WO2024080290A1 - Melanin pigment synthesis inhibitor - Google Patents
Melanin pigment synthesis inhibitor Download PDFInfo
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- WO2024080290A1 WO2024080290A1 PCT/JP2023/036830 JP2023036830W WO2024080290A1 WO 2024080290 A1 WO2024080290 A1 WO 2024080290A1 JP 2023036830 W JP2023036830 W JP 2023036830W WO 2024080290 A1 WO2024080290 A1 WO 2024080290A1
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- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960005219 gentisic acid Drugs 0.000 description 1
- 229940105040 geranium extract Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000000118 hair dye Substances 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- JBYSVQKTMBXLKJ-UHFFFAOYSA-N pyridine-3-carboxamide;pyridine-3-carboxylic acid Chemical compound NC(=O)C1=CC=CN=C1.OC(=O)C1=CC=CN=C1 JBYSVQKTMBXLKJ-UHFFFAOYSA-N 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007665 sagging Methods 0.000 description 1
- 210000004761 scalp Anatomy 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 210000004511 skin melanocyte Anatomy 0.000 description 1
- 230000005808 skin problem Effects 0.000 description 1
- YRWWOAFMPXPHEJ-OFBPEYICSA-K sodium L-ascorbic acid 2-phosphate Chemical compound [Na+].[Na+].[Na+].OC[C@H](O)[C@H]1OC(=O)C(OP([O-])([O-])=O)=C1[O-] YRWWOAFMPXPHEJ-OFBPEYICSA-K 0.000 description 1
- 229940048058 sodium ascorbyl phosphate Drugs 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000000498 stratum granulosum Anatomy 0.000 description 1
- 210000000437 stratum spinosum Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 235000015961 tonic Nutrition 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 229960000716 tonics Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 150000004370 vitamin A ester derivatives Chemical class 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019160 vitamin B3 Nutrition 0.000 description 1
- 239000011708 vitamin B3 Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/60—Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
- A61K8/9783—Angiosperms [Magnoliophyta]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- the present invention relates to a melanin pigment production inhibitor containing tranexamic acid, etc., for use on the skin of humans, etc.
- the epidermis is the skin tissue that exists in the outermost layer of the skin.
- the epidermis is mainly composed of the stratum corneum, stratum granulosum, stratum spinosum, and stratum basale. Basal cells in the stratum basale divide and migrate to the outer layer. During this migration, the cells undergo enucleation, flattening, and differentiation into the stratum corneum, which eventually peels off. This turnover period is said to be about 45 days. However, in aged skin, the turnover rate slows down and the entire epidermis becomes thinner. As a result, it is known that skin functions such as a decrease in barrier function and a decrease in moisture content occur (Patent Document 1, Patent Document 2).
- the problem that the present invention aims to solve is to provide a novel composition for use on human skin, etc., to prevent a decline in skin function (for example, by suppressing melanin pigment production).
- the inventors of the present invention therefore conducted extensive research and developed the present invention.
- the present invention includes the following items.
- [Item 1] A melanin pigment production inhibitor comprising the following components (A) to (E): (A) tranexamic acid (B) nicotinamide (C) glutathione (D) a vitamin C derivative (E) sodium pyrosulfite
- [Item 2] The agent according to [Item 1], further comprising citric acid.
- [Item 3] The agent according to [Item 1] or [Item 2], further comprising arbutin.
- [Item 4] A composition for external application to the skin, comprising any one of the agents according to [Item 1] to [Item 3].
- the present invention provides a novel composition for use on human skin to prevent a decline in skin function.
- composition of the present invention will be used as an example, but the explanation of the composition of the present invention can be used to explain the agent of the present invention.
- Tranexamic acid is an abbreviation for trans-4-aminomethylcyclohexane-1-carboxylic acid.
- Tranexamic acids include, for example, tranexamic acid, tranexamic acid salts, tranexamic acid esters, tranexamic acid amides, and tranexamic acid multimers.
- salts of tranexamic acid salts include metal salts such as sodium salts, potassium salts, and magnesium salts; and inorganic acid salts such as hydrochlorides, phosphates, and sulfates.
- esters of tranexamic acid esters include vitamin esters such as vitamin A ester, vitamin E ester, and vitamin C ester; and alkyl esters.
- amides of tranexamic acid amides include methyl amides.
- the tranexamic acid may include, for example, a derivative of tranexamic acid.
- the derivative of tranexamic acid include a dimer of tranexamic acid (trans-4-(trans-4-aminomethylcyclohexanecarbonyl)aminomethylcyclohexanecarboxylic acid hydrochloride), an ester of tranexamic acid and hydroquinone (trans-4-aminomethylcyclohexanecarboxylic acid 4'-hydroxyphenyl ester), an ester of tranexamic acid and gentisic acid (2-(trans-4-aminomethylcyclohexylcarbonyloxy)-5-hydroxybenzoic acid and its salts), and an amide of tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid methylamide and its salts, trans-4-acetylaminomethylcyclohexanecarboxylic acid and its salts, trans-4-(
- the content of tranexamic acid (including derivatives of said 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 said 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 even more preferably 0.1% by weight or more. Also, taking into consideration the desired effect, etc.
- the content of said 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 even more preferably 7% by weight or less.
- Nicotinic acid is an amide compound of nicotinic acid (vitamin B3, niacin), and is also called nicotinamide or niacinamide, and is a derivative of nicotinic acid.
- the nicotinamide is a water-soluble vitamin and a substance that is one of the vitamin B group, and can be extracted from natural products (such as rice bran) or synthesized by known methods. Specifically, those listed in the 15th revised Japanese Pharmacopoeia (revised in 2008) can be used.
- the content of nicotinamide contained in the composition of the present invention is not particularly limited, but in order to exert the desired effect, the content of nicotinamide is generally, for example, preferably 0.001% by weight or more, more preferably 0.01% by weight or more, and even more preferably 0.1% by weight or more, based on the total amount of the composition. Also, taking into consideration the desired effect, etc.
- the content of nicotinamide is generally, for example, preferably 20% by weight or less, more preferably 10% by weight or less, and even more preferably 8% by weight or less, based on the total amount of the composition.
- Glutathione Glutathione is an antioxidant and the most abundant SH compound (thiol compound) in the body. It reacts enzymatically and non-enzymatically with disulfides in proteins and other compounds to maintain their SH status, and is converted into oxidized glutathione through this reaction.
- the amount of glutathione contained in the composition of the present invention is not particularly limited, but in order to achieve the desired effect, the amount of glutathione contained in the composition is generally, for example, preferably 0.0001% by weight or more, more preferably 0.0005% by weight or more, relative to the total amount of the composition.
- the amount of glutathione contained in the composition is generally, for example, preferably 20% by weight or less, more preferably 10% by weight or less, relative to the total amount of the composition.
- vitamin C derivative The concept of vitamin C derivatives encompasses derivatives of L-ascorbic acid and their salts, and is produced by modifying the molecular structure of vitamin C by binding it with other molecules in order to increase its stability.
- the vitamin C derivatives include water-soluble, fat-soluble, and amphipathic.
- water-soluble vitamin C derivatives include ascorbic acid 2-glucoside, ascorbic acid 6-glucoside, 3-O-ethyl ascorbic acid, and sodium ascorbyl phosphate.
- examples of the fat-soluble vitamin C derivatives include ascorbyl tetrahexyldecanoate, ascorbyl palmitate, and ascorbyl stearate.
- Examples of the amphipathic vitamin C derivatives include trisodium ascorbyl palmitate phosphate, and glyceryl octyl ascorbic acid.
- 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 generally, for example, preferably 0.01% by weight or more, more preferably 0.1% by weight or more. Also, taking into consideration the desired effect, etc. (for example, even if more than a certain amount is added, the effect is not substantially increased, and it tends to be difficult to add the derivative to compositions for external use on the skin, etc.), the content of the vitamin C derivative relative to the total amount of the composition is generally, for example, preferably 10% by weight or less, more preferably 5% by weight or less.
- Sodium pyrosulfite sodium metabisulfite
- the sodium pyrosulfite can be produced by the dehydration reaction of sodium hydrogensulfite or by adding sulfur dioxide to sodium sulfite.
- 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 generally, for example, preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, and even more preferably 0.01% by weight or more. Also, taking into consideration the desired effect, etc.
- the content of sodium pyrosulfite relative to the total amount of the composition is generally, for example, preferably 2% by weight or less, more preferably 1% by weight or less, and even more preferably 0.5% by weight or less.
- Citric acid is a buffer (pH adjuster).
- the citric acid may include, for example, sodium citrate, trisodium citrate, etc.
- the amount of citric acid contained in the composition of the present invention is not particularly limited, but in order to achieve the desired effects, the amount of citric acid contained in the composition is generally, for example, preferably 0.5% by weight or less relative to the total amount of the composition.
- Arbutin Arbutin is an ingredient approved by the Ministry of Health, Labor and Welfare as a quasi-drug whitening active ingredient in 1989.
- the arbutin is present in the leaves of, for example, Ericaceae plants such as Arctostaphylos uva-ursi, Vaccinium vitis-idaea, and Vaccinium oxycoccos, and Rosaceae plants such as Pyrus communis.
- the arbutin may include, for example, ⁇ -arbutin (a hydroquinone derivative in which hydroquinone and glucose are ⁇ -bonded), ⁇ -arbutin, etc.
- 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 generally, for example, preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, and even more preferably 0.01% by weight or more. Also, taking into consideration the desired effect, etc. (for example, even if more than a certain amount is added, the effect cannot be substantially increased, and it tends to be difficult to add in compositions for external use on the skin), the content of arbutin relative to the total amount of the composition is generally, for example, preferably 2% by weight or less, more preferably 1% by weight or less, and even more preferably 0.5% by weight or less.
- Skin whitening refers to the prevention and/or improvement of pigmentation, and more specifically, refers to the prevention and/or improvement of pigmentation symptoms caused by increased production, excessive accumulation, and abnormal deposition of melanin pigment, such as age spots, dullness, freckles, sunburn, and darkening due to inflammation or irritation of the skin, as well as pigmentation symptoms caused by diseases that result in pigmentation, such as skin melanosis due to drugs such as steroids.
- Inhibition of melanin pigmentation refers to the inhibition of the formation of skin melanocytes and the prevention and/or improvement of skin pigmentation phenomena such as spots, freckles, age spots, etc. Such prevention and/or improvement can, for example, improve the overall skin tone, brighten the skin, and improve dark spots.
- the agent and composition of the present invention may contain, for example, a specific plant extract in order to exert a desired effect.
- the extraction method used to prepare the plant extract may be, for example, a method of extraction using an appropriate solvent.
- the plant may be used as is, or may be crushed or dried before use. It is preferable to crush the plant, and more preferable to use a dried plant.
- the plant while immersed in the extraction solvent, the plant may be stirred or left to stand.
- the plant extract of the present invention may be made into a high-concentration plant extract by repeating the extraction procedure.
- the solvent used for the extraction is not particularly limited, and examples thereof include water, lower monohydric alcohols such as methanol, ethanol, propanol, and butanol, polyhydric alcohols such as propylene glycol, dipropylene glycol, butylene glycol, and glycerin, esters such as methyl acetate and ethyl acetate, ketones such as acetone and methyl ethyl ketone, polar solvents such as ethers such as diethyl ether and tetrahydrofuran, halogenated hydrocarbons such as chloroform and carbon tetrachloride, and hydrocarbons such as hexane, heptane, and cyclohexane.
- lower monohydric alcohols such as methanol, ethanol, propanol, and butanol
- polyhydric alcohols such as propylene glycol, dipropylene glycol, butylene glycol, and glycerin
- the solvent used for the extraction may be, for example, a single solvent or a mixed solvent consisting of two or more solvents, and it is particularly preferable to use a polar solvent.
- the extraction procedure is not particularly limited, and examples thereof include a procedure in which the plant used for the extraction is immersed in the solvent at 20 to 40°C for 1 hour to 7 days and then filtered.
- the obtained extract may be used as it is as a plant extract, or may be used after dilution, concentration, freeze-drying, purification, etc.
- the total content of the plant extract in the composition of the present invention is not particularly limited, but in order to achieve the desired effect, it is preferably 0.000001 to 10% by mass, more preferably 0.00001 to 5% by mass, and even more preferably 0.0001 to 3% by mass, in terms of the mass of the dry matter, based on the total mass of the composition.
- Specific plant extracts include, for example, Peony root extract, Scutellaria root extract, Caraway extract, Thymus vulgaris extract, and Celastrus arbutus extract.
- the above-mentioned Paeonia suffruticosa extract is obtained, for example, by subjecting the root bark of the peony (Paeonia suffruticosa Andrews) of the family Paeoniaceae to an extraction treatment using an extraction solvent.
- the above-mentioned Paeonia suffruticosa extract was prepared by adding 1,3-butylene glycol and water to the residue obtained by removing the solvent from the extract of the root bark of the peony in ethanol, and dissolving it there; Paeonia suffruticosa Liquid B, Ichimaru Pharcos Co., Ltd.
- the Scutellaria root extract is obtained, for example, by subjecting the root, rhizome and/or root bark of Scutellaria baicalensis Georgia, a plant of the Scutellaria genus in the Lamiaceae family, to an extraction treatment using an extraction solvent.
- Scutellaria root extract an ethanol extract of the roots of Scutellaria baicalensis Georgia (Labiatae), with the periderm removed, dissolved in 1,3-butylene glycol solution, Scutellaria root liquid B, Ichimaru Pharcos Co., Ltd.
- the above-mentioned Geranium robertianum extract is obtained, for example, by subjecting Geranium robertianum L. (Geraniaceae) of the Geraniaceae family to an extraction process.
- Geranium robertianum extract obtained by extracting the whole plant of Geranium robertianum L. (Geraniaceae) with a 1,3-butylene glycol solution, Princess Care, Ichimaru Pharcos Co., Ltd. was used as the above-mentioned Geranium robertianum extract.
- thymus extract is obtained by subjecting, for example, Thymus serpyllum, which is native to Europe and is known as wild thyme or creeping thyme, to an extraction process.
- Thymus extract was obtained by concentrating an extract obtained by extracting the above-ground parts of Thymus serpyllum L. (Labiatae) with an ethanol solution and dissolving it by adding a 1,3-butylene glycol solution, Cinderella Care, Ichimaru Pharcos Co., Ltd.
- Zingiberaceae extract is obtained, for example, by subjecting the seeds of Alpinia katsumadai, a traditional Chinese plant, to an extraction process.
- Zingiberaceae extract an extract obtained by extracting the seeds of Alpinia katsumadai Hayata (Zingiberaceae) with an ethanol solution, concentrating the extract, and dissolving it by adding a 1,3-butylene glycol solution, Alpinia White, Ichimaru Pharcos Co., Ltd. was used as the above-mentioned Zingiberaceae extract.
- composition of the present invention may be in the form of ampoules, capsules, powders, granules, liquids, gels, foams, emulsions, sheets, mists, sprays, etc., and may be in the form of 1) medicines, 2) quasi-drugs, 3) topical or whole body external skin preparations (for example, basic cosmetics such as lotions, milky lotions, creams, ointments, lotions, oils, and packs, face washes and skin cleansers such as solid soaps, liquid soaps, and hand washes, massage preparations, cleansing preparations, hair removal preparations, depilatories, shaving treatments, aftershave lotions, preshave lotions, shaving creams, foundations, lipsticks, blushers, eye shadows, and eyeshadows).
- basic cosmetics such as lotions, milky lotions, creams, ointments, lotions, oils, and packs
- face washes and skin cleansers such as solid soaps, liquid soaps, and hand washes
- makeup cosmetics such as eyeliner and mascara, perfumes, nail beautifying agents, nail beautifying enamel, nail beautifying enamel remover, poultices, plasters, tapes, sheets, patches, aerosols, etc.); 4) medicinal and/or cosmetic preparations to be applied to the scalp and hair (for example, shampoos, rinses, hair treatments, pre-hair treatments, permanent solutions, hair dyes, hair styling products, hair tonics, hair growth and care products, poultices, plasters, tapes, sheets, aerosols, etc.); 5) bath products to be added to the bath; 6) other products such as underarm odor prevention agents, deodorants, antiperspirants, sanitary products, sanitary cotton, wet tissues, etc.
- medicinal and/or cosmetic preparations to be applied to the scalp and hair for example, shampoos, rinses, hair treatments, pre-hair treatments, permanent solutions, hair dyes, hair styling products, hair tonics, hair growth and care products, poultices, plasters, tapes, sheets, aerosol
- compositions may contain, as necessary, appropriate amounts of ingredients typically used in cosmetics, such as oily ingredients, lower alcohols, polyhydric alcohols, aqueous ingredients such as moisturizers, UV absorbers, antioxidants, cosmetic ingredients, preservatives, oil-soluble resins, dyes, cooling agents, pigments, fragrances, etc., within the scope of the effects of the present invention.
- ingredients typically used in cosmetics such as oily ingredients, lower alcohols, polyhydric alcohols, aqueous ingredients such as moisturizers, UV absorbers, antioxidants, cosmetic ingredients, preservatives, oil-soluble resins, dyes, cooling agents, pigments, fragrances, etc.
- the melanin pigment production inhibitor contained in the composition of the present invention is, for example, in order to exert a desired effect (such as a whitening effect), preferably 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 even more preferably 2 (v/v)% or more.
- the melanin pigment production inhibitor contained in the composition of the present invention is, for example, in consideration of the desired toxicity, etc., preferably 50 (v/v)% or less, more preferably 25 (v/v)% or less, and even more preferably 10 (v/v)% or less.
- the present invention will be described in more detail below with reference to examples, but the present invention is in no way limited to these examples.
- the unit % of the numerical values showing the amount of each component added means % by mass.
- B16 mouse melanoma cells (melanoma cells): B16 melanoma 4A5, RIKEN CELL BANK Preculture medium for the cells: MEM medium containing 5% fetal bovine serum; MEM medium: E-MEM (051-07615), Fujifilm Wako Pure Chemical Industries; Fetal bovine serum: Thermofisher Scientific Main culture medium: MEM medium containing 0.036% defolin
- Nicotinamide Product code 000-54225, CAS RNTM98-92-0, Kishida Chemical Co., Ltd.
- Tranexamic acid Japanese Pharmacopoeia tranexamic acid
- Glutathione L-glutathione, Kohjin Life Sciences Co., Ltd.
- Vitamin C derivative Pacificos VAP, Ichimaru Pharcos Co., Ltd.
- Sodium pyrosulfite Junsei Chemical Co., Ltd.
- Abrutin ⁇ -arbutin
- Product ID A6804, LKT Laboratories INC.
- ⁇ Moutan pea extract Moutan pea Liquid B, Ichimaru Pharcos Co., Ltd.
- ⁇ Scutellaria root extract Scutellaria root Liquid B, Ichimaru Pharcos Co., Ltd.
- ⁇ Geranium extract Princess Care, Ichimaru Pharcos Co., Ltd.
- Thymus vulgaris extract Cinderella Care, Ichimaru Pharcos Co., Ltd.
- ⁇ Soumony tree extract Alpinia White, Ichimaru Pharcos Co., Ltd.
- Example 1 Melanin production inhibition test
- a sample By adding a sample to a specific cell (the above-mentioned melanoma cell), it was confirmed whether there was a change in melanin production in the specific cell.
- B16 mouse melanoma cell was used as the cell to which the sample was added.
- Pre-culture step of melanoma cells The above-mentioned melanoma cells were cultured in the above-mentioned pre-culture medium (MEM medium containing 5% fetal bovine serum) under conditions of 5% CO2 and 37°C for 24 hours.
- MEM medium containing 5% fetal bovine serum
- melanoma cells were seeded in each well (wells containing the main culture medium, 24-well plate) at 8.5 ⁇ 10 4 cells/well. After the seeding, the cells were cultured for 24 hours under conditions of 5% CO 2 and 37° C.
- each group was divided into a cultured sample for use in the following measurement 1 and a cultured sample for use in the following measurement 2.
- Measurement 1 Melanin amount measurement
- the cultured sample for use in this measurement 1 was treated with trypsin to recover cells.
- the recovered cells were dissolved in a solution (containing 1N NaOH and 10% DMSO).
- the absorbance of the dissolved solution (control, positive control, Comparative Examples 1 to 5, and Examples 1 to 3) was measured at 420 nm.
- the measured value was taken as the amount of melanin.
- the example Compared to the comparative example, the example had the effect of inhibiting melanin pigment production and was also non-toxic.
- a melanin pigment production inhibitor or composition comprising the following components (A) to (E): (A) Tranexamic acid (B) Nicotinamide (C) Glutathione (D) Vitamin C derivatives (E) Sodium pyrosulfite (Appendix 2)
- Appendix 15 The agent or composition described in Appendix 13 or 14, wherein the plant extract is a plant extract selected from the group consisting of Peony root extract, Scutellaria root extract, Geranium globulus extract, Thymus vulgaris extract, and Celastrus arvensis extract.
- Appendix 16 A method for inhibiting melanin pigment production, comprising using an agent or composition according to any one of claims 1 to 15.
- Appendix 17 17.
- the method of claim 16 wherein the agent or composition is contacted with the skin of a subject.
- Appendix 18 18.
- the method of claim 17, wherein the subject is a human or a non-human animal.
- Appendix 19 Use of an agent or composition according to any one of claims 1 to 15 for inhibiting the production of melanin pigment.
- the composition can be used as a composition for preventing the deterioration of skin function for use on the skin of humans, etc.
Abstract
The present invention provides a new composition or the like for use on the skin of a human or the like and for preventing deterioration in skin functions. This melanin pigment synthesis inhibitor comprises (a) tranexamic acid, (b) a nicotinic acid amide, (c) glutathione, (d) a vitamin C derivative, and (e) sodium pyrosulfite.
Description
本発明は、例えば、ヒト等の皮膚に用いるための、トラネキサム酸等を含有するメラニン色素生成抑制剤等に関する。
The present invention relates to a melanin pigment production inhibitor containing tranexamic acid, etc., for use on the skin of humans, etc.
皮膚は紫外線、乾燥、加齢、ストレス等の様々な要因によって、肌荒れ、シワ、たるみ、色素沈着等の様々な問題を生じる。これらの肌悩みを多面的に改善するためには、作用の異なる複数の成分を皮膚に作用させることが有効であると考えられている。皮膚の表皮は、皮膚最外層に存在する皮膚組織である。表皮は、角層、顆粒層、有棘層、及び基底層から主に構成されている。基底層に存在する基底細胞が分裂し、外層へと移動する。この移動の過程で細胞において脱核が生じて扁平化し角層へと分化し、角層は最終的に剥がれ落ちる。このターンオーバーの期間はおよそ４５日程度と言われている。しかし、老化した皮膚では、ターンオーバー速度が遅くなり、表皮全体が薄くなる。その結果、バリア機能の低下、水分含量の低下等の皮膚機能の低下が生じることが知られている（特許文献１、特許文献２）。
Due to various factors such as ultraviolet rays, dryness, aging, and stress, the skin can develop various problems such as rough skin, wrinkles, sagging, and pigmentation. It is believed that applying multiple ingredients with different actions to the skin is effective in improving these skin problems from multiple angles. The epidermis is the skin tissue that exists in the outermost layer of the skin. The epidermis is mainly composed of the stratum corneum, stratum granulosum, stratum spinosum, and stratum basale. Basal cells in the stratum basale divide and migrate to the outer layer. During this migration, the cells undergo enucleation, flattening, and differentiation into the stratum corneum, which eventually peels off. This turnover period is said to be about 45 days. However, in aged skin, the turnover rate slows down and the entire epidermis becomes thinner. As a result, it is known that skin functions such as a decrease in barrier function and a decrease in moisture content occur (Patent Document 1, Patent Document 2).
本発明が解決しようとする課題は、皮膚機能の低下を防ぐこと（例えば、メラニン色素生成を抑制すること）を達成するための、ヒト等の皮膚に用いるための組成物を新規に提供すること等である。
The problem that the present invention aims to solve is to provide a novel composition for use on human skin, etc., to prevent a decline in skin function (for example, by suppressing melanin pigment production).
そこで、本発明の発明者は、鋭意検討を重ねた結果、本発明を完成した。
The inventors of the present invention therefore conducted extensive research and developed the present invention.
本発明は、以下の項を含む。
〔項１〕次の成分（Ａ）～（Ｅ）を含有する、メラニン色素生成抑制剤。
（Ａ）トラネキサム酸
（Ｂ）ニコチン酸アミド
（Ｃ）グルタチオン
（Ｄ）ビタミンＣ誘導体
（Ｅ）ピロ亜硫酸ナトリウム
〔項２〕クエン酸を更に含有する、〔項１〕に記載の剤。
〔項３〕アルブチンを更に含有する、〔項１〕又は〔項２〕に記載の剤。
〔項４〕〔項１〕から〔項３〕のいずれか１項の剤を含む、皮膚外用のための組成物。 The present invention includes the following items.
[Item 1] A melanin pigment production inhibitor comprising the following components (A) to (E):
(A) tranexamic acid (B) nicotinamide (C) glutathione (D) a vitamin C derivative (E) sodium pyrosulfite [Item 2] The agent according to [Item 1], further comprising citric acid.
[Item 3] The agent according to [Item 1] or [Item 2], further comprising arbutin.
[Item 4] A composition for external application to the skin, comprising any one of the agents according to [Item 1] to [Item 3].
〔項１〕次の成分（Ａ）～（Ｅ）を含有する、メラニン色素生成抑制剤。
（Ａ）トラネキサム酸
（Ｂ）ニコチン酸アミド
（Ｃ）グルタチオン
（Ｄ）ビタミンＣ誘導体
（Ｅ）ピロ亜硫酸ナトリウム
〔項２〕クエン酸を更に含有する、〔項１〕に記載の剤。
〔項３〕アルブチンを更に含有する、〔項１〕又は〔項２〕に記載の剤。
〔項４〕〔項１〕から〔項３〕のいずれか１項の剤を含む、皮膚外用のための組成物。 The present invention includes the following items.
[Item 1] A melanin pigment production inhibitor comprising the following components (A) to (E):
(A) tranexamic acid (B) nicotinamide (C) glutathione (D) a vitamin C derivative (E) sodium pyrosulfite [Item 2] The agent according to [Item 1], further comprising citric acid.
[Item 3] The agent according to [Item 1] or [Item 2], further comprising arbutin.
[Item 4] A composition for external application to the skin, comprising any one of the agents according to [Item 1] to [Item 3].
本発明により、ヒト等の皮膚に用いるための皮膚機能の低下を防ぐための組成物等を新規に提供できる。
The present invention provides a novel composition for use on human skin to prevent a decline in skin function.
以下、本発明を実施するための形態について説明する。なお、以下の説明においては、本発明の組成物を例に挙げて説明するが、本発明の組成物の説明は、本発明の剤の説明に援用できる。
Below, the mode for carrying out the present invention will be explained. In the following explanation, the composition of the present invention will be used as an example, but the explanation of the composition of the present invention can be used to explain the agent of the present invention.
（トラネキサム酸）
トラネキサム酸は、トランス－４－アミノメチルシクロヘキサン－１－カルボン酸の略称である。トラネキサム酸類は、例えば、トラネキサム酸、トラネキサム酸塩、トラネキサム酸エステル、トラネキサム酸アミド、及びトラネキサム酸の多量体等を意味する。トラネキサム酸塩における塩は、例えば、ナトリウム塩、カリウム塩、マグネシウム塩等の金属塩；塩酸塩、リン酸塩、硫酸塩等の無機酸塩が挙げられる。トラネキサム酸エステルにおけるエステルは、例えば、ビタミンＡエステル、ビタミンＥエステル、ビタミンＣエステル等のビタミンエステル、アルキルエステル等が挙げられる。また、トラネキサム酸アミドにおけるアミドは、例えば、メチルアミド等が挙げられる。 (Tranexamic acid)
Tranexamic acid is an abbreviation for trans-4-aminomethylcyclohexane-1-carboxylic acid. Tranexamic acids include, for example, tranexamic acid, tranexamic acid salts, tranexamic acid esters, tranexamic acid amides, and tranexamic acid multimers. Examples of salts of tranexamic acid salts include metal salts such as sodium salts, potassium salts, and magnesium salts; and inorganic acid salts such as hydrochlorides, phosphates, and sulfates. Examples of esters of tranexamic acid esters include vitamin esters such as vitamin A ester, vitamin E ester, and vitamin C ester; and alkyl esters. Examples of amides of tranexamic acid amides include methyl amides.
トラネキサム酸は、トランス－４－アミノメチルシクロヘキサン－１－カルボン酸の略称である。トラネキサム酸類は、例えば、トラネキサム酸、トラネキサム酸塩、トラネキサム酸エステル、トラネキサム酸アミド、及びトラネキサム酸の多量体等を意味する。トラネキサム酸塩における塩は、例えば、ナトリウム塩、カリウム塩、マグネシウム塩等の金属塩；塩酸塩、リン酸塩、硫酸塩等の無機酸塩が挙げられる。トラネキサム酸エステルにおけるエステルは、例えば、ビタミンＡエステル、ビタミンＥエステル、ビタミンＣエステル等のビタミンエステル、アルキルエステル等が挙げられる。また、トラネキサム酸アミドにおけるアミドは、例えば、メチルアミド等が挙げられる。 (Tranexamic acid)
Tranexamic acid is an abbreviation for trans-4-aminomethylcyclohexane-1-carboxylic acid. Tranexamic acids include, for example, tranexamic acid, tranexamic acid salts, tranexamic acid esters, tranexamic acid amides, and tranexamic acid multimers. Examples of salts of tranexamic acid salts include metal salts such as sodium salts, potassium salts, and magnesium salts; and inorganic acid salts such as hydrochlorides, phosphates, and sulfates. Examples of esters of tranexamic acid esters include vitamin esters such as vitamin A ester, vitamin E ester, and vitamin C ester; and alkyl esters. Examples of amides of tranexamic acid amides include methyl amides.
本発明において、前記トラネキサム酸は、例えば、トラネキサム酸の誘導体を含んでもよい。前記トラネキサム酸の誘導体は、例えば、トラネキサム酸の二量体（塩酸トランス－４－（トランス－４－アミノメチルシクロヘキサンカルボニル）アミノメチルシクロヘキサンカルボン酸）、トラネキサム酸とハイドロキノンとのエステル体（トランス－４－アミノメチルシクロヘキサンカルボン酸４’－ヒドロキシフェニルエステル）、トラネキサム酸とゲンチシン酸とのエステル体（２－（トランス－４－アミノメチルシクロヘキシルカルボニルオキシ）－５－ヒドロキシ安息香酸及びその塩）、トラネキサム酸のアミド体（トランス－４－アミノメチルシクロヘキサンカルボン酸メチルアミド及びその塩、トランス－４－アセチルアミノメチルシクロヘキサンカルボン酸及びその塩、トランス－４－（ｐ－メトキシベンゾイル）アミノメチルシクロヘキサンカルボン酸及びその塩、トランス－４－グアニジノメチルシクロヘキサンカルボン酸及びその塩等）等が挙げられる。
In the present invention, the tranexamic acid may include, for example, a derivative of tranexamic acid. Examples of the derivative of tranexamic acid include a dimer of tranexamic acid (trans-4-(trans-4-aminomethylcyclohexanecarbonyl)aminomethylcyclohexanecarboxylic acid hydrochloride), an ester of tranexamic acid and hydroquinone (trans-4-aminomethylcyclohexanecarboxylic acid 4'-hydroxyphenyl ester), an ester of tranexamic acid and gentisic acid (2-(trans-4-aminomethylcyclohexylcarbonyloxy)-5-hydroxybenzoic acid and its salts), and an amide of tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid methylamide 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.).
本発明の組成物に含有されるトラネキサム酸（当該トラネキサム酸の誘導体も含む）の含有量は、特に限定されないが、所望の効果を発揮するために、一般には組成物全量に対しての前記トラネキサム酸の含有量は、例えば、好ましくは、０．００１重量％以上、更に好ましくは、０．０１％以上、より更に好ましくは、０．１重量％以上である。また、所望の効果等（例えば、一定量超えて配合しても効果の増加が実質上望めない、皮膚外用のための組成物の処方における配合も難しくなる傾向等）を考慮して、一般には組成物全量に対して前記トラネキサム酸の含有量は、例えば、好ましくは、２０重量％以下、更に好ましくは、１０重量％以下、より更に好ましくは、７重量％以下である。
The content of tranexamic acid (including derivatives of said 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 said 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 even more preferably 0.1% by weight or more. Also, taking into consideration the desired effect, etc. (for example, even if more than a certain amount is added, the effect is not substantially increased, and it tends to be difficult to add in the formulation of a composition for external application to the skin, etc.), the content of said 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 even more preferably 7% by weight or less.
（ニコチン酸アミド）
ニコチン酸は、ニコチン酸（ビタミンＢ３、ナイアシン）のアミド化合物であり、ニコチン酸アミド、ナイアシンアミドとも呼ばれる、ニコチン酸の誘導体である。前記ニコチン酸アミドは、水溶性ビタミンで、ビタミンＢ群の一つである物質であり、例えば、天然物（米ぬか等）から抽出されたり、あるいは公知の方法によって合成することができる。具体的には、第十五改正日本薬局方（２００８年改正）に収載されているものを用いることが出来る。 (nicotinamide)
Nicotinic acid is an amide compound of nicotinic acid (vitamin B3, niacin), and is also called nicotinamide or niacinamide, and is a derivative of nicotinic acid. The nicotinamide is a water-soluble vitamin and a substance that is one of the vitamin B group, and can be extracted from natural products (such as rice bran) or synthesized by known methods. Specifically, those listed in the 15th revised Japanese Pharmacopoeia (revised in 2008) can be used.
ニコチン酸は、ニコチン酸（ビタミンＢ３、ナイアシン）のアミド化合物であり、ニコチン酸アミド、ナイアシンアミドとも呼ばれる、ニコチン酸の誘導体である。前記ニコチン酸アミドは、水溶性ビタミンで、ビタミンＢ群の一つである物質であり、例えば、天然物（米ぬか等）から抽出されたり、あるいは公知の方法によって合成することができる。具体的には、第十五改正日本薬局方（２００８年改正）に収載されているものを用いることが出来る。 (nicotinamide)
Nicotinic acid is an amide compound of nicotinic acid (vitamin B3, niacin), and is also called nicotinamide or niacinamide, and is a derivative of nicotinic acid. The nicotinamide is a water-soluble vitamin and a substance that is one of the vitamin B group, and can be extracted from natural products (such as rice bran) or synthesized by known methods. Specifically, those listed in the 15th revised Japanese Pharmacopoeia (revised in 2008) can be used.
本発明の組成物に含有されるニコチン酸アミドの含有量は特に限定されないが、所望の効果を発揮するために、一般には組成物全量に対してのニコチン酸アミドの含有量は、例えば、好ましくは、０．００１重量％以上、更に好ましくは、０．０１％重量以上、より更に好ましくは、０．１重量％以上である。また、所望の効果等（例えば、一定量超えて配合しても効果の増加が実質上望めない、皮膚外用のための組成物の処方における配合も難しくなる傾向等）を考慮して、一般には組成物全量に対してニコチン酸アミドの含有量は、例えば、好ましくは、２０重量％以下、更に好ましくは、１０重量％以下、より更に好ましくは、８重量％以下である。
The content of nicotinamide contained in the composition of the present invention is not particularly limited, but in order to exert the desired effect, the content of nicotinamide is generally, for example, preferably 0.001% by weight or more, more preferably 0.01% by weight or more, and even more preferably 0.1% by weight or more, based on the total amount of the composition. Also, taking into consideration the desired effect, etc. (for example, even if more than a certain amount is added, the effect is not substantially increased, and it tends to be difficult to add in compositions for external use on the skin), the content of nicotinamide is generally, for example, preferably 20% by weight or less, more preferably 10% by weight or less, and even more preferably 8% by weight or less, based on the total amount of the composition.
（グルタチオン）
グルタチオン（Ｇｌｕｔａｔｈｉｏｎｅ）は、抗酸化物質で、生体内に最も多く存在するＳＨ化合物（チオール化合物）で、タンパク質その他のジスルフィドと酵素的、非酵素的に反応し、そのＳＨを維持する機能を有し、この反応で酸化型グルタチオンに変換される。 (Glutathione)
Glutathione is an antioxidant and the most abundant SH compound (thiol compound) in the body. It reacts enzymatically and non-enzymatically with disulfides in proteins and other compounds to maintain their SH status, and is converted into oxidized glutathione through this reaction.
グルタチオン（Ｇｌｕｔａｔｈｉｏｎｅ）は、抗酸化物質で、生体内に最も多く存在するＳＨ化合物（チオール化合物）で、タンパク質その他のジスルフィドと酵素的、非酵素的に反応し、そのＳＨを維持する機能を有し、この反応で酸化型グルタチオンに変換される。 (Glutathione)
Glutathione is an antioxidant and the most abundant SH compound (thiol compound) in the body. It reacts enzymatically and non-enzymatically with disulfides in proteins and other compounds to maintain their SH status, and is converted into oxidized glutathione through this reaction.
本発明の組成物に含有されるグルタチオンの含有量は特に限定されないが、所望の効果を発揮するために、一般には組成物全量に対してのグルタチオンの含有量は、例えば、好ましくは、０．０００１重量％以上、更に好ましくは、０．０００５％以上である。また、所望の効果等（例えば、一定量超えて配合しても効果の増加が実質上望めない、皮膚外用のための組成物の処方における配合も難しくなる傾向等）を考慮して、一般には組成物全量に対してグルタチオンの含有量は、例えば、好ましくは、２０重量％以下、更に好ましくは１０重量％以下である。
The amount of glutathione contained in the composition of the present invention is not particularly limited, but in order to achieve the desired effect, the amount of glutathione contained in the composition is generally, for example, preferably 0.0001% by weight or more, more preferably 0.0005% by weight or more, relative to the total amount of the composition. In addition, taking into consideration the desired effect, etc. (for example, even if a certain amount is added, there is no substantial increase in the effect, and it tends to be difficult to add glutathione to compositions for external use on the skin), the amount of glutathione contained in the composition is generally, for example, preferably 20% by weight or less, more preferably 10% by weight or less, relative to the total amount of the composition.
（ビタミンＣ誘導体）
ビタミンＣ誘導体は、Ｌ－アスコルビン酸の誘導体及びその塩を包含する概念であり、ビタミンＣの安定性を高めるために、他の分子を結合させて分子構造を変化させて製造されたものである。前記ビタミンＣ誘導体には、水溶性、脂溶性、両新媒性のものがある。前記水溶性のビタミンＣ誘導体は、例えば、アスコルビン酸２－グルコシド、アスコルビン酸６－グルコシド、３－Ｏ－エチルアスコルビン酸、アスコルビン酸リン酸ナトリウム等が挙げられる。前記脂溶性のビタミンＣ誘導体は、例えば、テトラヘキシルデカン酸アスコルビル、パルミチン酸アスコルビル、ステアリン酸アスコルビル等が挙げられる。前記両新媒性のビタミンＣ誘導体は、例えば、パルミチン酸アスコルビルリン酸３ナトリウム、グリセリルオクチルアスコルビン酸等が挙げられる。 (Vitamin C derivative)
The concept of vitamin C derivatives encompasses derivatives of L-ascorbic acid and their salts, and is produced by modifying the molecular structure of vitamin C by binding it with other molecules in order to increase its stability. The vitamin C derivatives include water-soluble, fat-soluble, and amphipathic. Examples of the water-soluble vitamin C derivatives include ascorbic acid 2-glucoside, ascorbic acid 6-glucoside, 3-O-ethyl ascorbic acid, and sodium ascorbyl phosphate. Examples of the fat-soluble vitamin C derivatives include ascorbyl tetrahexyldecanoate, ascorbyl palmitate, and ascorbyl stearate. Examples of the amphipathic vitamin C derivatives include trisodium ascorbyl palmitate phosphate, and glyceryl octyl ascorbic acid.
ビタミンＣ誘導体は、Ｌ－アスコルビン酸の誘導体及びその塩を包含する概念であり、ビタミンＣの安定性を高めるために、他の分子を結合させて分子構造を変化させて製造されたものである。前記ビタミンＣ誘導体には、水溶性、脂溶性、両新媒性のものがある。前記水溶性のビタミンＣ誘導体は、例えば、アスコルビン酸２－グルコシド、アスコルビン酸６－グルコシド、３－Ｏ－エチルアスコルビン酸、アスコルビン酸リン酸ナトリウム等が挙げられる。前記脂溶性のビタミンＣ誘導体は、例えば、テトラヘキシルデカン酸アスコルビル、パルミチン酸アスコルビル、ステアリン酸アスコルビル等が挙げられる。前記両新媒性のビタミンＣ誘導体は、例えば、パルミチン酸アスコルビルリン酸３ナトリウム、グリセリルオクチルアスコルビン酸等が挙げられる。 (Vitamin C derivative)
The concept of vitamin C derivatives encompasses derivatives of L-ascorbic acid and their salts, and is produced by modifying the molecular structure of vitamin C by binding it with other molecules in order to increase its stability. The vitamin C derivatives include water-soluble, fat-soluble, and amphipathic. Examples of the water-soluble vitamin C derivatives include ascorbic acid 2-glucoside, ascorbic acid 6-glucoside, 3-O-ethyl ascorbic acid, and sodium ascorbyl phosphate. Examples of the fat-soluble vitamin C derivatives include ascorbyl tetrahexyldecanoate, ascorbyl palmitate, and ascorbyl stearate. Examples of the amphipathic vitamin C derivatives include trisodium ascorbyl palmitate phosphate, and glyceryl octyl ascorbic acid.
本発明の組成物に含有される前記ビタミンＣ誘導体の含有量は特に限定されないが、所望の効果を発揮するために、一般には組成物全量に対しての前記ビタミンＣ誘導体の含有量は、例えば、好ましくは、０．０１重量％以上、更に好ましくは、０．１％以上である。また、所望の効果等（例えば、一定量超えて配合しても効果の増加が実質上望めない、皮膚外用のための組成物の処方における配合も難しくなる傾向等）を考慮して、一般には組成物全量に対して前記ビタミンＣ誘導体の含有量は、例えば、好ましくは、１０重量％以下、更に好ましくは、５重量％以下である。
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 generally, for example, preferably 0.01% by weight or more, more preferably 0.1% by weight or more. Also, taking into consideration the desired effect, etc. (for example, even if more than a certain amount is added, the effect is not substantially increased, and it tends to be difficult to add the derivative to compositions for external use on the skin, etc.), the content of the vitamin C derivative relative to the total amount of the composition is generally, for example, preferably 10% by weight or less, more preferably 5% by weight or less.
（ピロ亜硫酸ナトリウム）
ピロ亜硫酸ナトリウム（Ｓｏｄｉｕｍ ｐｙｒｏｓｕｌｆｉｔｅ、Ｓｏｄｉｕｍ ｍｅｔａｂｉｓｕｌｆｉｔｅ）は、還元性を有しており、例えば、食品用漂白剤、ワインの酸化防止剤等として使用されている。前記ピロ亜硫酸ナトリウムは、亜硫酸水素ナトリウムの脱水反応又は亜硫酸ナトリウムに二酸化硫黄を加えることで生成することができる。 (Sodium pyrosulfite)
Sodium pyrosulfite (sodium metabisulfite) has reducing properties and is used, for example, as a food bleach, an antioxidant for wine, etc. The sodium pyrosulfite can be produced by the dehydration reaction of sodium hydrogensulfite or by adding sulfur dioxide to sodium sulfite.
ピロ亜硫酸ナトリウム（Ｓｏｄｉｕｍ ｐｙｒｏｓｕｌｆｉｔｅ、Ｓｏｄｉｕｍ ｍｅｔａｂｉｓｕｌｆｉｔｅ）は、還元性を有しており、例えば、食品用漂白剤、ワインの酸化防止剤等として使用されている。前記ピロ亜硫酸ナトリウムは、亜硫酸水素ナトリウムの脱水反応又は亜硫酸ナトリウムに二酸化硫黄を加えることで生成することができる。 (Sodium pyrosulfite)
Sodium pyrosulfite (sodium metabisulfite) has reducing properties and is used, for example, as a food bleach, an antioxidant for wine, etc. The sodium pyrosulfite can be produced by the dehydration reaction of sodium hydrogensulfite or by adding sulfur dioxide to sodium sulfite.
本発明の組成物に含有されるピロ亜硫酸ナトリウムの含有量は特に限定されないが、所望の効果を発揮するために、一般には組成物全量に対してのピロ亜硫酸ナトリウムの含有量は、例えば、好ましくは、０．０００１重量％以上、更に好ましくは、０．００１％以上、より更に好ましくは、０．０１％以上である。また、所望の効果等（例えば、一定量超えて配合しても効果の増加が実質上望めない、皮膚外用のための組成物の処方における配合も難しくなる傾向等）を考慮して、一般には組成物全量に対してピロ亜硫酸ナトリウムの含有量は、例えば、好ましくは、２重量％以下、更に好ましくは、１重量％以下、より更に好ましくは、０．５重量％以下である。
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 generally, for example, preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, and even more preferably 0.01% by weight or more. Also, taking into consideration the desired effect, etc. (for example, even if more than a certain amount is added, the effect is not substantially increased, and it tends to be difficult to add in compositions for external use on the skin, etc.), the content of sodium pyrosulfite relative to the total amount of the composition is generally, for example, preferably 2% by weight or less, more preferably 1% by weight or less, and even more preferably 0.5% by weight or less.
（クエン酸）
クエン酸は、緩衝剤（ｐＨ調整剤）である。本発明において、前記クエン酸は、例えば、クエン酸ナトリウム、クエン酸三ナトリウム等を含んでもよい。 (citric acid)
Citric acid is a buffer (pH adjuster). In the present invention, the citric acid may include, for example, sodium citrate, trisodium citrate, etc.
クエン酸は、緩衝剤（ｐＨ調整剤）である。本発明において、前記クエン酸は、例えば、クエン酸ナトリウム、クエン酸三ナトリウム等を含んでもよい。 (citric acid)
Citric acid is a buffer (pH adjuster). In the present invention, the citric acid may include, for example, sodium citrate, trisodium citrate, etc.
本発明の組成物に含有されるクエン酸の含有量は特に限定されないが、所望の効果等を発揮するために、一般には組成物全量に対しての前記クエン酸の含有量は、例えば、好ましくは、０．５重量％以下である。
The amount of citric acid contained in the composition of the present invention is not particularly limited, but in order to achieve the desired effects, the amount of citric acid contained in the composition is generally, for example, preferably 0.5% by weight or less relative to the total amount of the composition.
（アルブチン）
アルブチンは、１９８９年に医薬部外品美白有効成分として厚生労働省に承認された成分である。前記アルブチンは、例えば、ツツジ科植物であるウワウルシ（Ａｒｃｔｏｓｔａｐｈｙｌｏｓ ｕｖａ－ｕｒｓｉ）、コケモモ（Ｖａｃｃｉｎｉｕｍ ｖｉｔｉｓ－ｉｄａｅａ）、ツルコケモモ（Ｖａｃｃｉｎｉｕｍ ｏｘｙｃｏｃｃｏｓ）、バラ科植物セイヨウナシ（Ｐｙｒｕｓ ｃｏｍｍｕｎｉｓ）等の葉に存在している。本発明において、前記アルブチンは、例えば、αアルブチン（ハイドロキノンとグルコースがα結合したハイドロキノン誘導体）、βアルブチン等を含んでもよい。 (Arbutin)
Arbutin is an ingredient approved by the Ministry of Health, Labor and Welfare as a quasi-drug whitening active ingredient in 1989. The arbutin is present in the leaves of, for example, Ericaceae plants such as Arctostaphylos uva-ursi, Vaccinium vitis-idaea, and Vaccinium oxycoccos, and Rosaceae plants such as Pyrus communis. In the present invention, the arbutin may include, for example, α-arbutin (a hydroquinone derivative in which hydroquinone and glucose are α-bonded), β-arbutin, etc.
アルブチンは、１９８９年に医薬部外品美白有効成分として厚生労働省に承認された成分である。前記アルブチンは、例えば、ツツジ科植物であるウワウルシ（Ａｒｃｔｏｓｔａｐｈｙｌｏｓ ｕｖａ－ｕｒｓｉ）、コケモモ（Ｖａｃｃｉｎｉｕｍ ｖｉｔｉｓ－ｉｄａｅａ）、ツルコケモモ（Ｖａｃｃｉｎｉｕｍ ｏｘｙｃｏｃｃｏｓ）、バラ科植物セイヨウナシ（Ｐｙｒｕｓ ｃｏｍｍｕｎｉｓ）等の葉に存在している。本発明において、前記アルブチンは、例えば、αアルブチン（ハイドロキノンとグルコースがα結合したハイドロキノン誘導体）、βアルブチン等を含んでもよい。 (Arbutin)
Arbutin is an ingredient approved by the Ministry of Health, Labor and Welfare as a quasi-drug whitening active ingredient in 1989. The arbutin is present in the leaves of, for example, Ericaceae plants such as Arctostaphylos uva-ursi, Vaccinium vitis-idaea, and Vaccinium oxycoccos, and Rosaceae plants such as Pyrus communis. In the present invention, the arbutin may include, for example, α-arbutin (a hydroquinone derivative in which hydroquinone and glucose are α-bonded), β-arbutin, etc.
本発明の組成物に含有されるアルブチンの含有量は特に限定されないが、所望の効果を発揮するために、一般には組成物全量に対してのアルブチンの含有量は、例えば、好ましくは、０．０００１重量％以上、更に好ましくは、０．００１％以上、より更に好ましくは、０．０１％以上である。また、所望の効果等（例えば、一定量超えて配合しても効果の増加が実質上望めない、皮膚外用のための組成物の処方における配合も難しくなる傾向等）を考慮して、一般には組成物全量に対してアルブチンの含有量は、例えば、好ましくは、２重量％以下、更に好ましくは、１重量％以下、より更に好ましくは、０．５重量％以下である。
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 generally, for example, preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, and even more preferably 0.01% by weight or more. Also, taking into consideration the desired effect, etc. (for example, even if more than a certain amount is added, the effect cannot be substantially increased, and it tends to be difficult to add in compositions for external use on the skin), the content of arbutin relative to the total amount of the composition is generally, for example, preferably 2% by weight or less, more preferably 1% by weight or less, and even more preferably 0.5% by weight or less.
（美白）
美白は、色素沈着の予防及び／又は改善であり、より具体的には、シミ、くすみ、そばかす、日焼け、皮膚の炎症や刺激による黒ずみ等のメラニン色素の産生亢進、過剰蓄積、及び沈着異常等により生じる色素沈着症状、並びにステロイド等の薬物による皮膚の黒化症等の色素沈着をもたらす疾患等による色素沈着症状等の、予防及び／又は改善することである。 (Whitening)
Skin whitening refers to the prevention and/or improvement of pigmentation, and more specifically, refers to the prevention and/or improvement of pigmentation symptoms caused by increased production, excessive accumulation, and abnormal deposition of melanin pigment, such as age spots, dullness, freckles, sunburn, and darkening due to inflammation or irritation of the skin, as well as pigmentation symptoms caused by diseases that result in pigmentation, such as skin melanosis due to drugs such as steroids.
美白は、色素沈着の予防及び／又は改善であり、より具体的には、シミ、くすみ、そばかす、日焼け、皮膚の炎症や刺激による黒ずみ等のメラニン色素の産生亢進、過剰蓄積、及び沈着異常等により生じる色素沈着症状、並びにステロイド等の薬物による皮膚の黒化症等の色素沈着をもたらす疾患等による色素沈着症状等の、予防及び／又は改善することである。 (Whitening)
Skin whitening refers to the prevention and/or improvement of pigmentation, and more specifically, refers to the prevention and/or improvement of pigmentation symptoms caused by increased production, excessive accumulation, and abnormal deposition of melanin pigment, such as age spots, dullness, freckles, sunburn, and darkening due to inflammation or irritation of the skin, as well as pigmentation symptoms caused by diseases that result in pigmentation, such as skin melanosis due to drugs such as steroids.
（メラニン色素生成抑制）
メラニン色素生成抑制は、皮膚メラニン細胞の形成を抑制し、斑点、そばかす及びしみ等の皮膚色素沈着現象を予防及び／又は改善することである。当該予防及び／又は改善により、例えば、全体的な皮膚色調を改善され、皮膚がきれいになり、黒ずみが改善される。 (Inhibits melanin production)
Inhibition of melanin pigmentation refers to the inhibition of the formation of skin melanocytes and the prevention and/or improvement of skin pigmentation phenomena such as spots, freckles, age spots, etc. Such prevention and/or improvement can, for example, improve the overall skin tone, brighten the skin, and improve dark spots.
メラニン色素生成抑制は、皮膚メラニン細胞の形成を抑制し、斑点、そばかす及びしみ等の皮膚色素沈着現象を予防及び／又は改善することである。当該予防及び／又は改善により、例えば、全体的な皮膚色調を改善され、皮膚がきれいになり、黒ずみが改善される。 (Inhibits melanin production)
Inhibition of melanin pigmentation refers to the inhibition of the formation of skin melanocytes and the prevention and/or improvement of skin pigmentation phenomena such as spots, freckles, age spots, etc. Such prevention and/or improvement can, for example, improve the overall skin tone, brighten the skin, and improve dark spots.
（植物抽出物）
本発明の剤及び組成物は、所望の効果を発揮するために、例えば、所定の植物抽出物を含有してもよい。 (Plant Extract)
The agent and composition of the present invention may contain, for example, a specific plant extract in order to exert a desired effect.
本発明の剤及び組成物は、所望の効果を発揮するために、例えば、所定の植物抽出物を含有してもよい。 (Plant Extract)
The agent and composition of the present invention may contain, for example, a specific plant extract in order to exert a desired effect.
植物抽出物を作製する際に用いる抽出方法は、例えば、適当な溶媒を用いて抽出する方法が挙げられる。前記抽出において、使用する植物をそのまま用いてもよいし、粉砕や乾燥等を施して用いてもよいが、粉砕して用いることが好ましく、乾燥させたものを用いることが更に好ましい。また、抽出溶媒に浸漬している間、例えば、攪拌してもよいし、静置してもよい。本発明の植物抽出物は、抽出操作を繰り返して高濃度の植物抽出物とすることもできる。
The extraction method used to prepare the plant extract may be, for example, a method of extraction using an appropriate solvent. In the extraction, the plant may be used as is, or may be crushed or dried before use. It is preferable to crush the plant, and more preferable to use a dried plant. In addition, while immersed in the extraction solvent, the plant may be stirred or left to stand. The plant extract of the present invention may be made into a high-concentration plant extract by repeating the extraction procedure.
前記抽出に使用する溶媒は特に制限されず、水、メタノール、エタノール、プロパノール、ブタノール等の低級１価アルコール類、プロピレングリコール、ジプロピレングリコール、ブチレングリコール、グリセリン等の多価アルコール類、酢酸メチル、酢酸エチル等のエステル類、アセトン、メチルエチルケトン等のケトン類、ジエチルエーテル、テトラヒドロフラン等のエーテル類の極性溶媒や、クロロホルム、四塩化炭素等のハロゲン化炭化水素類、ヘキサン、ヘプタン、シクロヘキサン等の炭化水素類等が挙げられる。前記抽出に使用する溶媒は、例えば、１種を単独で用いても、２種以上からなる混合溶媒を用いてもよく、特に、極性溶媒を用いることが好ましい。前記抽出手順は特に制限されず、例えば、前記抽出に使用する植物を２０～４０℃の前記溶媒中に１時間～７日間浸漬し、濾過する手順が挙げられる。また、得られた抽出液は、そのまま植物抽出物として用いてもよいし、希釈、濃縮、凍結乾燥、精製等を行ったものを植物抽出物として用いてもよい。
The solvent used for the extraction is not particularly limited, and examples thereof include water, lower monohydric alcohols such as methanol, ethanol, propanol, and butanol, polyhydric alcohols such as propylene glycol, dipropylene glycol, butylene glycol, and glycerin, esters such as methyl acetate and ethyl acetate, ketones such as acetone and methyl ethyl ketone, polar solvents such as ethers such as diethyl ether and tetrahydrofuran, halogenated hydrocarbons such as chloroform and carbon tetrachloride, and hydrocarbons such as hexane, heptane, and cyclohexane. The solvent used for the extraction may be, for example, a single solvent or a mixed solvent consisting of two or more solvents, and it is particularly preferable to use a polar solvent. The extraction procedure is not particularly limited, and examples thereof include a procedure in which the plant used for the extraction is immersed in the solvent at 20 to 40°C for 1 hour to 7 days and then filtered. The obtained extract may be used as it is as a plant extract, or may be used after dilution, concentration, freeze-drying, purification, etc.
本発明の組成物における植物抽出物の総含有量は、特に限定されないが、所望の効果を発揮するために、前記組成物の総質量を基準として、乾燥物の質量で、好ましくは、０．０００００１～１０質量％、更に好ましくは、０．００００１～５質量％、より更に好ましくは、０．０００１～３質量％である。
The total content of the plant extract in the composition of the present invention is not particularly limited, but in order to achieve the desired effect, it is preferably 0.000001 to 10% by mass, more preferably 0.00001 to 5% by mass, and even more preferably 0.0001 to 3% by mass, in terms of the mass of the dry matter, based on the total mass of the composition.
所定の植物抽出物は、例えば、ボタンピ抽出物、オウゴン抽出物、ヒメフロウ抽出物、ヨウシュイブキジャコウソウ抽出物、ソウズク抽出物等である。
Specific plant extracts include, for example, Peony root extract, Scutellaria root extract, Caraway extract, Thymus vulgaris extract, and Celastrus arbutus extract.
前記ボタンピ抽出物は、例えば、ボタン科ボタン属ボタン（Ｐａｅｏｎｉａ ｓｕｆｆｒｕｔｉｃｏｓａ Ａｎｄｒｅｗｓ）の根皮に対して、抽出溶媒によって抽出処理を施すことによって得られるものである。以下で示す実施例では、前記ボタンピ抽出物として、ボタンピ抽出液（当該ボタンの根皮のエタノール溶液による抽出液から、溶媒を除去して得られた残留物に１，３－ブチレングリコール及び水を加えて溶解したもの、ボタンピリキッドＢ、一丸ファルコス株式会社）を用いた。
The above-mentioned Paeonia suffruticosa extract is obtained, for example, by subjecting the root bark of the peony (Paeonia suffruticosa Andrews) of the family Paeoniaceae to an extraction treatment using an extraction solvent. In the examples shown below, the above-mentioned Paeonia suffruticosa extract was prepared by adding 1,3-butylene glycol and water to the residue obtained by removing the solvent from the extract of the root bark of the peony in ethanol, and dissolving it there; Paeonia suffruticosa Liquid B, Ichimaru Pharcos Co., Ltd.
前記オウゴン抽出物は、例えば、シソ科（Ｌａｍｉａｃｅａｅ）タツナミソウ属（Ｓｃｕｔｅｌｌａｒｉａ）の植物：コガネバナ（Ｓｃｕｔｅｌｌａｒｉａ ｂａｉｃａｌｅｎｓｉｓ Ｇｅｏｒｇｉ）の根、根茎及び／又は根皮に対して、抽出溶媒によって抽出処理を施すことによって得られるものである。以下で示す実施例では、前記オウゴン抽出物として、オウゴン抽出液（当該コガネバナ Ｓｃｕｔｅｌｌａｒｉａ ｂａｉｃａｌｅｎｓｉｓ Ｇｅｏｒｇｉ（Ｌａｂｉａｔａｅ）の周皮を除いた根のエタノールによる抽出物を１，３－ブチレングリコール溶液に溶解したもの、オウゴンリキッドＢ、一丸ファルコス株式会社）を用いた。
The Scutellaria root extract is obtained, for example, by subjecting the root, rhizome and/or root bark of Scutellaria baicalensis Georgia, a plant of the Scutellaria genus in the Lamiaceae family, to an extraction treatment using an extraction solvent. In the examples shown below, Scutellaria root extract (an ethanol extract of the roots of Scutellaria baicalensis Georgia (Labiatae), with the periderm removed, dissolved in 1,3-butylene glycol solution, Scutellaria root liquid B, Ichimaru Pharcos Co., Ltd.) was used as the Scutellaria root extract.
前記ヒメフウロ抽出物は、例えば、フウロソウ科ヒメフウロ（姫風露）Ｇｅｒａｎｉｕｍ ｒｏｂｅｒｔｉａｎｕｍ Ｌ．（Ｇｅｒａｎｉａｃｅａｅ）に対して、抽出処理を施すことによって得られるものである。以下で示す実施例では、前記ヒメフウロ抽出物として、ヒメフウロ抽出液（ヒメフウロ Ｇｅｒａｎｉｕｍ ｒｏｂｅｒｔｉａｎｕｍ Ｌ．（Ｇｅｒａｎｉａｃｅａｅ）の全草から１，３－ブチレングリコール溶液で抽出して得られたもの、プリンセスケア、一丸ファルコス株式会社）を用いた。
The above-mentioned Geranium robertianum extract is obtained, for example, by subjecting Geranium robertianum L. (Geraniaceae) of the Geraniaceae family to an extraction process. In the examples shown below, Geranium robertianum extract (obtained by extracting the whole plant of Geranium robertianum L. (Geraniaceae) with a 1,3-butylene glycol solution, Princess Care, Ichimaru Pharcos Co., Ltd.) was used as the above-mentioned Geranium robertianum extract.
前記ヨウシュイブキジャコウソウ抽出物は、例えば、ワイルドタイム、クリーピングタイムと呼ばれるヨーロッパ原産のＴｈｙｍｕｓ ｓｅｒｐｙｌｌｕｍに対して、抽出処理を施すことによって得られるものである。以下で示す実施例では、前記ヨウシュイブキジャコウソウ抽出物として、ヨウシュイブキジャコウソウ抽出液（Ｔｈｙｍｕｓ ｓｅｒｐｙｌｌｕｍ Ｌ．（Ｌａｂｉａｔａｅ）の地上部からエタノール溶液にて抽出して得られるエキスを濃縮し、１，３－ブチレングリコール溶液を加えて溶解したもの、シンデレラケア、一丸ファルコス株式会社）を用いた。
The above-mentioned thymus extract is obtained by subjecting, for example, Thymus serpyllum, which is native to Europe and is known as wild thyme or creeping thyme, to an extraction process. In the examples shown below, thymus extract was obtained by concentrating an extract obtained by extracting the above-ground parts of Thymus serpyllum L. (Labiatae) with an ethanol solution and dissolving it by adding a 1,3-butylene glycol solution, Cinderella Care, Ichimaru Pharcos Co., Ltd.
前記ソウズク抽出物は、例えば、中国伝統植物の一つであるアルピニア・カツマダイの種子に対して、抽出処理を施すことによって得られるものである。以下で示す実施例では、前記ソウズク抽出物として、ソウズク抽出液（Ａｌｐｉｎｉａ ｋａｔｓｕｍａｄａｉ Ｈａｙａｔａ（Ｚｉｎｇｉｂｅｒａｃｅａｅ）の種子からエタノール溶液で抽出して得られるエキスを濃縮し、１，３－ブチレングリコール溶液を加えて溶解したもの、アルピニアホワイト、一丸ファルコス株式会社）を用いた。
The above-mentioned Zingiberaceae extract is obtained, for example, by subjecting the seeds of Alpinia katsumadai, a traditional Chinese plant, to an extraction process. In the examples shown below, Zingiberaceae extract (an extract obtained by extracting the seeds of Alpinia katsumadai Hayata (Zingiberaceae) with an ethanol solution, concentrating the extract, and dissolving it by adding a 1,3-butylene glycol solution, Alpinia White, Ichimaru Pharcos Co., Ltd.) was used as the above-mentioned Zingiberaceae extract.
（組成物の形態）
本発明の組成物（皮膚外用のための組成物等）は、アンプル、カプセル、粉末、顆粒、液体、ゲル、気泡、エマルジョン、シート、ミスト、スプレー剤等利用上の適当な形態の１）医薬品類、２）医薬部外品類、３）局所用又は全身用の皮膚外用剤類（例えば、化粧水、乳液、クリーム、軟膏、ローション、オイル、パック等の基礎化粧料、固形石鹸、液体ソープ、ハンドウォッシュ等の洗顔料や皮膚洗浄料、マッサージ用剤、クレンジング用剤、除毛剤、脱毛剤、髭剃り処理料、アフターシェーブローション、プレシェーブローション、シェービングクリーム、ファンデーション、口紅、頬紅、アイシャドウ、アイライナー、マスカラ等のメークアップ化粧料、香水類、美爪剤、美爪エナメル、美爪エナメル除去剤、パップ材、プラスター材、テープ剤、シート材、貼付剤、エアゾール剤等）、４）頭皮・頭髪に適用する薬用又は／及び化粧用の製剤類（例えば、シャンプー剤、リンス材、ヘアートリートメント材、プレヘアートリートメント材、パーマネント液、染毛料、整髪料、ヘアートニック剤、育毛・養毛料、パップ剤、プラスター剤、テープ剤、シート剤、エアゾール剤等）、５）浴湯に投じて使用する浴用剤、６）その他、腋臭防止剤や消臭剤、制汗剤、衛生用品、衛生綿類、ウエットティシュ等が挙げられる。 (Form of composition)
The composition of the present invention (composition for external application to the skin, etc.) may be in the form of ampoules, capsules, powders, granules, liquids, gels, foams, emulsions, sheets, mists, sprays, etc., and may be in the form of 1) medicines, 2) quasi-drugs, 3) topical or whole body external skin preparations (for example, basic cosmetics such as lotions, milky lotions, creams, ointments, lotions, oils, and packs, face washes and skin cleansers such as solid soaps, liquid soaps, and hand washes, massage preparations, cleansing preparations, hair removal preparations, depilatories, shaving treatments, aftershave lotions, preshave lotions, shaving creams, foundations, lipsticks, blushers, eye shadows, and eyeshadows). makeup cosmetics such as eyeliner and mascara, perfumes, nail beautifying agents, nail beautifying enamel, nail beautifying enamel remover, poultices, plasters, tapes, sheets, patches, aerosols, etc.); 4) medicinal and/or cosmetic preparations to be applied to the scalp and hair (for example, shampoos, rinses, hair treatments, pre-hair treatments, permanent solutions, hair dyes, hair styling products, hair tonics, hair growth and care products, poultices, plasters, tapes, sheets, aerosols, etc.); 5) bath products to be added to the bath; 6) other products such as underarm odor prevention agents, deodorants, antiperspirants, sanitary products, sanitary cotton, wet tissues, etc.
本発明の組成物（皮膚外用のための組成物等）は、アンプル、カプセル、粉末、顆粒、液体、ゲル、気泡、エマルジョン、シート、ミスト、スプレー剤等利用上の適当な形態の１）医薬品類、２）医薬部外品類、３）局所用又は全身用の皮膚外用剤類（例えば、化粧水、乳液、クリーム、軟膏、ローション、オイル、パック等の基礎化粧料、固形石鹸、液体ソープ、ハンドウォッシュ等の洗顔料や皮膚洗浄料、マッサージ用剤、クレンジング用剤、除毛剤、脱毛剤、髭剃り処理料、アフターシェーブローション、プレシェーブローション、シェービングクリーム、ファンデーション、口紅、頬紅、アイシャドウ、アイライナー、マスカラ等のメークアップ化粧料、香水類、美爪剤、美爪エナメル、美爪エナメル除去剤、パップ材、プラスター材、テープ剤、シート材、貼付剤、エアゾール剤等）、４）頭皮・頭髪に適用する薬用又は／及び化粧用の製剤類（例えば、シャンプー剤、リンス材、ヘアートリートメント材、プレヘアートリートメント材、パーマネント液、染毛料、整髪料、ヘアートニック剤、育毛・養毛料、パップ剤、プラスター剤、テープ剤、シート剤、エアゾール剤等）、５）浴湯に投じて使用する浴用剤、６）その他、腋臭防止剤や消臭剤、制汗剤、衛生用品、衛生綿類、ウエットティシュ等が挙げられる。 (Form of composition)
The composition of the present invention (composition for external application to the skin, etc.) may be in the form of ampoules, capsules, powders, granules, liquids, gels, foams, emulsions, sheets, mists, sprays, etc., and may be in the form of 1) medicines, 2) quasi-drugs, 3) topical or whole body external skin preparations (for example, basic cosmetics such as lotions, milky lotions, creams, ointments, lotions, oils, and packs, face washes and skin cleansers such as solid soaps, liquid soaps, and hand washes, massage preparations, cleansing preparations, hair removal preparations, depilatories, shaving treatments, aftershave lotions, preshave lotions, shaving creams, foundations, lipsticks, blushers, eye shadows, and eyeshadows). makeup cosmetics such as eyeliner and mascara, perfumes, nail beautifying agents, nail beautifying enamel, nail beautifying enamel remover, poultices, plasters, tapes, sheets, patches, aerosols, etc.); 4) medicinal and/or cosmetic preparations to be applied to the scalp and hair (for example, shampoos, rinses, hair treatments, pre-hair treatments, permanent solutions, hair dyes, hair styling products, hair tonics, hair growth and care products, poultices, plasters, tapes, sheets, aerosols, etc.); 5) bath products to be added to the bath; 6) other products such as underarm odor prevention agents, deodorants, antiperspirants, sanitary products, sanitary cotton, wet tissues, etc.
また、このような組成物は、必要に応じて、本発明の効果を妨げない範囲で、例えば、通常化粧料に使用する成分、すなわち油性成分、低級アルコール、多価アルコール、保湿剤等の水性成分、紫外線吸収剤、酸化防止剤、美容成分、防腐剤、油溶性樹脂、染料、清涼剤、色素、香料等を適宜含有してもよい。
Furthermore, such compositions may contain, as necessary, appropriate amounts of ingredients typically used in cosmetics, such as oily ingredients, lower alcohols, polyhydric alcohols, aqueous ingredients such as moisturizers, UV absorbers, antioxidants, cosmetic ingredients, preservatives, oil-soluble resins, dyes, cooling agents, pigments, fragrances, etc., within the scope of the effects of the present invention.
本発明の組成物に含有されるメラニン色素生成抑制剤は、例えば、所望の効果（美白効果等）を発揮するために、好ましくは、０．２５（ｖ／ｖ）％以上、より好ましくは、０．５（ｖ／ｖ）％以上、より好ましくは、０．７５（ｖ／ｖ）％以上、より好ましくは、１（ｖ／ｖ）％以上、更に好ましくは、２（ｖ／ｖ）％以上である。また、本発明の組成物に含有されるメラニン色素生成抑制剤は、例えば、所望の毒性等を考慮して、好ましくは、５０（ｖ／ｖ）％以下、より好ましくは、２５（ｖ／ｖ）％以下、更に好ましくは、１０（ｖ／ｖ）％以下である。
The melanin pigment production inhibitor contained in the composition of the present invention is, for example, in order to exert a desired effect (such as a whitening effect), preferably 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 even more preferably 2 (v/v)% or more. In addition, the melanin pigment production inhibitor contained in the composition of the present invention is, for example, in consideration of the desired toxicity, etc., preferably 50 (v/v)% or less, more preferably 25 (v/v)% or less, and even more preferably 10 (v/v)% or less.
次に実施例を挙げ、本発明を更に詳しく説明するが、本発明はこれら実施例に何ら制約されるものではない。なお、以下の実施例において、各種成分の添加量を示す数値の単位％は、質量％を意味する。
The present invention will be described in more detail below with reference to examples, but the present invention is in no way limited to these examples. In the following examples, the unit % of the numerical values showing the amount of each component added means % by mass.
以下、本発明の実施例について、説明する。以下、実施例で挙げる実験で用いた実験材料は次の通りである。
・Ｂ１６マウスメラノーマ細胞（メラノーマ細胞）：Ｂ１６ ｍｅｌａｎｏｍａ ４Ａ５、理化学研究所ＣＥＬＬ ＢＡＮＫ
・当該細胞の前培養培地：５％ウシ胎児血清を含むＭＥＭ培地
・ＭＥＭ培地：Ｅ－ＭＥＭ（０５１－０７６１５）、富士フイルム和光純薬株式会社
・ウシ胎児血清：Ｔｈｅｒｍｏｆｉｓｈｅｒ Ｓｃｉｅｎｔｉｆｉｃ
・本培養培地：デフォリン０．０３６％を含むＭＥＭ培地 The following examples of the present invention will be described. The following experimental materials were used in the experiments described in the examples.
B16 mouse melanoma cells (melanoma cells): B16 melanoma 4A5, RIKEN CELL BANK
Preculture medium for the cells: MEM medium containing 5% fetal bovine serum; MEM medium: E-MEM (051-07615), Fujifilm Wako Pure Chemical Industries; Fetal bovine serum: Thermofisher Scientific
Main culture medium: MEM medium containing 0.036% defolin
・Ｂ１６マウスメラノーマ細胞（メラノーマ細胞）：Ｂ１６ ｍｅｌａｎｏｍａ ４Ａ５、理化学研究所ＣＥＬＬ ＢＡＮＫ
・当該細胞の前培養培地：５％ウシ胎児血清を含むＭＥＭ培地
・ＭＥＭ培地：Ｅ－ＭＥＭ（０５１－０７６１５）、富士フイルム和光純薬株式会社
・ウシ胎児血清：Ｔｈｅｒｍｏｆｉｓｈｅｒ Ｓｃｉｅｎｔｉｆｉｃ
・本培養培地：デフォリン０．０３６％を含むＭＥＭ培地 The following examples of the present invention will be described. The following experimental materials were used in the experiments described in the examples.
B16 mouse melanoma cells (melanoma cells): B16 melanoma 4A5, RIKEN CELL BANK
Preculture medium for the cells: MEM medium containing 5% fetal bovine serum; MEM medium: E-MEM (051-07615), Fujifilm Wako Pure Chemical Industries; Fetal bovine serum: Thermofisher Scientific
Main culture medium: MEM medium containing 0.036% defolin
・ニコチン酸アミド（Ｎｉｃｏｔｉｎａｍｉｄｅ）：製品コード０００－５４２２５、ＣＡＳ ＲＮＴＭ９８－９２－０、キシダ化学株式会社
・トラネキサム酸：日本薬局方トラネキサム酸
・グルタチオン：Ｌ－グルタチオン、興人ライフサイエンス株式会社
・ビタミンＣ誘導体：パシフィコス ＶＡＰ、一丸ファルコス株式会社
・ピロ亜硫酸ナトリウム：純正化学株式会社
・アブルチン：β－アルブチン、Ｐｒｏｄｕｃｔ ＩＤ：Ａ６８０４、ＬＫＴ Ｌａｂｏｒａｔｏｒｉｅｓ ＩＮＣ
・ボタンピ抽出物：ボタンピリキッドＢ、一丸ファルコス株式会社
・オウゴン抽出物：オウゴンリキッドＢ、一丸ファルコス株式会社
・ヒメフウロ抽出物：プリンセスケア、一丸ファルコス株式会社
・ヨウシュイブキジャコウソウ抽出物：シンデレラケア、一丸ファルコス株式会社
・ソウズク抽出物：アルピニアホワイト、一丸ファルコス株式会社 Nicotinamide: Product code 000-54225, CAS RNTM98-92-0, Kishida Chemical Co., Ltd. Tranexamic acid: Japanese Pharmacopoeia tranexamic acid Glutathione: L-glutathione, Kohjin Life Sciences Co., Ltd. Vitamin C derivative: Pacificos VAP, Ichimaru Pharcos Co., Ltd. Sodium pyrosulfite: Junsei Chemical Co., Ltd. Abrutin: β-arbutin, Product ID: A6804, LKT Laboratories INC.
・Moutan pea extract: Moutan pea Liquid B, Ichimaru Pharcos Co., Ltd. ・Scutellaria root extract: Scutellaria root Liquid B, Ichimaru Pharcos Co., Ltd. ・Geranium extract: Princess Care, Ichimaru Pharcos Co., Ltd. ・Thymus vulgaris extract: Cinderella Care, Ichimaru Pharcos Co., Ltd. ・Souvenir tree extract: Alpinia White, Ichimaru Pharcos Co., Ltd.
・トラネキサム酸：日本薬局方トラネキサム酸
・グルタチオン：Ｌ－グルタチオン、興人ライフサイエンス株式会社
・ビタミンＣ誘導体：パシフィコス ＶＡＰ、一丸ファルコス株式会社
・ピロ亜硫酸ナトリウム：純正化学株式会社
・アブルチン：β－アルブチン、Ｐｒｏｄｕｃｔ ＩＤ：Ａ６８０４、ＬＫＴ Ｌａｂｏｒａｔｏｒｉｅｓ ＩＮＣ
・ボタンピ抽出物：ボタンピリキッドＢ、一丸ファルコス株式会社
・オウゴン抽出物：オウゴンリキッドＢ、一丸ファルコス株式会社
・ヒメフウロ抽出物：プリンセスケア、一丸ファルコス株式会社
・ヨウシュイブキジャコウソウ抽出物：シンデレラケア、一丸ファルコス株式会社
・ソウズク抽出物：アルピニアホワイト、一丸ファルコス株式会社 Nicotinamide: Product code 000-54225, CAS RNTM98-92-0, Kishida Chemical Co., Ltd. Tranexamic acid: Japanese Pharmacopoeia tranexamic acid Glutathione: L-glutathione, Kohjin Life Sciences Co., Ltd. Vitamin C derivative: Pacificos VAP, Ichimaru Pharcos Co., Ltd. Sodium pyrosulfite: Junsei Chemical Co., Ltd. Abrutin: β-arbutin, Product ID: A6804, LKT Laboratories INC.
・Moutan pea extract: Moutan pea Liquid B, Ichimaru Pharcos Co., Ltd. ・Scutellaria root extract: Scutellaria root Liquid B, Ichimaru Pharcos Co., Ltd. ・Geranium extract: Princess Care, Ichimaru Pharcos Co., Ltd. ・Thymus vulgaris extract: Cinderella Care, Ichimaru Pharcos Co., Ltd. ・Souvenir tree extract: Alpinia White, Ichimaru Pharcos Co., Ltd.
（実験１：メラニン生成抑制試験）
所定の細胞（上述のメラノーマ細胞）に対して試料を添加することにより、所定の細胞において、メラニン生成に変化があるかを確認した。試料を添加する細胞として、Ｂ１６マウスメラノーマ細胞を用いた。 (Experiment 1: Melanin production inhibition test)
By adding a sample to a specific cell (the above-mentioned melanoma cell), it was confirmed whether there was a change in melanin production in the specific cell. B16 mouse melanoma cell was used as the cell to which the sample was added.
所定の細胞（上述のメラノーマ細胞）に対して試料を添加することにより、所定の細胞において、メラニン生成に変化があるかを確認した。試料を添加する細胞として、Ｂ１６マウスメラノーマ細胞を用いた。 (Experiment 1: Melanin production inhibition test)
By adding a sample to a specific cell (the above-mentioned melanoma cell), it was confirmed whether there was a change in melanin production in the specific cell. B16 mouse melanoma cell was used as the cell to which the sample was added.
（１）メラノーマ細胞の前培養工程
上述のメラノーマ細胞を上述の前培養培地（５％ウシ胎児血清を含むＭＥＭ培地）を用いて、５％ＣＯ２、３７℃の条件で２４時間培養した。 (1) Pre-culture step of melanoma cells The above-mentioned melanoma cells were cultured in the above-mentioned pre-culture medium (MEM medium containing 5% fetal bovine serum) under conditions of 5% CO2 and 37°C for 24 hours.
上述のメラノーマ細胞を上述の前培養培地（５％ウシ胎児血清を含むＭＥＭ培地）を用いて、５％ＣＯ２、３７℃の条件で２４時間培養した。 (1) Pre-culture step of melanoma cells The above-mentioned melanoma cells were cultured in the above-mentioned pre-culture medium (MEM medium containing 5% fetal bovine serum) under conditions of 5% CO2 and 37°C for 24 hours.
（２）試料添加後の本培養工程
当該（１）の前培養後、８．５×１０４個／ウェルの細胞数で、メラノーマ細胞を各ウェル（本培養培地が存在するウェル、２４Ｗｅｌｌｐｌａｔｅ）に播種した。当該播種後、５％ＣＯ２、３７℃の条件で２４時間培養した。 After the pre-culture in (1), melanoma cells were seeded in each well (wells containing the main culture medium, 24-well plate) at 8.5×10 4 cells/well. After the seeding, the cells were cultured for 24 hours under conditions of 5% CO 2 and 37° C.
当該（１）の前培養後、８．５×１０４個／ウェルの細胞数で、メラノーマ細胞を各ウェル（本培養培地が存在するウェル、２４Ｗｅｌｌｐｌａｔｅ）に播種した。当該播種後、５％ＣＯ２、３７℃の条件で２４時間培養した。 After the pre-culture in (1), melanoma cells were seeded in each well (wells containing the main culture medium, 24-well plate) at 8.5×10 4 cells/well. After the seeding, the cells were cultured for 24 hours under conditions of 5% CO 2 and 37° C.
前記培養後、各ウェルの培地を新鮮な本培養培地に置換した。当該置換された培地（当該細胞が含有）に、下記表１に示す下記試料（コントロール、比較例１から５、実施例１から３）を最終濃度２（ｖ／ｖ）％となるように添加した。なお、この試料の添加は、以下の群を作製するように行った。なお、アルブチンのメラニン生成抑制作用が知られていることから（日皮会誌：１０１（６）、６０９－６１３，１９９１）、前記実験１では、ポジティブコントロールの試験例として、下記表１に示す試料（ポジディブコントロール）を最終濃度１（ｖ／ｖ）％となるように添加する群を設定した。
After the culture, the medium in each well was replaced with fresh main culture medium. The following samples (control, Comparative Examples 1 to 5, Examples 1 to 3) shown in Table 1 below were added to the replaced medium (containing the cells) to a final concentration of 2 (v/v)%. The samples were added to create the following groups. Since arbutin is known to have an inhibitory effect on melanin production (Journal of the Japanese Dermatological Association: 101 (6), 609-613, 1991), in the above Experiment 1, a group was set up to add the sample shown in Table 1 below (positive control) to a final concentration of 1 (v/v)% as a test example of a positive control.
当該添加後、５％ＣＯ２、３７℃の条件で、７２時間（３日間）培養した。この７２時間の培養後、各群において、下記測定１で用いるための当該培養したサンプル及び下記測定２で用いるための当該培養したサンプルに分けた。
After the addition, the cells were cultured for 72 hours (3 days) under conditions of 5% CO 2 and 37° C. After the 72-hour culture, each group was divided into a cultured sample for use in the following measurement 1 and a cultured sample for use in the following measurement 2.
（測定１：メラニン量測定）
この測定１で用いるための当該培養したサンプルをトリプシン処理によって細胞を回収した。回収した細胞を溶液（１Ｎ ＮａＯＨ、１０％ＤＭＳＯ含有）に溶解した。４２０ｎｍの吸光度にて当該溶解した液の吸光度（コントロール、ポジティブコントロール、比較例１から５、実施例１から３の吸光度）を各々測定した。当該測定した値をメラニン量とした。当該測定の数値（相対値）を次のように算出した。先ず、各群（ｎ＝３）の測定結果の吸光度を算出した。次に、当該平均値について、各群のコントロール群の数値を１００として、各群の数値はコントロール群と比較しての相対値を算出した。上記表１で示す「有効性（メラニン色素生成抑制効果）」は、コントロール群と比べて有意にメラニン色素生成抑制効果を確認した群を「〇（マル）」、それ以外を「×（バツ）」とした。なお、「―」は測定しなかった試料を示す。当該の有意の有無は、Ｄｕｎｎｅｔｔ検定において、コントロール群との比較による有意差（ｐ＜０．０５）により示した。 (Measurement 1: Melanin amount measurement)
The cultured sample for use in this measurement 1 was treated with trypsin to recover cells. The recovered cells were dissolved in a solution (containing 1N NaOH and 10% DMSO). The absorbance of the dissolved solution (control, positive control, Comparative Examples 1 to 5, and Examples 1 to 3) was measured at 420 nm. The measured value was taken as the amount of melanin. The numerical value (relative value) of the measurement was calculated as follows. First, the absorbance of the measurement results of each group (n=3) was calculated. Next, the average value of each group was calculated as a relative value compared to the control group, with the numerical value of the control group being set to 100. In the "Efficacy (melanin pigment production inhibitory effect)" shown in Table 1 above, the group in which a significant melanin pigment production inhibitory effect was confirmed compared to the control group was marked with "○ (circle)", and the others were marked with "× (cross)". In addition, "-" indicates a sample that was not measured. The presence or absence of significance was indicated by a significant difference (p<0.05) in comparison with the control group in the Dunnett test.
この測定１で用いるための当該培養したサンプルをトリプシン処理によって細胞を回収した。回収した細胞を溶液（１Ｎ ＮａＯＨ、１０％ＤＭＳＯ含有）に溶解した。４２０ｎｍの吸光度にて当該溶解した液の吸光度（コントロール、ポジティブコントロール、比較例１から５、実施例１から３の吸光度）を各々測定した。当該測定した値をメラニン量とした。当該測定の数値（相対値）を次のように算出した。先ず、各群（ｎ＝３）の測定結果の吸光度を算出した。次に、当該平均値について、各群のコントロール群の数値を１００として、各群の数値はコントロール群と比較しての相対値を算出した。上記表１で示す「有効性（メラニン色素生成抑制効果）」は、コントロール群と比べて有意にメラニン色素生成抑制効果を確認した群を「〇（マル）」、それ以外を「×（バツ）」とした。なお、「―」は測定しなかった試料を示す。当該の有意の有無は、Ｄｕｎｎｅｔｔ検定において、コントロール群との比較による有意差（ｐ＜０．０５）により示した。 (Measurement 1: Melanin amount measurement)
The cultured sample for use in this measurement 1 was treated with trypsin to recover cells. The recovered cells were dissolved in a solution (containing 1N NaOH and 10% DMSO). The absorbance of the dissolved solution (control, positive control, Comparative Examples 1 to 5, and Examples 1 to 3) was measured at 420 nm. The measured value was taken as the amount of melanin. The numerical value (relative value) of the measurement was calculated as follows. First, the absorbance of the measurement results of each group (n=3) was calculated. Next, the average value of each group was calculated as a relative value compared to the control group, with the numerical value of the control group being set to 100. In the "Efficacy (melanin pigment production inhibitory effect)" shown in Table 1 above, the group in which a significant melanin pigment production inhibitory effect was confirmed compared to the control group was marked with "○ (circle)", and the others were marked with "× (cross)". In addition, "-" indicates a sample that was not measured. The presence or absence of significance was indicated by a significant difference (p<0.05) in comparison with the control group in the Dunnett test.
（測定２：ＷＳＴ法によるメラノーマ細胞の細胞数測定）
Ｃｅｌｌ Ｃｏｕｎｔｉｎｇ Ｋｉｔ－８（Ｄｏｊｉｎｄｏ）を用いて当該測定を行った。測定２で用いるための当該培養したサンプルに当該ｋｉｔ－８を入れた。当該入れた後、５％ＣＯ２、３７℃の条件で２時間培養した。当該培養後、「Ｃｅｌｌ Ｃｏｕｎｔｉｎｇ Ｋｉｔ－８（Ｄｏｊｉｎｄｏ）」の説明書に沿って４５０ｎｍの吸光度で、各群の発色を確認した。各群（ｎ＝４）で行った。上記表１で示す「毒性（当該細胞数測定）」は、コントロール群と比べて有意に細胞数の減少を確認した群を「×（バツ、毒性あり）」、それ以外を「○（マル、毒性なし）」とした。なお、「―」は測定しなかった試料を示す。当該の有意の有無は、Ｄｕｎｎｅｔｔ検定において、コントロール群との比較による有意差（ｐ＜０．０５）により示した。 (Measurement 2: Melanoma cell count measurement using WST method)
The measurement was performed using Cell Counting Kit-8 (Dojindo). The kit-8 was added to the cultured sample for use in measurement 2. After the addition, the sample was cultured for 2 hours under conditions of 5% CO 2 and 37°C. After the culture, the color development of each group was confirmed by the absorbance at 450 nm according to the instructions of "Cell Counting Kit-8 (Dojindo)". This was performed for each group (n = 4). In the "toxicity (cell count measurement)" shown in Table 1 above, the group in which a significant decrease in cell count was confirmed compared to the control group was designated as "X (X, toxic)", and the others were designated as "○ (Circle, no toxicity)". Note that "-" indicates a sample that was not measured. The presence or absence of significance was indicated by a significant difference (p < 0.05) in comparison with the control group in the Dunnett test.
Ｃｅｌｌ Ｃｏｕｎｔｉｎｇ Ｋｉｔ－８（Ｄｏｊｉｎｄｏ）を用いて当該測定を行った。測定２で用いるための当該培養したサンプルに当該ｋｉｔ－８を入れた。当該入れた後、５％ＣＯ２、３７℃の条件で２時間培養した。当該培養後、「Ｃｅｌｌ Ｃｏｕｎｔｉｎｇ Ｋｉｔ－８（Ｄｏｊｉｎｄｏ）」の説明書に沿って４５０ｎｍの吸光度で、各群の発色を確認した。各群（ｎ＝４）で行った。上記表１で示す「毒性（当該細胞数測定）」は、コントロール群と比べて有意に細胞数の減少を確認した群を「×（バツ、毒性あり）」、それ以外を「○（マル、毒性なし）」とした。なお、「―」は測定しなかった試料を示す。当該の有意の有無は、Ｄｕｎｎｅｔｔ検定において、コントロール群との比較による有意差（ｐ＜０．０５）により示した。 (Measurement 2: Melanoma cell count measurement using WST method)
The measurement was performed using Cell Counting Kit-8 (Dojindo). The kit-8 was added to the cultured sample for use in measurement 2. After the addition, the sample was cultured for 2 hours under conditions of 5% CO 2 and 37°C. After the culture, the color development of each group was confirmed by the absorbance at 450 nm according to the instructions of "Cell Counting Kit-8 (Dojindo)". This was performed for each group (n = 4). In the "toxicity (cell count measurement)" shown in Table 1 above, the group in which a significant decrease in cell count was confirmed compared to the control group was designated as "X (X, toxic)", and the others were designated as "○ (Circle, no toxicity)". Note that "-" indicates a sample that was not measured. The presence or absence of significance was indicated by a significant difference (p < 0.05) in comparison with the control group in the Dunnett test.
比較例と比べ、実施例では、メラニン色素生成抑制効果があり、更に毒性もなかった。
Compared to the comparative example, the example had the effect of inhibiting melanin pigment production and was also non-toxic.
（測定３：臭いの確認）
官能試験として、各試料（コントロール、比較例１から５、実施例１から３）の臭い（酸臭に近い臭い、酸を感じる劣化臭）の有無を確認した。まず、各試料を蓋のついた１００ｍＬのサンプル瓶に入れて、３０分静置した。当該静置後、蓋を開け、臭いをかいで、以下の基準に基づき測定した。
○：臭いを感じない試料。
×：臭いを感じる試料。
―：測定しなかった試料。 (Measurement 3: Checking the odor)
As a sensory test, the presence or absence of odor (smell similar to an acidic odor, deterioration odor reminiscent of an acidic odor) was confirmed for each sample (control, Comparative Examples 1 to 5, Examples 1 to 3). First, each sample was placed in a 100 mL sample bottle with a lid and left to stand for 30 minutes. After the standing, the lid was opened, and the odor was smelled and measured based on the following criteria.
○: Sample has no odor.
×: Sample has an unpleasant odor.
-: Sample not measured.
官能試験として、各試料（コントロール、比較例１から５、実施例１から３）の臭い（酸臭に近い臭い、酸を感じる劣化臭）の有無を確認した。まず、各試料を蓋のついた１００ｍＬのサンプル瓶に入れて、３０分静置した。当該静置後、蓋を開け、臭いをかいで、以下の基準に基づき測定した。
○：臭いを感じない試料。
×：臭いを感じる試料。
―：測定しなかった試料。 (Measurement 3: Checking the odor)
As a sensory test, the presence or absence of odor (smell similar to an acidic odor, deterioration odor reminiscent of an acidic odor) was confirmed for each sample (control, Comparative Examples 1 to 5, Examples 1 to 3). First, each sample was placed in a 100 mL sample bottle with a lid and left to stand for 30 minutes. After the standing, the lid was opened, and the odor was smelled and measured based on the following criteria.
○: Sample has no odor.
×: Sample has an unpleasant odor.
-: Sample not measured.
当該測定した結果を上記表１（剤の臭い）に示す。比較例と比べて、実施例では当該臭いを感じなかった。
The results of this measurement are shown in Table 1 (odor of the agent) above. Compared to the comparative example, no odor was detected in the working example.
以上、本発明の実施の形態（実施例も含め）について、図面を参照して説明してきたが、本発明の具体的構成は、これに限られるものではなく、本発明の要旨を逸脱しない範囲において、設計変更等があっても、本発明に含まれるものである。
The above describes the embodiment of the present invention (including examples) with reference to the drawings, but the specific configuration of the present invention is not limited to this, and even if there are design changes, etc., within the scope that does not deviate from the gist of the present invention, they are still included in the present invention.
この出願は、２０２２年１０月１２日に出願された日本出願特願２０２２－１６４０９２を基礎とする優先権を主張し、その開示のすべてをここに取り込む。
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.
＜付記＞
上記の実施形態及び実施例の一部又は全部は、以下の付記のように記載されうるが、以下には限られない。
（付記１）
次の成分（Ａ）～（Ｅ）を含有する、メラニン色素生成抑制剤又は組成物。
（Ａ）トラネキサム酸
（Ｂ）ニコチン酸アミド
（Ｃ）グルタチオン
（Ｄ）ビタミンＣ誘導体
（Ｅ）ピロ亜硫酸ナトリウム
（付記２）
前記剤又は前記組成物の総重量を基準として、前記トラネキサム酸の含有量が、０．００１～２０重量％である、付記１に記載の剤または組成物。
（付記３）
前記剤又は前記組成物の総重量を基準として、前記ニコチン酸アミドの含有量が、０．００１～２０重量％である、付記１または２に記載の剤または組成物。
（付記４）
前記剤又は前記組成物の総重量を基準として、前記グルタチオンの含有量が、０．０００１～２０重量％である、付記１から３のいずれかに記載の剤または組成物。
（付記５）
前記剤又は前記組成物の総重量を基準として、前記ビタミンＣ誘導体の含有量が、０．０１～１０重量％である、付記１から４のいずれかに記載の剤又は組成物。
（付記６）
前記剤又は前記組成物の総重量を基準として、前記ピロ亜硫酸ナトリウムの含有量が、０．０００１～２重量％である、付記１から５のいずれかに記載の剤又は組成物。
（付記７）
クエン酸を更に含有する、付記１から６のいずれかに記載の剤又は組成物。
（付記８）
前記剤又は前記組成物の総重量を基準として、前記クエン酸の含有量が、０重量％超～０．５重量％である、付記７に記載の剤又は組成物。
（付記９）
アルブチンを更に含有する、付記１から８のいずれかに記載の剤又は組成物。
（付記１０）
前記剤又は前記組成物の総重量を基準として、前記アルブチンの含有量が、０．０００１～２重量％である、付記９に記載の剤又は組成物。
（付記１１）
付記１から１０のいずれかに記載の剤又は組成物を含む、皮膚外用のための剤又は組成物。
（付記１２）
付記１から１１のいずれかに記載の剤又は組成物を含む、メラニン色素生成抑制に用いるための剤又は組成物。
（付記１３）
更に、植物抽出物を含む、付記１から１２のいずれかに記載の剤又は組成物。
（付記１４）
前記剤又は前記組成物の総質量を基準として、前記植物抽出物の含有量が、０．０００００１～１０質量％である、付記１３に記載の剤又は組成物。
（付記１５）
前記植物抽出物は、ボタンピ抽出物、オウゴン抽出物、ヒメフウロ抽出物、ヨウシュイブキジャコウソウ抽出物、ソウズク抽出物からなる群から選択される植物抽出物である、付記１３又は１４に記載の剤又は組成物。
（付記１６）
付記１から１５のいずれかに記載の剤又は組成物を使用する、メラニン色素の生成抑制方法。
（付記１７）
対象の皮膚に、前記剤又は組成物を接触させる、付記１６に記載の方法。
（付記１８）
前記対象は、ヒト又は非ヒト動物である、付記１７に記載の方法。
（付記１９）
メラニン色素の生成抑制に用いるための、付記１から１５のいずれかに記載の剤又は組成物の使用。 <Additional Notes>
Some or all of the above-described embodiments and examples may be described as follows, but are not limited to the following.
(Appendix 1)
A melanin pigment production inhibitor or composition comprising the following components (A) to (E):
(A) Tranexamic acid (B) Nicotinamide (C) Glutathione (D) Vitamin C derivatives (E) Sodium pyrosulfite (Appendix 2)
The agent or composition according to claim 1, wherein the content of the tranexamic acid is 0.001 to 20% by weight, based on the total weight of the agent or composition.
(Appendix 3)
The agent or composition according to claim 1 or 2, wherein the content of the nicotinamide is 0.001 to 20% by weight based on the total weight of the agent or composition.
(Appendix 4)
The agent or composition according to any one of claims 1 to 3, wherein the content of the glutathione is 0.0001 to 20% by weight, based on the total weight of the agent or composition.
(Appendix 5)
5. The agent or composition according to any one of claims 1 to 4, wherein the content of the vitamin C derivative is 0.01 to 10% by weight based on the total weight of the agent or composition.
(Appendix 6)
6. The agent or composition according to any one of claims 1 to 5, wherein the content of the sodium pyrosulfite is 0.0001 to 2% by weight, based on the total weight of the agent or composition.
(Appendix 7)
7. The agent or composition according to any one of claims 1 to 6, further comprising citric acid.
(Appendix 8)
The agent or composition according to claim 7, wherein the content of the citric acid is more than 0% by weight to 0.5% by weight, based on the total weight of the agent or composition.
(Appendix 9)
The agent or composition described in any one of appendix 1 to 8, further comprising arbutin.
(Appendix 10)
The agent or composition according to claim 9, wherein the content of the arbutin is 0.0001 to 2% by weight, based on the total weight of the agent or composition.
(Appendix 11)
An agent or composition for external application to the skin, comprising the agent or composition described in any one of appendices 1 to 10.
(Appendix 12)
12. An agent or composition for use in inhibiting melanin pigment production, comprising the agent or composition according to any one of claims 1 to 11.
(Appendix 13)
13. The agent or composition according to any one of claims 1 to 12, further comprising a plant extract.
(Appendix 14)
The agent or composition according to claim 13, wherein the content of the plant extract is 0.000001 to 10% by mass, based on the total mass of the agent or composition.
(Appendix 15)
The agent or composition described in Appendix 13 or 14, wherein the plant extract is a plant extract selected from the group consisting of Peony root extract, Scutellaria root extract, Geranium globulus extract, Thymus vulgaris extract, and Celastrus arvensis extract.
(Appendix 16)
A method for inhibiting melanin pigment production, comprising using an agent or composition according to any one of claims 1 to 15.
(Appendix 17)
17. The method of claim 16, wherein the agent or composition is contacted with the skin of a subject.
(Appendix 18)
18. The method of claim 17, wherein the subject is a human or a non-human animal.
(Appendix 19)
Use of an agent or composition according to any one of claims 1 to 15 for inhibiting the production of melanin pigment.
上記の実施形態及び実施例の一部又は全部は、以下の付記のように記載されうるが、以下には限られない。
（付記１）
次の成分（Ａ）～（Ｅ）を含有する、メラニン色素生成抑制剤又は組成物。
（Ａ）トラネキサム酸
（Ｂ）ニコチン酸アミド
（Ｃ）グルタチオン
（Ｄ）ビタミンＣ誘導体
（Ｅ）ピロ亜硫酸ナトリウム
（付記２）
前記剤又は前記組成物の総重量を基準として、前記トラネキサム酸の含有量が、０．００１～２０重量％である、付記１に記載の剤または組成物。
（付記３）
前記剤又は前記組成物の総重量を基準として、前記ニコチン酸アミドの含有量が、０．００１～２０重量％である、付記１または２に記載の剤または組成物。
（付記４）
前記剤又は前記組成物の総重量を基準として、前記グルタチオンの含有量が、０．０００１～２０重量％である、付記１から３のいずれかに記載の剤または組成物。
（付記５）
前記剤又は前記組成物の総重量を基準として、前記ビタミンＣ誘導体の含有量が、０．０１～１０重量％である、付記１から４のいずれかに記載の剤又は組成物。
（付記６）
前記剤又は前記組成物の総重量を基準として、前記ピロ亜硫酸ナトリウムの含有量が、０．０００１～２重量％である、付記１から５のいずれかに記載の剤又は組成物。
（付記７）
クエン酸を更に含有する、付記１から６のいずれかに記載の剤又は組成物。
（付記８）
前記剤又は前記組成物の総重量を基準として、前記クエン酸の含有量が、０重量％超～０．５重量％である、付記７に記載の剤又は組成物。
（付記９）
アルブチンを更に含有する、付記１から８のいずれかに記載の剤又は組成物。
（付記１０）
前記剤又は前記組成物の総重量を基準として、前記アルブチンの含有量が、０．０００１～２重量％である、付記９に記載の剤又は組成物。
（付記１１）
付記１から１０のいずれかに記載の剤又は組成物を含む、皮膚外用のための剤又は組成物。
（付記１２）
付記１から１１のいずれかに記載の剤又は組成物を含む、メラニン色素生成抑制に用いるための剤又は組成物。
（付記１３）
更に、植物抽出物を含む、付記１から１２のいずれかに記載の剤又は組成物。
（付記１４）
前記剤又は前記組成物の総質量を基準として、前記植物抽出物の含有量が、０．０００００１～１０質量％である、付記１３に記載の剤又は組成物。
（付記１５）
前記植物抽出物は、ボタンピ抽出物、オウゴン抽出物、ヒメフウロ抽出物、ヨウシュイブキジャコウソウ抽出物、ソウズク抽出物からなる群から選択される植物抽出物である、付記１３又は１４に記載の剤又は組成物。
（付記１６）
付記１から１５のいずれかに記載の剤又は組成物を使用する、メラニン色素の生成抑制方法。
（付記１７）
対象の皮膚に、前記剤又は組成物を接触させる、付記１６に記載の方法。
（付記１８）
前記対象は、ヒト又は非ヒト動物である、付記１７に記載の方法。
（付記１９）
メラニン色素の生成抑制に用いるための、付記１から１５のいずれかに記載の剤又は組成物の使用。 <Additional Notes>
Some or all of the above-described embodiments and examples may be described as follows, but are not limited to the following.
(Appendix 1)
A melanin pigment production inhibitor or composition comprising the following components (A) to (E):
(A) Tranexamic acid (B) Nicotinamide (C) Glutathione (D) Vitamin C derivatives (E) Sodium pyrosulfite (Appendix 2)
The agent or composition according to claim 1, wherein the content of the tranexamic acid is 0.001 to 20% by weight, based on the total weight of the agent or composition.
(Appendix 3)
The agent or composition according to claim 1 or 2, wherein the content of the nicotinamide is 0.001 to 20% by weight based on the total weight of the agent or composition.
(Appendix 4)
The agent or composition according to any one of claims 1 to 3, wherein the content of the glutathione is 0.0001 to 20% by weight, based on the total weight of the agent or composition.
(Appendix 5)
5. The agent or composition according to any one of claims 1 to 4, wherein the content of the vitamin C derivative is 0.01 to 10% by weight based on the total weight of the agent or composition.
(Appendix 6)
6. The agent or composition according to any one of claims 1 to 5, wherein the content of the sodium pyrosulfite is 0.0001 to 2% by weight, based on the total weight of the agent or composition.
(Appendix 7)
7. The agent or composition according to any one of claims 1 to 6, further comprising citric acid.
(Appendix 8)
The agent or composition according to claim 7, wherein the content of the citric acid is more than 0% by weight to 0.5% by weight, based on the total weight of the agent or composition.
(Appendix 9)
The agent or composition described in any one of appendix 1 to 8, further comprising arbutin.
(Appendix 10)
The agent or composition according to claim 9, wherein the content of the arbutin is 0.0001 to 2% by weight, based on the total weight of the agent or composition.
(Appendix 11)
An agent or composition for external application to the skin, comprising the agent or composition described in any one of appendices 1 to 10.
(Appendix 12)
12. An agent or composition for use in inhibiting melanin pigment production, comprising the agent or composition according to any one of claims 1 to 11.
(Appendix 13)
13. The agent or composition according to any one of claims 1 to 12, further comprising a plant extract.
(Appendix 14)
The agent or composition according to claim 13, wherein the content of the plant extract is 0.000001 to 10% by mass, based on the total mass of the agent or composition.
(Appendix 15)
The agent or composition described in Appendix 13 or 14, wherein the plant extract is a plant extract selected from the group consisting of Peony root extract, Scutellaria root extract, Geranium globulus extract, Thymus vulgaris extract, and Celastrus arvensis extract.
(Appendix 16)
A method for inhibiting melanin pigment production, comprising using an agent or composition according to any one of claims 1 to 15.
(Appendix 17)
17. The method of claim 16, wherein the agent or composition is contacted with the skin of a subject.
(Appendix 18)
18. The method of claim 17, wherein the subject is a human or a non-human animal.
(Appendix 19)
Use of an agent or composition according to any one of claims 1 to 15 for inhibiting the production of melanin pigment.
本発明により、ヒト等の皮膚に用いるための皮膚機能の低下を防ぐための組成物等として利用される。
According to the present invention, the composition can be used as a composition for preventing the deterioration of skin function for use on the skin of humans, etc.
According to the present invention, the composition can be used as a composition for preventing the deterioration of skin function for use on the skin of humans, etc.
Claims (4)
- 次の成分（Ａ）～（Ｅ）を含有する、メラニン色素生成抑制剤。
（Ａ）トラネキサム酸
（Ｂ）ニコチン酸アミド
（Ｃ）グルタチオン
（Ｄ）ビタミンＣ誘導体
（Ｅ）ピロ亜硫酸ナトリウム A melanin pigment production inhibitor comprising the following components (A) to (E):
(A) Tranexamic acid (B) Nicotinamide (C) Glutathione (D) Vitamin C derivatives (E) Sodium pyrosulfite - クエン酸を更に含有する、請求項１記載の剤。 The agent according to claim 1, further comprising citric acid.
- アルブチンを更に含有する、請求項１記載の剤。 The agent according to claim 1, further comprising arbutin.
- 請求項１記載の剤を含む、皮膚外用のための組成物。
A composition for external application to the skin, comprising the agent according to claim 1.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022164092 | 2022-10-12 | ||
| JP2022-164092 | 2022-10-12 |
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| WO2024080290A1 true WO2024080290A1 (en) | 2024-04-18 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2023/036830 WO2024080290A1 (en) | 2022-10-12 | 2023-10-11 | Melanin pigment synthesis inhibitor |
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| Country | Link |
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| WO (1) | WO2024080290A1 (en) |
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| JP2005350405A (en) * | 2004-06-11 | 2005-12-22 | Shiseido Co Ltd | Polymerization inhibitor and skin care preparation for external use for preventing immediate melanism |
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| CN113768818A (en) * | 2021-10-12 | 2021-12-10 | 上海新高姿化妆品有限公司 | Whitening and anti-aging composition, cosmetic and preparation method thereof |
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2023
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