Melanin production inhibitor

Abstract

Provided are a novel composition and the like for preventing a decrease in the skin function of the skin of a person or the like. A melanin production inhibitor containing (A) tranexamic acid, (B) nicotinamide, (C) glutathione, (D) a vitamin C derivative, and (E) sodium pyrosulfite.

Description

Technical Field

[0001] The present invention relates to a melanin production inhibitor containing tranexamic acid or the like for use on the skin of humans or the like.

[0002] Skin has various problems such as rough skin, wrinkles, sagging, pigmentation, etc. due to various factors such as ultraviolet rays, dryness, aging, and stress. In order to improve these skin troubles in many aspects, it is believed that it is effective to act on the skin with multiple components with different effects. The epidermis of the skin is the skin tissue present in the outermost layer of the skin. The epidermis is mainly composed of the stratum corneum, the stratum granulosum, the stratum spinosum, and the stratum basale. The basal cells present in the basal layer divide and move to the outer layer. During this movement, denucleation occurs in the cells and they become flattened, and differentiate into the stratum corneum, which eventually peels off. It is said that the above-mentioned turnover period is about 45 days. However, in aging skin, the turnover rate slows down and the epidermis becomes thinner as a whole. As a result, it is known that the skin function decreases, such as the decrease in barrier function and the decrease in moisture content (Patent Document 1, Patent Document 2).

[0003] Prior art literature Patent Literature Patent Document 1: International Publication No. 2018 / 074606 Patent Document 2: Japanese Patent Application Publication No. 2021-16107 Summary of the invention

[0004] Technical problem to be solved by the invention The technical problem to be solved by the present invention is to provide a novel composition for use on the skin of humans etc. for preventing the decrease of skin function (for example, inhibiting the production of melanin).

[0005] Technical solutions for solving technical problems Therefore, the inventors of the present invention have repeatedly conducted intensive studies, and as a result, have completed the present invention.

[0006] The present invention includes the following items.

[0007] [Item 1] A melanin production inhibitor comprising the following components (A) to (E).

[0008] (A) Tranexamic acid, (B) Niacinamide, (C) Glutathione, (D) Vitamin C derivatives, (E) Sodium metabisulfite.

[0009] [Item 2] The melanin production inhibitor according to [Item 1], further comprising citric acid.

[0010] [Item 3] The melanin production inhibitor according to [Item 1] or [Item 2], further comprising arbutin.

[0011] [Item 4] A composition for external use on the skin, comprising the melanin production inhibitor according to any one of [Item 1] to [Item 3].

[0012] Effects of the Invention According to the present invention, a novel composition for preventing reduction in skin function, etc., which can be applied to the skin of humans or the like, can be provided. DETAILED DESCRIPTION

[0013] Hereinafter, the embodiment of the present invention will be described. It should be noted that, in the following description, the composition of the present invention is described as an example, but the description of the composition of the present invention can be applied to the description of the preparation of the present invention.

[0014] (Tranexamic Acid) Tranexamic acid is the abbreviation of trans-4-aminomethylcyclohexane-1-carboxylic acid. Tranexamic acids refer to, for example, tranexamic acid, tranexamic acid salts, tranexamic acid esters, tranexamic acid amides, and polymers of tranexamic acid. Examples of salts in tranexamic acid salts include metal salts such as sodium salts, potassium salts, and magnesium salts; inorganic acid salts such as hydrochlorides, phosphates, and sulfates. Examples of esters in tranexamic acid esters include vitamin esters such as vitamin A esters, vitamin E esters, and vitamin C esters, alkyl esters, and the like. In addition, examples of amides in tranexamic acid amides include formamide, and the like.

[0015] In the present invention, the tranexamic acid may include derivatives of tranexamic acid. Examples of the derivatives of tranexamic acid include dimers of tranexamic acid (trans-4-(trans-4-aminomethylcyclohexanecarbonyl)aminomethylcyclohexanecarboxylic acid hydrochloride), esters of tranexamic acid and hydroquinone (trans-4-aminomethylcyclohexanecarboxylic acid 4'-hydroxyphenyl ester), esters of tranexamic acid and gentisic acid (2-(trans-4-aminomethylcyclohexylcarbonyloxy)-5-hydroxybenzoic acid and its salts), amides of tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid formamide and its salts, trans-4-acetylaminomethylcyclohexanecarboxylic acid and its salts, trans-4-(p-methoxybenzoyl)aminomethylcyclohexanecarboxylic acid and its salts, trans-4-guanidinomethylcyclohexanecarboxylic acid and its salts, etc.).

[0016] The content of tranexamic acid (including derivatives of tranexamic acid) contained in the composition of the present invention is not particularly limited, but in order to exert the desired effect, the content of tranexamic acid relative to the total amount of the composition is, for example, preferably 0.001% by weight or more, more preferably 0.01% by weight or more, and more preferably 0.1% by weight or more. In addition, considering the desired effect, etc. (for example, even if more than a certain amount is matched, the increase of the effect cannot be expected in substance, and the matching of the skin external composition in the formulation also becomes difficult, etc.), the content of tranexamic acid relative to the total amount of the composition is, for example, preferably 20% by weight or less, more preferably 10% by weight or less, and more preferably 7% by weight or less.

[0017] (Niacinamide) Nicotinic acid is an amide compound of nicotinic acid (vitamin B3, nicotinic acid), and is a nicotinic acid derivative also known as nicotinamide or nicotinamide. The nicotinamide is a water-soluble vitamin and a substance that is one of the vitamin B group. For example, it can be extracted from natural products (rice bran, etc.) or synthesized by a known method. Specifically, the substances described in the 15th edition of the Japanese Pharmacopoeia (revised in 2008) can be used.

[0018] The content of niacinamide contained in the composition of the present invention is not particularly limited, but in order to exert the desired effect, the content of niacinamide relative to the total amount of the composition is preferably, for example, 0.001% by weight or more, more preferably 0.01% by weight or more, and even more preferably 0.1% by weight or more. In addition, considering the desired effect, etc. (for example, even if the amount exceeds a certain amount, the effect cannot be substantially increased, and the tendency of the external composition for skin application to be difficult to formulate, etc.), the content of niacinamide relative to the total amount of the composition is preferably, for example, 20% by weight or less, more preferably 10% by weight or less, and even more preferably 8% by weight or less.

[0019] (Glutathione) Glutathione is an antioxidant substance and the most abundant SH compound (thiol compound) in the body. It undergoes enzymatic and non-enzymatic reactions with proteins and other disulfides, and has the function of maintaining the SH, which is converted into oxidized glutathione through the reaction.

[0020] The content of glutathione contained in the composition of the present invention is not particularly limited, but in order to exert the desired effect, the content of glutathione relative to the total amount of the composition is preferably, for example, 0.0001% by weight or more, and more preferably 0.0005% by weight or more. In addition, considering the desired effect, etc. (for example, even if more than a certain amount is added, the effect cannot be substantially expected to increase, and the combination of the skin external composition in the formulation becomes difficult, etc.), the content of glutathione relative to the total amount of the composition is preferably, for example, 20% by weight or less, and more preferably 10% by weight or less.

[0021] (Vitamin C derivative) Vitamin C derivatives are concepts including derivatives of L-ascorbic acid and their salts, and are manufactured to improve the stability of vitamin C by bonding other molecules and changing the molecular structure. The vitamin C derivatives include water-soluble, fat-soluble, and amphiphilic substances. Examples of the water-soluble vitamin C derivatives include ascorbic acid 2-glucoside, ascorbic acid 6-glucoside, 3-O-ethyl ascorbic acid, sodium ascorbyl phosphate, etc. Examples of the fat-soluble vitamin C derivatives include ascorbic acid tetrahexyldecanoate, ascorbyl palmitate, ascorbyl stearate, etc. Examples of the amphiphilic vitamin C derivatives include trisodium palmitic acid ascorbyl phosphate, glyceryl octyl ascorbic acid, etc.

[0022] The content of the vitamin C derivative contained in the composition of the present invention is not particularly limited, but in order to exert the desired effect, the content of the vitamin C derivative relative to the total amount of the composition is preferably, for example, 0.01% by weight or more, and more preferably 0.1% by weight or more. In addition, considering the desired effect, etc. (for example, even if the amount exceeds a certain amount, the effect cannot be substantially increased, and the tendency of the external skin composition to be difficult to formulate, etc.), the content of the vitamin C derivative relative to the total amount of the composition is preferably, for example, 10% by weight or less, and more preferably 5% by weight or less.

[0023] (Sodium metabisulfite) Sodium pyrosulfite (Sodium pyrosulfite, Sodium metabisulfite) has reducing properties and is used, for example, as a bleaching agent for food, an antioxidant for wine, etc. The sodium pyrosulfite can be produced by a dehydration reaction of sodium bisulfite or by adding sulfur dioxide to sodium sulfite.

[0024] The content of sodium pyrosulfite contained in the composition of the present invention is not particularly limited, but in order to exert the desired effect, the content of sodium pyrosulfite relative to the total amount of the composition is preferably, for example, 0.0001% by weight or more, more preferably 0.001% or more, and even more preferably 0.01% or more. In addition, in consideration of the desired effect, etc. (for example, even if the amount exceeds a certain amount, the effect cannot be substantially increased, and the formulation of the skin external composition in the formulation also becomes difficult, etc.), the content of sodium pyrosulfite relative to the total amount of the composition is preferably, for example, 2% by weight or less, more preferably 1% by weight or less, and even more preferably 0.5% by weight or less.

[0025] (Citric Acid) Citric acid is a buffer (pH adjuster). In the present invention, the citric acid may include, for example, sodium citrate, trisodium citrate, and the like.

[0026] The content of citric acid contained in the composition of the present invention is not particularly limited, but in order to exert the desired effect, the content of citric acid is usually preferably 0.5% by weight or less based on the total amount of the composition.

[0027] (Arbutin) Arbutin is an ingredient approved by the Ministry of Health, Labor and Welfare of Japan as a quasi-drug whitening active ingredient in 1989. The arbutin is present in the leaves of, for example, the Ericaceae plant Arctostaphylos uva-ursi, the blueberry (Vaccinium vitis-idaea), the cranberry (Vaccinium oxycoccos), and the Rosaceae plant Pyrus communis. In the present invention, the arbutin may include, for example α- Arbutin (hydroquinone and glucose α bonded hydroquinone derivatives), β- Arbutin, etc.

[0028] The content of arbutin contained in the composition of the present invention is not particularly limited, but in order to exert the desired effect, the content of arbutin relative to the total amount of the composition is preferably, for example, 0.0001% by weight or more, more preferably 0.001% or more, and more preferably 0.01% or more. In addition, considering the desired effect, etc. (for example, even if the amount exceeds a certain amount, the effect cannot be substantially expected to increase, and the tendency of the skin external composition to be difficult to formulate), the content of arbutin relative to the total amount of the composition is preferably, for example, 2% by weight or less, more preferably 1% by weight or less, and more preferably 0.5% by weight or less.

[0029] (Whitening) Whitening is the prevention and / or improvement of pigmentation, more specifically, the prevention and / or improvement of pigmentation symptoms caused by increased production, excessive accumulation, and abnormal deposition of melanin such as spots, dullness, freckles, tanning, skin inflammation, darkening caused by irritation, etc.; and the prevention and / or improvement of pigmentation symptoms caused by diseases that cause pigmentation, such as skin melanosis caused by drugs such as steroids.

[0030] (Melanin production inhibition) Melanin production inhibition is to inhibit the formation of melanocytes in the skin, prevent and / or improve skin pigmentation phenomena such as spots, freckles and brown spots. Through this prevention and / or improvement, for example, the overall skin tone is improved, the skin becomes beautiful, and darkening is improved.

[0031] (Plant extract) In order to exert the desired effects, the preparations and compositions of the present invention may contain, for example, given plant extracts.

[0032] The extraction method used when making the plant extract, for example, can include a method of extracting using a suitable solvent. In the extraction, the plant used can be used directly, or it can be used after being crushed, dried, etc., preferably crushed, and more preferably dried. In addition, during the period of being immersed in the extraction solvent, for example, it can be stirred or left to stand. The plant extract of the present invention can also be repeatedly extracted to make a high-concentration plant extract.

[0033] The solvent used in the extraction is not particularly limited, and examples thereof include: water, methanol, ethanol, propanol, butanol and other lower monohydric alcohols, propylene glycol, dipropylene glycol, butanediol, glycerol and other polyols, methyl acetate, ethyl acetate and other esters, acetone, methyl ethyl ketone and other ketones, diethyl ether, tetrahydrofuran and other ethers of polar solvents, chloroform, carbon tetrachloride and other halogenated hydrocarbons, hexane, heptane, cyclohexane and other hydrocarbons. The solvent used in the extraction can be used alone, or a mixed solvent containing two or more can be used, and a polar solvent is particularly preferred. The extraction step is not particularly limited, and examples thereof include a step of immersing the plant used in the extraction in the solvent at 20°C to 40°C for 1 hour to 7 days and filtering. In addition, the obtained extract can be used directly as a plant extract, or the extract diluted, concentrated, freeze-dried, purified, etc. can be used as a plant extract.

[0034] The total content of the plant extract in the composition of the present invention is not particularly limited, but in order to exert the desired effect, it is preferably 0.000001% by mass to 10% by mass, more preferably 0.00001% by mass to 5% by mass, and even more preferably 0.0001% by mass to 3% by mass, based on the total mass of the composition and calculated as the mass of the dry matter.

[0035] The given plant extracts are, for example, Paeonia suffruticosa root extract, Scutellaria baicalensis root extract, Houttuynia cordata extract, Thymus vulgaris extract, Alpinia officinalis extract and the like.

[0036] The peony bark extract is obtained, for example, by extracting the root bark of Paeonia suffruticosa Andrews of the family Paeoniaceae using an extraction solvent. In the examples shown below, a peony bark extract (a residue obtained by removing the solvent from an extract prepared from an ethanol solution of the root bark of the peony, obtained by adding 1,3-butanediol and water to dissolve the residue, peony bark solution B, Ichimaru Natural Beauty Co., Ltd.) was used as the peony bark extract.

[0037] The scutellaria extract is obtained, for example, by extracting the root, rhizome and / or root bark of Scutellaria baicalensis Georgi, a plant of the genus Scutellaria in the family Lamiaceae, using an extraction solvent. In the examples shown below, as the scutellaria extract, a scutellaria extract solution (a substance obtained by dissolving an ethanol extract of the root of Scutellia baicalensis Georgi (Labiatae) from which the periderm has been removed, in a 1,3-butanediol solution, scutellaria solution B, Ichimaru Natural Beauty Co., Ltd.) was used.

[0038] The extract of Houttuynia cordata is obtained, for example, by extracting Geranium robertianum L. (Geraniaceae) of the Geraniaceae family. In the following examples, as the extract of Houttuynia cordata, a Houttuynia cordata extract solution (a substance extracted from the whole grass of Geranium robertianum L. (Geraniaceae) using a 1,3-butanediol solution, PrincessCare, Ichimaru Natural Beauty Co., Ltd.) was used.

[0039] The thyme extract is obtained by, for example, extracting thyme native to Europe, which is also called wild thyme or creeping thyme. In the following examples, a thyme extract (a concentrate of an extract obtained by extracting the aerial parts of Thymus serpyllum L. (Labiatae) using an ethanol solution and dissolving it in a 1,3-butanediol solution, CinderellaCare, Ichimaru Natural Beauty Co., Ltd.) was used as the thyme extract.

[0040] The Alpinia katsumadai Hayata extract can be obtained, for example, by extracting the seeds of Alpinia katsumadai Hayata, one of the traditional Chinese plants. In the following examples, an Alpinia katsumadai Hayata extract (a substance obtained by concentrating an extract obtained by extracting the seeds of Alpinia katsumadai Hayata (Zingiberaceae) using an ethanol solution and adding a 1,3-butanediol solution to dissolve the extract, Alpiniawhite, Ichimaru Natural Beauty Co., Ltd.) was used as the Alpinia katsumadai Hayata extract.

[0041] (Form of the composition) The composition of the present invention (skin external composition, etc.) includes: 1) pharmaceuticals in the form of ampoules, capsules, powders, granules, liquids, gels, bubbles, emulsions, sheets, mists, sprays, etc. in a suitable form for application, such as 1) pharmaceuticals, 2) quasi-pharmaceuticals, 3) topical or systemic skin external preparations (for example, lotions, emulsions, creams, ointments, lotions, oils, basic cosmetics such as facial masks, solid soaps, liquid soaps, face washes such as hand soaps, skin cleansers, massage preparations, cleansing preparations, hair removers, depilatory preparations, shaving preparations, aftershaves, preshaves, shaving creams, foundations, lipsticks, blushers, eye shadows, eyeliners, Make-up cosmetics such as mascara, perfumes, nail polish, nail polish removers, poultices, plasters, tapes, sheets, patches, aerosols, etc.), 4) medicinal and / or cosmetic preparations for scalp and hair (for example, shampoos, conditioners, hair care products, hair pre-care products, permanent perm solutions, hair dyes, hair styling products, hair treatments, hair growth and nourishment products, poultices, plasters, tapes, sheets, aerosols, etc.), 5) bath preparations for use in bath water, 6) other anti-armpit odor agents, deodorants, antiperspirants, sanitary products, sanitary napkins, wet wipes, etc.

[0042] In addition, such a composition may contain, as necessary, appropriate ingredients used in general cosmetics, such as oily ingredients, lower alcohols, polyols, aqueous ingredients such as humectants, ultraviolet absorbers, antioxidants, cosmetic ingredients, preservatives, oil-soluble resins, dyes, cooling agents, pigments, fragrances, etc., within a range that does not hinder the effects of the present invention.

[0043] In order to exert the desired effect (whitening effect, etc.), the melanin production inhibitor contained in the composition of the present invention is preferably, for example, 0.25 (v / v)% or more, more preferably 0.5 (v / v)% or more, more preferably 0.75 (v / v)% or more, more preferably 1 (v / v)% or more, and further preferably 2 (v / v)% or more. In addition, considering the desired toxicity, etc., the melanin production inhibitor contained in the composition of the present invention is preferably, for example, 50 (v / v)% or less, more preferably 25 (v / v)% or less, and further preferably 10 (v / v)% or less.

[0044] The present invention is further described in detail with reference to the following examples, but the present invention is not limited to these examples. It should be noted that in the following examples, the unit % representing the numerical value of the addition amount of each component refers to mass %.

[0045] Example Hereinafter, examples of the present invention will be described. Experimental materials used in the experiments given in the examples are as follows.

[0046] B16 mouse melanoma cells (melanoma cells): B16 melanoma 4A5, RIKEN CELLBANK Pre-culture medium for the cells: MEM medium containing 5% fetal bovine serum MEM culture medium: E-MEM (051-07615), Fujifilm Wako Pure Chemical Industries, Ltd. Fetal bovine serum: Thermofisher Scientific Main culture medium: MEM medium containing 0.36% theophylline Nicotinamide: Product code 000-54225, CAS RNTM98-92-0, Kishida Chemical Co., Ltd. · Tranexamic acid: Japanese Pharmacopoeia Tranexamic acid Glutathione: L-glutathione, Kojin Life Sciences Co., Ltd. Vitamin C derivatives: Pacificos VAP, Ichimaru Natural Beauty Co., Ltd. ·Sodium metabisulfite: Junsei Chemical Co., Ltd. Arbutin: β -Arbutin, Product ID: A6804, LKT Laboratories INC ·Mudan Bark Extract: Mudan Bark Solution B, Ichimaru Natural Beauty Co., Ltd. · Scutellaria baicalensis extract: Scutellaria baicalensis solution B, Ichimaru Natural Beauty Co., Ltd. ·Houttuynia cordata extract: PrincessCare, Ichimaru Natural Beauty Co., Ltd. · Thyme extract: CinderellaCare, Ichimaru Natural Beauty Co., Ltd. ·Alpinia white extract: Alpiniawhite, Ichimaru Natural Beauty Co., Ltd. (Experiment 1: Melanin production inhibition test) By adding a sample to a given cell (the above-mentioned melanoma cell), whether or not melanin production in the given cell changes is confirmed. As the cell to which the sample is added, B16 mouse melanoma cells are used.

[0047] (1) Pre-culture process of melanoma cells The melanoma cells were cultured in the above-mentioned pre-culture medium (MEM medium containing 5% fetal bovine serum) under the conditions of 5% CO 2 and 37° C. for 24 hours.

[0048] (2) Main culture process after sample addition After the pre-culture of (1), 8.5×10 4 Melanoma cells were seeded in each well (wells containing the main culture medium, 24-well plate) at a cell number of 100 cells / well. After seeding, the cells were cultured under 5% CO2 and 37°C for 24 hours.

[0049] After the culture, the culture medium of each well is replaced with a fresh main culture medium. In the replaced culture medium (containing the cells), the following samples (control, comparative examples 1 to 5, embodiments 1 to 3) shown in Table 1 are added in a manner to a final concentration of 2 (v / v)%. It should be noted that the addition of the sample is carried out in a manner to prepare the following groups. It should be noted that since the melanin production inhibitory effect of arbutin is known (Journal of the Japanese Society of Dermatology (Original Text: Journal of the Japanese Society of Dermatology): 101 (6) 609-613, 1991), in the experiment 1, as a test example of a positive control, a group of samples (positive controls) shown in Table 1 below are added in a manner to a final concentration of 1 (v / v)%.

[0050] [Table 1]

[0051] After the addition, the cells were cultured for 72 hours (3 days) under the conditions of 5% CO 2 and 37° C. After the 72-hour culture, the cultured samples were divided into samples used for the following measurement 1 and samples used for the following measurement 2 in each group.

[0052] (Measurement 1: Melanin Amount Measurement) The cultured sample used for the assay 1 was treated with trypsin to recover the cells. The recovered cells were dissolved in a solution (containing 1N NaOH, 10% DMSO). The absorbance of the dissolved liquid was measured at an absorbance of 420 nm (the absorbance of the control, positive control, comparative examples 1 to 5, and embodiments 1 to 3). The measured value was used as the amount of melanin. The numerical value (relative value) of the assay was calculated as follows. First, the absorbance of the measurement results of each group (n = 3) was calculated. Then, for the average value, the numerical value of the control group of each group was set to 100, and the relative value of the numerical value of each group compared with the control group was calculated. Regarding the "effectiveness (melanin production inhibitory effect)" shown in Table 1 above, the group in which the melanin production inhibitory effect was significantly confirmed compared with the control group was set to "0 (circle)", and the group other than this was set to "× (cross)". It should be noted that "-" represents an unmeasured sample. In the Dunnett test, the significance is expressed by the significant difference (p < 0.05) compared with the control group.

[0053] (Measurement 2: Determination of the number of melanoma cells using the WST method) The measurement was performed using Cell Counting Kit-8 (Dojindo). The kit-8 was placed in the cultured sample used for measurement 2. After the above placement, culture was performed for 2 hours under the conditions of 5% CO2 and 37°C. After the culture, the color development of each group was confirmed at an absorbance of 450nm according to the instructions of the "CellCounting Kit-8 (Dojindo)". It was performed in each group (n=4). Regarding the "Toxicity (the cell number measurement)" shown in Table 1 above, the group in which the cell number was significantly reduced compared with the control group was set as "×, (cross, toxic)", and the other groups were set as "○ (circle, non-toxic)". It should be noted that "-" indicates an unmeasured sample. In the Dunnett test, the significance is expressed by the significant difference (p<0.05) compared with the control group.

[0054] Compared with the comparative example, the examples have a melanin production inhibitory effect and are not toxic.

[0055] (Measurement 3: Confirmation of odor) As a sensory test, the presence or absence of odor (smell close to sour odor, deterioration odor that feels like sourness) of each sample (control, comparative examples 1 to 5, examples 1 to 3) was confirmed. First, each sample was placed in a 100 mL sample bottle with a lid and left to stand for 30 minutes. After standing, the lid was opened, the odor was smelled, and the measurement was performed based on the following criteria.

[0056] ○: Samples with no perceived odor.

[0057] ×: Samples in which an odor was felt.

[0058] -: Sample not measured.

[0059] The results of the measurement are shown in the above Table 1 (odor of preparation). Compared with the comparative example, the odor was not felt in the example.

[0060] Although the embodiments (including examples) of the present invention have been described above with reference to the drawings, the specific configuration of the present invention is not limited thereto, and any design changes or the like within the scope of the present invention are also included in the present invention.

[0061] This application claims priority based on Japanese patent application No. 2022-164092 filed on October 12, 2022, the disclosure of which is incorporated herein in its entirety.

[0062] <Note> A part or all of the above-mentioned embodiments and examples can be described as the following supplementary notes, but are not limited to the following.

[0063] (Note 1) A melanin production inhibitor or composition comprising the following components (A) to (E).

[0064] (A) Tranexamic acid (B) Niacinamide (C) Glutathione (D) Vitamin C derivatives (E) Sodium metabisulfite (Note 2) The preparation or composition according to Appendix 1, wherein the content of tranexamic acid is 0.001 wt % to 20 wt % based on the total weight of the preparation or the composition.

[0065] (Note 3) The preparation or composition according to Appendix 1 or 2, wherein the content of niacinamide is 0.001 wt % to 20 wt % based on the total weight of the preparation or the composition.

[0066] (Note 4) The preparation or composition according to any one of Appendixes 1 to 3, wherein the content of the glutathione is 0.0001% by weight to 20% by weight based on the total weight of the preparation or the composition.

[0067] (Note 5) The preparation or composition according to any one of Appendixes 1 to 4, wherein the content of the vitamin C derivative is 0.01% by weight to 10% by weight based on the total weight of the preparation or the composition.

[0068] (Note 6) The preparation or composition according to any one of Appendixes 1 to 5, wherein the content of the sodium pyrosulfite is 0.0001 wt % to 2 wt % based on the total weight of the preparation or the composition.

[0069] (Note 7) The preparation or composition according to any one of Supplementary Notes 1 to 6, further comprising citric acid.

[0070] (Note 8) The preparation or composition according to Appendix 7, wherein the content of citric acid is greater than 0 wt % to 0.5 wt % based on the total weight of the preparation or the composition.

[0071] (Note 9) The preparation or composition according to any one of Appendix 1 to 8, further comprising arbutin.

[0072] (Note 10) The preparation or composition according to Appendix 9, wherein the content of arbutin is 0.0001 wt % to 2 wt % based on the total weight of the preparation or the composition.

[0073] (Note 11) A preparation or composition for external use on the skin, comprising the preparation or composition according to any one of Appendix 1 to 10.

[0074] (Note 12) A preparation or composition for inhibiting melanin production, comprising the preparation or composition according to any one of Supplements 1 to 11.

[0075] (Note 13) The preparation or composition according to any one of Supplementary Notes 1 to 12, wherein the preparation or composition further comprises a plant extract.

[0076] (Note 14) The preparation or composition according to Supplementary Note 13, wherein the content of the plant extract is 0.000001% by mass to 10% by mass based on the total mass of the preparation or the composition.

[0077] (Note 15) The preparation or composition according to Appendix 13 or 14, wherein the plant extract is a plant extract selected from Paeonia suffruticosa extract, Scutellaria baicalensis extract, Houttuynia cordata extract, Thymus vulgaris extract, and Alpinia officinalis extract.

[0078] (Note 16) A method for inhibiting the production of melanin, comprising using the preparation or composition according to any one of Supplementary Notes 1 to 15.

[0079] (Note 17) The method according to Supplementary Note 16, wherein the preparation or composition is brought into contact with the skin of a subject.

[0080] (Note 18) The method according to Note 17, wherein the subject is a human or a non-human animal.

[0081] (Note 19) Use of the preparation or composition according to any one of Supplementary Notes 1 to 15 for inhibiting the production of melanin.

[0082] Industrial applicability According to the present invention, the composition can be used as a composition for preventing the decrease of skin function of human skin or the like.

Claims

1. A melanin production inhibitor, characterized in that Contains the following ingredients (A) to (E): (A) Tranexamic acid; (B) niacinamide; (C) Glutathione; (D) Vitamin C derivatives; (E) Sodium metabisulfite.

2. The melanin production inhibitor according to claim 1, wherein The melanin production inhibitor further contains citric acid.

3. The melanin production inhibitor according to claim 1, wherein The melanin production inhibitor further contains arbutin.

4. A composition for external use on skin, characterized in that: The invention comprises the melanin production inhibitor according to claim 1.

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