanoate, kojic acid monopalmitate, kojic acid monostearate and other kojic acid monoalkyl esters; kojic acid dibutyl ester, kojic acid dipalmitate, kojic acid distearate, kojic acid dioleate and other kojic acid dialkyl esters, etc.);

[0173] Ellagic acid, its derivatives and their salts (ellagic acid; ellagic acid ethers such as tetramethyl ellagic acid ether; ellagic acid acyl derivatives such as tetraethyl ellagic acid ester and tetrabenzoic acid ester, etc.);

[0174] Glutathione, its derivatives and their salts (glutathione; S-acylglutathione and other S-acylglutathiones; N,S-dioctylglutathione distearate, N,S-dipalmitoylglutathione diceryl and other N,S-diacylglutathione diesters, etc.);

[0175] Resorcinol and its derivatives (resorcinol; alkylated resorcinols such as 4-n-butylresorcinol, 4-isopentylresorcinol, 4-cyclohexylresorcinol, and 5-methylresorcinol; halogenated resorcinols such as 4-chlororesorcinol and 4-bromoresorcinol, etc.);

[0176] Glycoprotein;

[0177] Job's tears, witch hazel, saxifrage, agarwood, tea, Japanese knotweed, lemon balm, thyme, Artemisia argyi, yarrow, St. John's wort, St. John's wort, peony, Spanish licorice, licorice, mulberry, true mulberry, island mulberry, water locust, bearberry, longleaf plantain, needle wormwood, Sargassum, knotweed, rock wormwood, red seaweed, willowweed (large-leaved seaweed), Spirulina spp., knotweed, rock water cloud, sundew, small sundew, lavender, Coptis chinensis, Job's tears, rock pear, American rock pear, passionflower, fruit clock grass, water lemon, clock grass, moon leaf passionflower, snake king vine, cup leaf passionflower, wild pansy, fragrant pansy Violet, violet, small violet, wild violet, ruyi violet, zhuzi violet, white violet, ergot violet, Nepalese violet, white flower violet, round-leaved hairy violet, Altai violet, standing violet, ground grass fruit, violet asarum, piedra violet, clematis, clematis, windmill grass, cactus, eucommia, thorny fruit, hanging flower, asparagus, Ibuki tiger tail, pea, ying shi, scutellaria, scutellaria, stigmata, raspberry, sophora flavescens, cockscomb, eleutherococcus senticosus, asarum, hawthorn, three-whip grass, white lily, qianfu hua, mulberry bark, soybean, tea, molasses, white lotus, beech, grape seed, devil's flower (フローデマニータ, Florde) Manita), hops, rose, dried ink, monk fruit, aloe vera, marshmallow, arnica, ashtraya, artemisia capillaris, nettle, turmeric, phellodendron bark, chamomile, honeysuckle, watercress, sage, lithospermum, perilla, birch, calendula, elderberry, rhubarb, soapberry, astragalus, artemisia, eucalyptus, wild rose, ginkgo, yam, lycium bark, micromelum minutum, micromelum pubescens, morinda root, saposhnikovia root, red peony root, raspberry, Sichuan pepper, and their extracts; and

[0178] One or more of the placental extracts.

[0179] (Manufacturing method)

[0180] In this embodiment, the method for manufacturing the skin improver includes, for example, a process of combining ingredients (A) to (C) and other suitable ingredients. The skin improver can be manufactured according to, for example, its dosage form, to produce a formulation.

[0181] (Packaging)

[0182] The packaging is the container within which the skin-improving agent is housed. By creating a packaging design, the convenience of using the skin-improving agent can be improved, for example. The packaging container can be selected according to, for example, the dosage form of the skin-improving agent.

[0183] Specific examples of packaging formats include: bottle packaging, wide-mouth bottle packaging, PTP (Press Through Package), bag packaging, strip packaging, and SP (Strip Package). Skin improvers can be pre-packaged in these forms for airtight storage. That is, the skin improver can be contained within an airtight package. Furthermore, it can be further packaged in pillow-shaped packaging or boxes.

[0184] In addition, from the perspective of inhibiting moisture absorption, desiccants and other skin-improving agents can be contained together in the packaging container.

[0185] Materials used as packaging containers include, for example, one or more materials selected from inorganic materials such as resin, metal, and glass.

[0186] In addition, as needed, environmentally friendly materials such as recycled plastics, biomass plastics, and biodegradable plastics can be used as part or all of the packaging materials, or environmentally friendly containers or packaging can be used.

[0187] Specific examples of film materials constituting packaging containers include resin films such as polypropylene film, polyethylene terephthalate film, and polyethylene film, or film materials on which metal foils such as aluminum foil are attached by vapor deposition or other methods. Single-layer films and multi-layer films (e.g., laminated films) can be used.

[0188] The packaging container can be selected according to the shape of the skin improver. For example, when the skin improver is a tablet, the packaging container is a bag, preferably an aluminum foil bag. A zipper can be added to the bag.

[0189] (Skin improvement methods)

[0190] In this embodiment, the skin improvement method (excluding medical procedures on humans) includes, for example, applying the skin improvement agent of this embodiment to a subject, and more preferably, administering the skin improvement agent of this embodiment to the subject. Oral administration is a specific example of the administration method.

[0191] In this embodiment, the skin-improving agent has the aforementioned excellent effects, and therefore, by administering it to the subject, the subject's skin can be improved.

[0192] The embodiments of the present invention have been described above, but these are merely examples of the present invention, and various configurations other than those described above may be used.

[0193] Example

[0194] The following examples illustrate this implementation method in detail, but this implementation method is not limited to these examples.

[0195] (Experimental Example 1)

[0196] In this example, the gene expression levels in human epidermal keratinocytes were determined using the following steps.

[0197] Human immortalized keratinocytes (HaCat) were cultured using Dulbecco's Modified Eagle Medium (manufactured by Gibco) at a concentration of 7.5 × 10⁻⁶. 5 Cells / dish were seeded at a density of 1:1 in 6 cm culture dishes. The culture medium was removed the day after seeding and replaced with test solutions diluted with Dulbecco's Modified Eagle Medium (Gibco), and incubated for 24 hours. After incubation, the culture medium was removed and replaced with PBS (Gibco), incubated at 7.5 mJ / cm². 2 Irradiate with UVB. After culturing in each test solution for 4 hours, RNA is extracted using the RNeasy Mini Kit (QIAGEN), and cDNA is synthesized by reverse transcription using the Verso cDNASynthesis Kit (Thermo Fisher). The expression levels of various genes (RNA) are then determined by Real-time PCR.

[0198] For each gene, three measurements were performed in each experimental case.

[0199] The following lists the genes whose expression levels were measured. Primers used (all manufactured by Thermo Fisher Scientific) are shown in parentheses.

[0200] Genes related to melanin production and melanocyte stimulation: NOS2 (Hs01075529_m1), NOS3 (Hs01574659_m1), PTGS1 (Hs00377726_m1), EDN2 (Hs00266516_m1)

[0201] For the test substance, the component concentrations in the test solution are as follows.

[0202] (A) L-cysteine ​​(TCI): 0.2 mg / mL

[0203] (B) Ascorbic acid (TCI): 0.01 mg / mL

[0204] (C) Angelica sinensis: Dried Angelica sinensis extract (manufactured by Xiaocheng Pharmaceutical Co., Ltd.), with an Angelica sinensis concentration of 0.4 mg / mL based on the raw herb.

[0205] (C) Riboflavin hydrochloride (manufactured by Sigma): 0.03 mg / mL

[0206] (C) Pyridoxine hydrochloride (manufactured by Nakalai Tesque): 0.06 mg / mL

[0207] (C) Pantothenic acid (Ca): D-calcium pantothenate (manufactured by Nakalai Tesque), 0.12 mg / mL

[0208] (C) DL-α-tocopherol acetate (manufactured by Fujifilm and Hikari Pure Chemical Industries): 0.25 mg / mL

[0209] (C) γ-oryzanol (manufactured by Fujifilm and Hikari Pure Chemical Industries): 0.05 mg / mL

[0210] Calcium phosphorylated oligosaccharide (manufactured by Glico Nutritional Products): 1 mg / mL

[0211] 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).

[0212] The expression ratios of the examples listed in each table are the ratios of the expression levels of each composition when the expression level of the control example containing components (A) and (B) but not component (C) is 1.00. "*" in the table indicates a significant difference relative to the control examples in the same table (p<0.05, t-test).

[0213] The criteria for determining the expression ratios in each table are as follows. A through C are considered acceptable.

[0214] A: Less than 0.50

[0215] B: 0.50 or higher to less than 0.65

[0216] C: 0.65 or higher and 0.80 or lower

[0217] -: Exceeding 0.80

[0218] in addition, Figures 1-4 The figures show the evaluation results of the control and example examples for the gene expression levels of NOS3, NOS2, PTGS1, and EDN2, respectively.

[0219]

[0220]

[0221]

[0222] (Formulation Examples 1-13)

[0223] Tablets are manufactured according to the composition in Table 5 below (4 tablets per day) using conventional methods.

[0224]

[0225] This application claims priority based on Japanese Patent Application No. 2023-153908, filed on September 20, 2023, all of the disclosures of which are incorporated herein by reference.

Claims

1. A skin improver containing the following ingredients A to C: Component A is at least one selected from L-cysteine, its derivatives, and their salts. Component B is at least one selected from ascorbic acid, its derivatives, and their salts. Component C is selected from one or more of vitamins B5, B6, B2, E, γ-oryzanol, and Angelica sinensis and its extracts.

2. The skin improver according to claim 1 is a whitening agent.

3. The skin improver according to claim 1 or 2, wherein it is one or more reducing agents selected from spots, freckles and post-inflammatory hyperpigmentation.

4. The skin improver according to any one of claims 1 to 3, wherein it is a melanin production inhibitor.

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