Skin-improving agent

Abstract

Provided is a skin-improving agent comprising the component (A1) or (A2) and the component (B1) or (B2) mentioned below. (A1) At least one component selected from the group consisting of Japanese angelica root and an extract thereof; (A2) gamma oryzanol; (B1) one or more components selected from the group consisting of vitamin B5 compounds, vitamin B6 compounds, vitamin B2 compounds, vitamin B3 compounds, L-cysteine and derivatives thereof, and salts of L-cysteine and the derivatives, ascorbic acid and derivatives thereof, and salts of ascorbic acid and the derivatives, and vitamin E compounds; and (B2) one or more components selected from the group consisting of vitamin B5 compounds, vitamin B6 compounds, L-cysteine and derivatives thereof, and salts of L-cysteine and the derivatives, ascorbic acid and derivatives thereof, and salts of ascorbic acid and the derivatives, and vitamin B2 compounds.

Description

Skin improver

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

[0002] When skin is damaged by UV rays or other factors, melanin production is stimulated in melanocytes. This melanin is then transferred to keratinocytes, protecting the epidermis from UV rays. Meanwhile, keratinocytes divide and proliferate in the basal layer of the epidermis, synthesizing proteins and lipids while differentiating into spinous cells and granular cells. They then differentiate into keratinocytes, forming the stratum corneum, which then sheds as dead skin cells. This process is called epidermal turnover, and melanin produced by UV rays is shed along with old cells during epidermal turnover. However, a decrease in epidermal turnover due to external factors such as dryness and UV rays, or internal factors such as aging, can cause melanin to remain in the epidermis, resulting in age spots, freckles, and pigmentation caused by 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 characterized by 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] According to the present invention, the following skin improving agent is provided. [1] A skin improving agent containing the following component (A1) or (A2) and the following component (B1) or (B2): (A1) at least one selected from the group consisting of Angelica acutiloba and extracts thereof; (A2) gamma oryzanol; (B1) one or more selected from the group consisting of vitamin B5s, vitamin B6s, vitamin B2s, vitamin B3s, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin E; (B2) one or more selected from the group consisting of vitamin B5s, vitamin B6s, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin B2s. [2] The skin improving agent according to [1], which contains the components (A1) and (B1). [3] The skin improving agent according to [1], which contains the components (A2) and (B2). [4] The skin improving agent according to any one of [1] to [3], which is a skin whitening agent. [5] The skin improving agent according to any one of [1] to [4], which is a turnover promoter. [6] The skin improving agent according to any one of [1] to [5], which is a stratum corneum exfoliation promoter. [7] The skin improving agent according to any one of [1] to [6], which is a tight junction formation promoter.

[0009] According to the present invention, a new skin improving agent can be obtained.

[0010] FIG. 1 is a diagram showing the evaluation results of gene expression level of LOR. FIG. 1 is a diagram showing the evaluation results of gene expression level of TGM1. FIG. 1 is a diagram showing the evaluation results of gene expression level of KRT10. FIG. 1 is a diagram showing the evaluation results of gene expression level of FLG. FIG. 1 is a diagram showing the evaluation results of gene expression level of IVL. FIG. 1 is a diagram showing the evaluation results of gene expression level of KLK5. FIG. 1 is a diagram showing the evaluation results of gene expression level of KLK7. FIG. 1 is a diagram showing the evaluation results of gene expression level of CTSD. FIG. 1 is a diagram showing the evaluation results of gene expression level of CLDN1. FIG. 1 is a diagram showing the evaluation results of gene expression level of OCLN. FIG. 1 is a diagram showing the evaluation results of gene expression level of LOR. FIG. 1 is a diagram showing the evaluation results of gene expression level of TGM1. FIG. 1 is a diagram showing the evaluation results of gene expression level of FLG. FIG. 1 is a diagram showing the evaluation results of gene expression level of IVN.

[0011] 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.

[0012] In this embodiment, the skin improving agent contains the following component (A1) or (A2) and the following component (B1) or (B2): (A1) at least one selected from the group consisting of Angelica acutiloba and extracts thereof (A2) gamma oryzanol (B1) one or more selected from the group consisting of vitamins B5, vitamins B6, vitamins B2, vitamins B3, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin E (B2) one or more selected from the group consisting of vitamins B5, vitamins B6, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin B2.

[0013] By containing a combination of component (A1) or (A2) and component (B1) or (B2), the skin improving agent can achieve an excellent skin improving effect. Hereinafter, embodiments of the skin improving agent will be described in more detail. The configurations described in the following embodiments can be combined as appropriate.

[0014] First Embodiment The present inventors have found that an excellent skin-improving effect can be obtained by combining at least one member selected from the group consisting of Angelica acutiloba and extracts thereof with a specific component.

[0015] (Skin improving agent) In this embodiment, the skin improving agent contains the following components (A1) and (B1): (A1) at least one selected from the group consisting of Angelica acutiloba and extracts thereof (B1) one or more selected from the group consisting of vitamin B5, vitamin B6, vitamin B2, vitamin B3, L-cysteine, its derivatives and salts thereof, ascorbic acid, its derivatives and salts thereof, and vitamin E.

[0016] Specifically, the skin improving agent is a composition containing the above-mentioned components (A1) and (B1), i.e., component (A1) and one or more selected from the group consisting of vitamin B5s, vitamin B6s, vitamin B2s, vitamin B3s, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin Es.

[0017] In this embodiment, the combined use of components (A1) and (B1) can provide an excellent skin-improving effect. Specifically, it has been newly discovered that the combined use of components (A1) and (B1) enhances the expression levels of specific genes related to skin turnover and barrier function compared to the use of component (A1) alone.

[0018] That is, the skin improvement agent is preferably an agent for enhancing the expression level of genes related to skin turnover and barrier function, and more preferably an agent for enhancing the expression level of one or more genes selected from the group consisting of genes that characterize the differentiation and maturation of epidermal cells, genes that constitute tight junctions, and genes related to the exfoliation of the stratum corneum.

[0019] Enhancement of the expression level of genes that characterize the differentiation and maturation of epidermal cells indicates, for example, promotion of skin turnover. The skin improving agent is preferably a turnover promoter. The skin improving agent may also be, for example, an epidermal metabolism promoter or an epidermal differentiation promoter. Furthermore, promotion of turnover can, for example, suppress the retention of melanin, thereby imparting a whitening effect. The skin improving agent is preferably a whitening agent.

[0020] The gene associated with promoting differentiation of skin cells is specifically one or more genes selected from the group consisting of loricrin (LOR), transglutaminase 1 (TGM1), keratin 10 (KRT10), filaggrin (FLG), and involucrin (IVL). The skin improving agent is preferably an agent for enhancing the expression level of one or more genes selected from the group consisting of LOR, TGM1, KRT10, FLG, and IVL.

[0021] By enhancing the expression level of genes that constitute tight junctions, for example, it is possible to improve the skin barrier function. Furthermore, the skin improving agent is preferably a tight junction formation promoter. Furthermore, the skin improving agent may be, for example, a skin barrier function improving agent. Furthermore, when the skin barrier function is improved by promoting the formation of tight junctions, the effects of ultraviolet rays on the skin can be reduced, thereby providing a whitening effect.

[0022] Specifically, the gene associated with the promotion of tight junction formation is at least one gene selected from the group consisting of claudin 1 (CLDN1) and occludin (OCLN). Furthermore, the skin improving agent is preferably an agent for enhancing the expression level of at least one gene selected from the group consisting of CLDN1 and OCLN.

[0023] By enhancing the expression level of genes related to the peeling of the stratum corneum, for example, thickening of the stratum corneum can be suppressed. The skin improving agent is preferably an agent for promoting the peeling of the stratum corneum, more preferably an agent for promoting the degradation of corneodesmosomes. In addition, by promoting the peeling of the stratum corneum, for example, retention of melanin can be suppressed, thereby providing a whitening effect.

[0024] Specifically, the gene associated with stratum corneum peeling is one or more genes selected from the group consisting of kalliculin 5 (KLK5), kalliculin 7 (KLK7), and cathepsin D (CTDS). Furthermore, the skin improving agent is preferably an agent for enhancing the expression level of one or more genes selected from the group consisting of KLK5, KLK7, and CTDS.

[0025] (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.

[0026] 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.

[0027] 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.

[0028] 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.

[0029] (Component (A1)) Component (A1) is at least one member selected from the group consisting of Angelica acutiloba Kitagawa and extracts thereof. Component (A1) specifically includes at least one extract thereof, such as Angelica acutiloba Kitagawa (Angelica acutiloba Kitagawa) and its extract (Angelica acutiloba extract). There are no limitations on the part of Angelica acutiloba that is the raw material for the extract, and it may be, for example, one or more members selected from the group consisting of leaves, branches, stems, flowers, fruits, and roots, with roots being preferred.

[0030] 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.

[0031] Component (A1) is preferably a solid such as a powder. This can improve the production stability of the skin improving agent. Furthermore, in order to stably obtain the skin improving effect, it is preferable that component (A1) is a non-enzyme-treated product.

[0032] The content of component (A1) 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 component (A1) in a single dose of the skin improving agent is preferably 600 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.

[0033] The amount of component (A1) per daily application dose 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 original herbal medicine. This allows for a further enhancement of the skin-improving effect. Furthermore, the amount of component (A1) per daily application dose is preferably 1200 mg or less, more preferably 800 mg or less, and even more preferably 600 mg or less, in terms of the amount of the original herbal medicine. This allows for a more efficient enhancement of the skin-improving effect.

[0034] 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.

[0035] (Component (B1)) Component (B1) is one or more selected from the group consisting of vitamins B5, vitamin B6, vitamin B2, vitamin B3, L-cysteine, its derivatives and salts thereof, ascorbic acid, its derivatives and salts thereof, and vitamin E, and preferably two or more selected from the above group. This makes it possible to obtain a skin improving effect more stably. Component (B1) is preferably a solid such as a powder. This makes it possible to improve the production stability of the skin improving agent.

[0036] (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.

[0037] 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.

[0038] 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.

[0039] The mass ratio of the content of vitamin B5 to the content of component (A1) in terms of crude drug (vitamin B5 / (A1)) is preferably 0.001 or more, more preferably 0.005 or more, even more preferably 0.01 or more, and even more preferably 0.05 or more. This allows for a further enhancement of the skin-improving effect. Furthermore, the mass ratio (vitamin B5 / (A1)) is preferably 1 or less, more preferably 0.75 or less, even more preferably 0.5 or less, and even more preferably 0.25 or less. This allows for a more efficient enhancement of the skin-improving effect.

[0040] (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.

[0041] 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.

[0042] 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.

[0043] 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.

[0044] The mass ratio of the content of vitamin B6 to the content of component (A1) in terms of crude drug (vitamin B6 / (A1)) is preferably 0.001 or more, more preferably 0.0025 or more, even more preferably 0.005 or more, and even more preferably 0.01 or more. This allows for a further enhancement of the skin-improving effect. Furthermore, the mass ratio (vitamin B6 / (A1)) is preferably 1 or less, more preferably 0.75 or less, even more preferably 0.5 or less, and even more preferably 0.25 or less. This allows for a more efficient enhancement of the skin-improving effect.

[0045] (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.

[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, 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.

[0047] 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.

[0048] The mass ratio of the content of vitamin B2 to the content of component (A1) in terms of crude drug equivalent (vitamin B2 / (A1)) is preferably 0.001 or more, more preferably 0.0025 or more, even more preferably 0.005 or more, and even more preferably 0.01 or more. This allows for a further enhancement of the skin-improving effect. Furthermore, the mass ratio (vitamin B2 / (A1)) is preferably 0.5 or less, more preferably 0.25 or less, even more preferably 0.2 or less, and even more preferably 0.15 or less. This allows for a more efficient enhancement of the skin-improving effect.

[0049] (Vitamin B3) Specifically, the vitamin B3 is at least one compound selected from the group consisting of nicotinic acid and nicotinamide, and preferably nicotinamide. This allows for a more stable skin-improving effect. Nicotinamide is listed in the 18th revised Japanese Pharmacopoeia. As the vitamin B3, including nicotinamide, for example, commercially available products can be used.

[0050] The content of vitamin B3 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 B3 in the skin improving agent is preferably 100 mg or less, more preferably 75 mg or less, and even more preferably 60 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 B3 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 can further enhance the skin improving effect. Furthermore, the content of vitamin B3 in the skin improving agent is preferably 150 mg or less, more preferably 75 mg or less, and even more preferably 60 mg or less, per daily application amount. This can more efficiently enhance the skin improving effect.

[0052] The mass ratio of the content of vitamin B3 to the content of component (A1) in terms of crude drug equivalent (vitamin B3 / (A1)) is preferably 0.01 or more, more preferably 0.025 or more, even more preferably 0.05 or more, and even more preferably 0.1 or more. This allows for a further enhancement of the skin-improving effect. Furthermore, the mass ratio (vitamin B3 / (A1)) 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 enhancement of the skin-improving effect.

[0053] (L-cysteine, its derivatives, and salts thereof) The skin improving agent may contain, as component (B1), one or more compounds selected from the group consisting of L-cysteine, its derivatives, and salts thereof. L-cysteine, its derivatives, and salts thereof may be hydrates. L-cysteine, its derivatives, and salts thereof are known compounds, and may be obtained as commercially available products or may be produced based on known methods. L-cysteine ​​is listed in the 18th edition of the Japanese Pharmacopoeia. Specific examples of L-cysteine, its derivatives, and salts thereof include L-cysteine; L-cysteine ​​derivatives such as N-acetyl-L-cysteine, L-homocysteine, L-cysteic acid, L-homocysteic acid, L-cysteine ​​sulfinic 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 such as hydrochloride, nitrate, and sulfate, alkali metal salts such as sodium salt, potassium salt, calcium salt, and magnesium salt, and alkaline earth metal salts. L-cysteine, its derivatives, and salts thereof may contain one or more compounds selected from this group, and preferably contain at least one compound selected from the group consisting of L-cysteine ​​and L-cysteine ​​salts such as L-cysteine ​​hydrochloride hydrate, and more preferably L-cysteine. This allows for more stable skin-improving effects to be obtained.

[0054] The content of L-cysteine, its derivatives, and salts thereof 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 allows for a further enhancement of the skin improving effect. Furthermore, the content of L-cysteine, its derivatives, and salts 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 allows for a more efficient enhancement of the skin improving effect.

[0055] The content of L-cysteine, its derivatives, and salts thereof 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 allows for a further enhancement of the skin improving effect. Furthermore, the content of L-cysteine, its derivatives, and salts thereof 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 allows for a more efficient enhancement of the skin improving effect.

[0056] The mass ratio of the content of L-cysteine, its derivatives, and salts thereof to the content of component (A1) in terms of the crude drug (L-cysteine, its derivatives, and salts thereof / (A1)) is preferably 0.01 or more, more preferably 0.05 or more, even more preferably 0.1 or more, and even more preferably 0.5 or more. This allows for a more enhanced skin-improving effect. Furthermore, the mass ratio (L-cysteine, its derivatives, and salts thereof / (A1)) is preferably 10 or less, more preferably 5 or less, even more preferably 3 or less, and even more preferably 2.5 or less. This allows for a more efficient enhancement of the skin-improving effect.

[0057] (Ascorbic acid, its derivatives, and salts thereof) The skin improving agent may contain, as component (B1), one or more compounds selected from the group consisting of ascorbic acid, its derivatives, and salts thereof. Ascorbic acid, its derivatives, and salts thereof may be hydrates. Ascorbic acid, its derivatives, and salts thereof are known compounds, and may be obtained as commercially available products or may be produced according to known methods. Ascorbic acid is listed in the 18th edition of the Japanese Pharmacopoeia. Specific examples of ascorbic acid, its derivatives, and salts thereof include ascorbic acid; ascorbate salts such as sodium ascorbate, magnesium ascorbate, potassium ascorbate, and calcium ascorbate; ascorbate monoalkyl or monoalkenyl esters such as ascorbate monostearate, ascorbate monopalmitate, and ascorbate monooleate; ascorbate dialkyl or dialkenyl esters such as ascorbate distearate, ascorbate dipalmitate, and ascorbate dioleate; ascorbate tristearate, ascorbate diglyceride ... Examples of the ascorbic acid trialkyl or trialkenyl esters include ascorbic acid tripalmitate and ascorbic acid trioleate; ascorbic acid sulfate 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. Ascorbic acid, its derivatives, and salts thereof may contain one or more compounds selected from these groups, and preferably contain at least one 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 a more stable skin improvement effect.

[0058] The content of ascorbic acid, its derivatives and salts thereof 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, in terms of 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 ascorbic acid, its derivatives and salts thereof in a single dose of the skin improving agent is 500 mg or more. In addition, the content of ascorbic acid, its derivatives and salts thereof in the skin improving agent is preferably 4000 mg or less, more preferably 3500 mg or less, and even more preferably 2000 mg or less, in terms of the content in a single dose of the skin improving agent. This can more efficiently enhance the skin improving effect.

[0059] The content of ascorbic acid, its derivatives, and salts thereof 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, 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 ascorbic acid, its derivatives, and salts thereof in a daily dose of the skin improving agent is preferably 800 mg or more, and more preferably 1000 mg or more. In addition, the content of ascorbic acid, its derivatives, and salts thereof in the skin improving agent may be, for example, 4000 mg or less, preferably 3500 mg or less, per daily application amount. In addition, in order to obtain a more efficient skin improving effect, the content of ascorbic acid, its derivatives, and salts thereof per daily application amount is preferably 3000 mg or less, more preferably 2500 mg or less, and even more preferably 2000 mg or less.

[0060] The mass ratio of the content of ascorbic acid, its derivatives, and salts thereof to the content of component (A1) in terms of the crude drug equivalent (ascorbic acid, its derivatives, and salts thereof / (A1)) is preferably 0.01 or more, more preferably 0.05 or more, even more preferably 0.1 or more, and even more preferably 0.5 or more. This can further enhance the skin-improving effect. Furthermore, the mass ratio (ascorbic acid, its derivatives, and salts thereof / (A1)) is preferably 50 or less, more preferably 30 or less, even more preferably 25 or less, and even more preferably 20 or less. This can more efficiently enhance the skin-improving effect. Furthermore, the mass ratio (ascorbic acid, its derivatives, and salts thereof / (A1)) can be, for example, 1 or less.

[0061] (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 Extra Pharmaceutical Standards 2002, such as d-α-tocopherol, d-α-tocopherol acetate, DL-α-tocopherol acetate, and d-α-tocopherol succinate; and synthetic vitamin E such as dl-α-tocopherol succinate, more preferably 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.

[0062] 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 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 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 can more efficiently enhance the skin improving effect.

[0063] 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 5 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.

[0064] The mass ratio of the content of vitamin E to the content of component (A1) in terms of crude drug (vitamin E / (A1)) is preferably 0.005 or more, more preferably 0.01 or more, even more preferably 0.025 or more, and even more preferably 0.1 or more. This allows for a further enhancement of the skin-improving effect. Furthermore, the mass ratio (vitamin E / (A1)) is preferably 3 or less, more preferably 2 or less, even more preferably 1 or less, and even more preferably 0.5 or less. This allows for a more efficient enhancement of the skin-improving effect.

[0065] Component (B1) preferably contains one or more compounds selected from the group consisting of L-cysteine, its derivatives and salts thereof, vitamin B6, vitamin B5, vitamin E, and ascorbic acid, its derivatives and salts thereof, and more preferably contains one or more compounds selected from the group consisting of L-cysteine, pyridoxine hydrochloride, calcium pantothenate, tocopherol, and ascorbic acid. This can enhance the expression level of at least one of genes that characterize the differentiation and maturation of epidermal cells, genes that constitute tight junctions, and genes related to the exfoliation of the stratum corneum. This can, for example, promote skin turnover and provide a whitening effect.

[0066] Component (B1) preferably contains at least one of vitamin B5, L-cysteine, its derivatives, and salts thereof, and ascorbic acid, its derivatives, and salts thereof, and more preferably contains calcium pantothenate, L-cysteine, and at least one of ascorbic acid. This can promote differentiation of epidermal cells and accelerate cell turnover. It can also promote exfoliation of keratin.

[0067] Furthermore, component (B1) may contain, for example, at least one of ascorbic acid, a derivative thereof, and a salt thereof, and one or more selected from the group consisting of vitamins B5, B6, B2, B3, L-cysteine, a derivative thereof, and a salt thereof, and vitamin E; more specifically, component (B1) may contain ascorbic acid and one or more selected from the group consisting of calcium pantothenate, pyridoxine hydrochloride, riboflavin or riboflavin butyrate, nicotinamide, L-cysteine, and tocopherol succinate.

[0068] When the skin improving agent is an LOR expression promoter, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent. Furthermore, in the following mass ratios, each component can take a value within a numerical range. For example, if "x:y=1-10:1-15", 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. Component (A1): L-cysteine ​​= 1-10: 1-300 Component (A1): riboflavin = 1-100: 1-50 Component (A1): pyridoxine hydrochloride = 1-100: 2-100 Component (A1): calcium pantothenate = 1-100: 1-80 Component (A1): ascorbic acid = 1-10: 1-20 Component (A1): tocopherol succinate = 1-100: 1-200 Component (A1): calcium pantothenate: L-cysteine ​​or ascorbic acid = 1-100: 1-100: 1-200

[0069] When the skin improving agent is a TGM1 expression promoter, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent. Component (A1): calcium pantothenate = 1-100: 1-80 Component (A1): ascorbic acid = 1-10: 1-20 Component (A1): calcium pantothenate: L-cysteine ​​= 1-100: 1-100: 1-200

[0070] When the skin improving agent is an expression promoter for KRT10, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent. Component (A1): calcium pantothenate = 1-100: 1-80 Component (A1): tocopherol succinate = 1-100: 1-200 Component (A1): pyridoxine hydrochloride = 1-100: 2-100 Component (A1): ascorbic acid = 1-10: 1-20 Component (A1): nicotinamide = 1-100: 1-10 Component (A1): L-cysteine ​​or ascorbic acid: calcium pantothenate = 1-100: 1-200: 1-100

[0071] When the skin improving agent is an FLG expression promoter, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent. Component (A1): pyridoxine hydrochloride = 1-100: 2-100 Component (A1): calcium pantothenate = 1-100: 1-80 Component (A1): L-cysteine ​​= 1-10: 1-300 Component (A1): riboflavin = 1-100: 1-50 Component (A1): tocopherol succinate = 1-100: 1-200 Component (A1): L-cysteine ​​or ascorbic acid: calcium pantothenate = 1-100: 1-200: 1-100

[0072] When the skin improving agent is an agent for promoting the expression of IVL, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent. Component (A1): calcium pantothenate = 1-100: 1-80 Component (A1): pyridoxine hydrochloride = 1-100: 2-100 Component (A1): tocopherol succinate = 1-100: 1-200 Component (A1): L-cysteine ​​or ascorbic acid: calcium pantothenate = 1-100: 1-200: 1-100

[0073] When the skin improving agent is an agent for promoting KLK5 expression, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent: Component (A1): calcium pantothenate = 1-100: 1-80 Component (A1): tocopherol succinate = 1-100: 1-200

[0074] When the skin improving agent is a KLK7 expression promoter, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent: Component (A1): ascorbic acid = 1-10: 1-20 Component (A1): calcium pantothenate: ascorbic acid = 1-100: 1-100: 1-200

[0075] When the skin improving agent is a promoter for the development of CTSD, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent: Component (A1): calcium pantothenate = 1-100: 1-80 Component (A1): tocopherol succinate = 1-100: 1-200

[0076] When the skin improving agent is a CLDN1 expression promoter, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent. Component (A1): pyridoxine hydrochloride = 1-100: 2-100 Component (A1): ascorbic acid = 1-10: 1-20 Component (A1): tocopherol succinate = 1-100: 1-200

[0077] When the skin improving agent is an agent for promoting the expression of OCLN, preferred examples of combinations of components (A1) and (B1) include the following. The following ratios are mass ratios of the components in the skin improving agent: Component (A1): L-cysteine ​​= 1-10: 1-300 Component (A1): ascorbic acid = 1-10: 1-20 Component (A1): tocopherol succinate = 1-100: 1-200

[0078] The total content of component (B1) in the skin improving agent, as the content in a single dose of the skin improving agent, is preferably 15 mg or more, more preferably 50 mg or more, and even more preferably 300 mg or more. This makes it possible to further enhance the skin improving effect. Furthermore, the total content of component (B1) in the skin improving agent, as the content in a single dose of the skin improving agent, is preferably 4000 mg or less, more preferably 3000 mg or less, and even more preferably 2000 mg or less. This makes it possible to more efficiently enhance the skin improving effect.

[0079] The total content of component (B1) in the skin improving agent is preferably 50 mg or more, more preferably 200 mg or more, and even more preferably 1000 mg or more, as a content per daily application amount. This can further enhance the skin improving effect. Furthermore, the total content of component (B1) in the skin improving agent is preferably 4000 mg or less, more preferably 3000 mg or less, and even more preferably 2000 mg or less, as a content per daily application amount. This can more efficiently enhance the skin improving effect.

[0080] The mass ratio of the total content of component (B1) in the skin improving agent to the content of component (A1) in terms of the crude drug equivalent (total content of component (B1) in the skin improving agent / (A1)) is preferably 0.02 or more, more preferably 0.05 or more, even more preferably 0.075 or more, and even more preferably 0.1 or more. This can further enhance the skin improving effect. The mass ratio (total content of component (B1) in the skin improving agent / (A1)) may be, for example, 2 or more. The mass ratio (total content of component (B1) in the skin improving agent / (A1)) is preferably 100 or less, more preferably 75 or less, even more preferably 50 or less, and even more preferably 25 or less. This can more efficiently enhance the skin improving effect. The mass ratio (total content of component (B1) in the skin improving agent / (A1)) may be, for example, 5 or less.

[0081] (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.

[0082] 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.

[0083] 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.

[0084] 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.

[0085] 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.

[0086] 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.

[0087] 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.

[0088] 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.

[0089] 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.

[0090] 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.

[0091] Furthermore, when the skin improving agent is provided as a composition that exhibits a whitening effect, the skin improving agent may further contain a known component other than components (A1) and (B1) that exhibits a whitening effect or a component that enhances the whitening effect. 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); 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.

[0092] (Production Method) In the present embodiment, the production method of the skin improving agent includes, for example, a step of blending components (A1) and (B1) and, if necessary, other components. The production method of the skin improving agent can be, for example, produced according to its dosage form, and made into a preparation.

[0093] (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.

[0094] 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.

[0095] 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.

[0096] 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 be provided with a zipper function.

[0097] (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.

[0098] According to this embodiment, for example, the following skin improving agents can be provided. [1-1] A skin improving agent containing the following components (A1) and (B1): (A1) at least one selected from the group consisting of Angelica acutiloba and extracts thereof; (B1) one or more selected from the group consisting of vitamin B5s, vitamin B6s, vitamin B2s, vitamin B3s, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin E; [1-2] The skin improving agent according to [1-1], which is a skin whitening agent; [1-3] The skin improving agent according to [1-1] or [1-2], which is a turnover promoter; [1-4] The skin improving agent according to any one of [1-1] to [1-3], which is an agent for promoting exfoliation of the stratum corneum; [1-5] The skin improving agent according to any one of [1-1] to [1-4], which is a tight junction formation promoter.

[0099] Second Embodiment The present inventors have found that an excellent skin improving effect can be obtained by combining gamma oryzanol with a specific component.

[0100] (Skin improving agent) In the present embodiment, the skin improving agent contains the following components (A2) and (B2): (A2) gamma oryzanol (B2) one or more selected from the group consisting of vitamin B5s, vitamin B6s, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin B2s The skin improving agent is specifically a composition containing the above components (A2) and (B2).

[0101] In this embodiment, the combined use of components (A2) and (B2) can provide an excellent skin-improving effect. Specifically, it has been newly discovered that the combined use of components (A2) and (B2) enhances the expression levels of specific genes related to skin turnover and barrier function compared to the use of component (A2) alone.

[0102] That is, the skin improvement agent is preferably an agent for enhancing the expression level of genes related to skin turnover and barrier function, and more preferably an agent for enhancing the expression level of one or more genes selected from the group consisting of genes that characterize the differentiation and maturation of epidermal cells and genes that constitute tight junctions.

[0103] Enhancement of the expression level of genes that characterize the differentiation and maturation of epidermal cells indicates, for example, promotion of skin turnover. The skin improving agent is preferably a turnover promoter. The skin improving agent may also be, for example, an epidermal metabolism promoter or an epidermal differentiation promoter. Furthermore, by enhancing the expression level of genes related to the promotion of skin cell differentiation, it is possible to improve, for example, the skin barrier function. The skin improving agent may also be, for example, a skin barrier function improver. Furthermore, when the skin barrier function is improved by promoting turnover, the effects of ultraviolet rays on the skin can be reduced. Promotion of turnover can, for example, suppress the retention of melanin. Therefore, it is possible to impart a whitening effect to the skin. The skin improving agent is preferably a whitening agent.

[0104] Specifically, the gene associated with promoting differentiation of skin cells is one or more genes selected from the group consisting of loricrin (LOR), transglutaminase 1 (TGM1), keratin 10 (KRT10), filaggrin (FLG), and involucrin (IVN). The skin improving agent is preferably an expression enhancer for one or more genes selected from the group consisting of LOR, TGM1, KRT10, FLG, and IVN, and more preferably an expression enhancer for one or more genes selected from the group consisting of LOR, TGM1, FLG, and IVN.

[0105] (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.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] (Component (A2)) Component (A2) is gamma oryzanol. As component (A2), for example, a commercially available product can be used. Component (A2) is preferably a solid such as a powder. This can improve the production stability of the skin improving agent.

[0110] 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.

[0111] 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.

[0112] 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.

[0113] (Component (B2)) Component (B2) is one or more selected from the group consisting of vitamins B5, vitamin B6, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin B2, and preferably two or more selected from the above group. This makes it possible to obtain a skin improving effect more stably. Component (B2) is preferably a solid such as a powder. This makes it possible to improve the production stability of the skin improving agent.

[0114] (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.

[0115] 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.

[0116] 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.

[0117] The mass ratio of the content of vitamin B5 to the content of component (A2) (vitamins B5 / (A2)) is preferably 0.25 or more, more preferably 0.5 or more, even more preferably 0.75 or more, even more preferably 1 or more, and even more preferably 2 or more. This allows the skin improving effect to be further enhanced. Furthermore, the mass ratio (vitamins B5 / (A2)) is preferably 10 or less, more preferably 6 or less, even more preferably 4.5 or less, and even more preferably 3 or less. This allows the skin improving effect to be more efficiently enhanced.

[0118] (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.

[0119] 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.

[0120] 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.

[0121] 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.

[0122] The mass ratio of the content of vitamin B6 to component (A2) (vitamin B6 / (A2)) is preferably 0.25 or more, more preferably 0.5 or more, even more preferably 0.75 or more, and even more preferably 1 or more. This allows the skin improving effect to be further enhanced. Furthermore, the mass ratio (vitamin B6 / (A2)) is preferably 25 or less, more preferably 12 or less, even more preferably 6 or less, and even more preferably 3 or less. This allows the skin improving effect to be more efficiently enhanced.

[0123] (L-cysteine, its derivatives, and salts thereof) The skin improving agent may contain, as component (B2), one or more compounds selected from the group consisting of L-cysteine, its derivatives, and salts thereof. L-cysteine, its derivatives, and salts thereof may be hydrates. L-cysteine, its derivatives, and salts thereof are known compounds, and may be obtained as commercially available products or may be produced according to known methods. L-cysteine ​​is listed in the 18th edition of the Japanese Pharmacopoeia. Specific examples of L-cysteine, its derivatives, and salts thereof include L-cysteine; L-cysteine ​​derivatives such as N-acetyl-L-cysteine, L-homocysteine, L-cysteic acid, L-homocysteic acid, L-cysteine ​​sulfinic 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 such as hydrochloride, nitrate, and sulfate, alkali metal salts such as sodium salt, potassium salt, calcium salt, and magnesium salt, and alkaline earth metal salts. L-cysteine, its derivatives, and salts thereof may contain one or more compounds selected from this group, and preferably contain at least one compound selected from the group consisting of L-cysteine ​​and L-cysteine ​​salts such as L-cysteine ​​hydrochloride hydrate, and more preferably L-cysteine. This allows for more stable skin-improving effects to be obtained.

[0124] The content of L-cysteine, its derivatives, and salts thereof 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 allows for a further enhancement of the skin improving effect. Furthermore, the content of L-cysteine, its derivatives, and salts 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 allows for a more efficient enhancement of the skin improving effect.

[0125] The content of L-cysteine, its derivatives, and salts thereof 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 allows for a further enhancement of the skin improving effect. Furthermore, the content of L-cysteine, its derivatives, and salts thereof 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 allows for a more efficient enhancement of the skin improving effect.

[0126] The mass ratio of the content of L-cysteine, its derivatives, and salts thereof to component (A2) (L-cysteine, its derivatives, and salts thereof / (A2)) is preferably 1 or more, more preferably 2.5 or more, even more preferably 5 or more, still more preferably 10 or more, and even more preferably 20 or more. This allows for a further enhancement of the skin improving effect. Furthermore, the mass ratio (L-cysteine, its derivatives, and salts thereof / (A2)) is preferably 100 or less, more preferably 75 or less, even more preferably 50 or less, and even more preferably 30 or less. This allows for a more efficient enhancement of the skin improving effect.

[0127] (Ascorbic acid, its derivatives, and salts thereof) The skin improving agent may contain, as component (B2), one or more compounds selected from the group consisting of ascorbic acid, its derivatives, and salts thereof. Ascorbic acid, its derivatives, and salts thereof may be hydrates. Ascorbic acid, its derivatives, and salts thereof are known compounds, and may be obtained as commercially available products or may be produced according to known methods. Ascorbic acid is listed in the 18th edition of the Japanese Pharmacopoeia. Specific examples of ascorbic acid, its derivatives, and salts thereof include ascorbic acid; ascorbate salts such as sodium ascorbate, magnesium ascorbate, potassium ascorbate, and calcium ascorbate; ascorbate monoalkyl or monoalkenyl esters such as ascorbate monostearate, ascorbate monopalmitate, and ascorbate monooleate; ascorbate dialkyl or dialkenyl esters such as ascorbate distearate, ascorbate dipalmitate, and ascorbate dioleate; ascorbate tristearate, ascorbate diglyceride ... Examples of the ascorbic acid trialkyl or trialkenyl esters include ascorbic acid tripalmitate and ascorbic acid trioleate; ascorbic acid sulfate 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. Ascorbic acid, its derivatives, and salts thereof may contain one or more compounds selected from these groups, and preferably contain at least one 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 a more stable skin improvement effect.

[0128] The content of ascorbic acid, its derivatives and salts thereof 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, in terms of 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 ascorbic acid, its derivatives and salts thereof in a single dose of the skin improving agent is 500 mg or more. In addition, the content of ascorbic acid, its derivatives and salts thereof 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, in terms of the content in a single dose of the skin improving agent. This can more efficiently enhance the skin improving effect.

[0129] The content of ascorbic acid, its derivatives, and salts thereof 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, 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 ascorbic acid, its derivatives, and salts thereof in the daily application amount of the skin improving agent is preferably 800 mg or more, and more preferably 1000 mg or more. In addition, the content of ascorbic acid, its derivatives, and salts thereof in the skin improving agent may be, for example, 4000 mg or less, preferably 3500 mg or less, per daily application amount. In addition, in order to obtain a more efficient skin improving effect, the content of ascorbic acid, its derivatives, and salts thereof per daily application amount is preferably 3000 mg or less, more preferably 2500 mg or less, and even more preferably 2000 mg or less.

[0130] The mass ratio of the content of ascorbic acid, its derivatives, and salts thereof to component (A2) (ascorbic acid, its derivatives, and salts thereof / (A2)) is preferably 0.01 or more, more preferably 0.05 or more, even more preferably 0.1 or more, even more preferably 0.25 or more, and even more preferably 0.5 or more. This can further enhance the skin improving effect. The mass ratio may be, for example, 150 or more. The mass ratio (ascorbic acid, its derivatives, and salts thereof / (A2)) is preferably 1000 or less, more preferably 500 or less, even more preferably 250 or less, and even more preferably 200 or less. This can more efficiently enhance the skin improving effect. The mass ratio may be, for example, 2 or less.

[0131] (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.

[0132] 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.

[0133] 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.

[0134] The mass ratio of the content of vitamin B2 to component (A2) (vitamin B2 / (A2)) is preferably 0.1 or more, more preferably 0.2 or more, even more preferably 0.4 or more, and even more preferably 0.6 or more. This can further enhance the skin improving effect. Furthermore, the mass ratio (vitamin B2 / (A2)) is preferably 4.8 or less, more preferably 2.4 or less, even more preferably 2 or less, and even more preferably 1.2 or less. This can more efficiently enhance the skin improving effect.

[0135] Component (B2) preferably contains one or more compounds selected from the group consisting of L-cysteine, riboflavin, riboflavin hydrochloride, riboflavin butyrate, pyridoxine hydrochloride, calcium pantothenate, and ascorbic acid. This allows for more stable enhancement of the expression level of at least one of the genes that characterize the differentiation and maturation of epidermal cells and the genes that constitute tight junctions. This allows for, for example, promotion of skin turnover and a whitening effect.

[0136] When the skin improving agent is an LOR expression promoter, preferred examples of combinations of components (A2) and (B2) include the following. The following ratios are mass ratios of the components in the skin improving agent. Furthermore, in the following mass ratios, each component can take a value within a numerical range. For example, if "x:y=1-10:1-15", 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. Component (A2): pyridoxine hydrochloride = 1-10: 1-15 Component (A2): L-cysteine: riboflavin, riboflavin hydrochloride, riboflavin butyrate, pyridoxine hydrochloride, or calcium pantothenate = 1-10: 1-200: 1-50 Component (A2): calcium pantothenate: ascorbic acid = 10-100: 1-500: 1-2000

[0137] When the skin improving agent is a TGM1 expression promoter, preferred examples of combinations of components (A2) and (B2) include the following. The following ratios are mass ratios of the components in the skin improving agent. Component (A2): L-cysteine ​​= 1-100: 1-2000 Component (A2): riboflavin, riboflavin hydrochloride, riboflavin butyrate, or pyridoxine hydrochloride = 1-10: 1-10 Component (A2): L-cysteine: riboflavin, riboflavin hydrochloride, riboflavin butyrate, pyridoxine hydrochloride, or calcium pantothenate = 1-10: 1-2000: 1-500 Component (A2): riboflavin, riboflavin hydrochloride, riboflavin butyrate, pyridoxine hydrochloride, or calcium pantothenate: ascorbic acid = 1-100: 1-500: 1-2000

[0138] When the skin improving agent is an FLG expression promoter, preferred examples of combinations of components (A2) and (B2) include the following. The following ratios are mass ratios of the components in the skin improving agent: Component (A2): L-cysteine ​​= 1-100: 1-2000 Component (A2): riboflavin, riboflavin hydrochloride, or riboflavin butyrate = 1-10: 1-10 Component (A2): L-cysteine: calcium pantothenate = 1-10: 1-200: 1-50

[0139] When the skin improving agent is an agent for promoting the expression of IVN, preferred examples of combinations of components (A2) and (B2) include the following. The following ratios are mass ratios of the components in the skin improving agent. Component (A2): riboflavin, riboflavin hydrochloride, riboflavin butyrate, or pyridoxine hydrochloride = 1-100: 1-100 Component (A2): ascorbic acid = 1-100: 1-2000

[0140] The total content of component (B2) in the skin improving agent, as the content in a single dose of the skin improving agent, is preferably 0.001 mg or more, more preferably 1 mg or more, and even more preferably 3 mg or more. This makes it possible to further enhance the skin improving effect. Furthermore, the total content of component (B2) in the skin improving agent, as the content in a single dose of the skin improving agent, is preferably 5000 mg or less, more preferably 4000 mg or less, and even more preferably 3000 mg or less. This makes it possible to more efficiently enhance the skin improving effect.

[0141] The total content of component (B2) in the skin improving agent is preferably 0.001 mg or more, more preferably 1 mg or more, and even more preferably 5 mg or more, as the content per daily application amount. This can further enhance the skin improving effect. Furthermore, the total content of component (B2) in the skin improving agent is preferably 5000 mg or less, more preferably 4000 mg or less, and even more preferably 3000 mg or less, as the content per daily application amount. This can more efficiently enhance the skin improving effect.

[0142] The mass ratio of the total content of component (B2) in the skin improving agent to component (A2) (total content of component (B2) in the skin improving agent / (A2)) is preferably 0.5 or more, more preferably 1 or more, even more preferably 10 or more, even more preferably 20 or more, still more preferably 25 or more, and is preferably 1000 or less, more preferably 750 or less, even more preferably 500 or less, and still more preferably 250 or less. This makes it possible to obtain a more stable skin improvement effect. Furthermore, the mass ratio (total content of component (B2) in the skin improving agent / (A2)) may be, for example, 200 or more. Furthermore, the mass ratio (total content of component (B2) in the skin improving agent / (A2)) may be, for example, 50 or less.

[0143] (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.

[0144] 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.

[0145] Of these, specific examples of the excipient, binder, disintegrant, flavoring agent, sweetener, sugar-coating agent, and coating agent include the excipient, binder, disintegrant, flavoring agent, sweetener, sugar-coating agent, and coating agent described above in the first embodiment, respectively.

[0146] Furthermore, when the skin improving agent is provided as a composition that exhibits a whitening effect, the skin improving agent may further contain a known component other than components (A2) and (B2) that exhibits a whitening effect or a component that enhances the whitening effect. 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; Tocopherol, its derivatives and salts thereof (tocopherols such as α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, etc.; tocopherol esters such as d-α-tocopherol acetate, DL-α-tocopherol acetate, d-α-tocopherol succinate, etc., dl-α-tocopherol succinate, etc.; salts thereof such as calcium salts); 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 their salts (glycyrrhizic acid; glycyrrhizinate salts such as dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, etc.; glycyrrhizic acid alkyl esters such as stearyl glycyrrhizinate, etc.); kojic acid, its derivatives, and their salts (kojic acid;Kojic acid monoalkyl esters such as kojic acid monobutyrate, kojic acid monocaprate, kojic acid monopalmitate, and kojic acid monostearate; kojic acid dialkyl esters such as kojic acid dibutyrate, kojic acid dipalmitate, kojic acid distearate, and 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; glutathione, its derivatives, and salts thereof (glutathione; S-acyl glutathiones such as S-lactoyl glutathione; N,S-diacyl glutathione diesters such as N,S-dioctanoyl glutathione distearyl, N,S-dipalmitoyl glutathione dicetyl); 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, 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, Licorice, Mulberry, Morus alba, Japanese mulberry, Sophora floriflora, Uva-ursi, Scutellaria baicalensis, Hariamiji, Hijiki, Artemisia japonica, Rock hyacinth, Dulse, Sargassum serrata (Sargassum serrata), Sargassum serrata, Sargassum fusiformis, Ishi Mozuku, 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 holly Millet, butterbur, tall violet, earth fruits, violet-like bellflower, tubular violet, Irezumi, Japanese anemone, Chinese laurel, Chinese laurel, Clematis, Eucommia, thorny jasmine, Japanese angelica, asparagus, Japanese laurel, pea, Chinese laurel, Scutellaria, Ononis, bramble, raspberry, lily, Chinese laurel, Chinese laurel, hawthorn, sunflower, white lily, Japanese anemone, mulberry, soybean, tea, angelica extract, molasses, white angelica , beech, grape seed, flordemanita, hops, octopus, mocca, monk fruit, aloe, althaea, arnica, angelica tree, inchinko, nettle, turmeric, phellodendron bark, chamomile, goldenrod, 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, raspberry, kakyoin, and extracts thereof; and placenta extract.

[0147] (Production Method) In the present embodiment, the production method of the skin improving agent includes, for example, a step of blending components (A2) and (B2) and other components as appropriate. The skin improving agent can be produced, for example, according to its dosage form, and made into a preparation.

[0148] (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.

[0149] 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.

[0150] 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.

[0151] 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 be provided with a zipper function.

[0152] (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.

[0153] According to the present embodiment, for example, the following skin improving agent can also be provided. [2-1] A skin improving agent containing the following components (A2) and (B2): (A2) gamma oryzanol (B2) one or more selected from the group consisting of vitamin B5s, vitamin B6s, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin B2s [2-2] The skin improving agent according to [2-1], which is a skin whitening agent. [2-3] The skin improving agent according to [2-1] or [2-2], which is a turnover promoter.

[0154] 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.

[0155] The present embodiment will be specifically described below with reference to examples, but the present embodiment is not limited to these examples.

[0156] Test Example 1 In this example, gene expression levels in human epidermal keratinocytes were measured by the following procedure: A human immortalized keratinocyte cell line (HaCat) was cultured in a 6-cm dish at 6.6 × 10 s by using Dulbecco's Modified Eagle Medium (Gibco). ５The 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), followed by 24 hours of culture. After removing the medium, 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 RNA expression levels of various genes were then measured by real-time PCR. Measurements were performed three times for each gene in each test example.

[0157] The genes whose expression levels were measured are shown below. The primers used are shown in parentheses (all manufactured by Thermo Fisher). Genes related to promoting skin cell differentiation: LOR (Hs01894962_s1), TGM1 (Hs00165929_m1), KRT10 (Hs00166289_m1), FLG (Hs00856927_g1), and IVL (Hs00846307_s1). Genes related to promoting tight junction formation: CLDN1 (Hs00221623_m1) and OCLN (Hs00170162_m1). Genes related to promoting stratum corneum peeling: KLK5 (Hs01548153_m1), KLK7 (Hs00192503_m1), and CTSD (Hs00157205_m1).

[0158] The test substances were contained in the test solutions with the following concentrations: Dried Angelica acutiloba extract (manufactured by Ogi Pharmaceutical Co., Ltd.): 0.4 mg / mL or 0.2 mg / mL as the concentration of Angelica acutiloba calculated as the crude drug L-cysteine ​​(manufactured by TCI): 0.06 mg / mL or 0.12 mg / mL Riboflavin (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.): 0.003 mg / mL Pyridoxine hydrochloride (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.): 0.003 mg / mL or 0.006 mg / mL D-calcium pantothenate (manufactured by Nacalai Tesque): 0.006 mg / mL or 0.012 mg / mL Ascorbic acid (manufactured by TCI): 0.25 mg / mL or 0.025 mg / mL Tocopherol succinate (d-α-tocopherol succinate, manufactured by TCI): 0.0125 mg / mL or 0.025 mg / mL Nicotinamide (Nacalai Tesque): 0.03 mg / mL Phosphorylated oligosaccharide calcium (Glyco Nutrition Foods): 0.1% by mass

[0159] The correspondence between each example and the gene is shown below. Examples 1 to 12, Control Examples 1-1, 1-2, Comparative Examples 1-1 and 1-2: LOR Examples 2-1 to 2-4, Control Examples 2-1, 2-2 and Comparative Example 2-1: TGM1 Examples 3-1 to 3-8, Control Examples 3-1, 3-2, Comparative Examples 3-1 and 3-2: KRT10 Examples 4-1 to 4-9, Control Examples 4-1, 4-2, Comparative Examples 4-1 and 4-2: FLG Examples 5-1 to 5-6, Control Examples 5-1, 5-2, Comparative Examples 5-1 and 5-2: IVL Examples 6-1 to 6-3, Control Examples 6-1, 6-2, Comparative Examples 6-1 and 6-2: KLK5 Examples 7-1 to 7-3, Control Example 7-1, Comparative Example 7-1: KLK7 Example 8-1, 8-2, Control Example 8-1 and Comparative Example 8-1: CTSD Examples 9-1 to 9-4, Control Examples 9-1, 9-2, Comparative Examples 9-1 and 9-2: CLDN1 Examples 10-1 to 10-3, Control Examples 10-1, 10-2, Comparative Examples 10-1 and 10-2: OCLN

[0160] The average expression levels of LOR, TGM1, KRT10, FLG, IVL, KLK5, KLK7, CTSD, CLDN1, and OCLN are shown in Tables 1-1 to 1-3, Tables 2-1 and 2-2, Tables 3-1 to 3-3, Tables 4-1 to 4-3, Tables 5-1 and 5-2, Table 6, Table 7-1 and Table 7-2, Table 8, Table 9, and Table 10, respectively. The "*" in each table except Table 5-2 indicates a significant difference (p<0.05, t-test) compared to the control example with the same concentration of component (A1). The "*" in Table 5-2 indicates a significant difference (p<0.05, t-test) compared to Example 5-1 in the same table. The expression level ratios in the examples listed in each table except for Tables 1-3, 2-2, 3-3, 4-3, 5-2, and 7-2 are the ratios of the expression level of each composition when the expression level of a control example containing the same concentration of component (A1) but not containing component (B1) is taken as 1.00. The expression level ratios in the examples listed in Tables 1-3, 2-2, 3-3, 4-3, 5-2, and 7-2 are the ratios of the expression level of each composition when the expression level of an example containing component (A1) and one component (B1) is taken as 1.00. Furthermore, the converted values ​​listed in each table except for Table 7-2 are calculated values ​​based on the expression levels in an example containing component (A1) and one component (B1).

[0161] The criteria for the expression level ratio in each table (except for Tables 7-1 and 7-2) are as follows: A to C were considered to be acceptable. A: 3.00 or more B: 2.00 or more but less than 3.00 C: 1.10 or more but less than 2.00 -: 1.00 or less than 1.10

[0162] 1(a) and (b), 2(a) and (b), 3(a) and (b), 4(a) and (b), 5(a) and (b), 6, 7(a) and (b), 8, 9, and 10 are diagrams showing the evaluation results of the expression levels of LOR, TGM1, KRT10, FLG, IVL, KLK5, KLK7, CTSD, CLDN1, and OCLN, respectively. 1(b), 2(b), 3(b), 4(b), 5(b), and 7(b) show the expression level ratios of each example when the expression level in an example containing component (A1) and one kind of component (B1) is set to 1.

[0163]

[0164]

[0165]

[0166]

[0167]

[0168]

[0169]

[0170]

[0171]

[0172]

[0173]

[0174]

[0175]

[0176]

[0177]

[0178]

[0179]

[0180]

[0181]

[0182] (Formulation Examples 1-1 to 1-13) Tablets were prepared by a conventional method using the compositions shown in Table 11 below (daily dose: 4 tablets).

[0183]

[0184] Test Example 2 In this example, gene expression levels in human epidermal keratinocytes were measured by the following procedure: A human immortalized keratinocyte cell line (HaCat) was plated in a 6-cm dish at approximately 4.0 × 10 cells using Dulbecco's Modified Eagle Medium (Gibco). ５The cells were seeded at 1000 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). The cells were then cultured for 48 hours. After removing the medium, RNA was extracted using an RNeasy Mini Kit (QIAGEN). cDNA was synthesized by reverse transcription using a Verso cDNA Synthesis Kit (Thermo Fisher). Expression levels of various genes (RNA2) were then measured by real-time PCR. Measurements were performed three times for each gene in each test example.

[0185] 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 promoting differentiation of skin cells: LOR (Hs01894962_s1), TGM1 (Hs00165929_m1), FLG (Hs00856927_g1), and IVN (Hs00846307_s1).

[0186] The test substances were tested at the following concentrations in the test solution: (A2) gamma oryzanol (Fujifilm Wako Pure Chemical Industries, Ltd.): 0.005 mg / mL or 0.05 mg / mL; (B2) L-cysteine ​​(TCI): 0.12 mg / mL or 1.2 mg / mL; (B2) riboflavin hydrochloride (Sigma): 0.003 mg / mL or 0.03 mg / mL; (B2) pyridoxine hydrochloride (Fujifilm Wako Pure Chemical Industries, Ltd.): 0.006 mg / mL or 0.06 mg / mL; (B2) calcium pantothenate (Nacalai Tesque): 0.12 mg / mL; (B2) ascorbic acid (TCI): 0.025 mg / mL; and phosphorylated oligosaccharide calcium (Glyco Nutrition Foods Co., Ltd.): 1 mg / mL.

[0187] The average gene expression levels of LOR, TGM1, FLG, and IVN are shown in Table 12 (Control Examples 11-1 and 11-2, Comparative Example 11, Examples 11-1 to 11-5), Table 13 (Control Examples 12-1 and 12-2, Comparative Example 12, Examples 12-1 to 12-10), Table 14 (Control Examples 13-1 and 13-2, Comparative Example 13, Examples 13-1 to 13-4), and Table 15 (Control Examples 14-1 and 14-2, Comparative Example 14, Examples 14-1 to 14-3), respectively. The expression level ratio in each table is the ratio of the expression level of each composition when the expression level of a control example containing the same concentration of component (A2) but not component (B2) is set to 1.00. In the tables, "*" indicates a significant difference (p<0.05, t-test) from the control example in the same table.

[0188] The criteria for the expression level ratio in each table are as follows: A to C were considered to be acceptable. A: 3.00 or more B: 2.00 or more and less than 3.00 C: 1.15 or more and less than 2.00 -: 1.00 or less than 1.15

[0189] 11 to 14 are diagrams showing the evaluation results of the control example and the example with respect to the expression levels of LOR, TGM1, FLG, and IVN, respectively.

[0190]

[0191]

[0192]

[0193]

[0194] (Formulation Examples 2-1 to 2-13) Tablets were prepared by a conventional method according to the composition shown in Table 16 below (daily dose: 4 tablets).

[0195]

[0196] This application claims priority based on Japanese Patent Application Nos. 2023-153917 and 2023-153935, filed on September 20, 2023, the disclosures of which are incorporated herein in their entireties.

Claims

1. A skin improving agent containing the following component (A1) or (A2) and the following component (B1) or (B2): (A1) at least one selected from the group consisting of Angelica sinensis and extracts thereof (A2) gamma oryzanol (B1) one or more selected from the group consisting of vitamin B5, vitamin B6, vitamin B2, vitamin B3, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin E (B2) one or more selected from the group consisting of vitamin B5, vitamin B6, L-cysteine, derivatives thereof and salts thereof, ascorbic acid, derivatives thereof and salts thereof, and vitamin B2.

2. The skin improving agent according to claim 1, containing the components (A1) and (B1).

3. The skin improving agent according to claim 1, containing the components (A2) and (B2).

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

5. A skin improving agent according to any one of claims 1 to 4, which is a turnover promoter.

6. A skin improving agent according to any one of claims 1 to 5, which is an agent for promoting exfoliation of the stratum corneum.

7. A skin improvement agent according to any one of claims 1 to 6, which is a tight junction formation promoter.

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