Composition
The combination of vitamin C, cysteine, vitamin B6, and thioctic acid or vitamin E in an oral composition effectively reduces melanin production and deposition, addressing the limitations of existing treatments for skin pigmentation issues by enhancing melanin metabolism and providing significant pigmentation relief.
Patent Information
- Application Number
- PCT/JP2024/027485
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-08-01
- Filing Date
- 2024-08-01
- Publication Date
- 2025-02-06
AI Technical Summary
Current compositions for alleviating skin pigmentation, such as those combining vitamin C, L-cysteine, and vitamin B6, have shown limited effectiveness in reducing melanin production and deposition, necessitating further improvements to address hormonal abnormalities and UV-induced skin issues.
A composition combining vitamin C, cysteine or its salts, vitamin B6, and one or more ingredients selected from thioctic acid and vitamin E, which is administered orally to inhibit melanin production and promote its excretion, thereby reducing skin pigmentation.
The composition achieves significant reduction in melanin content and alleviates skin pigmentation by synergistically improving melanin metabolism, making it effective for treating spots, freckles, and sunburn-related issues.
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Figure JP2024027485_06022025_PF_FP_ABST
Abstract
Description
composition
[0001] The present invention relates to a composition.
[0002] Skin pigmentation, such as age spots and freckles, occurs when melanin production in epidermal pigment cells is accelerated due to hormonal abnormalities, UV exposure, aging, etc., resulting in excessive deposition of melanin in the epidermis. An oral composition combining vitamin C, L-cysteine, and vitamin B6 has been proposed as a means of alleviating such skin pigmentation (Non-Patent Document 1), but in recent years, further improvement in the effect of alleviating pigmentation has been desired.
[0003] Package insert "Hythiol Whiteia Premium" SS Pharmaceuticals Co., Ltd., March 2022
[0004] An object of the present invention is to provide a new means for reducing skin pigmentation.
[0005] As a result of extensive research, the inventors have discovered that an excellent pigmentation alleviating effect can be obtained by combining one or more components selected from thioctic acids and vitamin E compounds with vitamin C compounds, cysteine or a salt thereof or a solvate thereof, and vitamin B6 compounds to form a composition, and have completed the present invention.
[0006] That is, the present invention provides the following <1> to <4>. <1> A composition (hereinafter also referred to as "the composition of the present invention") containing the following components (A), (B), (C), and (D): (A) vitamin C (B) cysteine or a salt thereof, or a solvate of the same (C) vitamin B6 (D) one or more components selected from thioctic acids and vitamin E <2> The composition according to <1>, in which component (D) is thioctic acid. <3> The composition according to <1> or <2>, which is an oral composition. <4> The composition according to any of <1> to <3>, which is for reducing pigmentation.
[0007] <5> Use of a combination of the components (A), (B), (C), and (D) for producing a composition for reducing pigmentation. <6> Use of a composition containing the components (A), (B), (C), and (D) for reducing pigmentation. <7> A method for reducing pigmentation, comprising the step of using a composition containing the components (A), (B), (C), and (D). <8> A method for reducing pigmentation, comprising the step of orally administering a composition containing the components (A), (B), (C), and (D) (hereinafter also referred to as the "pigmentation reduction method of the present invention").
[0008] The composition of the present invention has an excellent effect of reducing pigmentation.
[0009] 4 shows the results of a significant difference test for the combination of vitamin C, cysteine, vitamin B6, and thioctic acid regarding the melanin content in a three-dimensional cultured skin model. 4 shows the results of a significant difference test for the combination of vitamin C, cysteine, vitamin B6, and vitamin E regarding the melanin content in a three-dimensional cultured skin model.
[0010] The composition of the present invention contains the following components (A), (B), (C), and (D): (A) vitamin C, (B) cysteine or a salt thereof, or a solvate thereof, (C) vitamin B6, and (D) one or more components selected from thioctic acids and vitamin E.
[0011] (Component (A)) Examples of vitamin C include ascorbic acid, calcium ascorbate, and sodium ascorbate. Among these, ascorbic acid is preferred. Vitamin C can be produced by known methods, and commercially available products can also be used.
[0012] From the viewpoint of pigmentation alleviation effect, etc., the content of component (A) in the composition of the present invention is preferably 1% by mass or more, more preferably 5% by mass or more, even more preferably 10% by mass or more, particularly preferably 20% by mass or more, and is preferably 99% by mass or less, more preferably 95% by mass or less, even more preferably 90% by mass or less, particularly preferably 80% by mass or less, in the composition of the present invention. As a specific range, in the composition of the present invention, 1% by mass or more and 99% by mass or less is preferred, 5% by mass or more and 95% by mass or less is more preferred, 10% by mass or more and 90% by mass or less is even more preferred, and 20% by mass or more and 80% by mass or less is particularly preferred.
[0013] (Component (B)) Examples of cysteine, a salt thereof, or a solvate thereof include L-cystine, L-cysteine, L-cysteine hydrochloride hydrate, etc. Among these, L-cysteine is preferred. Cysteine, a salt thereof, or a solvate thereof can be produced by known methods, or commercially available products can also be used.
[0014] From the viewpoint of pigmentation alleviation effect, etc., the content of component (B) in the composition of the present invention is preferably 0.1% by mass or more, more preferably 1% by mass or more, even more preferably 5% by mass or more, particularly preferably 10% by mass or more, and is preferably 99% by mass or less, more preferably 90% by mass or less, even more preferably 70% by mass or less, particularly preferably 50% by mass or less, in the composition of the present invention. As a specific range, in the composition of the present invention, 0.1% by mass or more and 99% by mass or less, more preferably 1% by mass or more and 90% by mass or less, even more preferably 5% by mass or more and 70% by mass or less, particularly preferably 10% by mass or more and 50% by mass or less is preferred.
[0015] The mass ratio of component (B) to component (A) [(B) / (A)] is preferably 0.05 or more, more preferably 0.1 or more, even more preferably 0.2 or more, and particularly preferably 0.3 or more in order to synergistically improve the pigmentation alleviating effect, and is preferably 1.0 or less, more preferably 0.8 or less, even more preferably 0.7 or less, and particularly preferably 0.6 or less in order to synergistically improve the pigmentation alleviating effect. Specific ranges are preferably 0.05 or more and 1.0 or less, more preferably 0.1 or more and 0.8 or less, even more preferably 0.2 or more and 0.7 or less, and particularly preferably 0.2 or more and 0.6 or less.
[0016] (Component (C)) Examples of vitamin B6 include one or more selected from pyridoxine, pyridoxal, pyridoxamine, and salts thereof (for example, alkaline earth metal salts such as calcium salts; inorganic acid salts such as hydrochlorides and phosphates). Among these, from the viewpoint of pigmentation alleviation effect, one or more selected from pyridoxine and its salts are preferred, and one or more selected from pyridoxine and pyridoxine hydrochloride are more preferred. Vitamin B6 can be produced by known methods, and commercially available products can also be used.
[0017] From the viewpoint of pigmentation alleviation effect, etc., the content of component (C) in the composition of the present invention is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.5% by mass or more, particularly preferably 1% by mass or more, and is preferably 80% by mass or less, more preferably 40% by mass or less, even more preferably 20% by mass or less, particularly preferably 10% by mass or less, in the composition of the present invention. As a specific range, in the composition of the present invention, 0.01% by mass or more and 80% by mass or less, more preferably 0.1% by mass or more and 40% by mass or less, even more preferably 0.5% by mass or more and 20% by mass or less, particularly preferably 1% by mass or more and 10% by mass or less is preferred.
[0018] Furthermore, the mass ratio of component (C) to component (A) [(C) / (A)] is preferably 0.01 or more, more preferably 0.02 or more, even more preferably 0.03 or more, and particularly preferably 0.04 or more in order to synergistically improve the pigmentation alleviating effect, and is preferably 0.5 or less, more preferably 0.4 or less, even more preferably 0.3 or less, and particularly preferably 0.2 or less in order to synergistically improve the pigmentation alleviating effect. Specifically, the range is preferably 0.01 or more and 0.5 or less, more preferably 0.02 or more and 0.4 or less, even more preferably 0.03 or more and 0.3 or less, and particularly preferably 0.04 or more and 0.2 or less.
[0019] (Component (D)) Component (D) is one or more components selected from thioctic acids and vitamin E compounds. Examples of thioctic acids include thioctic acid and thioctic acid amide. Of these, thioctic acid is preferred from the viewpoint of pigmentation alleviation effects, etc. Examples of vitamin E compounds include tocopherol, tocopherol succinate, tocopherol calcium succinate, tocopherol acetate, tocopherol nicotinate, etc. Of these, tocopherol is preferred from the viewpoint of pigmentation alleviation effects, etc. As component (D), one or more components selected from thioctic acids and tocopherol are preferred from the viewpoint of pigmentation alleviation effects, etc., more preferably thioctic acids, and particularly preferably thioctic acid. The one or more components selected from thioctic acids and vitamin E compounds can be produced by known methods, or commercially available products can also be used.
[0020] From the viewpoint of pigmentation alleviation effect, etc., the content of component (D) in the composition of the present invention is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, even more preferably 0.2% by mass or more, particularly preferably 0.5% by mass or more, and is preferably 40% by mass or less, more preferably 30% by mass or less, even more preferably 20% by mass or less, particularly preferably 10% by mass or less, in the composition of the present invention. As a specific range, in the composition of the present invention, 0.01% by mass or more and 40% by mass or less, more preferably 0.1% by mass or more and 30% by mass or less, even more preferably 0.2% by mass or more and 20% by mass or less, particularly preferably 0.5% by mass or more and 10% by mass or less is preferred.
[0021] Furthermore, the mass ratio of component (D) to component (A) [(D) / (A)] is preferably 0.001 or more, more preferably 0.002 or more, even more preferably 0.005 or more, and particularly preferably 0.01 or more in order to synergistically improve the pigmentation alleviating effect. Furthermore, in order to synergistically improve the pigmentation alleviating effect, it is preferably 0.6 or less, more preferably 0.5 or less, even more preferably 0.4 or less, and particularly preferably 0.3 or less. Specific ranges are preferably 0.001 or more and 0.6 or less, more preferably 0.002 or more and 0.5 or less, even more preferably 0.005 or more and 0.4 or less, and even more preferably 0.01 or more and 0.3 or less. When thioctic acids are used as component (D), a ratio of 0.01 or more and 0.1 or less is particularly preferred. When vitamin E compounds are used as component (D), a ratio of 0.1 or more and 0.3 or less is particularly preferred.
[0022] The composition of the present invention may contain drugs, herbal medicines, or functional food ingredients other than components (A) to (D). Examples of drugs include fursultiamine, fursultiamine hydrochloride, thiamine nitrate, nicotinamide, calcium pantothenate, riboflavin, riboflavin acetate, biotin, orotic acid, tranexamic acid, glutamic acid, glycine, coix seed extract, and licorice. The composition may contain one of these drugs alone or two or more in combination. Examples of herbal medicines include keishibukuryogan, tokishakuyakusan, kamishoyosan, orengedokuto, keikeirenkyoto, jutoukiinshi, and jumihaidokuto. The composition may contain one of these drugs alone or two or more in combination. Examples of functional food ingredients include ellagic acid, hydroxytyrosol, lotus germ extract powder, and resveratrol. These may be used alone or in combination of two or more.
[0023] The composition of the present invention may be in any form of solid, semi-solid or liquid.For example, it may be granules, fine granules, powders, tablets (plain tablets, OD tablets, chewable tablets, dispersible tablets, dissolving tablets, troches, sublingual tablets, buccal tablets, adhesive tablets, effervescent tablets, gums, sugar-coated tablets, etc.), pills, capsules (soft capsules, hard capsules, etc.), dry syrups, jellies, and other oral solid or semi-solid preparations; suspensions, syrups, drinks, and other oral liquid preparations; suppositories.Among these, oral solid or semi-solid preparations are preferred, oral solid preparations are more preferred, and tablets are particularly preferred.
[0024] The composition of the present invention can be a pharmaceutical product, a quasi-drug product, a cosmetic product, or a food product, and can be produced according to a known method in the field of pharmaceutical products, quasi-drug products, cosmetics, or food products, by adding additives (excipients, disintegrants, binders, lubricants, fluidizing agents, adsorbents, solubilizers, buffers, preservatives, fragrances, colorants, flavoring agents, etc.) as needed.
[0025] Examples of additives include excipients such as light anhydrous silicic acid, heavy anhydrous silicic acid, titanium oxide, aluminum silicate, lactose, sucrose, glucose, crystalline cellulose, mannitol, sorbitol, xylitol, reduced maltose syrup, and corn starch; disintegrants such as carmellose sodium, crospovidone, carboxymethylcellulose calcium, low-substituted hydroxypropylcellulose (preferably having a hydroxypropyl group content of 5 to 16% by mass), crystalline cellulose, and calcium carbonate; binders such as gelatin, sodium alginate, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, carboxymethylcellulose, polyvinyl alcohol, and polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer; lubricants such as magnesium stearate, calcium stearate, talc, and dimethylpolysiloxane; fluidizers such as light anhydrous silicic acid and fine silicon dioxide; and adsorbents such as composite potassium aluminum silicate granules. These may be used alone or in combination of two or more. Furthermore, solubilizing agents, buffering agents, preservatives, flavoring agents, coloring agents, flavoring agents, etc. may be used as needed.
[0026] The composition of the present invention can be prepared as an oral or parenteral composition depending on the intended use, but is preferably an oral composition. When the composition of the present invention is orally administered, for example, the composition can be divided into 1 to 4 doses per day and taken before meals, between meals, after meals, before bedtime, etc. The dosage or intake of the composition of the present invention is preferably an amount that allows 100 to 2000 mg of component (A) to be administered or ingested per adult per day. Also preferably, an amount that allows 100 to 1000 mg of component (B) to be administered or ingested per adult per day. Also preferably, an amount that allows 10 to 100 mg of component (C) to be administered or ingested per adult per day. Also preferably, an amount that allows 5 to 200 mg of component (D) to be administered or ingested per adult per day. These amounts are preferably administered or ingested in a single dose.
[0027] The composition of the present invention inhibits excessive production and accumulation of melanin, promotes smooth excretion of melanin by aiding skin metabolism, and further lightens the color of dark melanin deposited on the skin. Therefore, the composition of the present invention has an excellent pigmentation alleviating effect. The composition of the present invention is particularly useful for alleviating pigmentation caused by age spots, freckles, sunburn, rash, etc. Furthermore, the composition of the present invention is useful as a pigmentation alleviating composition or an ingredient for a pigmentation alleviating composition. As used herein, "pigmentation alleviation" refers to alleviating skin pigmentation, specifically, alleviating skin pigmentation by inhibiting excessive production and deposition of melanin by melanocytes and keratinocytes in the skin.
[0028] Therefore, the composition of the present invention can be used as is or, if necessary, combined with other ingredients to form a composition for reducing pigmentation. The composition of the present invention can be used for reducing pigmentation, or can be used to produce a composition for reducing pigmentation. The above-mentioned "use" is preferably non-therapeutic use (non-medical procedure). The term "non-therapeutic" does not include medical procedures, i.e., methods of surgery, treatment, or diagnosis on humans. More specifically, it does not include methods of surgery, treatment, or diagnosis on humans performed by a physician, a medical professional, or a person under the direction of a physician.
[0029] [Method for reducing pigmentation] The method for reducing pigmentation of the present invention is characterized by including a step of using a composition containing the components (A), (B), (C), and (D). Oral administration is preferred for this step. In the method for reducing pigmentation, the meanings of various terms, the content (amount used), and the content ratio (use ratio) of each component are all the same as those explained for the composition of the present invention above.
[0030] In relation to the above-described embodiment, the present invention further discloses the following composition etc. [1] A composition containing the following components (A), (B), (C), and (D): (A) vitamin C (B) cysteine or a salt thereof, or a solvate thereof (C) vitamin B6 (D) one or more components selected from thioctic acids and vitamin E
[0031] [2] The composition according to [1], wherein component (A) is preferably one or more selected from ascorbic acid, calcium ascorbate, and sodium ascorbate, more preferably ascorbic acid.
[0032] [3] The composition according to [1] or [2], wherein component (B) is preferably one or more selected from the group consisting of L-cystine, L-cysteine, and L-cysteine hydrochloride hydrate, more preferably L-cysteine. [4] The composition according to any one of [1] to [3], wherein the mass ratio of component (B) to component (A) [(B) / (A)] is preferably 0.05 or more and 1.0 or less, more preferably 0.1 or more and 0.8 or less, even more preferably 0.2 or more and 0.7 or less, and particularly preferably 0.2 or more and 0.6 or less.
[0033] [5] The composition according to any one of [1] to [4], wherein component (C) is preferably one or more selected from pyridoxine, pyridoxal, pyridoxamine, and salts thereof, more preferably one or more selected from pyridoxine and salts thereof, and particularly preferably one or more selected from pyridoxine and pyridoxine hydrochloride. [6] The composition according to any one of [1] to [5], wherein the mass ratio of component (C) to component (A) [(C) / (A)] is preferably 0.01 or more and 0.5 or less, more preferably 0.02 or more and 0.4 or less, even more preferably 0.03 or more and 0.3 or less, and particularly preferably 0.04 or more and 0.2 or less.
[0034] [7] The composition according to any one of [1] to [6], wherein component (D) is preferably one or more components selected from thioctic acids, tocopherol, tocopherol succinate, tocopherol calcium succinate, tocopherol acetate, and tocopherol nicotinate, more preferably one or more components selected from thioctic acids and tocopherol, even more preferably thioctic acids, even more preferably one or more components selected from thioctic acid and thioctic acid amide, and particularly preferably thioctic acid. [8] The composition according to any one of [1] to [7], wherein the content mass ratio of component (D) to component (A) [(D) / (A)] is preferably 0.001 or more and 0.6 or less, more preferably 0.002 or more and 0.5 or less, even more preferably 0.005 or more and 0.4 or less, and even more preferably 0.01 or more and 0.3 or less; when thioctic acids are used as component (D), it is particularly preferably 0.01 or more and 0.1 or less; and when vitamin E is used as component (D), it is particularly preferably 0.1 or more and 0.3 or less.
[0035] [9] The composition according to any one of [1] to [8], which is an oral composition.
[10] The composition according to any one of [1] to [9], which is used for reducing pigmentation.
[0036]
[11] Use of a combination of the following components (A), (B), (C), and (D) for producing a composition for reducing pigmentation: (A) vitamin C, (B) cysteine or a salt thereof, or a solvate thereof, (C) vitamin B6, and (D) one or more components selected from thioctic acids and vitamin E.
[0037]
[12] Use of a composition containing the following components (A), (B), (C), and (D) for reducing pigmentation: (A) vitamin C; (B) cysteine or a salt thereof, or a solvate thereof; (C) vitamin B6; and (D) one or more components selected from thioctic acids and vitamin E.
[0038]
[13] The use according to
[11] or
[12] , wherein component (A) is preferably one or more selected from ascorbic acid, calcium ascorbate, and sodium ascorbate, more preferably ascorbic acid.
[14] The use according to any of
[11] to
[13] , wherein component (B) is preferably one or more selected from L-cystine, L-cysteine, and L-cysteine hydrochloride hydrate, more preferably L-cysteine.
[15] The use according to any of
[11] to
[14] , wherein the mass ratio of component (B) to component (A) in the composition [(B) / (A)] is preferably 0.05 or more and 1.0 or less, more preferably 0.1 or more and 0.8 or less, even more preferably 0.2 or more and 0.7 or less, and particularly preferably 0.2 or more and 0.6 or less.
[0039]
[16] The use according to any one of
[11] to
[15] , wherein component (C) is preferably one or more selected from pyridoxine, pyridoxal, pyridoxamine, and salts thereof, more preferably one or more selected from pyridoxine and salts thereof, and particularly preferably one or more selected from pyridoxine and pyridoxine hydrochloride.
[17] The use according to any one of
[11] to
[16] , wherein the mass ratio of component (C) to component (A) in the composition [(C) / (A)] is preferably 0.01 or more and 0.5 or less, more preferably 0.02 or more and 0.4 or less, even more preferably 0.03 or more and 0.3 or less, and particularly preferably 0.04 or more and 0.2 or less.
[0040]
[18] The use according to any one of
[11] to
[17] , wherein component (D) is preferably one or more components selected from thioctic acids, tocopherol, tocopherol succinate, tocopherol calcium succinate, tocopherol acetate, and tocopherol nicotinate, more preferably one or more components selected from thioctic acids and tocopherol, even more preferably thioctic acids, even more preferably one or more components selected from thioctic acid and thioctic acid amide, and particularly preferably thioctic acid.
[19] The use according to any one of
[11] to
[18] , wherein the mass ratio of component (D) to component (A) in the composition [(D) / (A)] is preferably 0.001 to 0.6, more preferably 0.002 to 0.5, even more preferably 0.005 to 0.4, and even more preferably 0.01 to 0.3, and when thioctic acids are used as component (D), it is particularly preferably 0.01 to 0.1, and when vitamin E is used as component (D), it is particularly preferably 0.1 to 0.3.
[20] The use according to any one of
[11] to
[19] , wherein the composition is an oral composition.
[0041]
[21] A method for reducing pigmentation, comprising a step of using a composition containing the following components (A), (B), (C), and (D): (A) vitamin C; (B) cysteine or a salt thereof, or a solvate thereof; (C) vitamin B6; and (D) one or more components selected from thioctic acids and vitamin E.
[0042]
[22] A method for reducing pigmentation, comprising the step of orally administering a composition containing the following components (A), (B), (C), and (D): (A) vitamin C; (B) cysteine or a salt thereof, or a solvate thereof; (C) vitamin B6; and (D) one or more components selected from thioctic acids and vitamin E.
[0043]
[23] The method according to
[21] or
[22] , wherein component (A) is preferably one or more selected from ascorbic acid, calcium ascorbate, and sodium ascorbate, more preferably ascorbic acid.
[24] The method according to any one of
[21] to
[23] , wherein component (B) is preferably one or more selected from L-cystine, L-cysteine, and L-cysteine hydrochloride hydrate, more preferably L-cysteine.
[25] The method according to any one of
[21] to
[24] , wherein the mass ratio of component (B) to component (A) in the composition [(B) / (A)] is preferably 0.05 or more and 1.0 or less, more preferably 0.1 or more and 0.8 or less, even more preferably 0.2 or more and 0.7 or less, and particularly preferably 0.2 or more and 0.6 or less.
[0044]
[26] The method according to any one of
[21] to
[25] , wherein component (C) is preferably one or more selected from pyridoxine, pyridoxal, pyridoxamine, and salts thereof, more preferably one or more selected from pyridoxine and salts thereof, and particularly preferably one or more selected from pyridoxine and pyridoxine hydrochloride.
[27] The method according to any one of
[21] to
[26] , wherein the mass ratio of component (C) to component (A) in the composition [(C) / (A)] is preferably 0.01 or more and 0.5 or less, more preferably 0.02 or more and 0.4 or less, even more preferably 0.03 or more and 0.3 or less, and particularly preferably 0.04 or more and 0.2 or less.
[0045]
[28] The method according to any one of
[21] to
[27] , wherein component (D) is preferably one or more components selected from thioctic acids, tocopherol, tocopherol succinate, tocopherol calcium succinate, tocopherol acetate, and tocopherol nicotinate, more preferably one or more components selected from thioctic acids and tocopherol, even more preferably thioctic acids, even more preferably one or more components selected from thioctic acid and thioctic acid amide, and particularly preferably thioctic acid.
[29] The method according to any one of
[21] to
[28] , wherein the mass ratio of the content of component (D) to component (A) in the composition [(D) / (A)] is preferably 0.001 or more and 0.6 or less, more preferably 0.002 or more and 0.5 or less, even more preferably 0.005 or more and 0.4 or less, and even more preferably 0.01 or more and 0.3 or less; when thioctic acids are used as component (D), it is particularly preferably 0.01 or more and 0.1 or less; and when vitamin E is used as component (D), it is particularly preferably 0.1 or more and 0.3 or less.
[0046] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.
[0047] [Test Substances] The test substances used in the test examples are as follows: Ascorbic acid: manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. L-cysteine: manufactured by Tokyo Chemical Industry Co., Ltd. Pyridoxine hydrochloride: manufactured by BASF Corporation Tocopherol: manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. Thioctic acid: manufactured by Tokyo Chemical Industry Co., Ltd.
[0048] Test Example: Effect of Inhibiting Melanin Production and Alleviating Pigmentation in a Three-Dimensional Cultured Skin Model Asian donor-derived MEL-300 (Kurashiki Boseki Co., Ltd.) was used as the three-dimensional cultured skin model, and EPI-100 long-term maintenance medium (Kurashiki Boseki Co., Ltd.) was used as the culture medium. For each group, the following test substances were dissolved in PBS (Fujifilm Wako Pure Chemical Industries, Ltd.) for water-soluble substances (ascorbic acid, L-cysteine, pyridoxine hydrochloride) and ethanol (Fujifilm Wako Pure Chemical Industries, Ltd.) for fat-soluble substances (thioctic acid, tocopherol), and then added to the culture medium. The culture medium was changed every two days. After 21 days of culture, a portion of the cells was removed, and melanin was solubilized using SOLVABLE (Perkin Elmer), and the amount of melanin was measured using a plate reader (BMS).
[0049] (Figure 1) Group 1-1: Control group (PBS concentration 1%, ethanol concentration 0.1%) Group 1-2: ALA group (thioctic acid: 4 μg / mL) Group 1-3: VC, Cys, VB6 group (ascorbic acid: 200 μg / mL, L-cysteine: 96 μg / mL, pyridoxine hydrochloride: 20 μg / mL) Group 1-4: VC, Cys, VB6, ALA group (ascorbic acid: 200 μg / mL, L-cysteine: 96 μg / mL, pyridoxine hydrochloride: 20 μg / mL, thioctic acid: 4 μg / mL) (Figure 2) Group 2-1: Control group (PBS concentration 1%, ethanol concentration 0.1%) Group 2-2: VE group (tocopherol: 40 μg / mL) Group 2-3: VC, Cys, VB6 group (ascorbic acid: 200 μg / mL, L-cysteine: 96 μg / mL, pyridoxine hydrochloride: 20 μg / mL) Group 2-4: VC, Cys, VB6, VE group (ascorbic acid: 200 μg / mL, L-cysteine: 96 μg / mL, pyridoxine hydrochloride: 20 μg / mL, tocopherol: 40 μg / mL)
[0050] As shown in FIG. 1 , Group 1-4 (combination of vitamin C, cysteine, vitamin B6, and thioctic acid) showed a significantly reduced amount of melanin compared to the control group, and was also confirmed to have a significantly reduced amount of melanin compared to Group 1-3 (combination of vitamin C, cysteine, and vitamin B6) and Group 1-2 (thioctic acid). From the above, it was found that the combination of vitamin C, cysteine, vitamin B6, and thioctic acid exhibits an excellent melanin production inhibitory effect and an excellent pigmentation alleviating effect due to a synergistic effect. Furthermore, as shown in FIG. 2 , it was confirmed that Group 2-4 (combination of vitamin C, cysteine, vitamin B6, and vitamin E) showed a significantly reduced amount of melanin compared to the control group and Group 2-2 (vitamin E). Since no significant difference was observed between Group 2-3 (combination of vitamin C, cysteine, and vitamin B6) and the control group or Group 2-2 (vitamin E), it was confirmed that the combination of vitamin C, cysteine, vitamin B6, and vitamin E exhibits an excellent melanin production inhibitory effect and an excellent pigmentation alleviating effect due to a synergistic effect.
Claims
1. A composition containing the following components (A), (B), (C) and (D): (A) vitamin C; (B) cysteine or a salt thereof or a solvate thereof; (C) vitamin B6; and (D) one or more components selected from thioctic acids and vitamin E.
2. The composition according to claim 1, wherein component (A) is one or more selected from the group consisting of ascorbic acid, calcium ascorbate, and sodium ascorbate.
3. The composition according to claim 1 or 2, wherein component (B) is one or more members selected from the group consisting of L-cystine, L-cysteine, and L-cysteine hydrochloride hydrate.
4. The composition according to any one of claims 1 to 3, wherein the mass ratio of component (B) to component (A) [(B) / (A)] is 0.05 or more and 1.0 or less.
5. The composition according to any one of claims 1 to 4, wherein component (C) is one or more members selected from the group consisting of pyridoxine, pyridoxal, pyridoxamine, and salts thereof.
6. The composition according to any one of claims 1 to 5, wherein the mass ratio of component (C) to component (A) [(C) / (A)] is 0.01 or more and 0.5 or less.
7. The composition according to any one of claims 1 to 6, wherein component (D) is one or more components selected from the group consisting of thioctic acids, tocopherol, tocopherol succinate, tocopherol calcium succinate, tocopherol acetate, and tocopherol nicotinate.
8. The composition according to any one of claims 1 to 6, wherein component (D) is thioctic acid.
9. The composition according to any one of claims 1 to 8, wherein the mass ratio of the content of the component (D) to the content of the component (A) [(D) / (A)] is 0.001 or more and 0.6 or less.
10. The composition according to any one of claims 1 to 9, which is an oral composition.
11. The composition according to any one of claims 1 to 10, which is for reducing pigmentation.
12. Use of a combination of the following components (A), (B), (C) and (D) for the manufacture of a composition for reducing pigmentation: (A) vitamin C; (B) cysteine or a salt thereof, or a solvate thereof; (C) vitamin B6; and (D) one or more components selected from thioctic acids and vitamin E.
13. Use of a composition containing the following components (A), (B), (C) and (D) for reducing pigmentation: (A) vitamin C; (B) cysteine or a salt thereof, or a solvate thereof; (C) vitamin B6; and (D) one or more components selected from thioctic acids and vitamin E.
14. The use according to claim 12 or 13, wherein component (A) is one or more members selected from ascorbic acid, calcium ascorbate, and sodium ascorbate.
15. The use according to any one of claims 12 to 14, wherein component (B) is one or more members selected from the group consisting of L-cystine, L-cysteine, and L-cysteine hydrochloride hydrate.
16. The use according to any one of claims 12 to 15, wherein the mass ratio of component (B) to component (A) in the composition [(B) / (A)] is 0.05 or more and 1.0 or less.
17. The use according to any one of claims 12 to 16, wherein component (C) is one or more selected from pyridoxine, pyridoxal, pyridoxamine, and salts thereof.
18. The use according to any one of claims 12 to 17, wherein the mass ratio of component (C) to component (A) in the composition [(C) / (A)] is 0.01 or more and 0.5 or less.
19. The use according to any one of claims 12 to 18, wherein component (D) is one or more components selected from thioctic acids, tocopherol, tocopherol succinate, tocopherol calcium succinate, tocopherol acetate, and tocopherol nicotinate.
20. The use according to any one of claims 12 to 18, wherein component (D) is thioctic acid.
21. The use according to any one of claims 12 to 20, wherein the mass ratio of component (D) to component (A) in the composition [(D) / (A)] is 0.001 or more and 0.6 or less.
22. The use according to any one of claims 12 to 21, wherein the composition is an oral composition.
23. A method for reducing pigmentation, comprising the step of using a composition containing the following components (A), (B), (C) and (D): (A) vitamin C; (B) cysteine or a salt thereof, or a solvate thereof; (C) vitamin B6; and (D) one or more components selected from thioctic acids and vitamin E.
24. A method for reducing pigmentation, comprising the step of orally administering a composition containing the following components (A), (B), (C) and (D): (A) vitamin C; (B) cysteine or a salt thereof, or a solvate thereof; (C) vitamin B6; and (D) one or more components selected from thioctic acids and vitamin E.
25. The method according to claim 23 or 24, wherein component (A) is one or more selected from ascorbic acid, calcium ascorbate, and sodium ascorbate.
26. The method according to any one of claims 23 to 25, wherein component (B) is one or more members selected from the group consisting of L-cystine, L-cysteine, and L-cysteine hydrochloride hydrate.
27. The method according to any one of claims 23 to 26, wherein the mass ratio of component (B) to component (A) in the composition [(B) / (A)] is 0.05 or more and 1.0 or less.
28. The method according to any one of claims 23 to 27, wherein component (C) is one or more selected from pyridoxine, pyridoxal, pyridoxamine, and salts thereof.
29. The method according to any one of claims 23 to 28, wherein the mass ratio of component (C) to component (A) in the composition [(C) / (A)] is 0.01 or more and 0.5 or less.
30. The method according to any one of claims 23 to 29, wherein component (D) is one or more components selected from thioctic acids, tocopherol, tocopherol succinate, tocopherol calcium succinate, tocopherol acetate, and tocopherol nicotinate.
31. The method of any one of claims 23 to 29, wherein component (D) is thioctic acid.
32. The method according to any one of claims 23 to 31, wherein the mass ratio of component (D) to component (A) in the composition [(D) / (A)] is 0.001 or more and 0.6 or less.
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