WO2004112815A1 - Melanogenesis promoter and melanogenesis promoter composition - Google Patents

Melanogenesis promoter and melanogenesis promoter composition Download PDF

Info

Publication number
WO2004112815A1
WO2004112815A1 PCT/JP2004/006436 JP2004006436W WO2004112815A1 WO 2004112815 A1 WO2004112815 A1 WO 2004112815A1 JP 2004006436 W JP2004006436 W JP 2004006436W WO 2004112815 A1 WO2004112815 A1 WO 2004112815A1
Authority
WO
WIPO (PCT)
Prior art keywords
melanin production
composition
extract
promoting
hair
Prior art date
Application number
PCT/JP2004/006436
Other languages
French (fr)
Japanese (ja)
Inventor
Kenji Sakamoto
Toshiyuki Mukaiyama
Keishi Hata
Kazuyuki Hori
Saori Takahashi
Original Assignee
Sakamoto Bio Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sakamoto Bio Co., Ltd. filed Critical Sakamoto Bio Co., Ltd.
Priority to CN2004800123491A priority Critical patent/CN1784215B/en
Priority to BRPI0410251-7A priority patent/BRPI0410251A/en
Priority to KR1020057021403A priority patent/KR101112006B1/en
Publication of WO2004112815A1 publication Critical patent/WO2004112815A1/en

Links

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
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/63—Steroids; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • 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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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
    • A61K8/9706—Algae
    • 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
    • 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]
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • 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
    • 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
    • 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
    • A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring
    • A61Q5/065—Preparations for temporary colouring the hair, e.g. direct dyes
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat

Definitions

  • the present invention relates to the use of an extract of Akinonokeshi and a fatty acid ester represented by palmitoyl diol as an active ingredient thereof, which promotes melanin production in melanocytes and prevents gray hair on hair.
  • the present invention relates to a melanin production promoter, which can improve and blacken skin with respect to skin, and a composition for promoting melanin production such as cosmetics, medicines, and foods.
  • the color tone of hair and skin depends on the amount of melanin pigment present in hair and skin.
  • Melanin is biosynthesized by tyrosinase catalysis from tyrosine via dopa in pigment-producing cells (melanocytes) present in the hair bulb and epidermal basal layer.
  • Patent Document 1 JP-A-2000-169348
  • Patent Document 2 Japanese Patent Application Laid-Open No. 2002-47130
  • Patent Document 3 JP 2002-212039 A
  • Patent Document 4 JP-A-2002-3381
  • Non-Patent Document 1 Keiji Hata et al., Biological and Pharmaceutical Bulletin, 2000, Vol. 23, No. 8, p. 96 2—967
  • Non-patent Document 2 Keishi Hata et al., Journal of Natural Products. 2002, 65, p. 645—648
  • the present invention has been made in view of the above circumstances, and an object of the present invention is to provide a substance which has an excellent action of promoting melanin production, is effective in preventing and improving white hair, and is effective in darkening skin. It is to provide a composition used.
  • the present invention relates to an extract of Akinonogeshi or the following general formula:
  • R represents an acinole group having 12 to 22 carbon atoms
  • R represents a melanin production promoter comprising a fluor fatty acid ester or an isomer thereof.
  • the present invention relates to the extract of Akinonogeshi or the following general formula:
  • R represents an acyl group having 12 to 22 carbon atoms.
  • a melanin production promoter containing, as an active ingredient, a diol fatty acid ester and / or an isomer thereof.
  • R in the fluoric acid fatty acid ester represented by the above general formula is preferably an acyl group having 14 to 18 carbon atoms. More preferably, it is an acyl group having 14 to 18 carbon atoms having a saturated hydrocarbon, and particularly preferably a palmitoyl group.
  • the present invention is also a composition for promoting melanin production, comprising the melanin production promoter.
  • the present invention relates to the extract of Akinonogeshi or the following general formula:
  • R represents an asinole group having 12 to 22 carbon atoms.
  • a composition for promoting melanin production comprising a diol fatty acid ester and / or an isomer thereof.
  • R in the fluor fatty acid ester represented by the above general formula is preferably an acyl group having 14 to 18 carbon atoms. More preferably, it is a C14-C18 acyl group having a saturated hydrocarbon, and particularly preferably a palmitoinole group.
  • the composition for promoting melanin production may be a composition for preventing gray hair or a composition for darkening skin.
  • composition is preferably a cosmetic, pharmaceutical or food containing quasi-drugs.
  • a novel melanin production promoter and a composition having a melanin production promotion effect can be obtained.
  • cosmetics, pharmaceuticals, and foods having an excellent effect of preventing and improving white hair and darkening skin by promoting melanin production can be obtained.
  • the extract of Akinonokeshi according to the present invention can be obtained by an extraction method generally used for plant extraction using Akinonokeshi, that is, a method of extracting Akinonokeshi with a solvent.
  • the Akinonogeshi used in the present invention is a plant of the genus Aactinidae (Lactuca indica) of the Asteraceae family. It is an annual plant, widely distributed in East and Southeast Asia, and can be found throughout Japan. It is a large plant with a height of about 60cm 2m. It grows in sunny places on wastelands, riverbanks, abandoned fields and fields. 9-October: A yellow-white flower blooms on the top of the stem in October. Akinonogeshi has a Japanese name that includes the word "Nogeshi". Its taxonomic genus is different from that of Nogeshi and Ononigeshi, which belong to the same Asteraceae family. It is said that the name came from blooming similar flowers. Akinonogeshi has long been used as a feed for livestock, and is highly safe and powerful as a plant.
  • Akinonogeshi whole plants, leaves, stems, roots, flowers, seeds and the like are used. In particular, it is preferable to use whole plants in terms of effectiveness, extraction efficiency, and the like.
  • the form of Akinonogeshi used to obtain the extract may be, for example, raw as cut, finely cut, dried, or dried and finely chopped or crushed. The force is not limited to these, and other forms can be used as long as the effects of the present invention are not impaired.
  • the extract is formed into a form having high extraction efficiency such as drying and pulverization and then subjected to solvent extraction.
  • the solvent used for the extraction is not particularly limited, but, for example, alcohols such as ethanol, methanol, isopropanol, and 1,3-butylene glycol, hexane, heptane, and cyclohexane.
  • examples thereof include hydrocarbons such as xane, esters such as ethyl acetate, ketones such as acetone, and water.
  • These solvents can be used alone or as a mixture of two or more.
  • ethanol, methanol, or a mixed solvent thereof is preferred for exhibiting the effectiveness of the present invention.
  • the extraction means such as immersion in a solvent and reflux of the solvent are used.
  • the extraction temperature is not particularly limited, and is usually in the range of room temperature to the boiling point of the solvent under normal pressure.
  • the extraction time is not particularly limited, and the extraction is performed at an arbitrary time.
  • solvent After extraction solids such as extraction residues are removed from the extract by filtration, centrifugation, or the like, and then the extract is obtained by removing the extraction solvent.
  • R in the fluoric acid fatty acid ester and its isomer represented by is an acyl group having 12 to 22 carbon atoms, and preferably an acyl group having 14 to 18 carbon atoms.
  • the hydrocarbon constituting the acyl group may contain an unsaturated bond such as a double bond, and may be linear or branched.
  • Specific examples of the acyl group include a lauroyl group, a myristoyl group, a palmito inole group, a stearoyl group, an oleoyl group, an isostearyl group, a behenyl group, and a linoleyl group.
  • R is more preferably a C14-C18 acyl group having a saturated hydrocarbon, and the hydrocarbon may be linear or branched, but is preferably linear.
  • the hydrocarbon may be linear or branched, but is preferably linear.
  • an acyl group having 16 carbon atoms having a saturated hydrocarbon is preferred.
  • palmitoyl groups are most preferred.
  • the fluor fatty acid ester represented by the above general formula (hereinafter simply referred to as fluor fatty acid) It is called an ester. ) And isomers thereof can be obtained, for example, by a method of acylating a fluor.
  • acylation although it is carried out in a usual manner, it is permissible to carry out an asinolelation reaction on a plant containing a rule or an extract thereof.
  • the extract can be used in the form of an extract obtained by removing the solvent from the solvent extract of the plant, that is, in the form of an extract.
  • an extract diluent obtained by arbitrarily diluting the extract with a solvent or an extract concentrate obtained by removing an arbitrary amount of the solvent and concentrating the extract can be used as an extract diluent obtained by arbitrarily diluting the extract with a solvent or an extract concentrate obtained by removing an arbitrary amount of the solvent and concentrating the extract.
  • an operation such as deodorization can be performed after the operation of the present invention is performed as long as the effects of the present invention are not impaired.
  • palmitoyl diol having a palmitoyl group as R of the diol fatty acid ester is a component contained in the above-mentioned akinonogeshi. It can be obtained by isolating from the Aquinococcus extract of the invention by a known method. For example, the power that can be isolated and obtained by repeating fractionation of an Aquinonogeshi extract by column chromatography or the like is not limited thereto. The present inventors have found for the first time that palmitoylrubeol in the present invention is present in Akinonogeshi.
  • the extract of Akinonogeshi used for the isolation of palmitoylrubeol is a dry extract obtained by removing the solvent from the solvent extract of Akinonogeshi, that is, it is used in the form of an extract.
  • the extract obtained by extraction can be used as it is, or it can be used as an extract diluent obtained by arbitrarily diluting the extract with a solvent or an extract concentrate obtained by removing an arbitrary amount of the solvent and concentrating the extract. You can also. Further, it can be used after an operation such as deodorization is added as long as the effect of the present invention is not impaired.
  • Palmitoylrubeol preferably used in the present invention can be obtained by other means, such as isolation from a plant other than Akinonogeshi containing palmitoylnorreol, in addition to the extraction from Akinonogeshi. it can.
  • the extract of Akinonoki, the fatty acid fatty acid ester and isomers thereof according to the present invention have an excellent melanin production promoting action as described later. Therefore, they are useful as melanin production promoters.
  • This melanin production enhancer is useful for extracting the novel functions of Akinonogeshi extract and diol fatty acid esters and isomers thereof. It is a new and useful use based on the discovery, and exhibits a function as a melanin production promoter by containing an extract of Aquinonoki-shi or a fluor fatty acid ester and / or an isomer thereof as an active ingredient.
  • the melanin production promoter promotes the production of melanin in melanocytes, and exhibits functions such as prevention of gray hair or improvement of gray hair, ie, darkening, and browning of skin.
  • the melanin production promoter of the present invention can be applied to various fields having a very wide range of applications.
  • Examples of the field include cosmetics, quasi-drugs, pharmaceuticals, foods, and the like, and these are suitable.
  • the use form of the extract of Akinonokishi and the fatty acid ester of the chlorophyll and the isomers thereof are as follows.
  • a dried extract from which the solvent has been removed that is, in the form of an extract
  • it can be used as it is in the form of an extract obtained by extraction with a solvent, and the extract is optionally diluted with a solvent
  • the extract diluent and the solvent can be used as an extract concentrate after removing an arbitrary amount of the solvent.
  • deodorization deodorized substance
  • purification refined substance
  • the extract-dried product may be dissolved in a solvent at an arbitrary concentration and used as a solution of the extract-dried product. Further, the product may be further purified by column chromatography or the like, and used as a fraction, or as an active ingredient.
  • the diol fatty acid ester and its isomer contain the fluoric acid fatty acid ester and / or its isomer as an active ingredient, and the melanin production promoting action (function) is effectively exerted.
  • It may be used in the form of a plant or an extract thereof containing a concentration of a diol fatty acid ester and / or an isomer thereof.
  • the extract may be in the form of a solvent extract, a concentrated solution thereof, or an extract (extract) obtained by purifying the extract (extract) to an arbitrary amount containing a diol fatty acid ester and / or an isomer thereof. Any form may be used as long as it satisfies the above conditions.
  • the melanin production promoter of the present invention can be added to a composition as a melanin production promotion component to form a new and useful composition having a melanin production promotion action, that is, a composition for promoting melanin production. .
  • the composition for promoting melanin production in the present invention It works especially on hair and skin. In the case of hair, it blackens the hair and is effectively used, for example, as a composition for preventing gray hair. In the skin, the skin is blackened (browned), and is effectively used as a skin blackening composition.
  • the composition is not particularly limited and is optional. Examples thereof include cosmetics, quasi-drugs, pharmaceuticals, foods, and the like, and these are suitable.
  • compositions include cosmetics for promoting melanin production, medicinal products for promoting melanin production, foods for promoting melanin production, cosmetics for preventing white hair, pharmaceuticals for preventing white hair, foods for preventing white hair, cosmetics for darkening the skin, Drugs for skin darkening, foods for skin darkening, and the like.
  • the extract of Akinonokeshi in terms of an extracted dry product
  • the content of diol fatty acid ester and its isomer amount, applications, dosage form varies depending formulation purposes such as, in general, preferable than the total amount of the composition in 0.1 00001- 20 mass 0/0 force Mashigu ⁇ a 0. 0001- 10 mass% is there.
  • the dosage in the case of a drug can be appropriately changed based on the age and weight of the patient, the route of application, the degree of progression of the disease, and the treatment performed in parallel, and is specified. However, it is generally about 1-10 ml (liquid) or 1-20 mg (taliform, ointment, etc.) per day, administered once or twice or three times a day. Can, but is not limited to.
  • composition for promoting melanin production according to the present invention, cosmetics, pharmaceuticals, foods and the like are blended with other components usually used in cosmetics, pharmaceuticals, foods and the like as long as the effects of the present invention are not impaired. be able to.
  • a specific component contained in the component may cover a plurality of components.
  • an oil component a surfactant, a humectant, Polyhydric alcohols, thickeners, water-soluble polymers, film-forming agents, water-insoluble polymers, powders, pigments, dyes, lakes, lower alcohols, ultraviolet absorbers, sequestering agents, organic amines, pH adjusters And medicinal ingredients, sugars, other hair or skin darkening ingredients, preservatives, antioxidants, fragrances, water and the like.
  • oil components include jojoba oil, olive oil, apogado oil, castor oil, coconut oil, tallow, and hard oil. Oils and derivatives thereof, waxes such as liquid lanolin, carnaupa wax, beeswax and lanolin, liquid paraffin, squalane, vaseline, microcrystalline wax, hydrocarbons such as solid paraffin, stearic acid, behenic acid, etc.
  • Higher fatty acids higher alcohols such as cetyl alcohol, stearyl alcohol and cetostearyl alcohol, glyceryl trioctanoate, isopropyl myristate, diisostearyl malate, glyceryl tri-2-ethyl glyceryl hexate, diglyceryl diisostearate, triglyceride Esters such as trimethylolpropane 2-ethylhexanoate, trimethylolpropane trioctanoate, di-2-ethylhexyl sebacate, dimethylpolysiloxane, methylphenylpolysiloxane, decamethylcyclope And silicone oils such as n-siloxane.
  • higher alcohols such as cetyl alcohol, stearyl alcohol and cetostearyl alcohol, glyceryl trioctanoate, isopropyl myristate, diisostearyl malate, glyceryl tri-2-
  • Examples of the powder include tanolek, myric, kaolin, silica, zinc white, titanium mica, titanium oxide, iron oxide, and nylon powder.
  • surfactant examples include polyoxyethylene (hereinafter also referred to as P ⁇ ⁇ ⁇ ⁇ E) alkyl ether, POE fatty acid ester, POE sorbitan fatty acid ester, glycerin fatty acid ester, POE hydrogenated castor oil, POE sorbitol fatty acid
  • Nonionic surfactants such as esters and polyoxyalkylene-modified polysiloxanes, anionic surfactants such as sodium palmitate, cationic surfactants such as stearyltrimethylammonium chloride, betaine, amidobetaine, imidazolinium, and sulfobetaine And the like.
  • humectant examples include glycerin, 1,3-butylene glycol, and polyethylene glycol.
  • PEG poly(ethylene glycol)
  • dipropylene glycol poly(ethylene glycol)
  • sorbitol poly(ethylene glycol)
  • Examples of the thickener include water-soluble polymers such as carboxyvinyl polymer, carboxymethyl cellulose, and polybutyl alcohol, and clay minerals such as bentonite.
  • Examples of the ultraviolet absorber include para-aminobenzoic acid (hereinafter abbreviated as PABA), glycerinole PABA, ethyldihydroxypropyl PABA, octyl methoxycinnamate, and 2_ethoxyxetinole ⁇ -methoxycinnamate.
  • PABA para-aminobenzoic acid
  • glycerinole PABA glycerinole PABA
  • ethyldihydroxypropyl PABA ethyldihydroxypropyl PABA
  • octyl methoxycinnamate octyl methoxycinnamate
  • 2_ethoxyxetinole ⁇ -methoxycinnamate 2-ethoxyxetinole ⁇ -methoxycinnamate.
  • 2,4-dihydroxybenzophenone 2-hydroxy-1-methoxybenzophenone, 2-hydroxy-4-methoxy-14-methylbenzophenone, 2-hydroxy-4-methoxy-14-methylbenzophenone sulfone Acid salt, ethyl perocyanate, 2-phenylenoxy 5-methylbenzoxazole, 4-methoxy-l 4-t-butyldibenzoy Noremethane, ethyl hexyl paramethoxy cake, and the like.
  • Examples of sequestering agents include tetrasodium edetate, citric acid and the like.
  • lower alcohols include ethanol and the like.
  • Examples of organic amines include monoethanolamine, triethanolamine and the like.
  • Examples of the pH adjuster include buffers such as sodium lactate-monolactate and sodium citrate-monocitrate.
  • Examples of the medicinal component include pantothenyleethyl ether, glycyrrhizinate, nicotinate, and the like.
  • antioxidants include tocoproles, dibutylhydroxytoluene, propyl gallate and the like.
  • sugars include erythritol, sucrose, hyaluronic acid and the like.
  • preservatives include ethylparaben, butylparaben, sodium benzoate and the like.
  • it can be selected from the components that can be blended with the following pharmaceuticals and foods, and can be blended.
  • components contained in the components may extend over a plurality of components.
  • examples thereof include excipients, stabilizers, and wetting agents. , Emulsifiers, absorption enhancers, pH adjusters, surfactants, diluents, carriers, dissolution aids, flavoring agents, preservatives, fragrances, coloring agents, various additives such as coating agents, water, etc. Is mentioned.
  • Specific examples of these additive components include starch, sugars such as lactose, magnesium sulfate, talc, gelatin, cellulose derivatives such as hydroxypropylcellulose, vegetable oils such as soybean oil and sesame oil, animal oils and synthetic oils, and the like. Examples include gums, alcohols such as ethanol, 1,3-butylene glycol, and polyalkylene glycol.
  • it can also be selected from the above-mentioned cosmetics and components that can be added to the following foods, and can be added.
  • a specific component contained in the component may cover a plurality of components.
  • a sweetener an acidulant, a preservative, and a flavor
  • various additives such as coloring agents, excipients, stabilizers, wetting agents, emulsifiers, absorption promoters, pH adjusters, surfactants, diluents and carriers, and water.
  • specific examples of these additional components include various extracts such as ginseng extract, ginger extract and honey, cyclic oligosaccharides, reduced maltose, trehalose, lactose, and sugars such as fatty acid esters of sucrose.
  • Lifting power S can.
  • it is selected from ingredients that can be blended with the above-mentioned cosmetics and pharmaceuticals, and can be combined with each other.
  • composition of the present invention can be prepared in various forms.
  • cosmetics for example, creams, lotions, emulsions, ointments, solutions, lotions, jewels, foams, essences (cosmetics), foundations, packs' masks, and aerosols can be applied. .
  • the dosage form of the cosmetic includes solution, solubilizing, emulsifying, powder, powder dispersing, oil-liquid, gel, ointment, aerosol, foam, stick, and water.
  • a wide range of dosage forms is possible, such as a two-layer system for one oil and a three-layer system for water-oil-powder.
  • any of oral administration and parenteral administration methods can be adopted, and a pharmaceutical preparation form suitable for each can be adopted.
  • Pharmaceutical preparations include, for example, liquid preparations such as solutions, syrups, injections, liquid inhalants, emulsions, tablets, powders, granules, capsules, ointments, solid inhalants, suppositories, etc. Can be mentioned.
  • Foods are useful as so-called functional foods, and are widely applicable, for example, as confectionery, beverages such as soft drinks, processed vegetables or fruits, livestock meat products, seasonings and the like. Its form is powder, solid product, solution and the like.
  • the composition of the present invention is particularly preferably used as an external preparation for cosmetics, pharmaceuticals and the like.
  • the composition for preventing gray hair includes, for example, creams, lotions, emulsions, ointments, solutions, gels, aerosols, foams, and the like, as hair creams, hair tonics, hair liquids, hair rinses, hair shampoos, hair treatments, and hair. It is preferably used as a product such as a conditioner.
  • the composition for skin darkening it is preferable to use, for example, creams, lotions, emulsions, ointments, jewels, nuts, foams, solutions, essences, sticks, powders, and the like, as products.
  • composition of the present invention can be prepared in any form and dosage form by a conventional method.
  • the whole plant was freeze-dried and powdered using a fiber mixer. This powder 100 ml of methanol was added to lOg, and the mixture was allowed to stand at room temperature for 30 minutes to extract. After the extraction, 0.26 g of an extraction powder (extracted dried product) was obtained by filtration and drying under reduced pressure.
  • the whole freeze-dried Akinonogeshi was ground with a fiber mixer, 3 L of methanol was added to 300 g of the powder, the mixture was allowed to stand for 90 minutes, and the filtrate was dried under reduced pressure to obtain an extraction powder.
  • a fresh 3 L of methanol was added to the filtered Akinonogeshi powder, the mixture was allowed to stand for 90 minutes, and the filtrate was dried under reduced pressure to obtain an extraction powder again. This extraction operation was repeated a total of 5 times, giving a total of 33.7 g of extraction powder.
  • the melanin production promoting action in B16 melanoma cells was evaluated by the following method.
  • a culture of B16 2F2 cells (1 X 10 5 cells / ml) was mixed with an extract of Akinonokishi or a dandelion root extract to a concentration of 20 Aig / ml, and mixed with a 24-well culture plate (0 After culturing at 5 ml / well for 72 hours, the cells were measured for cell number and melanin content.
  • To determine the melanin content of B162F2 cells add IN Na ⁇ H solution (300 ⁇ / ⁇ ) to a 24-well culture plate, leave at room temperature for 60 minutes to dissolve intracellular melanin pigment, and measure the absorbance at 470 nm. And quantified.
  • the same experiment was carried out with the same amount of methanol added in place of the extract of Akinonokishi or dandelion root extract.
  • Figure 3 shows the results.
  • the extract of Akinonogeshi induced about three-fold melanin production on B162F2 cells compared to the dandelion root extract.
  • Dandelion root extract increases the amount of soup Even so, melanin production hardly changed.
  • palmitoylrubeol strongly induced melanin production in ⁇ 162F2 cells.
  • the extract of Akinonogeshi in the synthesizing component is the extract of Akinonokeshi (dried extract) obtained in Preparation Example 1 above, except where otherwise specified.
  • the ethanol extract of the whole plant of Akinonogeshi was prepared according to the method of the above Preparation Example. Also, in all of the examples, an excellent melanin production promoting effect was observed, and when used for hair, the effect of preventing graying of hair was observed. When used, the effect of blackening the skin was observed.
  • 1,3-butylene glycol 1.0 methylphenylpolysiloxane 1.0 collagen hydrolyzate 1.0 ethanol ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ ⁇ - ⁇ ⁇ 0.5 Purified water
  • Acetic acid dl a—tocopherol / re 0. 05
  • Vitamin E derivative appropriate amount
  • Vitamin E derivative appropriate amount
  • a novel melanin production promoter and a composition having a melanin production promoting effect can be obtained. It can be applied to foods, medicines, foods, etc.
  • FIG. 1 is a 1 H-NMR spectrum of palmitoylrubeol.
  • FIG. 2 is a 13 C-NMR spectrum of palmitoylrubeol.
  • Fig. 3 is a view showing the effect of the extract of Akinonogeshi on melanin production.
  • FIG. 4 is a graph showing the effect of palmitoyl lubeol on promoting melanin production.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Chemical & Material Sciences (AREA)
  • Birds (AREA)
  • Microbiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Dermatology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medical Informatics (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Emergency Medicine (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Steroid Compounds (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

A substance excelling in the efficacy of melanogenesis promotion and being effective in hair graying prevention and amelioration and in skin melanism; and a composition making effective use of the substance. In particular, such a substance consists of a melanogenesis promoter comprising as an active ingredient a Lactuca indica extract or a lupeol fatty acid ester and/or an isomer thereof. There are provided the above melanogenesis promoter and a melanogenesis promoter composition comprising as an active ingredient a Lactuca indica extract or a lupeol fatty acid ester and/or an isomer thereof. This melanogenesis promoter composition can be used as a hair graying prevention composition or a skin melanism composition and can find appropriate application in cosmetics, drugs or food products.

Description

明 細 書  Specification
メラニン産生促進剤及びメラニン産生促進用組成物  Melanin production promoter and melanin production promotion composition
技術分野  Technical field
[0001] 本発明はアキノノゲシの抽出物及びその活性成分であるパルミトイルルぺオールを 代表とするルぺオール脂肪酸エステルの用途に関し、メラノサイトにおけるメラニン生 成を促進し、毛髪に対しては白髪を予防、改善し、皮膚に対しては皮膚を黒化するこ とができる、メラニン産生促進剤、及び化粧料、医薬品、食品等のメラニン産生促進 用組成物に関する。  [0001] The present invention relates to the use of an extract of Akinonokeshi and a fatty acid ester represented by palmitoyl diol as an active ingredient thereof, which promotes melanin production in melanocytes and prevents gray hair on hair. The present invention relates to a melanin production promoter, which can improve and blacken skin with respect to skin, and a composition for promoting melanin production such as cosmetics, medicines, and foods.
背景技術  Background art
[0002] 毛髪や皮膚の色調は、毛髪や皮膚に存在するメラニン色素の量に依存している。メ ラニンは、毛髪の毛球部や表皮の基底層に存在する色素産生細胞 (メラノサイト）の 中で、チロシンからドーパを経てチロシナーゼの触媒作用により生合成される。  [0002] The color tone of hair and skin depends on the amount of melanin pigment present in hair and skin. Melanin is biosynthesized by tyrosinase catalysis from tyrosine via dopa in pigment-producing cells (melanocytes) present in the hair bulb and epidermal basal layer.
[0003] したがって、毛髪においてメラノサイトの機能亢進あるいはチロシナーゼの活性化 によりメラニン産生量が増大すれば、毛髪は黒々とした色調を示すようになり、白髪に なることが防止され、また白髪は改善される。現在までに、白色化した髪を黒髪へと 変化させる方法として、白髪の防止又は改善成分等の報告が数多くなされている（例 えば、特許文献 1、 2、 3参照）が、いまだ有効性や安全性の点で充分なものは得られ ていない。  [0003] Therefore, if the amount of melanin is increased in the hair due to the enhancement of the function of melanocytes or the activation of tyrosinase, the hair will show a dark color tone, the gray hair will be prevented, and the gray hair will be improved. You. To date, there have been many reports on methods for converting whitened hair to black hair, such as components for preventing or improving white hair (for example, see Patent Documents 1, 2, and 3). Sufficient in terms of safety has not been obtained.
[0004] また、皮膚のメラニン量を増加させれば、皮膚の色は濃くなる。流行の波はあるもの の褐色の肌を好む人も多ぐ 日光浴や日焼けサロン等で紫外線照射を受けたり、ある いはジヒドロアセトンを主成分とするタンユング剤により目的を達するのが通常である 。しかし、これらについては安全上問題が多い。  [0004] In addition, if the amount of melanin in the skin is increased, the color of the skin becomes darker. Despite the trend of the epidemic, many people prefer brown skin. It is usually the case that the skin is irradiated with ultraviolet rays in sunbathing or a tanning salon, or a tanjung agent containing dihydroacetone as a main component is used for the purpose. However, these have many safety problems.
[0005] 以上から、毛髪や皮膚のメラニン量を増加させる安全な成分が見出されれば、安全 にかつ有効に白髪の防止又は改善や肌の褐色化が実現できる。  [0005] From the above, if a safe component that increases the amount of melanin in hair or skin is found, prevention or improvement of gray hair and browning of skin can be realized safely and effectively.
[0006] 現在までの、メラニン産生を促進する物質の研究のうち、本発明に関連するものとし て、例えば、キク科タンポポ属の植物である西洋タンポポ（Taraxacum officinale)につ レ、て、その根のメタノールエキスの培養細胞レベルでの実験でメラニン産生促進活性 力 Sあるとの発明者等による報告があり、前記エキス中の活性成分としてルぺオール及 びその類縁物質が同定されている (非特許文献 1、 2参照)。また、同じく培養細胞レ ベルでの実験でキク科ハルジヨウナ属ォニノゲシ（Sonchus asper)及びノゲシ（ [0006] Among the studies on substances that promote melanin production to date, related to the present invention are, for example, Western dandelions (Taraxacum officinale), which is a plant belonging to the genus Asteraceae. Melanin production promoting activity of root methanol extract at the cultured cell level There is a report by the inventors of the present invention that the extract has a strong power, and it has been identified that the active ingredient in the extract is Ruol and its related substances (see Non-Patent Documents 1 and 2). Similarly, in experiments at the cultured cell level, Asteraceae Harchuyona spp. (Sonchus asper) and Nogeshi (
Sonchus oleraceus)の各エキスにメラニン産生促進活性が検出される力 同じキク科 のコゥモリソゥ属モミジガサ（Cacalia delphiniiforia)、同科キオン属ノボロギク（Senecio vulgaris)には同活性が認められていなレ、（非特許文献 1参照）。しかし、いずれにして もメラニン産生促進活性が認められているものでもその効力は充分でない。さらに、 ジヒドロルぺオール誘導体を含有したメラニン産生促進剤の報告がある（例えば、特 許文献 4参照）が、このものは天然物中に存在する物質ではなぐまた効力も充分で ない。  The ability of each extract of Sonchus oleraceus to detect the melanin production-promoting activity. Patent Document 1). However, in any case, the activity of promoting melanin production is not sufficient. Furthermore, there is a report of a melanin production promoter containing a dihydrodiol derivative (for example, see Patent Document 4), but this is not a substance existing in a natural product and its efficacy is not sufficient.
特許文献 1 :特開 2000 - 169348号公報  Patent Document 1: JP-A-2000-169348
特許文献 2：特開 2002 - 47130号公報  Patent Document 2: Japanese Patent Application Laid-Open No. 2002-47130
特許文献 3 :特開 2002— 212039号公報  Patent Document 3: JP 2002-212039 A
特許文献 4 :特開 2002— 3381号公報  Patent Document 4: JP-A-2002-3381
非特許文献 1：畠恵司（Keishi Hata)等、バイオロジカノぃアンド'ファーマシューティカ ノレ 'ブレティン（Biological and Pharmaceutical Bulletin)ヽ 2000年、 23卷、 8号、 p. 96 2— 967  Non-Patent Document 1: Keiji Hata et al., Biological and Pharmaceutical Bulletin, 2000, Vol. 23, No. 8, p. 96 2—967
非特許文献 2 :畠恵司（Keishi Hata)等、ジャーナル'ォブ 'ナチュラル 'プロダクツ（ Journal of Natural Products.) , 2002年、 65卷、 p. 645— 648  Non-patent Document 2: Keishi Hata et al., Journal of Natural Products. 2002, 65, p. 645—648
発明の開示  Disclosure of the invention
発明が解決しょうとする課題  Problems the invention is trying to solve
[0007] 本発明は上記事情に鑑みてなされたもので、その目的は、メラニン産生を促進する 作用に優れ、白髪の予防、改善や皮膚の黒化に有効な物質及び該物質を有効に活 用した組成物を提供することにある。  [0007] The present invention has been made in view of the above circumstances, and an object of the present invention is to provide a substance which has an excellent action of promoting melanin production, is effective in preventing and improving white hair, and is effective in darkening skin. It is to provide a composition used.
[0008] 本発明者らは上記課題を解決するために鋭意研究を行った結果、アキノノゲシの 抽出物に強いメラニン産生促進作用があり、さらに該抽出物の活性成分を探求した 結果、特定構造のルぺオール脂肪酸エステルに強レ、メラニン産生促進作用があり、 これらが白髪の予防、改善や皮膚の黒化に有効であることを見出し、本発明を完成 するに至った。 [0008] The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems. As a result, the extract of Aquinonoki has a strong melanin production-promoting effect, and as a result of exploring the active ingredient of the extract, it was found that Completed the present invention by discovering that the fluoric acid fatty acid ester has a strong level and a melanin production promoting action, and that these are effective for preventing and improving gray hair and for darkening skin. I came to.
すなわち、本発明は、アキノノゲシの抽出物又は下記一般式  That is, the present invention relates to an extract of Akinonogeshi or the following general formula:
[化 4] [Formula 4]
Figure imgf000005_0001
Figure imgf000005_0001
(式中、 Rは炭素数 12— 22のアシノレ基を表す。）で示されるルぺオール脂肪酸エス テル又はその異性体からなるメラニン産生促進剤である。 (Wherein, R represents an acinole group having 12 to 22 carbon atoms), which is a melanin production promoter comprising a fluor fatty acid ester or an isomer thereof.
また、本発明は、前記アキノノゲシの抽出物又は下記一般式 In addition, the present invention relates to the extract of Akinonogeshi or the following general formula:
Figure imgf000006_0001
Figure imgf000006_0001
(式中、 Rは炭素数 12— 22のアシノレ基を表す。）で示されるルぺオール脂肪酸エス テル及び/又はその異性体を有効成分として含有するメラニン産生促進剤である。 (In the formula, R represents an acyl group having 12 to 22 carbon atoms.) A melanin production promoter containing, as an active ingredient, a diol fatty acid ester and / or an isomer thereof.
[0011] 前記メラニン産生促進剤において、前記一般式で示されるルぺオール脂肪酸エス テル中の Rは炭素数 14一 18のァシル基であることが好ましい。さらに好ましくは、飽 和の炭化水素を有する炭素数 14一 18のァシル基であり、特に、パルミトイル基であ ることが好ましい。 [0011] In the melanin production promoter, R in the fluoric acid fatty acid ester represented by the above general formula is preferably an acyl group having 14 to 18 carbon atoms. More preferably, it is an acyl group having 14 to 18 carbon atoms having a saturated hydrocarbon, and particularly preferably a palmitoyl group.
[0012] また、本発明は、前記メラニン産生促進剤を含有したメラニン産生促進用組成物で ある。  [0012] The present invention is also a composition for promoting melanin production, comprising the melanin production promoter.
[0013] また、本発明は、前記アキノノゲシの抽出物又は下記一般式 [0013] Further, the present invention relates to the extract of Akinonogeshi or the following general formula:
Figure imgf000007_0001
Figure imgf000007_0001
(式中、 Rは炭素数 12— 22のアシノレ基を表す。）で示されるルぺオール脂肪酸エス テル及び/又はその異性体を含有したメラニン産生促進用組成物である。 (In the formula, R represents an asinole group having 12 to 22 carbon atoms.) A composition for promoting melanin production, comprising a diol fatty acid ester and / or an isomer thereof.
[0014] 前記メラニン産生促進用組成物において、前記一般式で示されるルぺオール脂肪 酸エステル中の Rは、炭素数 14一 18のァシル基であることが好ましい。さらに好まし くは、飽和の炭化水素を有する炭素数 14一 18のァシル基であり、特に、パルミトイノレ 基であることが好ましい。  [0014] In the composition for promoting melanin production, R in the fluor fatty acid ester represented by the above general formula is preferably an acyl group having 14 to 18 carbon atoms. More preferably, it is a C14-C18 acyl group having a saturated hydrocarbon, and particularly preferably a palmitoinole group.
[0015] 前記メラニン産生促進用組成物は、白髪防止用組成物または皮膚黒化用組成物 であることができる。  [0015] The composition for promoting melanin production may be a composition for preventing gray hair or a composition for darkening skin.
前記組成物としては、医薬部外品を含む化粧料、医薬品又は食品であることが好 適である。  The composition is preferably a cosmetic, pharmaceutical or food containing quasi-drugs.
[0016] 本発明によれば、新規なメラニン産生促進剤及びメラニン産生促進作用を有した組 成物が得られる。特に、メラニン産生促進作用による、白髪の予防、改善、皮膚の黒 化に優れた効果を有する化粧料、医薬品、食品が得られる。  According to the present invention, a novel melanin production promoter and a composition having a melanin production promotion effect can be obtained. In particular, cosmetics, pharmaceuticals, and foods having an excellent effect of preventing and improving white hair and darkening skin by promoting melanin production can be obtained.
発明を実施するための最良の形態 [0017] 以下、本発明の実施形態について詳述する。 BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described in detail.
本発明に係るアキノノゲシの抽出物は、アキノノゲシを用いて植物の抽出に一般的 に用いられている抽出方法、すなわちアキノノゲシを溶媒によって抽出する方法等で 得ること力 Sできる。  The extract of Akinonokeshi according to the present invention can be obtained by an extraction method generally used for plant extraction using Akinonokeshi, that is, a method of extracting Akinonokeshi with a solvent.
[0018] 本発明において用いられるアキノノゲシは、キク科アキノノゲシ属（Lactuca indica) の植物である。一年草で、東アジアや東南アジアに広く分布し日本でも各地で見られ る。高さ 60cm 2mほどにもなる大型の植物である。荒れ地や河原、放棄された畑、 野原の日当たりのよいところに生育する。 9一 10月に茎の上部に黄白色の花を咲か せる。なお、アキノノゲシは和名では「ノゲシ」の字句を含む力 同じキク科のノゲシや ォニノゲシとは分類学上の属が異なり種類が違う。よく似た花を咲かせることから名が ついたとされる。アキノノゲシはこれまで家畜の餌として長く利用されており、安全性 の高レ、植物である力 そのメラニン産生促進作用につレ、ては知られてレ、なレ、。  [0018] The Akinonogeshi used in the present invention is a plant of the genus Aactinidae (Lactuca indica) of the Asteraceae family. It is an annual plant, widely distributed in East and Southeast Asia, and can be found throughout Japan. It is a large plant with a height of about 60cm 2m. It grows in sunny places on wastelands, riverbanks, abandoned fields and fields. 9-October: A yellow-white flower blooms on the top of the stem in October. Akinonogeshi has a Japanese name that includes the word "Nogeshi". Its taxonomic genus is different from that of Nogeshi and Ononigeshi, which belong to the same Asteraceae family. It is said that the name came from blooming similar flowers. Akinonogeshi has long been used as a feed for livestock, and is highly safe and powerful as a plant.
[0019] アキノノゲシの抽出部位としては、全草、葉、茎、根、花、種子等が用いられる。特 に、有効性、抽出効率等の面から全草を用いることが好ましい。また、抽出物を得る 際のアキノノゲシの形態としては、例えば、切り取ったままの生のもの、それを細かく 切ったもの、乾燥させたもの、乾燥させて細力べ切ったり粉砕したもの等が用いられる 力 これらに限定されるものではなく本発明の効果を損なわない範囲でその他の形 態のものも用いることができる。本発明においては、乾燥、粉末化等抽出効率の高い 形態にした後溶媒抽出に供するのが望ましい。  [0019] As the extraction site of Akinonogeshi, whole plants, leaves, stems, roots, flowers, seeds and the like are used. In particular, it is preferable to use whole plants in terms of effectiveness, extraction efficiency, and the like. The form of Akinonogeshi used to obtain the extract may be, for example, raw as cut, finely cut, dried, or dried and finely chopped or crushed. The force is not limited to these, and other forms can be used as long as the effects of the present invention are not impaired. In the present invention, it is preferable that the extract is formed into a form having high extraction efficiency such as drying and pulverization and then subjected to solvent extraction.
[0020] 抽出に用いる溶媒としては、特に限定されるものではなレ、が、例えば、エタノール， メタノーノレ，イソプロパノーノレ， 1 , 3—ブチレングリコール等のアルコール類、へキサン ,ヘプタン，シクロへキサン等の炭化水素、酢酸ェチル等のエステル、アセトン等のケ トン、水等が挙げられ、これらの溶媒を単独で又は 2種以上を混合して用いることがで きる。溶媒のなかでも、エタノール、メタノール又はこれらの混合溶媒が本発明の有効 性を発揮させる上で好ましレヽ。  [0020] The solvent used for the extraction is not particularly limited, but, for example, alcohols such as ethanol, methanol, isopropanol, and 1,3-butylene glycol, hexane, heptane, and cyclohexane. Examples thereof include hydrocarbons such as xane, esters such as ethyl acetate, ketones such as acetone, and water. These solvents can be used alone or as a mixture of two or more. Among the solvents, ethanol, methanol, or a mixed solvent thereof is preferred for exhibiting the effectiveness of the present invention.
[0021] 抽出に当たっては、溶媒に浸漬、溶媒還流する等の手段が用いられる。また、抽出 温度については、特に限定されず、通常室温から常圧下での溶媒の沸点の範囲で 行われる。なお、抽出時間については特に限定されず任意の時間で行われる。溶媒 で抽出した後は、抽出液から抽出残查等の固形物をろ過、遠心分離等の方法で除 去した後、抽出溶媒を除去することにより抽出物を得る。 In the extraction, means such as immersion in a solvent and reflux of the solvent are used. The extraction temperature is not particularly limited, and is usually in the range of room temperature to the boiling point of the solvent under normal pressure. The extraction time is not particularly limited, and the extraction is performed at an arbitrary time. solvent After extraction, solids such as extraction residues are removed from the extract by filtration, centrifugation, or the like, and then the extract is obtained by removing the extraction solvent.
本発明に係る下記一般式  The following general formula according to the present invention
[化 7]  [Formula 7]
Figure imgf000009_0001
で示されるルぺオール脂肪酸エステル及びその異性体の Rは炭素数 12— 22のァシ ル基であり、好ましくは炭素数 14一 18のアシノレ基である。なお、ァシル基を構成する 炭化水素は、二重結合等の不飽和結合を含んでも、また直鎖状でも分岐鎖状であつ ても構わない。前記ァシル基の具体例としては、ラウロイル基、ミリストイル基、パルミト イノレ基、ステアロイル基、ォレオイル基、イソステアロイル基、ベへノィル基、リノレオィ ル基等が挙げられる。本発明において、さらに好ましい Rは飽和の炭化水素を有する 炭素数 14一 18のアシノレ基であり、前記炭化水素は直鎖状でも分岐鎖状でも構わな いが、直鎖状が好ましい。特に、飽和の炭化水素を有する炭素数 16のアシノレ基が好 ましレ、。さらに、パルミトイル基が最も好ましい。
Figure imgf000009_0001
R in the fluoric acid fatty acid ester and its isomer represented by is an acyl group having 12 to 22 carbon atoms, and preferably an acyl group having 14 to 18 carbon atoms. Note that the hydrocarbon constituting the acyl group may contain an unsaturated bond such as a double bond, and may be linear or branched. Specific examples of the acyl group include a lauroyl group, a myristoyl group, a palmito inole group, a stearoyl group, an oleoyl group, an isostearyl group, a behenyl group, and a linoleyl group. In the present invention, R is more preferably a C14-C18 acyl group having a saturated hydrocarbon, and the hydrocarbon may be linear or branched, but is preferably linear. In particular, an acyl group having 16 carbon atoms having a saturated hydrocarbon is preferred. Furthermore, palmitoyl groups are most preferred.
前記一般式で示されるルぺオール脂肪酸エステル (以下、単にルぺオール脂肪酸 エステルという。）及びその異性体は、例えば、ルぺオールをァシル化する方法で得 ること力 Sできる。なお、ァシル化による方法においては、常法で行われるが、ルぺォ一 ルを含有する植物又はその抽出物に対してアシノレ化反応を行つても構わなレ、。抽出 物としては、植物の溶媒抽出液から溶媒を除去した抽出乾燥物、すなわち抽出物の 形態で用いる以外に、溶媒によって抽出して得られる抽出液のそのままの形態で用 レ、ることができ、また、抽出液を溶媒で任意に希釈した抽出希釈液や溶媒を任意の 量除去して濃縮した抽出濃縮液として用いることもできる。また本発明の効果を損な わない範囲で脱臭等の操作をカ卩えてから用いることもできる。 The fluor fatty acid ester represented by the above general formula (hereinafter simply referred to as fluor fatty acid) It is called an ester. ) And isomers thereof can be obtained, for example, by a method of acylating a fluor. In addition, in the method by acylation, although it is carried out in a usual manner, it is permissible to carry out an asinolelation reaction on a plant containing a rule or an extract thereof. The extract can be used in the form of an extract obtained by removing the solvent from the solvent extract of the plant, that is, in the form of an extract. Further, it can be used as an extract diluent obtained by arbitrarily diluting the extract with a solvent or an extract concentrate obtained by removing an arbitrary amount of the solvent and concentrating the extract. In addition, an operation such as deodorization can be performed after the operation of the present invention is performed as long as the effects of the present invention are not impaired.
[0024] 本発明においては、前記ルぺオール脂肪酸エステルの Rとしてパルミトイル基を有 するパルミトイルルぺオール（以下、単にパルミトイルルぺオールという。）は、前記ァ キノノゲシに含有する成分であり、本発明の前記アキノノゲシ抽出物から公知の方法 で単離して得ることができる。例えば、アキノノゲシの抽出物をカラムクロマトグラフィ 一等による分画を繰り返すことにより、単離して得ることができる力 これらに限定され るものではなレ、。本発明におけるパルミトイルルベオールがアキノノゲシ中に存在す ることは、本発明者らがはじめて見出したものである。  [0024] In the present invention, palmitoyl diol having a palmitoyl group as R of the diol fatty acid ester (hereinafter, simply referred to as palmitoyl diol) is a component contained in the above-mentioned akinonogeshi. It can be obtained by isolating from the Aquinococcus extract of the invention by a known method. For example, the power that can be isolated and obtained by repeating fractionation of an Aquinonogeshi extract by column chromatography or the like is not limited thereto. The present inventors have found for the first time that palmitoylrubeol in the present invention is present in Akinonogeshi.
[0025] 前記パルミトイルルべオールの単離に用いられるアキノノゲシの抽出物は、アキノノ ゲシの溶媒抽出液から溶媒を除去した抽出乾燥物、すなわち抽出物の形態で用レ、 る以外に、溶媒によって抽出して得られる抽出液のそのままの形態で用いることがで き、また、抽出液を溶媒で任意に希釈した抽出希釈液や溶媒を任意の量除去して濃 縮した抽出濃縮液として用いることもできる。また本発明の効果を損なわない範囲で 脱臭等の操作を加えてから用いることもできる。  [0025] The extract of Akinonogeshi used for the isolation of palmitoylrubeol is a dry extract obtained by removing the solvent from the solvent extract of Akinonogeshi, that is, it is used in the form of an extract. The extract obtained by extraction can be used as it is, or it can be used as an extract diluent obtained by arbitrarily diluting the extract with a solvent or an extract concentrate obtained by removing an arbitrary amount of the solvent and concentrating the extract. You can also. Further, it can be used after an operation such as deodorization is added as long as the effect of the present invention is not impaired.
[0026] 本発明において好ましく用いられるパルミトイルルベオールは、前記アキノノゲシか らの抽出以外に、例えば、パルミトイルノレぺオールを含有するアキノノゲシ以外の植 物からの単離等の他の手段によって得ることができる。  [0026] Palmitoylrubeol preferably used in the present invention can be obtained by other means, such as isolation from a plant other than Akinonogeshi containing palmitoylnorreol, in addition to the extraction from Akinonogeshi. it can.
[0027] 本発明に係る前記アキノノゲシの抽出物並びにルぺオール脂肪酸エステル及びそ の異性体は、後述するように優れたメラニン産生促進作用を有する。したがって、これ らはメラニン産生促進剤として有用である。このメラニン産生促進剤は、アキノノゲシ の抽出物並びにルぺオール脂肪酸エステル及びその異性体の前記新規な機能の 発見に基づく新規で有用な用途であり、アキノノゲシの抽出物或いはルぺオール脂 肪酸エステル及び/又はその異性体を有効成分として含有することによりメラニン産 生促進剤としての機能を発揮する。前記メラニン産生促進剤はメラノサイトにおけるメ ラニン生成を促進し、白髪毛化の防止、又は白髪毛の改善すなわち黒髪化、また、 皮膚の褐色化等の機能を発揮する。 [0027] The extract of Akinonoki, the fatty acid fatty acid ester and isomers thereof according to the present invention have an excellent melanin production promoting action as described later. Therefore, they are useful as melanin production promoters. This melanin production enhancer is useful for extracting the novel functions of Akinonogeshi extract and diol fatty acid esters and isomers thereof. It is a new and useful use based on the discovery, and exhibits a function as a melanin production promoter by containing an extract of Aquinonoki-shi or a fluor fatty acid ester and / or an isomer thereof as an active ingredient. The melanin production promoter promotes the production of melanin in melanocytes, and exhibits functions such as prevention of gray hair or improvement of gray hair, ie, darkening, and browning of skin.
[0028] 本発明のメラニン産生促進剤は極めて応用範囲が広ぐ種々の分野に応用するこ と力 Sできる。前記分野としては、例えば、医薬部外品を含む化粧料、医薬品、食品等 が挙げられ、これらが好適である。  [0028] The melanin production promoter of the present invention can be applied to various fields having a very wide range of applications. Examples of the field include cosmetics, quasi-drugs, pharmaceuticals, foods, and the like, and these are suitable.
[0029] 本発明のメラニン産生促進剤を応用するにあたっての、アキノノゲシの抽出物並び にルぺオール脂肪酸エステル及びその異性体の使用形態としては、アキノノゲシの 抽出物においては、アキノノゲシの溶媒抽出液から溶媒を除去した抽出乾燥物、す なわち抽出物の形態で用いる以外に、溶媒によって抽出して得られる抽出液のその ままの形態で用いることができ、また、抽出液を溶媒で任意に希釈した抽出希釈液や 溶媒を任意の量除去して濃縮した抽出濃縮液として用いることもできる。また本発明 の効果を損なわなレ、範囲で脱臭 (脱臭物）、精製 (精製物)等の操作を加えてから用 レ、ることもできる。さらに、抽出乾燥物を溶媒に任意の濃度で溶力して抽出乾燥物の 溶液として用いてもよい。また、さらにカラムクロマトグラフィー等を用いて精製し、分 画物、さらに活性成分として用いてもよい。  [0029] In applying the melanin production promoter of the present invention, the use form of the extract of Akinonokishi and the fatty acid ester of the chlorophyll and the isomers thereof are as follows. In addition to being used in the form of a dried extract from which the solvent has been removed, that is, in the form of an extract, it can be used as it is in the form of an extract obtained by extraction with a solvent, and the extract is optionally diluted with a solvent The extract diluent and the solvent can be used as an extract concentrate after removing an arbitrary amount of the solvent. In addition, as long as the effects of the present invention are not impaired, deodorization (deodorized substance), purification (refined substance), and other operations may be performed before use. Further, the extract-dried product may be dissolved in a solvent at an arbitrary concentration and used as a solution of the extract-dried product. Further, the product may be further purified by column chromatography or the like, and used as a fraction, or as an active ingredient.
[0030] また、ルぺオール脂肪酸エステル及びその異性体においては、ルぺオール脂肪酸 エステル及び/又はその異性体を有効成分として含有し、かつメラニン産生促進作 用（機能）が有効に発揮される濃度のルぺオール脂肪酸エステル及び/又はその異 性体を含む植物またはその抽出物の形態で用いても構わない。該抽出物は溶媒抽 出液の形態でも、またそれを濃縮した液でも、またさらに抽出物 (抽出液）を精製によ りルぺオール脂肪酸エステル及び/又はその異性体が含まれる任意の分画物にし たものでも、前記条件を満たすことができればどのような形態でも構わなレ、。  [0030] In addition, the diol fatty acid ester and its isomer contain the fluoric acid fatty acid ester and / or its isomer as an active ingredient, and the melanin production promoting action (function) is effectively exerted. It may be used in the form of a plant or an extract thereof containing a concentration of a diol fatty acid ester and / or an isomer thereof. The extract may be in the form of a solvent extract, a concentrated solution thereof, or an extract (extract) obtained by purifying the extract (extract) to an arbitrary amount containing a diol fatty acid ester and / or an isomer thereof. Any form may be used as long as it satisfies the above conditions.
[0031] 本発明のメラニン産生促進剤は、メラニン産生促進成分として組成物に配合され、 メラニン産生促進作用を有した新規で有用な組成物、すなわちメラニン産生促進用 組成物を形成することができる。前記本発明におけるメラニン産生促進用組成物は、 特に毛髪や皮膚において機能する。毛髪においては、毛髪を黒化し、例えば白髪防 止用組成物として有効に用いられる。また、皮膚においては、皮膚を黒化 (褐色化）し 、皮膚黒化用組成物として有効に用いられる。なお、前記組成物としては、特に限定 されるものではなく任意であるが、例えば、医薬部外品を含む化粧料、医薬品、食品 等が挙げられ、これらが好適である。具体的な組成物としては、メラニン産生促進用 化粧料、メラニン産生促進用医薬品、メラニン産生促進用食品、白髪防止用化粧料 、白髪防止用医薬品、白髪防止用食品、皮膚黒化用化粧料、皮膚黒化用医薬品、 皮膚黒化用食品等が挙げられる。 [0031] The melanin production promoter of the present invention can be added to a composition as a melanin production promotion component to form a new and useful composition having a melanin production promotion action, that is, a composition for promoting melanin production. . The composition for promoting melanin production in the present invention, It works especially on hair and skin. In the case of hair, it blackens the hair and is effectively used, for example, as a composition for preventing gray hair. In the skin, the skin is blackened (browned), and is effectively used as a skin blackening composition. The composition is not particularly limited and is optional. Examples thereof include cosmetics, quasi-drugs, pharmaceuticals, foods, and the like, and these are suitable. Specific compositions include cosmetics for promoting melanin production, medicinal products for promoting melanin production, foods for promoting melanin production, cosmetics for preventing white hair, pharmaceuticals for preventing white hair, foods for preventing white hair, cosmetics for darkening the skin, Drugs for skin darkening, foods for skin darkening, and the like.
[0032] 本発明のメラニン産生促進剤を組成物に配合してメラニン産生促進用組成物を得 る場合、アキノノゲシの抽出物 (抽出乾燥物換算）並びにルぺオール脂肪酸エステル 及びその異性体の含有量は、用途、剤型、配合目的等によって異なるが、一般的に は、組成物全量中 0. 00001— 20質量0 /0力 ましぐより好まし <は 0. 0001— 10質 量％である。 When the composition for promoting melanin production is obtained by adding the melanin production promoting agent of the present invention to a composition, the extract of Akinonokeshi (in terms of an extracted dry product) and the content of diol fatty acid ester and its isomer amount, applications, dosage form, varies depending formulation purposes such as, in general, preferable than the total amount of the composition in 0.1 00001- 20 mass 0/0 force Mashigu <a 0. 0001- 10 mass% is there.
[0033] なお、医薬品の場合の投与量については、患者の年齢及び体重、適用経路、疾病 の進行度及び並行して行われている処置に基づいて適宜変えられるものであり、特 定されるものではなレ、が、一般的には 1日当たり 1一 10ml (液状）又は 1一 20mg (タリ ーム状、軟膏状等）程度で、 1日に 1回又は 2— 3回に分けて投与することができるが 、これに限られるものではない。  [0033] The dosage in the case of a drug can be appropriately changed based on the age and weight of the patient, the route of application, the degree of progression of the disease, and the treatment performed in parallel, and is specified. However, it is generally about 1-10 ml (liquid) or 1-20 mg (taliform, ointment, etc.) per day, administered once or twice or three times a day. Can, but is not limited to.
[0034] 本発明に係るメラニン産生促進用組成物における化粧料、医薬品、食品等には、 本発明の効果を損なわない範囲で通常化粧料、医薬品、食品等に用いられる他の 成分を配合することができる。  [0034] In the composition for promoting melanin production according to the present invention, cosmetics, pharmaceuticals, foods and the like are blended with other components usually used in cosmetics, pharmaceuticals, foods and the like as long as the effects of the present invention are not impaired. be able to.
[0035] 例えば、化粧料についての他の成分としては、成分中に含まれる具体的な成分が 複数の成分にまたがる場合がある記載であるが、例えば、油分、界面活性剤、保湿 剤、多価アルコール、増粘剤、水溶性高分子、皮膜形成剤、非水溶性高分子、粉末 、顔料、染料、レーキ、低級アルコール、紫外線吸収剤、金属イオン封鎖剤、有機ァ ミン類、 pH調整剤、薬効成分、糖類、他の毛髪又は皮膚黒化成分、防腐剤、酸化防 止剤、香料、水等が挙げられる。  [0035] For example, as another component of the cosmetic, there is a description that a specific component contained in the component may cover a plurality of components. For example, an oil component, a surfactant, a humectant, Polyhydric alcohols, thickeners, water-soluble polymers, film-forming agents, water-insoluble polymers, powders, pigments, dyes, lakes, lower alcohols, ultraviolet absorbers, sequestering agents, organic amines, pH adjusters And medicinal ingredients, sugars, other hair or skin darkening ingredients, preservatives, antioxidants, fragrances, water and the like.
[0036] 油分の例としては、ホホバ油、ォリーブ油、アポガド油、ヒマシ油、ヤシ油、牛脂、硬 化油等の天然油脂及びその誘導体、液状ラノリン、カルナウパロウ、ミツロウ、ラノリン 等のロウ類、流動パラフィン、スクヮラン、ワセリン、マイクロクリスタリンワックス、固形パ ラフィン等の炭化水素類、ステアリン酸、ベヘン酸等の高級脂肪酸類、セチルアルコ ール、ステアリルアルコール、セトステアリルアルコール等の高級アルコール類、トリオ クタン酸グリセリル、ミリスチン酸イソプロピル、リンゴ酸ジイソステアリル、トリ 2_ェチル へキサン酸グリセリル、ジイソステアリン酸ジグリセリル、トリ 2—ェチルへキサン酸トリメ チロールプロパン、トリオクタン酸トリメチロールプロパン、セバシン酸ジ 2_ェチルへ キシル等のエステル類、ジメチルポリシロキサン、メチルフエ二ルポリシロキサン、デカ メチルシクロペンタシロキサン等のシリコーン油類等が挙げられる。 Examples of oil components include jojoba oil, olive oil, apogado oil, castor oil, coconut oil, tallow, and hard oil. Oils and derivatives thereof, waxes such as liquid lanolin, carnaupa wax, beeswax and lanolin, liquid paraffin, squalane, vaseline, microcrystalline wax, hydrocarbons such as solid paraffin, stearic acid, behenic acid, etc. Higher fatty acids, higher alcohols such as cetyl alcohol, stearyl alcohol and cetostearyl alcohol, glyceryl trioctanoate, isopropyl myristate, diisostearyl malate, glyceryl tri-2-ethyl glyceryl hexate, diglyceryl diisostearate, triglyceride Esters such as trimethylolpropane 2-ethylhexanoate, trimethylolpropane trioctanoate, di-2-ethylhexyl sebacate, dimethylpolysiloxane, methylphenylpolysiloxane, decamethylcyclope And silicone oils such as n-siloxane.
[0037] 粉体の例としては、タノレク、マイ力、カオリン、シリカ、亜鉛華、雲母チタン、酸化チタ ン、酸化鉄、ナイロン粉末等が挙げられる。  [0037] Examples of the powder include tanolek, myric, kaolin, silica, zinc white, titanium mica, titanium oxide, iron oxide, and nylon powder.
[0038] 界面活性剤の例としては、ポリオキシエチレン（以下、 P〇Eともいう。 )アルキルエー テル、 POE脂肪酸エステル、 POEソルビタン脂肪酸エステル、グリセリン脂肪酸エス テル、 POE硬化ヒマシ油、 POEソルビトール脂肪酸エステル、ポリオキシアルキレン 変性ポリシロキサン等の非イオン界面活性剤、パルミチン酸ナトリウム等のァニオン界 面活性剤、塩化ステアリルトリメチルアンモニゥム等のカチオン界面活性剤、ベタイン 、アミドべタイン、イミダゾリニゥム、スルホベタイン等の両性界面活性剤等が挙げられ る。  [0038] Examples of the surfactant include polyoxyethylene (hereinafter also referred to as P ア ル キ ル E) alkyl ether, POE fatty acid ester, POE sorbitan fatty acid ester, glycerin fatty acid ester, POE hydrogenated castor oil, POE sorbitol fatty acid Nonionic surfactants such as esters and polyoxyalkylene-modified polysiloxanes, anionic surfactants such as sodium palmitate, cationic surfactants such as stearyltrimethylammonium chloride, betaine, amidobetaine, imidazolinium, and sulfobetaine And the like.
[0039] 保湿剤の例としては、グリセリン、 1 , 3—ブチレングリコール、ポリエチレングリコール  [0039] Examples of the humectant include glycerin, 1,3-butylene glycol, and polyethylene glycol.
(以下、 PEGともいう。）、ジプロピレングリコール、ソルビトール等が挙げられる。  (Hereinafter also referred to as PEG), dipropylene glycol, sorbitol and the like.
[0040] 増粘剤の例としては、カルボキシビ二ルポリマー、カルボキシメチルセルロース、ポリ ビュルアルコール等の水溶性高分子、ベントナイト等の粘土鉱物が挙げられる。  [0040] Examples of the thickener include water-soluble polymers such as carboxyvinyl polymer, carboxymethyl cellulose, and polybutyl alcohol, and clay minerals such as bentonite.
[0041] 紫外線吸収剤の例としては、パラアミノ安息香酸 (以下、 PABAと略す。）、グリセリ ノレ PABA、ェチルジヒドロキシプロピル PABA、ォクチルメトキシシンナメ—ト、 2_エト キシェチノレー ρ—メトキシシンナメート、 2, 4—ジヒドロキシベンゾフエノン、 2—ヒドロキシ一 4—メトキシベンゾフエノン、 2—ヒドロキシー 4—メトキシ一 4一メチルベンゾフエノン、 2—ヒ ドロキシー 4ーメトキシ一 4一メチルベンゾフヱノンスルホン酸塩、ゥロカニン酸ェチルエス テル、 2_フエニノレー 5—メチルベンゾキサゾール、 4ーメトキシ一 4_t—ブチルジベンゾィ ノレメタン、パラメトキシケィ皮酸ェチルへキシル等が挙げられる。 [0041] Examples of the ultraviolet absorber include para-aminobenzoic acid (hereinafter abbreviated as PABA), glycerinole PABA, ethyldihydroxypropyl PABA, octyl methoxycinnamate, and 2_ethoxyxetinole ρ-methoxycinnamate. 2,4-dihydroxybenzophenone, 2-hydroxy-1-methoxybenzophenone, 2-hydroxy-4-methoxy-14-methylbenzophenone, 2-hydroxy-4-methoxy-14-methylbenzophenone sulfone Acid salt, ethyl perocyanate, 2-phenylenoxy 5-methylbenzoxazole, 4-methoxy-l 4-t-butyldibenzoy Noremethane, ethyl hexyl paramethoxy cake, and the like.
[0042] 金属イオン封鎖剤の例としては、ェデト酸四ナトリウム、クェン酸等が挙げられる。低 級アルコールの例としては、エタノール等が挙げられる。有機アミン類の例としては、 モノエタノールァミン、トリエタノールァミン等が挙げられる。 pH調整剤の例としては、 乳酸一乳酸ナトリウム、クェン酸一クェン酸ナトリウム等の緩衝剤が挙げられる。  [0042] Examples of sequestering agents include tetrasodium edetate, citric acid and the like. Examples of lower alcohols include ethanol and the like. Examples of organic amines include monoethanolamine, triethanolamine and the like. Examples of the pH adjuster include buffers such as sodium lactate-monolactate and sodium citrate-monocitrate.
[0043] 薬効成分の例としては、パントテニールェチルエーテル、グリチルリチン酸塩、ニコ チン酸エステル等が挙げられる。酸化防止剤の例としては、トコフヱロール類、ジブチ ルヒドロキシトルエン、没食子酸プロピル等が挙げられる。  Examples of the medicinal component include pantothenyleethyl ether, glycyrrhizinate, nicotinate, and the like. Examples of antioxidants include tocoproles, dibutylhydroxytoluene, propyl gallate and the like.
[0044] 糖類の例としては、エリスリトール、ショ糖、ヒアルロン酸等が上げられる。防腐剤の 例としては、ェチルパラベン、ブチルパラベン、安息香酸ナトリウム等が挙げられる。 その他、後記医薬品及び食品に配合し得る成分の中から選択され配合することもで きる。  [0044] Examples of sugars include erythritol, sucrose, hyaluronic acid and the like. Examples of preservatives include ethylparaben, butylparaben, sodium benzoate and the like. In addition, it can be selected from the components that can be blended with the following pharmaceuticals and foods, and can be blended.
[0045] 次に、医薬品についての他の成分としては、成分中に含まれる具体的な成分が複 数の成分にまたがる場合がある記載であるが、例えば、賦形剤、安定剤、湿潤剤、乳 化剤、吸収促進剤、 pH調整剤、界面活性剤、稀釈剤、担体、溶解助剤、矯味剤、保 存剤、芳香剤、着色剤、コーティング剤等の種々の添加成分、水等が挙げられる。こ れらの添加成分の具体例としては、例えば、でん粉、乳糖等の糖類、硫酸マグネシゥ ム、タルク、ゼラチン、ヒドロキシプロピルセルロース等のセルロース誘導体、大豆油、 ゴマ油等の植物油、動物油若しくは合成油、ガム類、エタノール、 1 , 3-ブチレンダリ コール、ポリアルキレングリコール等のアルコール類等を挙げることができる。その他 、前記化粧料及び後記食品に配合し得る成分の中から選択され配合することもでき る。  [0045] Next, as other components of the drug, there are cases where specific components contained in the components may extend over a plurality of components. Examples thereof include excipients, stabilizers, and wetting agents. , Emulsifiers, absorption enhancers, pH adjusters, surfactants, diluents, carriers, dissolution aids, flavoring agents, preservatives, fragrances, coloring agents, various additives such as coating agents, water, etc. Is mentioned. Specific examples of these additive components include starch, sugars such as lactose, magnesium sulfate, talc, gelatin, cellulose derivatives such as hydroxypropylcellulose, vegetable oils such as soybean oil and sesame oil, animal oils and synthetic oils, and the like. Examples include gums, alcohols such as ethanol, 1,3-butylene glycol, and polyalkylene glycol. In addition, it can also be selected from the above-mentioned cosmetics and components that can be added to the following foods, and can be added.
[0046] 次に、食品についての他の成分としては、成分中に含まれる具体的な成分が複数 の成分にまたがる場合がある記載であるが、例えば、甘味料、酸味料、保存料、香料 、着色剤、賦形剤、安定剤、湿潤剤、乳化剤、吸収促進剤、 pH調整剤、界面活性剤 、稀釈剤、担体等の種々の添加成分、水等が挙げられる。これらの添加成分の具体 例としては、例えば、人参抽出液、ショウガ抽出液、ハチミツ等の各種抽出エキス、環 状オリゴ糖、還元麦芽糖、トレハロース、乳糖、ショ糖脂肪酸エステル等の糖類等を 挙げること力 Sできる。その他、前記化粧料及び医薬品に配合し得る成分の中から選 択され酉己合することちでさる。 [0046] Next, as another component of the food, there is a description that a specific component contained in the component may cover a plurality of components. For example, a sweetener, an acidulant, a preservative, and a flavor And various additives such as coloring agents, excipients, stabilizers, wetting agents, emulsifiers, absorption promoters, pH adjusters, surfactants, diluents and carriers, and water. Specific examples of these additional components include various extracts such as ginseng extract, ginger extract and honey, cyclic oligosaccharides, reduced maltose, trehalose, lactose, and sugars such as fatty acid esters of sucrose. Lifting power S can. In addition, it is selected from ingredients that can be blended with the above-mentioned cosmetics and pharmaceuticals, and can be combined with each other.
[0047] 本発明における前記組成物は、種々の形態の製剤とすることができる。  [0047] The composition of the present invention can be prepared in various forms.
例えば、化粧料としては、例えば、クリーム、ローション、乳液、軟膏剤、溶液、化粧 水、ジエル、フォーム、エッセンス（美容液）、ファンデーション、パック'マスク、エアゾ ール等広い範囲で適用可能である。  For example, as cosmetics, for example, creams, lotions, emulsions, ointments, solutions, lotions, jewels, foams, essences (cosmetics), foundations, packs' masks, and aerosols can be applied. .
[0048] また、化粧料の剤型としては、溶液系、可溶化系、乳化系、粉末系、粉末分散系、 油液系、ゲル系、軟膏系、エアゾール系、フォーム系、スティック系、水一油 2層系、水 -油 -粉末 3層系等、幅広い剤型を採り得る。  [0048] The dosage form of the cosmetic includes solution, solubilizing, emulsifying, powder, powder dispersing, oil-liquid, gel, ointment, aerosol, foam, stick, and water. A wide range of dosage forms is possible, such as a two-layer system for one oil and a three-layer system for water-oil-powder.
[0049] また、医薬品としては、経口投与、非経口投与いずれの投与方法をも採用すること ができ、それぞれに適した医薬製剤の形態とすることができる。医薬製剤としては、例 えば、液剤，シロップ剤，注射剤，液状吸入剤，乳剤等の液状剤、錠剤，粉剤，顆粒 剤，カプセル剤，軟膏剤，固形吸入剤，座剤等の固形剤等を挙げることができる。  [0049] Further, as a pharmaceutical, any of oral administration and parenteral administration methods can be adopted, and a pharmaceutical preparation form suitable for each can be adopted. Pharmaceutical preparations include, for example, liquid preparations such as solutions, syrups, injections, liquid inhalants, emulsions, tablets, powders, granules, capsules, ointments, solid inhalants, suppositories, etc. Can be mentioned.
[0050] また、食品としては、いわゆる機能食品への用途として有用であり、例えば、菓子、 清涼飲料等の飲料、野菜又は果実加工品、畜肉製品、調味料等として広く適用可能 である。その形態としては、粉末、固形製品、溶液等である。  [0050] Foods are useful as so-called functional foods, and are widely applicable, for example, as confectionery, beverages such as soft drinks, processed vegetables or fruits, livestock meat products, seasonings and the like. Its form is powder, solid product, solution and the like.
[0051] 本発明の前記組成物は、特に、化粧料、医薬品等の外用剤として用いることが好ま しい。例えば、白髪防止用組成物としては、例えばクリーム、ローション、乳液、軟膏、 溶液、ゲル、エアゾール、フォーム等の形態として、ヘアクリーム、ヘアトニック、ヘアリ キッド、ヘアーリンス、ヘアーシャンプー、ヘアートリートメント、ヘアーコンディショナ 一等の製品として用いることが好ましい。皮膚黒化用組成物としては、例えばクリーム 、 ローション、乳液、軟膏、ジエル、ノ ノク、フォーム、溶液、エッセンス、スティック、パ ウダ一等の形態、製品として用いることが好ましい。  [0051] The composition of the present invention is particularly preferably used as an external preparation for cosmetics, pharmaceuticals and the like. For example, the composition for preventing gray hair includes, for example, creams, lotions, emulsions, ointments, solutions, gels, aerosols, foams, and the like, as hair creams, hair tonics, hair liquids, hair rinses, hair shampoos, hair treatments, and hair. It is preferably used as a product such as a conditioner. As the composition for skin darkening, it is preferable to use, for example, creams, lotions, emulsions, ointments, jewels, nuts, foams, solutions, essences, sticks, powders, and the like, as products.
本発明の前記組成物は、常法により任意の形態、剤型に調製することができる。  The composition of the present invention can be prepared in any form and dosage form by a conventional method.
[0052] 以下実施例を挙げて本発明を具体的に説明する。組成物の配合量中、特に記載 のないものは質量％である。  Hereinafter, the present invention will be specifically described with reference to examples. In the compounding amounts of the compositions, those not particularly described are% by mass.
[0053] [調製例 1 ;アキノノゲシの抽出物]  [Preparation Example 1; Extract of Akinonogeshi]
アキノノゲシ全草を凍結乾燥し、ファイバーミキサーを用いて粉末化した。この粉末 lOgに対して 100mlのメタノールを添加して室温で 30分間静置し、抽出した。抽出 後、ろ過、減圧乾固により 0. 26gの抽出末 (抽出乾燥物）を得た。 The whole plant was freeze-dried and powdered using a fiber mixer. This powder 100 ml of methanol was added to lOg, and the mixture was allowed to stand at room temperature for 30 minutes to extract. After the extraction, 0.26 g of an extraction powder (extracted dried product) was obtained by filtration and drying under reduced pressure.
[0054] [調製例 2；パルミトイルルベオール] [Preparation Example 2: Palmitoyl Rubeol]
凍結乾燥したアキノノゲシの全草をファイバーミキサーで粉砕し、その粉末 300gに 対して 3Lのメタノールを添加して 90分間静置、そのろ液を減圧乾固して抽出末を得 た。ろ過したアキノノゲシ粉末に新たに 3Lのメタノールをカ卩えて 90分間静置し、ろ液 を減圧乾固して再び抽出末を得た。この抽出操作を計 5回繰り返し行レ、、あわせて 3 3. 7gの抽出末を得た。  The whole freeze-dried Akinonogeshi was ground with a fiber mixer, 3 L of methanol was added to 300 g of the powder, the mixture was allowed to stand for 90 minutes, and the filtrate was dried under reduced pressure to obtain an extraction powder. A fresh 3 L of methanol was added to the filtered Akinonogeshi powder, the mixture was allowed to stand for 90 minutes, and the filtrate was dried under reduced pressure to obtain an extraction powder again. This extraction operation was repeated a total of 5 times, giving a total of 33.7 g of extraction powder.
[0055] 次にクロ口ホルム：メタノール：水 =4： 4： 3の容積比の溶媒系による分配分画を行レヽ 、クロ口ホルム層（下層）から 13. 6gの乾燥物を得た。この乾燥物に対し 4段階のシリ 力ゲルカラムクロマトグラフィーを適用することによりさらに分画、精製を行った。すな わち、各段階で活性のある画分の一部を集めて乾固し、次段のクロマトグラフィーを 行った。用いた溶媒系はクロ口ホルム：メタノール = 5 : 1、 n—へキサン：酢酸ェチル = 5 : 1、 n—へキサン：酢酸ェチル = 20： 1および n—へキサン：クロ口ホルム = 10： 1の順 である。最終的に 99. 4mgの未同定活性化合物を単離した。  [0055] Next, distribution fractionation was performed using a solvent system having a volume ratio of chloroform: methanol: water = 4: 4: 3, and 13.6 g of a dried product was obtained from the chromatography layer (lower layer). The dried product was further fractionated and purified by applying four-stage silica gel column chromatography. That is, a part of the active fraction at each stage was collected, dried, and subjected to the next stage of chromatography. The solvent system used was chromate form: methanol = 5: 1, n-hexane: ethyl acetate = 5: 1, n-hexane: ethyl acetate = 20: 1 and n-hexane: chromate form = 10: The order is 1. Finally, 99.4 mg of an unidentified active compound were isolated.
[0056] 同化合物を1 H_NMR (400MHz、図 1)及び13 C_NMR (100MHz、図 2)により分 析したところ、ルぺオールの誘導体であることが判明した。また、高分解能 EI— MSに より分析したところ（表 1)、分子量 664. 6125及び 665. 6163の位置に主なピーク が検出された。これはルぺオールの C一 3位にパルミチン酸が結合した化合物パルミ トイルルベオールの分子式 C H Oから計算した分子量 (炭素原子はすべて12 Cの The compound was analyzed by 1 H_NMR (400 MHz, FIG. 1) and 13 C_NMR (100 MHz, FIG. 2) and found to be a derivative of diol. Analysis by high-resolution EI-MS (Table 1) revealed major peaks at molecular weights of 666.6125 and 666.6163. This is the molecular formula of palmitoyl-rubeol, a compound in which palmitic acid is bonded to the C- 13 position of ruole. The molecular weight calculated from CHO (all carbon atoms are 12 C
46 80 2  46 80 2
場合） 664. 6158及びその炭素原子の一つが13 Cである場合の分子量 665. 6192と よく一致する。旋光度測定、 IRスペクトル測定の結果とあわせ、同化合物はルぺォ一 ルの C—3位に脂肪酸がエステル結合した化合物であることが分かり、パルミトイルノレ ぺオールであると考えられた。さらに同化合物のエステル結合をアルカリ加水分解し 、遊離した脂肪酸を FID— GCで分析したところ、パルミチン酸であった。また、トリテ ルペン部分をシリカゲルカラムで精製し、 NMR等によりルペールであることも確認し た。 If) 664. 6158 and one of its carbon atoms is in good agreement with the molecular weight 665. 6192 when it is 13 C. Together with the results of optical rotation measurement and IR spectrum measurement, the compound was found to be a compound in which a fatty acid was ester-bonded to the C-3 position of the label, and was considered to be palmitoyl phenol. Further, the ester bond of the compound was subjected to alkaline hydrolysis, and the released fatty acid was analyzed by FID-GC to find that it was palmitic acid. Further, the triterpen portion was purified with a silica gel column, and it was confirmed by NMR and the like that it was ruper.
[0057] [表 1] Measured Mass Formula Calculated Mass Error(mmu)[0057] [Table 1] Measured Mass Formula Calculated Mass Error (mmu)
664.6125 C 46H80O2 664.6158 3.3 664.6125 C 46 H 80 O 2 664.6158 3.3
665.6163 C 45H8o13 C 02 665.6192 2.9 665.6163 C 45 H 8 o 13 C 0 2 665.6192 2.9
以上の分析により、得られた化合物は、パルミトイルルベオールであると同定された From the above analysis, the obtained compound was identified as palmitoyl rubeol.
実施例 1 Example 1
[0058] メラニン産生促進効果一 1 [0058] Melanin production promoting effect 1
以下の方法で、 B 16メラノーマ細胞におけるメラニン産生促進作用を評価した。  The melanin production promoting action in B16 melanoma cells was evaluated by the following method.
[0059] (方法） [0059] (Method)
マウスメラノーマ細胞株 B16より選択、樹立されたメラノサイト刺激ホルモン高感受 性株 B16 2F2の培養は、 10%牛胎児血清を含むダルベッコ変法イーグル培地を用 いて 37°C、 5%/Airの条件下で行った。予め培養しておいた B16 2F2細胞をトリプ シンで剥離して回収、計数し、以下の培養に使用した。前記調製例 1で調製したアキ ノノゲシ抽出物又はタンポポ根抽出物（ (株)ゥチダ和漢薬より購入した蒲公英根をァ キノノゲシと同様に処理して得た抽出末）を 20mg/mlの濃度のメタノール溶液を下 記に従い培地に添加した。  Culture of melanocyte stimulating hormone hypersensitive strain B16 2F2, selected and established from mouse melanoma cell line B16, was performed at 37 ° C and 5% / Air using Dulbecco's modified Eagle's medium containing 10% fetal calf serum. I went in. B162F2 cells cultured in advance were detached with trypsin, collected, counted, and used for the following culture. The extract of Akinonokishi or the extract of dandelion root prepared in Preparation Example 1 (extract obtained by treating Gakong Eikon purchased from Chida Wakan Yakuhin in the same manner as Akinonogeshi) at a concentration of 20 mg / ml in methanol The solution was added to the medium as described below.
[0060] B16 2F2細胞（1 X 105cells/ml)の培養液にアキノノゲシの抽出物又はタンポポ 根抽出物を 20 Ai g/mlになるように添カ卩混合し、 24ゥエル培養プレート（0· 5ml/ゥ エル）にて 72時間培養後、細胞数及びメラニン含量の測定に供した。 B16 2F2細胞 のメラニン含量は、 24ゥエル培養プレートに IN Na〇H溶液（300 μ ΐ/ゥエル）を加 え 60分間室温放置して、細胞内メラニン色素を溶解させ、 470nmの吸収を測定する ことにより、定量した。対照として、アキノノゲシの抽出物又はタンポポ根抽出物に換 えて同用量のメタノールを添加し、同様に実験を行った。この結果を図 3に示す。 [0060] A culture of B16 2F2 cells (1 X 10 5 cells / ml) was mixed with an extract of Akinonokishi or a dandelion root extract to a concentration of 20 Aig / ml, and mixed with a 24-well culture plate (0 After culturing at 5 ml / well for 72 hours, the cells were measured for cell number and melanin content. To determine the melanin content of B162F2 cells, add IN Na〇H solution (300 μΐ / ゥ) to a 24-well culture plate, leave at room temperature for 60 minutes to dissolve intracellular melanin pigment, and measure the absorbance at 470 nm. And quantified. As a control, the same experiment was carried out with the same amount of methanol added in place of the extract of Akinonokishi or dandelion root extract. Figure 3 shows the results.
[0061] (結果）  [0061] (Result)
図 3から分かるように、アキノノゲシの抽出物はタンポポ根抽出物と比較して、 B16 2F2細胞に対して約 3倍のメラニン産生を誘導した。タンポポ根抽出物は添力卩量を増 やしてもメラニン産生量はほとんど変わらなかった。 As can be seen from FIG. 3, the extract of Akinonogeshi induced about three-fold melanin production on B162F2 cells compared to the dandelion root extract. Dandelion root extract increases the amount of soup Even so, melanin production hardly changed.
実施例 2  Example 2
[0062] メラニン産生促進効果一 2 [0062] Melanin production promoting effect 1
[B16メラノーマ細胞におけるメラニン産生促進作用 ]  [Melanin production promoting action in B16 melanoma cells]
[0063] (方法） [0063] (Method)
実施例 1と同様にしてマウスメラノーマ細胞株 B16 2F 2を用いてパルミトイルルぺ オールのメラニン産生促進作用を評価した。実施例 1で用いたアキノノゲシの抽出物 に換えて調製例 2で単離したパルミトイルルベオールを 10 /i M、 20 μ Μ又は 30 μ Μの濃度となるよう培地中に添加した。この結果を図 4に示す。  In the same manner as in Example 1, the melanin production-promoting effect of palmitoyl toluene was evaluated using the mouse melanoma cell line B162F2. Palmitoylrubeol isolated in Preparation Example 2 was added to the medium at a concentration of 10 / iM, 20 μΜ, or 30 μ て in place of the extract of Akinonokeshi used in Example 1. Fig. 4 shows the results.
[0064] (結果） [0064] (Results)
図 4から分かるように、パルミトイルルベオールは Β 16 2F2細胞に対して強度にメラ ニン産生を誘導した。  As can be seen from FIG. 4, palmitoylrubeol strongly induced melanin production in Β162F2 cells.
[0065] 以下、種々の処方の組成物を常法により調製した本発明の実施例を示す。配合成 分中のアキノノゲシの抽出物は、特に断りのあるものを除いて前記調製例 1で得たァ キノノゲシの抽出物（抽出乾燥物）である。なお、アキノノゲシ全草のエタノール抽出 物は、前記調製例の方法に準じて調製したものである。また、いずれの実施例にお いても優れたメラニン産生促進効果が見られ、毛髪に使用した場合には、毛髪の白 髪化を防ぎ、白髪に対しては白髪改善効果が見られ、皮膚に使用した場合には皮膚 を黒化する効果が見られた。  Hereinafter, examples of the present invention in which compositions having various formulations are prepared by a conventional method will be described. The extract of Akinonogeshi in the synthesizing component is the extract of Akinonokeshi (dried extract) obtained in Preparation Example 1 above, except where otherwise specified. In addition, the ethanol extract of the whole plant of Akinonogeshi was prepared according to the method of the above Preparation Example. Also, in all of the examples, an excellent melanin production promoting effect was observed, and when used for hair, the effect of preventing graying of hair was observed. When used, the effect of blackening the skin was observed.
実施例 3  Example 3
[0066] クリーム [0066] cream
成分 配合量 (質量％)  Ingredients Amount (% by mass)
ステアリルアルコール 6. 0  Stearyl alcohol 6.0
ステアリン酸 2. 0  Stearic acid 2.0
水添ラノリン 4. 0  Hydrogenated lanolin 4.0
スクヮラン 9. 0  Squalane 9.0
オタチルドデカノール 10. 0  Otachildodecanol 10.0
1 , 3—ブチレングリコール 6. 0 PEG1500 4. 01,3—butylene glycol 6.0 PEG1500 4.0
POE (25)セチルアルコールエーテル 3· 0 モノステアリン酸グリセリル 2· 0 POE (25) Cetyl alcohol ether3.0 Glyceryl monostearate2.0
アキノノゲシの抽出物 5. 0  Akinonoshi extract 5.0
防腐剤 適量  Preservative appropriate amount
酸化防止剤 適量 香料 適量  Antioxidant qs perfume qs
イオン交換水 残量 実施例 4  Example 4
[0067] クリーム [0067] cream
成分 配合量 (質量％) ステアリルアルコール 6· 0  Ingredients Amount (% by mass) Stearyl alcohol 6.0
ステアリン酸 2. 0  Stearic acid 2.0
水添ラノリン 4. 0  Hydrogenated lanolin 4.0
スクヮラン 9. 0  Squalane 9.0
オタチルドデカノール 10. 0  Otachildodecanol 10.0
1 , 3—ブチレングリコール 6. 0  1,3—butylene glycol 6.0
PEG1500 4. 0  PEG1500 4.0
Ρ〇Ε (25)セチルアルコールエーテル 3. 0 モノステアリン酸グリセリノレ 2. 0  Ρ〇Ε (25) Cetyl alcohol ether 3.0 Glycerin monostearate 2.0
パノレミトイルルぺオール 0. 003 防腐剤 適量  Panolemitoiruol 0.003 Preservatives qs
酸化防止剤 適量 香料 適量  Antioxidant qs perfume qs
精製水 残量  Purified water balance
実施例 5  Example 5
[0068] 乳液 [0068] Emulsion
成分 配合量 (質量％) ステアリン酸 2. 0 セチノレアノレコーノレ 1. 5 ワセリン 4. 0 スクヮラン 5. 0 トリオクタン酸グリセリノレ 2. 0 ソルビタンモノォレイン酸エステル 2. 0 グリセリン 5. 0 Ingredients Amount (% by mass) Stearic acid 2.0 Cetinoleano recono 1.5 Vaseline 4.0 Squalane 5.0 Glycerinol trioctanoate 2.0 Sorbitan monooleate 2.0 Glycerin 5.0
PEG1500 3. 0 トリエタノールァミン 1. 0 アキノノゲシの抽出物 0. 08 防腐剤 適量 酸化防止剤 適量 香料 適量 精製水 残量 実施例 6  PEG1500 3.0 Triethanolamine 1.0 Extract of Akinonogeshi 0.08 Preservatives Appropriate Antioxidant Appropriate Flavor Appropriate Purified Water Remaining Example 6
ジヱル Jewel
成分 配合量 (質量％) ジプロピレングリコール 7. 0 PEG1500 8. 0 カノレボキシビニノレポリマー 0. 4 メチノレセノレロース 0. 2 Ingredients Blended amount (% by mass) Dipropylene glycol 7.0 PEG 1500 8.0 Canoleboxybininole polymer 0.4 Methinoresenorelose 0.2
POE (15)ォレイルエーテル 1. 0 水酸化カリウム 0. 1 アキノノゲシの抽出物 1. 0 防腐剤 適量 酸化防止剤 適量 キレート剤 適量 香料 適量 実施例 7 POE (15) oleyl ether 1.0 Potassium hydroxide 0.1 Extract of Akinonogeshi 1.0 Preservatives qs Antioxidant qs Chelating agent qs Flavor qs Example 7
ジエル Jiel
成分 配合量 (質量％) Ingredients Amount (% by mass)
—ノレ 7. 0  —Nore 7.0
PEG1500 8. 0 PEG1500 8.0
カノレボキシビ二/レポリマー 0. 4 Canoleboxivini / Repolymer 0.4
メチノレセノレロース 0. 2 Methynoresenorelose 0.2
POE (15)ォレイルエーテル 1. 0  POE (15) oleyl ether 1.0
水酸化カリウム 0. 1 Potassium hydroxide 0.1
/ ノレミ卜ィノレノレぺ才ーノレ 0. 1  / Noremitinorenore
防腐剤 Preservative
酸化防止剤 Antioxidant
キレート剤 Chelating agent
香料 Spice
精製水 purified water
実施例 8 Example 8
ローション Lotion
成分 配合量 (重量％) Ingredient Content (% by weight)
1 , 3—ブチレングリコール 6. 0 1,3—butylene glycol 6.0
グリセリン 4. 0 Glycerin 4.0
イソステアリルアルコール 0. 1 ヒアルロン酸ナトリウム 0. 3 Isostearyl alcohol 0.1 Sodium hyaluronate 0.3
0. 5 0.5
POE (20)ラウリルエーテル 0. 5 POE (20) lauryl ether 0.5
エタノーノレ 10. 0 Ethanor 10.0
全草のエタノール抽出液 0. 5  Ethanol extract of whole plant 0.5
(抽出乾燥物質量として) 防腐剤 適量 酸化防止剤 適量 (As the amount of dry matter extracted) Preservative appropriate amount Antioxidant appropriate amount
香料 適量  Appropriate amount of fragrance
精製水 残量  Purified water balance
実施例 9  Example 9
[0072] ローション [0072] lotion
成分 配合量 (重量％) Ingredient Content (% by weight)
1 , 3—ブチレングリコール 6· 0 1, 3—butylene glycol 6.0
グリセリン 4. 0  Glycerin 4.0
イソステアリルアルコール 0. 1  Isostearyl alcohol 0.1
ヒアルロン酸ナトリウム 0. 3  Sodium hyaluronate 0.3
POE (20)ラウリルエーテル 0· 5 POE (20) lauryl ether 0
エタノーノレ 10· 0  Ethanore 10 · 0
ノヽ °ノレミ卜ィノレノレぺ才ーノレ 0. 5  No ヽ ° Noremitinorenore ぺ sai-nore 0.5
防腐剤 適量  Preservative appropriate amount
酸化防止剤 適量  Antioxidant appropriate amount
香料 適量  Appropriate amount of fragrance
精製水 残量  Purified water balance
実施例 10  Example 10
[0073] ヘアクリーム [0073] Hair cream
成分 配合量 (質量％) 流動パラフィン 15. 0 ワセリン 15. 0 ミツロウ 2· 0 カノレボキシビ二/レポリマー 0. 1 キサンタンガム 0. 1 Ingredients Amount (% by mass) Liquid paraffin 15.0 Vaseline 15.0 Beeswax 2.0 Canoleboxivini / Repolymer 0.1 Xanthan gum 0.1
1 , 3—ブチレングリコール 5. 0 POE (20)ベへニルエーテノレ 2. 01,3—butylene glycol 5.0 POE (20) Behenyle Tenoré 2.0
POE (40)テトラオレイン酸ソルビット 1 · 0 アキノノゲシの抽出物 4· 0 防腐剤 適量 酸化防止剤 適量 香料 適量 精製水 残量 実施例 11 POE (40) Sorbit tetraoleate 1.0 · Akinonoshi extract 4.0 · Preservatives Appropriate Antioxidant Appropriate Flavor Appropriate Purified water Remaining Example 11
[0074] ヘアトリートメントローション [0074] hair treatment lotion
成分 配合量 (質量％) グリセリン 2. 0  Ingredients Amount (% by mass) Glycerin 2.0
1 , 3—ブチレングリコール 1. 0 メチルフエ二ルポリシロキサン 1. 0 コラーゲン加水分解物 1. 0 エタノーノレ 50. 0 アキノノゲシの抽出物 0. 1 精製水 残量 香料 適量 実施例 12  1,3-butylene glycol 1.0 Methylphenylpolysiloxane 1.0 Collagen hydrolyzate 1.0 Ethanore 50.0 Extract of Akinonogeshi 0.1 Purified water Remaining amount Perfume Appropriate amount Example 12
[0075] ヘアトリートメントローション [0075] hair treatment lotion
成分 配合量 (質量％) グリセリン 2. 0  Ingredients Amount (% by mass) Glycerin 2.0
1 , 3—ブチレングリコール 1. 0 メチルフエ二ルポリシロキサン 1. 0 コラーゲン加水分解物 1. 0 エタノーノレ 50. 0 ノ ノレミ卜ィノレノレぺ才ーノレ 0. 5 精製水 1,3-butylene glycol 1.0 methylphenylpolysiloxane 1.0 collagen hydrolyzate 1.0 ethanol ノ レ ミ ト イ ノ レ ノ レ ぺ ぺ ｰ ー-ノ レ 0.5 Purified water
香料 Spice
実施例 13 Example 13
ヘアトニック Hair tonic
成分 配合量 (質量％) ェチノレアノレコーノレ 70. 0  Ingredients Amount (% by mass)
POE (60)硬化ヒマシ油 0. 5 POE (60) hydrogenated castor oil 0.5
L—メントール 0. 05 L—Menthol 0.05
酢酸 dl— a—トコフェローノレ 0. 05 Acetic acid dl—a—Tocopherolone 0. 05
グリチルリチン酸ジカリウム 0. 05 Dipotassium glycyrrhizinate 0.05
1 , 3—ブチレングリコール 0. 5 1,3—butylene glycol 0.5
グリセリン 0. 5 Glycerin 0.5
全草のエタノール抽出液 1. 5  Ethanol extract of whole plant 1.5
(抽出乾燥物質量として) 精製水  (As dry matter extracted) Purified water
香料 Spice
実施例 14 Example 14
ヘアトニック Hair tonic
成分 配合量 (質量％) ェチノレアノレコーノレ 70. 0  Ingredients Amount (% by mass)
POE (60)硬化ヒマシ油 0. 5 POE (60) hydrogenated castor oil 0.5
L—メントール 0. 05 L—Menthol 0.05
酢酸 dl— a—トコフェロー/レ 0. 05 Acetic acid dl—a—tocopherol / re 0. 05
グリチルリチン酸ジカリウム 0. 05 Dipotassium glycyrrhizinate 0.05
1 , 3—ブチレングリコール 0. 5 1,3—butylene glycol 0.5
グリセリン 0. 5 Glycerin 0.5
ノヽ °ノレミトイノレノレぺォーノレ 0. 5 精製水 ヽ ° Noremitinorenore ぺ onore 0.5 purified water
香料  Spice
実施例 15  Example 15
[0078] 育毛剤 [0078] Hair restorer
成分 配合量 (質量％) ェチノレアノレコーノレ 60. 0 ヒノキチォーノレ 適量 センブリエキス 適量 ビタミン B 適量  Ingredients Amount (% by mass) Echinoleanoreconore 60.0 Hinokionore Appropriate Assembly extract Appropriate Vitamin B Appropriate
6  6
ビタミン E誘導体 適量  Vitamin E derivative appropriate amount
1 , 3—ブチレングリコール 2. 0 グリセリン 0. 5  1, 3-butylene glycol 2.0 glycerin 0.5
POE (60)硬化ヒマシ油 0. 5  POE (60) hydrogenated castor oil 0.5
アキノノゲシの抽出物 0. 5 精製水 残量 香料 適量  Akinonogi extract 0.5 Purified water Remaining amount of perfume
実施例 16  Example 16
[0079] 育毛剤 [0079] Hair restorer
成分 配合量 (質量％) ェチノレアノレコーノレ 60. 0 ヒノキチォーノレ 適量 センブリエキス 適量 ビタミン B 適量  Ingredients Amount (% by mass) Echinoleanoreconore 60.0 Hinokionore Appropriate Assembly extract Appropriate Vitamin B Appropriate
6  6
ビタミン E誘導体 適量  Vitamin E derivative appropriate amount
1 , 3—ブチレングリコール 2. 0 グリセリン 0. 5  1, 3-butylene glycol 2.0 glycerin 0.5
POE (60)硬化ヒマシ油 0. 5  POE (60) hydrogenated castor oil 0.5
ノヽ °ノレミ卜ィノレノレぺ才—ノレ 3. 0 精製水 残量 香料 適量 実施例 17 ノ ヽ ° ノ レ ミ ト イ ノ レ ノ レ ぺ gift-Nore 3.0 Purified water Remaining amount Perfume Appropriate amount Example 17
[0080] ドリンク剤 [0080] Drink preparation
成分 配合量（30mL中） アキノノゲシ全草のエタノール抽出乾燥物 0. 085mg 人参抽出液 50mg  Ingredients Amount (in 30 mL) Dry extract of whole Akinonogeshi with ethanol 0.085 mg Ginseng extract 50 mg
冬虫夏草抽出液 lOOmg  Cordyceps extract lOOmg
シ 3ゥガ抽出液 300mg  Shiga extract 3300mg
ハチミツ 150mg  Honey 150mg
環状オリゴ糖 300mg  Cyclic oligosaccharide 300mg
甘味料 適量  Sweetener appropriate amount
酸味料 適量  Sour seasoning appropriate amount
保存料 適量  Preservative appropriate amount
香料 適量  Appropriate amount of fragrance
水 残量  Water remaining
実施例 18  Example 18
[0081] ドリンク斉 IJ [0081] Drink Hit IJ
成分 配合量（30mL中） アキノノゲシ全草のエタノール抽出乾燥物 0. 5mg 人参抽出液 50mg  Ingredients Amount (in 30mL) Dried whole extract of Akinonogeshi with ethanol 0.5mg Ginseng extract 50mg
冬虫夏草抽出液 lOOmg  Cordyceps extract lOOmg
シ 3ゥガ抽出液 300mg  Shiga extract 3300mg
ハチミツ 150mg  Honey 150mg
環状オリゴ糖 300mg  Cyclic oligosaccharide 300mg
甘味料 適量  Sweetener appropriate amount
酸味料 適量  Sour seasoning appropriate amount
保存料 適量 香料 適量 Preservative appropriate amount Appropriate amount of fragrance
水 残量  Water remaining
実施例 19  Example 19
[0082] ドリンク剤 [0082] Drink preparation
成分 配合量 (30mL中） パノレミトイノレノレぺォーノレ 0. 05mg 人参抽出液 50mg  Ingredients Amount (in 30mL) Panoremitoinorerenoreonore 0.05mg Carrot extract 50mg
冬虫夏草抽出液 lOOmg  Cordyceps extract lOOmg
ショウガ抽出液 300mg  Ginger extract 300mg
ハチミツ 150mg  Honey 150mg
環状オリゴ糖 300mg  Cyclic oligosaccharide 300mg
甘味料 適量  Sweetener appropriate amount
酸味料 適量  Sour seasoning appropriate amount
保存料 適量  Preservative appropriate amount
香料 適量  Appropriate amount of fragrance
水 残量  Water remaining
実施例 20  Example 20
[0083] 食品タブレット [0083] Food tablet
成分 配合量（300mg中） アキノノゲシ全草のエタノール抽出乾燥物 0· 025mg 還元麦芽糖 87. 8mg トレハロース 41. 2mg  Ingredients Amount (in 300mg) Dry extract of whole Akinonogeshi with ethanol 0.025mg Reduced maltose 87.8mg Trehalose 41.2mg
乳糖 16. 5mg  Lactose 16.5mg
ショ糖脂肪酸エステル 6· 2mg デキス卜リン 148. 275mg 実施例 21  Sucrose fatty acid ester 6.2 mg Dextrin 148. 275 mg Example 21
[0084] 食品タブレット [0084] Food tablet
成分 配合量（300mg中） アキノノゲシ全草のエタノール抽出乾燥物 Ingredients Amount (in 300mg) Dried ethanol extract of whole plant
還元麦芽糖 87. 8mg  87.8 mg reduced maltose
トレノヽロース 41. 2mg  Truenoperose 41.2 mg
乳糖 lo. 5mg  Lactose lo.5mg
ショ糖脂肪酸エステル 6. 2mg  6.2 mg sucrose fatty acid ester
デキストリン 147. 8mg  Dextrin 147.8 mg
実施例 22  Example 22
[0085] 食品タブレット [0085] Food tablet
成分 配合量（300mg中)  Ingredients Amount (in 300mg)
/ ノレミ卜ィノレノレぺ才ーノレ 0. 05mg  / Noremitinorenore 0,05mg
還元麦牙糖 87. 8mg  Reduced maltose 87.8 mg
トレノヽロース 41. 2mg  Truenoperose 41.2 mg
乳糖 16. 5mg  Lactose 16.5mg
ショ糖脂肪酸エステル 6. 2mg  6.2 mg sucrose fatty acid ester
デキストリン 147. 8mg  Dextrin 147.8 mg
産業上の利用可能性  Industrial applicability
[0086] 新規なメラニン産生促進剤及びメラニン産生促進作用を有した組成物が得られ、特 に、メラニン産生促進作用による、白髪の予防、改善、皮膚の黒化に優れた効果を有 する化粧料、医薬品、食品等に応用することができる。 [0086] A novel melanin production promoter and a composition having a melanin production promoting effect can be obtained. It can be applied to foods, medicines, foods, etc.
図面の簡単な説明  BRIEF DESCRIPTION OF THE FIGURES
[0087] [図 1]図 1は、パルミトイルルベオールの1 H—NMRスペクトル図である。 FIG. 1 is a 1 H-NMR spectrum of palmitoylrubeol.
[図 2]図 2は、パルミトイルルベオールの13 C—NMRスペクトル図である。 FIG. 2 is a 13 C-NMR spectrum of palmitoylrubeol.
[図 3]図 3は、アキノノゲシの抽出物のメラニン産生促進効果を示す図である。  [Fig. 3] Fig. 3 is a view showing the effect of the extract of Akinonogeshi on melanin production.
[図 4]図 4は、パルミトイルルベオールのメラニン産生促進効果を示す図である。  FIG. 4 is a graph showing the effect of palmitoyl lubeol on promoting melanin production.

Claims

請求の範囲 The scope of the claims
[1] アキノノゲシの抽出物からなるメラニン産生促進剤。  [1] A melanin production promoter comprising an extract of Akinonokeshi.
[2] アキノノゲシの抽出物を有効成分として含有することを特徴とするメラニン産生促進 剤。  [2] A melanin production promoter characterized by containing an extract of Aquinonoki as an active ingredient.
[3] 下記一般式  [3] The following general formula
[化 1]  [Formula 1]
Figure imgf000029_0001
Figure imgf000029_0001
(式中、 Rは炭素数 12— 22のアシノレ基を表す。）で示されるルぺオール脂肪酸エス テル又はその異性体からなるメラニン産生促進剤。 (In the formula, R represents an acyl group having 12 to 22 carbon atoms.) A melanin production promoter comprising a fluor fatty acid ester or an isomer thereof.
[4] 下記一般式 [4] The following general formula
[化 2] [Formula 2]
Figure imgf000030_0001
Figure imgf000030_0001
(式中、 Rは炭素数 12— 22のアシノレ基を表す。）で示されるルぺオール脂肪酸エス テル及び/又はその異性体を有効成分として含有することを特徴とするメラニン産生 促進剤。 (Wherein, R represents an asinole group having 12 to 22 carbon atoms).
[5] Rが炭素数 14一 18のアシノレ基である請求項 3又は請求項 4記載のメラニン産生促 進剤。  [5] The melanin production promoter according to [3] or [4], wherein R is an acyl group having 14 to 18 carbon atoms.
[6] Rが飽和の炭化水素を有する炭素数 14一 18のアシノレ基である請求項 3又は請求 項 4記載のメラニン産生促進剤。  6. The melanin production promoter according to claim 3, wherein R is a C14-C18 asinole group having a saturated hydrocarbon.
[7] Rがパルミトイル基である請求項 3又は請求項 4記載のメラニン産生促進剤。 7. The melanin production promoter according to claim 3, wherein R is a palmitoyl group.
[8] 請求項 1乃至請求項 7のいずれか一項に記載のメラニン産生促進剤を含有するメラ ニン産生促進用組成物。  [8] A composition for promoting melanin production, comprising the melanin production promoter according to any one of claims 1 to 7.
[9] アキノノゲシの抽出物を含有することを特徴とするメラニン産生促進用組成物。 [9] A composition for accelerating melanin production, comprising an extract of Akinonogeshi.
[10] 下記一般式 [10] The following general formula
[化 3] [Formula 3]
Figure imgf000031_0001
Figure imgf000031_0001
(式中、 Rは炭素数 12— 22のアシノレ基を表す。）で示されるルぺオール脂肪酸エス テル及び/又はその異性体を含有することを特徴とするメラニン産生促進用組成物 (Wherein, R represents an asinole group having 12 to 22 carbon atoms).
[11] Rが炭素数 14一 18のアシノレ基である請求項 10記載のメラニン産生促進用組成物 [11] The composition for promoting melanin production according to [10], wherein R is an acyl group having 14 to 18 carbon atoms.
[12] Rが飽和の炭化水素を有する炭素数 14一 18のァシル基である請求項 10記載のメ ラニン産生促進用組成物。 12. The composition for promoting melanin production according to claim 10, wherein R is a 14-18 carbon atom-containing acyl group having a saturated hydrocarbon.
[13] Rがパルミトイル基である請求項 10記載のメラニン産生促進用組成物。  13. The composition for promoting melanin production according to claim 10, wherein R is a palmitoyl group.
[14] メラニン産生促進用組成物が、白髪防止用組成物である請求項 8乃至請求項 13の いずれか一項に記載のメラニン産生促進用組成物。  14. The composition for promoting melanin production according to any one of claims 8 to 13, wherein the composition for promoting melanin production is a composition for preventing gray hair.
[15] メラニン産生促進用組成物が、皮膚黒化用組成物である請求項 8乃至請求項 13の いずれか一項に記載のメラニン産生促進用組成物。 [15] The composition for promoting melanin production according to any one of claims 8 to 13, wherein the composition for promoting melanin production is a composition for darkening the skin.
[16] 組成物が、化粧料、医薬品又は食品である請求項 8乃至請求項 15のいずれか一 項に記載のメラニン産生促進用組成物。 [16] The composition for promoting melanin production according to any one of claims 8 to 15, wherein the composition is a cosmetic, a pharmaceutical or a food.
PCT/JP2004/006436 2003-05-14 2004-05-13 Melanogenesis promoter and melanogenesis promoter composition WO2004112815A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CN2004800123491A CN1784215B (en) 2003-05-14 2004-05-13 Melanogenesis promoter and melanogenesis promoter composition
BRPI0410251-7A BRPI0410251A (en) 2003-05-14 2004-05-13 melanogenesis promoter, and, melanogenesis promoter composition
KR1020057021403A KR101112006B1 (en) 2003-05-14 2004-05-13 Melanogenesis promoter and melanogenesis promoter composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2003-136439 2003-05-14
JP2003136439A JP4517249B2 (en) 2003-05-14 2003-05-14 Melanin production promoter and composition for promoting melanin production

Publications (1)

Publication Number Publication Date
WO2004112815A1 true WO2004112815A1 (en) 2004-12-29

Family

ID=33526406

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2004/006436 WO2004112815A1 (en) 2003-05-14 2004-05-13 Melanogenesis promoter and melanogenesis promoter composition

Country Status (5)

Country Link
JP (1) JP4517249B2 (en)
KR (1) KR101112006B1 (en)
CN (1) CN1784215B (en)
BR (1) BRPI0410251A (en)
WO (1) WO2004112815A1 (en)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008138200A1 (en) 2007-05-11 2008-11-20 Hong Kong University Of Science & Technology Nmda and mc receptor antagonists exhibiting neuroprotective and memory enhancing activities
JP5428000B2 (en) * 2007-06-27 2014-02-26 株式会社スカイライト・バイオテック Lupeol-containing pharmaceutical composition, food and feed
JP6027752B2 (en) * 2011-02-21 2016-11-16 第一三共ヘルスケア株式会社 AGEs production inhibitor
JP6142342B2 (en) * 2013-02-22 2017-06-07 株式会社東洋新薬 Novel uses of Akinonogeshi extract
KR101692851B1 (en) * 2015-10-16 2017-01-05 경상대학교산학협력단 Composition for skin whitening comprising amorphigeni as effective component
CN108113927A (en) * 2018-02-28 2018-06-05 周海英 A kind of composition with white-skinned face function in cosmetics and preparation method thereof
CN108815066B (en) * 2018-06-14 2019-10-15 广州植境生物科技有限公司 A kind of draft Haircare composition of the seed extract containing millet
WO2020032297A1 (en) * 2018-08-10 2020-02-13 탑월드(주) Composition for alleviating vitiligo symptoms and preparation method thereof
JP2020143032A (en) * 2019-03-08 2020-09-10 国立大学法人 東京医科歯科大学 White hair preventing/improving agent and phosphorylated mitf/mitf production ratio increasing agent
KR102249072B1 (en) * 2019-07-11 2021-05-06 인하대학교 산학협력단 Pharmaceutical composition for preventing or treating vitiligo or canities comprising extract of Cichorium intybus as an active ingredient
CN111387505B (en) * 2020-04-21 2023-04-07 中国农业科学院都市农业研究所 Lettuce extract for inhibiting melanin synthesis and lettuce matching cultivation method

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002003381A (en) * 2000-06-26 2002-01-09 Kao Corp Melanin production accelerator
JP2002308753A (en) * 2001-04-10 2002-10-23 Mitsui Chemicals Inc Elastase activity inhibitor, estrogenic activator and anti- aging agent for skin containing the same inhibitor or the same activator

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002003381A (en) * 2000-06-26 2002-01-09 Kao Corp Melanin production accelerator
JP2002308753A (en) * 2001-04-10 2002-10-23 Mitsui Chemicals Inc Elastase activity inhibitor, estrogenic activator and anti- aging agent for skin containing the same inhibitor or the same activator

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
HATA K. ET AL: "Activators of Melanin Biosynthesis from Lactuca Indica", NATURAL MEDICINES, vol. 57, no. 6, 20 December 2003 (2003-12-20), pages 238 - 241, XP002980460 *
HATA K. ET AL: "DIFFERENTIATION- AND APOPTOSIS-INDUCING ACTIVITIES BY PENTACYCLIC TRITERPENES ON A MOUSE MELANOMA CELL LINE", NATURAL PRODUCTS, vol. 65, no. 5, 2002, pages 645 - 648, XP002967006 *
HATA K. ET AL: "Differentiation-Inducing Activity of Lupeol, a Lupane-Type Triterpene from Chinese Dandelion Root (Hokouei-kon), on a Mouse Melanoma Cell Line", BIOL. PHARM. BULL., vol. 23, no. 8, 2000, pages 962 - 967, XP002980461 *
NAMBA T. ET AL: "Pharmacognostical Studies on the Chinese Crude Drug "Pu gong ying" (2) The Plant Origin of "Pu gong ying" from Taiwan(II)", SHOYAKUGAKU ZASSHI, vol. 41, no. 4, 1987, pages 301 - 307, XP002980462 *
NIKIEMA J.B. ET AL: "Effects of Antiinflammatory Triterpenes Isolated from Leptadenia hastata Latex on Keratinocyte Proliferation", PHYTOTHERAPIE RESEARCH, vol. 15, no. 2, 2001, pages 131 - 134, XP002980463 *
RAJIC A. ET AL: "Inhibition of Serine Protease by Anti-Inflammatory Triterpenoids", PLANTA MEDICA, vol. 66, no. 3, 2000, pages 206 - 210, XP002980464 *

Also Published As

Publication number Publication date
JP2004345959A (en) 2004-12-09
CN1784215A (en) 2006-06-07
KR101112006B1 (en) 2012-03-13
KR20060014397A (en) 2006-02-15
JP4517249B2 (en) 2010-08-04
BRPI0410251A (en) 2006-05-16
CN1784215B (en) 2010-10-06

Similar Documents

Publication Publication Date Title
TWI381834B (en) Abnormal protein removal composition
JP6196346B2 (en) Use of lignan compounds to improve wrinkles
KR101971837B1 (en) Cosmetic composition for improving skin whitening and wrinkle comprising adventitious root extract of Centella asiatica as effective component
JP2004131431A (en) Composition for preventing or ameliorating ultraviolet damage
WO2004112815A1 (en) Melanogenesis promoter and melanogenesis promoter composition
JP5773111B2 (en) Composition for inhibiting skin pigmentation and use thereof
JP2012001467A (en) Skin external preparation
KR102150488B1 (en) A composition comprising supercritical fluid extract of Sargassum horneri having antioxidant and skin whitening effect
JPH10330219A (en) Melanogenesis inhibitor and skin whitening agent
JP2007277120A (en) Method for extracting ganoderma lucidum extract and bleaching agent containing the ganoderma lucidum extract
JP2003160461A (en) Skin care preparation
JP6765090B2 (en) Black ginger-containing composition
KR101848252B1 (en) A composition comprising the Leukodin isolated from the extract of Artemisia Capillaris for skin whitening
KR101050484B1 (en) Skin whitening composition containing lactone compound as an active ingredient
KR101854766B1 (en) Skin whitening complex containing trihydroxyisoflavone and glycyrrhiza uralensis extracts
KR20100028202A (en) Composition having skin whitening activity comprising an extract of buddleja officinalis
JP2008280249A (en) Skin-lightening cosmetic
CN103796631A (en) Compositions for whitening skin comprising madecassoside
JP4076477B2 (en) Skin preparation
JP2005029494A (en) Melanocyte proliferation inhibitor and cosmetic containing the same
KR102292114B1 (en) Composition for Improving Skin Conditions Having Moisturizing, Anti-Inflammatory Caused by Fine Dust and Pore Shrinkage Property Comprising Plant Complex Extracts as Active Ingredient
JP6017259B2 (en) Endothelin action inhibitor
JP3608776B2 (en) Topical skin preparation
JP4632115B2 (en) Melanin production inhibitor and whitening agent comprising egonol derivative, and composition containing egonol derivative
KR101922131B1 (en) Composition for skin-whitener containing extract of stauntonia hexaphylla

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 20048123491

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 1020057021403

Country of ref document: KR

WWP Wipo information: published in national office

Ref document number: 1020057021403

Country of ref document: KR

ENP Entry into the national phase

Ref document number: PI0410251

Country of ref document: BR

122 Ep: pct application non-entry in european phase