WO2020153466A1 - 美容用組成物 - Google Patents
美容用組成物 Download PDFInfo
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- WO2020153466A1 WO2020153466A1 PCT/JP2020/002464 JP2020002464W WO2020153466A1 WO 2020153466 A1 WO2020153466 A1 WO 2020153466A1 JP 2020002464 W JP2020002464 W JP 2020002464W WO 2020153466 A1 WO2020153466 A1 WO 2020153466A1
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- 0 *c(c(*)c1*)c(*)c2c1OC(c1c(*)*(*)c(*)*(*)*1*)=C(*)C2=O Chemical compound *c(c(*)c1*)c(*)c2c1OC(c1c(*)*(*)c(*)*(*)*1*)=C(*)C2=O 0.000 description 1
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- 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
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
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- 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
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- 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]
- A61K8/9794—Liliopsida [monocotyledons]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
-
- 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
-
- 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
- A61Q19/04—Preparations for care of the skin for chemically tanning the skin
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- 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
- A61Q19/08—Anti-ageing preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/10—Preparations for permanently dyeing the hair
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/74—Biological properties of particular ingredients
- A61K2800/78—Enzyme modulators, e.g. Enzyme agonists
- A61K2800/782—Enzyme inhibitors; Enzyme antagonists
Definitions
- Non-patent document 1 (the entire description of which is incorporated herein by reference) describes the anti-wrinkle effect of black ginger extract.
- Patent Document 1 (the entire description of which is incorporated herein by reference) describes that the black ginger extract has an antioxidant effect.
- Non-Patent Document 2 (the entire description of which is incorporated herein by reference), among the components contained in black ginger, 5,7-dimethoxyflavone has a melanin formation promoting action. There is.
- the present invention is a composition containing an active ingredient capable of promoting melanin synthesis and suppressing or improving whitening of hair and skin while being an ingredient derived from a highly safe natural product. Providing a product is the second problem to be solved by the invention.
- the inventors of the present invention conducted extensive research and development to solve the above-mentioned problems, and examined the physiologically active actions of a wide variety of natural products and components derived from natural products. As a result, 11 polymethoxyflavonoids contained in black ginger were identified. Was successfully isolated. As a result of repeated trial and error tests on the physiologically active actions of these polymethoxyflavonoids, surprisingly, 5,7,3′,4′-tetramethoxyflavone, 5,7,4′-trimethoxyflavone and It was found that 5-OH-3,7,3′,4′-tetramethoxyflavone has an action of suppressing the activity of proteolytic enzymes involved in wrinkle formation and inflammatory factors in skin.
- the composition is at least one composition selected from the group consisting of an anti-wrinkle composition, an anti-talumi composition, an anti-skin inflammation composition, an anti-aging composition and a skin improving composition.
- the composition according to any one of [1] to [2], which is [4] 3,5,7,3′,4′-pentamethoxyflavone, 3,5,7-trimethoxyflavone, 3,5,7,4′-tetramethoxyflavone, 5-OH-3,7, 3',4'-tetramethoxyflavone, 5-OH-7-methoxyflavone, 5-OH-7,4'-dimethoxyflavone, 5-OH-3,7-dimethoxyflavone and 5-OH-3,7, A cosmetic composition containing 4'-trimethoxyflavone and at least one active ingredient selected from the group consisting of at least one of these inclusions.
- composition according to [4] which has a tyrosinase activation promoting action.
- the above-mentioned composition is a group consisting of an anti-whitening composition, an anti-hair graying composition, an anti-white spot composition, an anti-aging composition, a sunburn promoting composition and a skin blackening composition.
- composition of one embodiment of the present invention has been proven to be safe as originally used as a herbal medicine, and the ingredients contained in black ginger which is a natural product little known to exhibit side effects are included. Since it is contained as an active ingredient, it can be safely used for individual use.
- black ginger is native to Southeast Asia and is available in large quantities, and since the above-mentioned components contained in black ginger are commercially available, it can be produced with high economic efficiency on an industrial scale. Can be expected.
- composition of one embodiment of the present invention through the action of suppressing the activity of proteolytic enzymes involved in wrinkle formation and the action of suppressing the production of inflammatory factors involved in wrinkle formation, wrinkles, tarmi, skin inflammation, aging, skin abnormalities
- it can be expected to treat, prevent, suppress, or improve various skin diseases, symptoms and abnormalities.
- composition of one embodiment of the present invention can be expected to treat, prevent, suppress or improve leukoplakia, gray hair, leukoplakia, aging, etc. through the action of activating an enzyme involved in the melanin synthesis pathway. Furthermore, it can be expected to be used for cosmetic purposes such as promoting sunburn and blackening the skin.
- composition of one embodiment of the present invention is not only used for external use, but also has few side effects and contains an internal and external cosmetic ingredient (inner cosmetic) that can be orally ingested. Therefore, it can be used as a health food. Can be expected.
- FIG. 1 shows the structural formula of methoxyflavonoids isolated from black ginger extract as described in the Examples below.
- FIG. 2 is a diagram showing the results of measuring the enzyme activity of elastase in IL-1 ⁇ -stimulated normal human dermal fibroblasts, as described in Examples described later.
- FIG. 3 is a diagram showing the results of measuring the gene expression level of elastase in normal human dermal fibroblasts stimulated with IL-1 ⁇ , as described in Examples described later.
- FIG. 4 is a diagram showing the results of measuring the expression level of elastase protein in normal human dermal fibroblasts stimulated with IL-1 ⁇ , as described in Examples described later.
- FIG. 1 shows the structural formula of methoxyflavonoids isolated from black ginger extract as described in the Examples below.
- FIG. 2 is a diagram showing the results of measuring the enzyme activity of elastase in IL-1 ⁇ -stimulated normal human dermal fibroblasts, as described in Examples described later.
- composition is synonymous with concentration and means the ratio of the amount of components to the total amount of the composition. However, the total content of the components does not exceed 100%.
- “to” is a range including numerical values before and after that, for example, “0% by mass to 100% by mass” means 0% by mass or more and 100% by mass or less. Means a range.
- activation-promoting action of a substance means to enhance the degree of the catalytic action or physiological action originally possessed by the substance, to increase the expression level of the gene of the substance, and to translate the gene product (protein) of the substance. And at least one of promoting the production of the gene product of the substance.
- production promoting action of a substance refers to increasing the expression level of the gene of the substance, increasing the translation amount of the gene product (protein) of the substance, and promoting the production of the gene product of the substance. At least any one action.
- the composition of the first aspect of the present invention comprises at least one selected from the group consisting of an inhibitory effect on the activation of proteolytic enzymes involved in wrinkle formation and an inhibitory effect on the activation of inflammatory factors in the skin, depending on the contained active ingredient. Can have an effect.
- the composition of the first aspect of the present invention by having these actions, is typically an anti-wrinkle composition, an anti-talumi composition, an anti-skin inflammation composition, an anti-aging composition and skin disorders. It may take the form of an improving composition or the like.
- Another aspect of the present invention is a method for treating, preventing, suppressing or ameliorating wrinkles, tarmi, skin inflammation, aging and skin abnormalities by applying an active ingredient to a use individual.
- composition of the second aspect of the present invention comprises 3,5,7,3',4'-pentamethoxyflavone, 3,5,7-trimethoxyflavone, 3,5,7,4'-tetramethoxyflavone, 5-OH-3,7,3',4'-tetramethoxyflavone, 5-OH-7-methoxyflavone, 5-OH-7,4'-dimethoxyflavone, 5-OH-3,7-dimethoxyflavone and It contains at least one active ingredient selected from the group consisting of 5-OH-3,7,4′-trimethoxyflavone and the inclusion of at least one of these ingredients.
- composition of the first aspect of the present invention and the composition of the second aspect of the present invention may be collectively referred to as "a composition of one aspect of the present invention".
- active ingredient contained in the composition of the first aspect of the present invention and the active ingredient contained in the composition of the second aspect of the present invention may be collectively referred to as "active ingredient”, and the active ingredient of the first aspect of the present invention
- active ingredient the active ingredient contained in the composition of the first aspect of the present invention
- active ingredient the active ingredient contained in the composition of the second aspect of the present invention
- active ingredient the active ingredient contained in the composition of the second aspect of the present invention
- active ingredient the active ingredient of the first aspect of the present invention
- the action which the composition may have and the action which the composition of the second aspect of the present invention may have may be collectively referred to as “effective action”.
- the active ingredient is classified into polymethoxyflavonoid and has the following general formula (I).
- R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 each independently represent hydrogen, a hydroxyl group or a methoxy group.
- the active ingredient in the composition of the first aspect of the present invention is 5,7,3′,4′-tetramethoxyflavone, 5,7,4′-trimethoxyflavone and 5-OH-3,7,3′, It can be any one, two, or all three of the 4'-tetramethoxyflavones.
- the active ingredient in the composition of the second aspect of the present invention is 3,5,7,3',4'-pentamethoxyflavone, 3,5,7-trimethoxyflavone, 3,5,7,4'-tetra Methoxyflavone, 5-OH-3,7,3',4'-tetramethoxyflavone, 5-OH-7-methoxyflavone, 5-OH-7,4'-dimethoxyflavone, 5-OH-3,7- It can be any one, two, three, four, five or six or all seven of dimethoxyflavone and 5-OH-3,7,4'-trimethoxyflavone.
- the active ingredient may be a content containing any one kind or two or more kinds of polymethoxyflavonoid.
- the inclusion is not particularly limited as long as it contains the polymethoxyflavonoid, but is, for example, a plant extract, and preferably a black ginger extract.
- Black ginger ( Kaempferia parviflora ) is a plant belonging to the genus Asteraceae of the ginger family known to grow naturally in Southeast Asia and the like. It is known that black ginger has effects such as energy enhancement, nourishing tonicity, lowering of blood sugar level, physical strength recovery, improvement of digestive system, vaginal discharge, hemorrhoids, hemorrhoids, nausea, stomatitis, arthralgia, and stomach pain. has been. Black ginger is a natural plant that has a long history of being ingested by humans and is highly safe. Therefore, the composition of one embodiment of the present invention can be applied in a parenteral or oral form. ..
- the use site of black ginger is not particularly limited as long as it is a site containing an active ingredient that contributes to a desired effective action, and examples thereof include roots, stems, leaves, flowers and branches, but polymethoxyflavonoids are preferable.
- the rhizome contains a lot.
- the method for producing a black ginger extract containing polymethoxyflavonoids from black ginger is not particularly limited, and examples thereof include a method including at least contacting the black ginger extract with a polymethoxyflavonoid-soluble solvent.
- the black ginger which is a raw material of the black ginger extract, may be in a state as collected, or may be in a state after being collected and subjected to processing such as drying.
- a storage means usually used by those skilled in the art such as low temperature storage in order to prevent alteration of the raw material of black ginger.
- the drying treatment is not particularly limited, and for example, the mass (dry mass) of the raw material of the black ginger extract after drying is about 1/2 to 1/10, preferably 1 Examples include a treatment of drying so as to be about 1 ⁇ 3 to 1 ⁇ 6.
- the drying treatment can be performed by any method known to those skilled in the art, such as hot air drying, high pressure steam drying, electromagnetic wave drying, and freeze drying. Drying by heating can be performed, for example, at 30° C. to 100° C. for 24 hours to 72 hours at a temperature and for a time and time at which the raw material of the black ginger extract does not discolor by heating.
- the raw material of the black ginger extract is preferably in a crushed, crushed or ground state from the viewpoint of efficiently performing the extraction operation.
- the method of crushing, crushing or mashing the raw material is not particularly limited, and examples thereof include a method using a cutter, a cutter, a crusher, a blender, a mixer, a mill, a grinder, a kneader, a mortar and the like.
- the extraction solvent for extracting the black ginger extract is preferably an extraction solvent containing at least an organic solvent.
- the extraction solvent include a mixed solvent of water and an organic solvent, a lower alcohol such as methanol, ethanol, propanol, isopropanol and butanol; a lower ester such as ethyl acetate and methyl acetate; dimethyl sulfoxide, acetonitrile, acetone, hexane and glycerin. , Organic solvents such as propylene glycol, and the like, but are not limited to these.
- the organic solvent a single species may be used, or a mixed solvent prepared by mixing a plurality of species may be used.
- the content of the organic solvent in the mixed solvent is preferably 50% by volume or more, more preferably 80% by volume or more.
- the content of the organic solvent in the mixed solvent is less than 50% by volume, it tends to be difficult to efficiently extract the polymethoxyflavonoid.
- the organic solvent lower alcohols are preferable, and ethanol and methanol are more preferable.
- the raw material of the black ginger extract is immersed in the extraction solvent for a predetermined time.
- stirring operation, heating, etc. may be carried out as necessary in order to enhance the extraction efficiency.
- a water extraction operation or a hot water extraction operation may be separately performed prior to the extraction operation. Since polymethoxyflavonoid is an insoluble component in water, unnecessary impurities can be removed prior to the extraction operation by boiling black ginger in boiling water, for example.
- the method of solid-liquid separation operation is not particularly limited, but known separation methods such as filtration and centrifugation can be used.
- the black ginger extract may be concentrated if necessary. By removing the extraction solvent contained in the black ginger extract as needed, an oily or solid black ginger extract having a viscosity can be obtained.
- the method of concentration is not particularly limited, and may be carried out, for example, by placing it at room temperature under reduced pressure or heating, or by freeze-drying.
- Black ginger contains flavonoids other than the polymethoxyflavonoids listed as active ingredients.
- an extract containing a desired polymethoxyflavonoid at a high concentration can be obtained.
- the packing material used in the separation operation using a column is not particularly limited, and examples thereof include silica gel having an octadecyl group bonded thereto.
- the method for confirming and quantifying the polymethoxyflavonoid contained in the black ginger extract is not particularly limited, and for example, high performance liquid chromatography (HPLC) as described in Examples described later can be used.
- HPLC high performance liquid chromatography
- the content of 5-OH-3,7,3′,4′-tetramethoxyflavone in the black ginger extract is, for example, 0.1 mass% or more, preferably 0.5 mass, based on the mass of the black ginger extract. % Or more.
- the content of 3,5,7,3′,4′-pentamethoxyflavone in the black ginger extract is, for example, 1.0 mass% or more, preferably 5.0 mass% or more, based on the mass of the black ginger extract.
- the content of 3,5,7-trimethoxyflavone in the black ginger extract is, for example, 0.1% by mass or more, preferably 0.5% by mass or more, based on the mass of the black ginger extract.
- composition The composition of the first aspect of the present invention, by containing the active ingredient, exhibits one or both of the activity of suppressing the activation of proteolytic enzymes and inflammatory factors involved in wrinkle formation.
- the inhibitory effect on the wrinkle-forming proteolytic enzyme possessed by the composition of the first aspect of the present invention is preferably one of an elastase activation inhibitory effect and a collagenase activation inhibitory effect, It is more preferable that both of these effects are exerted.
- the activity of suppressing the activation of an inflammatory factor involved in wrinkle formation, which the composition of the first aspect of the present invention has, is preferably an activity of suppressing inflammatory cytokine activation, and interleukin-1 ⁇ (IL-1 ⁇ ) activation. More preferably, it has an inhibitory effect.
- the effective action possessed by the composition of the first aspect of the present invention is an activity relating to an enzyme or an inflammatory factor induced by external stimulation of skin fibroblasts or epidermal keratinocytes, as described in Examples below. It can be confirmed by measuring the titer, gene expression level and/or protein production level. At this time, the system to which the composition of the first aspect of the present invention is not added is used as a control, and the system to which the composition of the first aspect of the present invention is added is more effective than the control for the enzyme or inflammatory factor caused by external stimulation of cells.
- the composition of the first aspect of the present invention can be evaluated to have an effective effect if the activity titer, the gene expression level and/or the protein production level according to (1) are low.
- composition of the second aspect of the present invention exhibits an activity of promoting activation of an enzyme involved in the melanin synthesis pathway by containing the active ingredient.
- the activation promoting action of the enzyme involved in the melanin synthesis pathway possessed by the composition of the second aspect of the present invention is preferably a tyrosinase activation promoting action.
- the effective action of the composition of the second aspect of the present invention is to measure the activity titer, the gene expression amount and/or the protein production amount of the enzyme produced by melanoma cells, as described in the Examples below. It can be confirmed by doing.
- the system to which the composition of the second aspect of the present invention was not added was used as a control, and the system to which the composition of the second aspect of the present invention was added was more potent than the control in terms of the activity of the enzyme relating to the cell and the gene expression level. And/or the amount of protein produced is small, it can be evaluated that the composition of the second aspect of the present invention has an effective effect.
- composition of one aspect of the present invention is not particularly limited as long as it is a composition used for cosmetic purposes, but may be in various forms such as a cosmetic composition, a food/beverage composition, and a pharmaceutical composition. .. Therefore, a specific embodiment of the present invention, containing an active ingredient, parenteral or oral cosmetic composition, food and drink composition, pharmaceutical composition, quasi drug composition, For example, a composition for animal feed.
- the content of the active ingredient contained in the composition of one embodiment of the present invention is not particularly limited as long as the desired effective action is recognized, but for example, as a parenteral cosmetic composition, 0.00001. Mass% or more, preferably 0.0001 mass% or more, more preferably 0.001 mass% or more; 0.0001 mass% or more, preferably 0.001 mass% as an oral cosmetic composition As described above, more preferably 0.01% by mass or more.
- the upper limit of the content is not particularly limited, but it is typically 1% by mass.
- compositions of one embodiment of the present invention There is no particular limitation on the individual or method of using the composition of one embodiment of the present invention.
- Examples of the individual include animals, particularly mammals, and examples of mammals include humans, dogs, cats, cows, horses, and the like. Of these, humans are preferable.
- the usage and dose such as one-time usage, daily usage, usage period, usage interval, etc. of the composition according to one embodiment of the present invention are not particularly limited, and are appropriately set according to the usage mode and the condition of the individual to be used. Can be done.
- the use interval is, for example, once, twice, three times or several times a day for a certain period, that is, two days or more, preferably one week or more, more preferably two weeks or more, further preferably one month or more, Still more preferably, continuous application for 6 months or 1 year or more can be mentioned.
- the application of the composition of one aspect of the present invention is preferably performed daily, but the composition of the aspect of the present invention may not be applied daily as long as it is applied continuously for a period of time.
- the composition according to one aspect of the present invention may be applied parenterally or orally, but may be directly applied to the affected area where the effective action is exerted. It is preferably a parenteral cosmetic composition, and more preferably a cosmetic composition and a parenteral pharmaceutical composition, because they can be applied to the skin.
- composition of one aspect of the present invention may contain other components in addition to the active ingredient, as long as it can solve the problems of the present invention.
- a parenteral cosmetic composition include, for example, components contained in ordinary cosmetics and pharmaceuticals, and more specifically, a base such as water, an oil component, a moisturizing agent.
- Agents, cooling agents, preservatives, chelating agents, pH adjusters, antioxidants, UV absorbers, UV scattering agents, thickeners, whitening agents, vitamins, other various medicinal ingredients, powders, fragrances, coloring materials, etc. are listed.
- the contents of other components can be appropriately set by those skilled in the art as long as they do not prevent the solution of the problems of the present invention.
- Ester oils such as lithyl, diethylhexyl succinate, and alkyl benzoates having 12 to 15 carbon atoms; Silicone oils such as dimethylpolysiloxane, dimethylcyclopolysiloxane, methylphenylpolysiloxane, methylhydrogenpolysiloxane, and higher alcohol-modified silicone oils; Glyceride oils such as acetoglyceryl, glyceryl triisooctanoate, glyceryl triisostearate, glyceryl triisopalmitate, glyceryl monostearate, glyceryl di-2-heptylundecanoate, glyceryl trimyristate; animal oils such as liquid lanolin; fluoropoly Fluorine oils such as ether and perfluoroalkyl ether silicones; olive oil, jojoba oil, lavender oil, evening primrose oil, avocado oil, camellia oil, turtle oil, mac
- humectant examples include glycerin, diglycerin, trehalose, butylene glycol (BG), xylitol, maltitol, maltose, sorbitol, glucose, fructose, hydrolyzed elastin, sodium lactate, cyclodextrin, pyrrolidonecarboxylic acid and the like. , These 1 type can be used individually or in combination of 2 or more types.
- the content of the moisturizer is preferably 0% by mass to 15% by mass.
- preservative examples include benzoic acid, salicylic acid, carboxylic acid, sorbic acid, methyl paraoxybenzoate, parachlorometacresol, hexachlorophene, benzalkonium chloride, chlorhexidine chloride, trichlorocarbanilide, photosensitizer, and phenoxyethanol. These may be used alone or in combination of two or more.
- the content of the preservative is preferably 0% by mass to 1% by mass.
- Examples of the pH adjuster include lactic acid, citric acid, glycolic acid, succinic acid, tartaric acid, malic acid, etidronic acid, potassium carbonate, sodium hydrogen carbonate, ammonium hydrogen carbonate, sodium hydroxide, potassium hydroxide, triethanolamine, Monoethanolamine etc. are mentioned, These 1 type can be used individually or in combination of 2 or more types.
- the content of the pH adjuster is preferably 0% by mass to 1% by mass.
- antioxidants include vitamin E and its derivatives such as dibutylhydroxytoluene, butylhydroxyanisole, and ⁇ -tocopherol, thiotaurine, evening primrose extract, ⁇ -carotene, catechin compounds, flavonoid compounds, and polyphenol compounds. They may be used alone or in combination of two or more.
- the content of the antioxidant is preferably 0% by mass to 1% by mass.
- the thickener examples include water-soluble polysaccharides such as hyaluronic acid, sodium hyaluronate, acetylated hyaluronic acid, acetylated sodium hyaluronate, chondroitin sulfate, sodium chondroitin sulfate, fucoidan, tuberose polysaccharide, xanthan gum; carrageenan, alginic acid.
- water-soluble polysaccharides such as hyaluronic acid, sodium hyaluronate, acetylated hyaluronic acid, acetylated sodium hyaluronate, chondroitin sulfate, sodium chondroitin sulfate, fucoidan, tuberose polysaccharide, xanthan gum; carrageenan, alginic acid.
- Such as natural polymers; semi-synthetic polymers such as sodium carboxymethyl cellulose; carbomer, polyacrylic
- Carboxymethylcellulose sodium is commercially available as, for example, "CMC Daicel” (manufactured by Daicel Chemical Industries, Ltd.). These thickeners may be used alone or in combination of two or more. The content of the thickener is preferably 0% by mass to 1% by mass.
- the use form and dosage form as a cosmetic composition are not particularly limited, and examples thereof include skin care cosmetics, makeup cosmetics, fragrance cosmetics, body care cosmetics, and the like, more specifically creams, emulsions, foundations, lotions. , Beauty essence, hair tonic, hair cream, shampoo, hair rinse, treatment, facial cleanser, foundation, hair restorer, aqueous ointment, spray, gel, lotion, pack, facial cleansing cream, hand cream, makeup cleansing, makeup base, concealer, cheek Examples include red, eye shadow, eyeliner, eyebrow, lipstick, depilatory/hair removal cream, and all-in-one cosmetics.
- composition of one aspect of the present invention is used as an oil-in-water emulsion cosmetic composition in a dosage form having a certain viscosity such as gel, emulsion, lotion, and cream, so that the composition is well used for skin and hair. It is preferable because it gives a feel.
- the mode of use and dosage form as a parenteral pharmaceutical composition are not particularly limited, and examples thereof include injections, patches, ointments, creams and the like.
- composition of one aspect of the present invention may be an oral cosmetic composition, and in this case, it is preferably a food/beverage composition and an oral pharmaceutical composition.
- composition for food and drink is, for example, a functional food and drink that is a food and drink having a certain functionality with respect to a living body.
- Functional foods and drinks include foods and drinks for specified health use, foods and drinks with functional indication, foods and drinks with nutritional function, foods and drinks with health function, foods and drinks for special purposes, foods and drinks with nutritional supplements, foods and drinks with health supplements, supplements, and beauty foods
- foods and drinks for specific persons such as foods and drinks for infants, foods and drinks for pregnant women, foods and drinks for elderly people are included.
- the functional food and drink includes healthy food and drink to which the health claim based on the food standard of Codex (FAO/WHO Joint Food Standards Committee) is applied.
- the mode of use and dosage form of the cosmetic composition for oral use are not particularly limited and may be in the form of tablets, powders, granules, powders, capsules, pills, troches, liquids, etc. Not limited. Tablets include sugar-coated tablets, coated tablets, buccal agents and the like. Capsules include both hard capsules and soft capsules. Granules also include coated granules.
- the liquid formulation includes suspensions, emulsions, syrups, elixirs and the like. Syrups include dry syrup and the like.
- composition for food and drink for example, bread, cookies, biscuits, barley for rice addition, millet, udon, buckwheat, pasta and other noodles, cheese, yogurt and other dairy products, jam, mayonnaise, miso, soy sauce and others Soybean products, tea, coffee, cocoa, soft drinks, fruit drinks and other non-alcoholic drinks, medicinal liquor, other alcoholic drinks, candies, chocolates and other snacks, chewing gum, rice crackers, yokan and other soybeans It can be added to confectionery or the like to form a general food or drink.
- excipient examples include lactose, glucose, sucrose, mannitol, potato starch, dextrin, corn starch, calcium carbonate, calcium phosphate, calcium sulfate, crystalline cellulose, licorice powder, gentian powder and the like.
- binder examples include starch, tragacanth gum, gelatin, syrup, polyvinyl alcohol, polyvinyl ether, polyvinylpyrrolidone, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose and the like.
- the method of using the composition according to one embodiment of the present invention is not particularly limited, and for example, a commonly used method can be adopted depending on the usage of cosmetics, foods and drinks, pharmaceuticals and the like.
- the composition of one embodiment of the present invention can be a container-filled composition in which a container is filled and sealed.
- the container is not particularly limited, for example, metal such as aluminum, paper, plastic such as PET or PTP, film bag of one layer or laminate (laminate), retort pouch, vacuum pack, aluminum container, plastic container, glass container, bottle, Examples include packaging containers such as cans.
- the composition of one embodiment of the present invention is preferably one that has been sterilized by pressurization and/or heating after being packed in a container and sealed.
- the packaged composition is preferably one that can be dispensed, filled, and/or individually packaged with the composition obtained by the production, and can be put into distribution and marketed independently by itself.
- the composition of the first aspect of the present invention is a composition for suppressing, ameliorating, alleviating, treating and/or preventing the formation of wrinkles that occur in the skin through the activity of suppressing the activation of proteolytic enzymes involved in wrinkle formation, That is, it can take the form of an anti-wrinkle composition.
- the composition of the first aspect of the present invention can be used as an anti-tarumi composition, an anti-aging composition, a skin abnormality-improving composition, etc., through the activity of suppressing the activation of proteolytic enzymes involved in wrinkle formation. It can be taken.
- composition of the first aspect of the present invention is a composition for suppressing, ameliorating, alleviating, treating and/or preventing inflammation in the skin through the action of suppressing the activation of inflammatory factors in the skin, that is, for anti-skin inflammation. It may take the form of a composition or the like.
- the composition of the second aspect of the present invention suppresses, improves, or alleviates leukoplakia or leukoplakia by promoting melanin synthesis of skin or hair through the action of promoting activation of an enzyme involved in the melanin synthesis pathway. It may be in the form of a composition for treating and/or preventing, that is, an anti-hirsutism composition and an anti-white spot disease composition.
- the composition of the second aspect of the present invention is an anti-hair gray composition, an anti-aging composition, a sunburn promoting composition, and a skin blackening agent through the action of promoting activation of enzymes involved in the melanin synthesis pathway. It may take the form of a composition or the like.
- the composition of one aspect of the present invention is used for treating, preventing, suppressing, alleviating and/or improving symptoms or diseases of skin and hair, which are particularly caused by aging, through the corresponding effective action. It is preferably a composition. Further, the composition of one aspect of the invention can be used for the treatment of prognosis.
- the individual using the composition according to one embodiment of the present invention may be a healthy individual, but wrinkles, tarmi, inflammation, etc. are manifested on the skin, or whitening of the skin or hair is manifested. , And individuals that are at risk of manifestation.
- the active ingredient in the composition of the first aspect of the present invention has an elastase activation inhibitory action, a collagenase activation inhibitory action, and an inflammatory cytokine activation inhibitory action. Therefore, another aspect of the present invention is a composition for suppressing elastase activation or a composition for suppressing elastase activation, a composition for suppressing collagenase activation or a composition for suppressing collagenase activation, which contains an active ingredient, and inflammatory cytokine activation.
- the active ingredient in the composition of the second aspect of the present invention has a tyrosinase activation promoting action. Therefore, another aspect of the present invention is a tyrosinase activation-promoting composition or tyrosinase activation-promoting agent containing an active ingredient.
- the method according to one aspect of the present invention comprises 5,7,3′,4′-tetramethoxyflavone, 5,7,4′-trimethoxyflavone, 5-for producing the composition according to one aspect of the present invention.
- the method according to another aspect of the present invention is a condition or disease selected from the group consisting of albinism, gray hair, leukoplakia and aging, which comprises applying the composition of the second aspect of the present invention to an individual to be used. Is a method for treating, preventing, suppressing or improving.
- Another aspect of the present invention is a method for promoting sunburn or blackening skin, which comprises applying to a subject individual the composition of the second aspect of the present invention.
- normal human skin fibroblasts have increased elastase activity upon IL-1 ⁇ stimulation. Therefore, normal human skin fibroblasts were prepared at 5.0 ⁇ 10 4 cells/ml using a medium (DMEM medium containing 10 vol% FBS (fetal serum)), and 100 ⁇ l of this was prepared in a 96-well microplate. /Well. The cells were cultured for 24 hours at 37° C. in the presence of 5% CO 2 .
- DMEM medium containing 10 vol% FBS (fetal serum) fetal serum
- Suc-(Ala) 3 -pNA(STANA) was used as a substrate, and the amount of p-nitroaniline generated by the action of elastase was measured by the absorbance at 405 nm.
- the result obtained by adding DMSO instead of the test sample and performing the test was used as a control (CN).
- the results obtained by using normal human dermal fibroblasts not stimulated with IL-1 ⁇ without adding the test sample and DMSO were used as blanks (BL).
- As a positive control 30 ⁇ M resveratrol was used in place of the test sample to obtain the results obtained by the test.
- the obtained value was subjected to Dunnett's test for CN. The significance level was set to 5% and 1%.
- Elastase protein expression test A test sample was added to each well of the precultured culture plate so that the final concentration of the isolated compound was 10, 15 and 30 ⁇ M. The plate to which the test sample was added was cultured for 24 hours, washed with PBS, and then the cells were lysed using a RIPA Buffer (catalog number: 182-02451) manufactured by Fujifilm Wako Pure Chemical Industries, Ltd. to prepare a cell extract. The expression level of elastase protein (NEP) was measured by Western blotting (control: ⁇ -actin).
- MF1, MF4, and MF7 suppress elastase, which is a proteolytic enzyme involved in wrinkle formation, at the enzyme level, gene level, and protein level, and thus suppress elastase activity, which is useful for preventing and improving wrinkles. I found out.
- a human epidermal keratinocyte cell line (human keratinocyte HaCaT)
- a human epidermal keratinocyte cell line was prepared using a medium (DMEM medium containing 10 vol% FBS (fetal serum)) at 5.0 ⁇ 10 4 cells/ml, and 500 ⁇ l of this was prepared in a 24-well multiplate. /Well.
- a culture plate containing the human epidermal keratinocyte cell line was cultured for 24 hours at 37° C. in the presence of 5% CO 2 . Then, after removing the culture supernatant, the cells were further cultured for 24 hours using a new medium (DMEM medium containing 0.1 vol% FBS (fetal serum)).
- a human epidermal keratinocyte cell line was prepared using a medium (DMEM medium containing 10 vol% FBS (fetal serum)) at 5.0 ⁇ 10 4 cells/ml, and this was prepared in a 12-well co-culture system plate. 500 ⁇ l/well was dispensed into each transwell.
- DMEM medium containing 10 vol% FBS (fetal serum)
- the total RNA was recovered from the cells after the culture and the expression level of the collagenase (MMP-1) gene was measured by the real-time PCR method.
- MF4 suppresses the increase in elastase enzyme activity and the increase in collagenase (MMP-1) gene expression of skin fibroblasts induced by UV-B-exposed keratinocytes, and thus it is effective in preventing and improving wrinkles. It turned out to be useful.
- a Lysis Buffer 1% sodium deoxycholate+0.5% Triton X-100+100 mM PMSF (Phenylmethylsulfonefluoride) was added, and the cells were lysed by shaking for 30 minutes.
- the composition of one embodiment of the present invention contains, as an active ingredient, methoxyflavonoids derived from black ginger, an anti-inflammatory effect based on an inflammatory factor inhibitory action, an elastase activation inhibitory action and a collagenase activation inhibitory action.
- methoxyflavonoids derived from black ginger
- an anti-inflammatory effect based on an inflammatory factor inhibitory action
- an elastase activation inhibitory action a collagenase activation inhibitory action
- a collagenase activation inhibitory action a collagenase activation inhibitory action.
- a composition for drinking, edible and cosmetics, which exhibits a blackening promotion effect on hair and skin based on a wrinkle effect and a tyrosinase activation promoting action and a melanin production promoting action in particular, a composition for suppressing skin aging, for improving skin metabolism It can be used as a composition and a cosmetic composition.
Abstract
Description
[1]5,7,3’,4’-テトラメトキシフラボン、5,7,4’-トリメトキシフラボン及び5-OH-3,7,3’,4’-テトラメトキシフラボン並びにこれらの少なくとも1種の含有物からなる群から選択される少なくとも1種の有効成分を含有する、美容用組成物。
[2]前記組成物は、エラスターゼ活性化抑制作用、コラゲナーゼ活性化抑制作用及び炎症性サイトカイン活性化抑制作用からなる群から選ばれる少なくとも1種の作用を有する、[1]に記載の組成物。
[3]前記組成物は、抗シワ用組成物、抗タルミ用組成物、抗皮膚炎症用組成物、抗老化用組成物及び皮膚改善用組成物からなる群から選ばれる少なくとも1種の組成物である、[1]~[2]のいずれか1項に記載の組成物。
[4]3,5,7,3’,4’-ペンタメトキシフラボン、3,5,7-トリメトキシフラボン、3,5,7,4’-テトラメトキシフラボン、5-OH-3,7,3’,4’-テトラメトキシフラボン、5-OH-7-メトキシフラボン、5-OH-7,4’-ジメトキシフラボン、5-OH-3,7-ジメトキシフラボン及び5-OH-3,7,4’-トリメトキシフラボン並びにこれらの少なくとも1種の含有物からなる群から選択される少なくとも1種の有効成分を含有する、美容用組成物。
[5]前記組成物は、チロシナーゼ活性化促進作用を有する、[4]に記載の組成物。
[6]前記組成物は、抗白毛症用組成物、抗白髪用組成物、抗白斑症用組成物、抗老化用組成物、日焼け促進用組成物及び皮膚黒色化用組成物からなる群から選ばれる少なくとも1種の組成物である、[4]~[5]のいずれか1項に記載の組成物。
[7]前記組成物は、化粧品用組成物である、[1]~[6]のいずれか1項に記載の組成物。
[8][1]~[7]のいずれか1項に記載の組成物を製造するための、5,7,3’,4’-テトラメトキシフラボン、5,7,4’-トリメトキシフラボン、5-OH-3,7,3’,4’-テトラメトキシフラボン、3,5,7,3’,4’-ペンタメトキシフラボン、3,5,7-トリメトキシフラボン、3,5,7,4’-テトラメトキシフラボン、5-OH-3,7,3’,4’-テトラメトキシフラボン、5-OH-7-メトキシフラボン、5-OH-7,4’-ジメトキシフラボン、5-OH-3,7-ジメトキシフラボン及び5-OH-3,7,4’-トリメトキシフラボン並びにこれらの少なくとも1種の成分の含有物からなる群から選択される少なくとも1種の有効成分の使用方法。
[9]使用個体に、[1]~[7]のいずれか1項に記載の組成物を適用することを含む、シワ、タルミ、皮膚炎症、老化、皮膚異常、白毛症、白髪及び白斑症からなる群から選ばれる症状又は疾患を治療、予防、抑制又は改善する方法。
[10]使用個体に、[4]~[7]のいずれか1項に記載の組成物を適用することを含む、日焼けを促進する方法又は皮膚を黒色化する方法。
本発明の第1態様の組成物は、5,7,3’,4’-テトラメトキシフラボン、5,7,4’-トリメトキシフラボン及び5-OH-3,7,3’,4’-テトラメトキシフラボン並びにこれらの少なくとも1種の成分の含有物からなる群から選択される少なくとも1種の有効成分を少なくとも含有する。
有効成分は、ポリメトキシフラボノイドに分類されるものであり、下記一般式(I)
に示される化合物に包含される。
本発明の第1態様の組成物は、有効成分を含有することにより、シワ形成に関わるタンパク質分解酵素及び炎症性因子の活性化抑制作用のいずれか一方又は両方の作用を示す。
本発明の第1態様の組成物は、シワ形成に関わるタンパク質分解酵素の活性化抑制作用を通じて、皮膚において発生するシワの形成を抑制、改善、緩和、治療及び/又は予防するための組成物、すなわち、抗シワ用組成物の態様をとり得る。同様に、本発明の第1態様の組成物は、シワ形成に関わるタンパク質分解酵素の活性化抑制作用を通じて、抗タルミ用組成物、抗老化用組成物、皮膚異常改善用組成物などの態様をとり得る。
本発明の一態様の組成物の製造方法及び使用方法は、別の一態様として本発明に包含される。
(1-1)被験試料及び材料
正常ヒト皮膚繊維芽細胞(正常ヒト皮膚線維芽細胞)は、TOYOBO社(カタログ番号:GCA10605F)より購入した。DMEMは、SIGMA社(カタログ番号:D6429-500ML)より購入した。その他の試薬は富士フイルム和光純薬社又はSIGMA社より購入した。96ウェルマイクロプレートは、Nunc社(カタログ番号:161093)より購入した。
正常ヒト皮膚線維芽細胞は、IL-1α刺激によって、エラスターゼ活性が上昇する。そこで、正常ヒト皮膚線維芽細胞を培地(10vol% FBS(胎児血清)を含むDMEM培地)を用いて5.0×104細胞/mlとなるように調製し、これを96ウェルマイクロプレートに100μl/ウェルにて分注した。24時間、37℃、5%CO2存在下で培養した。
前培養した培養プレートの各ウェルに、IL-1α(終濃度0.1nM)と被験試料を、単離化合物の最終濃度が15又は30μMになるように添加した。被験試料を加えたプレートを72時間培養した後、培養上清を抜き取った。次いで、ウェル内に残った細胞に0.5vol% TritonX-100溶液を加えて細胞を溶解した後、さらに基質緩衝液を添加することにより、エラスターゼの酵素活性をプレートリーダーで測定した。なお、基質としてはSuc-(Ala)3-pNA(STANA)を用いて、エラスターゼが作用することにより生じるp-ニトロアニリンの量を、405nmの吸光度により測定した。なお、被験試料に代えてDMSOを加えて試験して得られた結果をコントロール(CN)とした。IL-1α刺激していない正常ヒト皮膚線維芽細胞を用いて被験試料及びDMSOを加えずに試験して得られた結果をブランク(BL)とした。また、ポジティブコントロールとして、被験試料の代わりに30μM レスベラトロールを用いて試験して得られた結果を得た。得られた値をCNに対してDunnett検定を行った。有意水準は危険率5%及び1%とした。
前培養した培養プレートの各ウェルに、被験試料を、単離化合物の最終濃度が30μMになるように添加した。被験試料を加えたプレートを24時間培養した後、細胞からThermo Fisher Scientific社製 TRIZOL Reagent(カタログ番号:15596-018)を用いて、全RNAの抽出とcDNAを調製し、リアルタイムPCRによりエラスターゼ遺伝子の発現量を測定した。
前培養した培養プレートの各ウェルに、被験試料を、単離化合物の最終濃度が10、15及び30μMになるように添加した。被験試料を加えたプレートを24時間培養した後、PBSで洗浄後に、細胞を富士フイルム和光純薬社製 RIPA Buffer(カタログ番号:182-02451)を用いて、溶解して細胞抽出液を調製し、ウェスタンブロッティング法(コントロール:β-アクチン)によりエラスターゼタンパク質(NEP)の発現量を測定した。
図1に示すとおり、黒ショウガ抽出物から、MF1~MF11の11種類のポリメトキシフラボノイドを単離した。
(2-1)被験試料及び材料
ヒト表皮角化細胞株として、ヒトケラチノサイトHaCaT(Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line.Boukamp P,Petrussevska RT,Breitkreutz D,Hornung J,Markham A,Fusenig NE.J Cell Biol.1988 Mar;106(3):761-71.)を用いた。24ウェルマイクロプレートは、TPP社(カタログ番号:92024)より購入した。
ヒト表皮角化細胞株(ヒトケラチノサイトHaCaT)は、UV-B照射刺激によって、IL-1αなどの炎症性遺伝子発現が上昇する。そこで、ヒト表皮角化細胞株を培地(10vol% FBS(胎児血清)を含むDMEM培地)を用いて5.0×104細胞/mlとなるように調製し、これを24ウェルマルチプレートに500μl/ウェルにて分注した。ヒト表皮角化細胞株を含む培養プレートを、24時間、37℃、5%CO2存在下で培養した。次いで培養上清を抜き取った後、新たな培地(0.1vol%FBS(胎児血清)を含むDMEM培地)を用いて、さらに24時間培養した。
前培養した培養プレートの各ウェルに、被験試料を、単離化合物の最終濃度が10、20及び30μMになるように添加した。被験試料を加えた培養プレートに、50mJ/cm2でUV-Bを照射し、24時間培養した。次いで、培養後の細胞からTotal RNAを回収して、リアルタイムPCR法によりIL-1α遺伝子の発現量を測定した。得られた値をCNに対してDunnett検定を行った。有意水準は危険率5%及び1%とした。
メトキシフラボノイドのうち、5,7,4’-trimethoxyflavone(MF4)はUV-B刺激で上昇するIL-1αの発現を有意に抑制した(図5)。
(3-1)被験試料及び材料
12ウェル共培養システムプレートは、Falcon社(カタログ番号:353043)より購入した。
正常ヒト皮膚線維芽細胞は、UV-B刺激したヒト表皮角化細胞株(ヒトケラチノサイトHaCaT)との共培養によって、エラスターゼ酵素活性及びコラゲナーゼ(MMP-1)遺伝子発現が上昇する。そこで、ヒト表皮角化細胞株を培地(10vol% FBS(胎児血清)を含むDMEM培地)を用いて5.0×104細胞/mlとなるように調製し、これを12ウェル共培養システムプレートのトランスウェルに500μl/ウェルにて分注した。
トランスウェルのヒト表皮角化細胞株(ヒトケラチノサイトHaCaT)のみにUV-Bを50mJ/cm2で照射し、トランス・プレートの各ウェルに、被験試料を、単離化合物の最終濃度が15及び30μMになるように添加した。
培養プレートを48時間培養した後、上記(1-3)と同様にして、エラスターゼの酵素活性を測定した。
メトキシフラボノイドのうち、5,7,4’-trimethoxyflavone(MF4)はエラスターゼ活性の上昇を抑制した(図6)。また、MF4はコラゲナーゼ(MMP-1)遺伝子の発現上昇も抑制した(図7)。
(4-1)被験試料及び材料
ヒトHMV-IIメラノーマ細胞株は、RIKEN BRC(カタログ番号:RCB07777)より購入した。Ham’s F-12培地は、富士フイルム和光純薬社(カタログ番号:087-08335)より購入した。その他の試薬は富士フイルム和光純薬社又はSIGMA社より購入した。
ヒトHMV-IIメラノーマ細胞株を、培地(10vol% FBS(胎児血清)を含むDMEM培地)を用いて、96ウェルマイクロプレートに1.0×104cells/ウェルで播種し、24時間、37℃、5%CO2存在下で培養した。
前培養した培養プレートの各ウェルに、被験試料を、単離化合物の最終濃度が40μMになるように添加した。被験試料を加えたプレートを72時間培養した後、培養上清を抜き取った。
メトキシフラボノイドのうち、3,5,7,3’,4’-pentamethoxyflavone(MF2)、3,5,7-trimethoxyflavone(MF5)、3,5,7,4’-tetramethoxyflavone(MF6)、5-OH-3,7,3’,4’-tetramethoxyflavone(MF7)、5-OH-7-methoxyflavone(MF8)、5-OH-7,4’-dimethoxyflavone(MF9)、5-OH-3,7-dimethoxyflavone(MF10)及び5-OH-3,7,4’-trimethoxyflavone(MF11)は、ヒトHMV-IIメラノーマ細胞株において、メラニン合成の律速酵素であるチロシナーゼ活性を上昇させた(図8)。
Claims (7)
- 5,7,3’,4’-テトラメトキシフラボン、5,7,4’-トリメトキシフラボン及び5-OH-3,7,3’,4’-テトラメトキシフラボン並びにこれらの少なくとも1種の成分の含有物からなる群から選択される少なくとも1種の有効成分を含有する、美容用組成物。
- 前記組成物は、エラスターゼ活性化抑制作用、コラゲナーゼ活性化抑制作用及び炎症性サイトカイン活性化抑制作用からなる群から選ばれる少なくとも1種の作用を有する、請求項1に記載の組成物。
- 前記組成物は、抗シワ用組成物、抗タルミ用組成物、抗皮膚炎症用組成物、抗老化用組成物及び皮膚異常改善用組成物からなる群から選ばれる少なくとも1種の組成物である、請求項1~2のいずれか1項に記載の組成物。
- 3,5,7,3’,4’-ペンタメトキシフラボン、3,5,7-トリメトキシフラボン、3,5,7,4’-テトラメトキシフラボン、5-OH-3,7,3’,4’-テトラメトキシフラボン、5-OH-7-メトキシフラボン、5-OH-7,4’-ジメトキシフラボン、5-OH-3,7-ジメトキシフラボン及び5-OH-3,7,4’-トリメトキシフラボン並びにこれらの少なくとも1種の成分の含有物からなる群から選択される少なくとも1種の有効成分を含有する、美容用組成物。
- 前記組成物は、チロシナーゼ活性化促進作用を有する、請求項4に記載の組成物。
- 前記組成物は、抗白毛症用組成物、抗白髪用組成物、抗白斑症用組成物、抗老化用組成物、日焼け促進用組成物及び皮膚黒色化用組成物からなる群から選ばれる少なくとも1種の組成物である、請求項4~5のいずれか1項に記載の組成物。
- 前記組成物は、化粧品用組成物である、請求項1~6のいずれか1項に記載の組成物。
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JP2012176976A (ja) * | 2012-06-04 | 2012-09-13 | Maruzen Pharmaceut Co Ltd | マトリックスメタロプロテアーゼ−2(MMP−2)活性阻害剤、マトリックスメタロプロテアーゼ−9(MMP−9)mRNA発現上昇抑制剤、表皮角化細胞増殖促進剤、アンドロゲンレセプター拮抗剤、毛乳頭細胞増殖促進剤、エンドセリン−1mRNA発現上昇抑制剤、及びSCFmRNA発現上昇抑制剤、並びに化粧料 |
WO2015170681A1 (ja) * | 2014-05-09 | 2015-11-12 | サントリーホールディングス株式会社 | 黒ショウガ油脂抽出物及びその製造方法 |
JP2016160181A (ja) * | 2015-02-26 | 2016-09-05 | 株式会社東洋新薬 | 化粧用組成物、美容組成物、関節保護組成物、組成物 |
JP2016210703A (ja) * | 2015-04-30 | 2016-12-15 | 株式会社東洋新薬 | 時計遺伝子発現促進用組成物 |
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- 2020-01-24 WO PCT/JP2020/002464 patent/WO2020153466A1/ja active Application Filing
- 2020-01-24 JP JP2020567712A patent/JPWO2020153466A1/ja active Pending
- 2020-01-24 KR KR1020217027203A patent/KR20210130730A/ko unknown
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JP2012176976A (ja) * | 2012-06-04 | 2012-09-13 | Maruzen Pharmaceut Co Ltd | マトリックスメタロプロテアーゼ−2(MMP−2)活性阻害剤、マトリックスメタロプロテアーゼ−9(MMP−9)mRNA発現上昇抑制剤、表皮角化細胞増殖促進剤、アンドロゲンレセプター拮抗剤、毛乳頭細胞増殖促進剤、エンドセリン−1mRNA発現上昇抑制剤、及びSCFmRNA発現上昇抑制剤、並びに化粧料 |
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