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WO2019143197A1 - Composition de blanchiment de la peau contenant un extrait de cimicifuga dahurica ou une fraction associée - Google Patents

Composition de blanchiment de la peau contenant un extrait de cimicifuga dahurica ou une fraction associée Download PDF

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Publication number
WO2019143197A1
WO2019143197A1 PCT/KR2019/000789 KR2019000789W WO2019143197A1 WO 2019143197 A1 WO2019143197 A1 WO 2019143197A1 KR 2019000789 W KR2019000789 W KR 2019000789W WO 2019143197 A1 WO2019143197 A1 WO 2019143197A1
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WIPO (PCT)
Prior art keywords
extract
fraction
active ingredient
riding
chemical formula
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
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PCT/KR2019/000789
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English (en)
Korean (ko)
Inventor
이영미
김대기
송혜선
박민
강사행
이다슬
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Industry Academic Cooperation Foundation of Wonkwang University
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Industry Academic Cooperation Foundation of Wonkwang University
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Publication date
Priority claimed from KR1020180071735A external-priority patent/KR20190089696A/ko
Application filed by Industry Academic Cooperation Foundation of Wonkwang University filed Critical Industry Academic Cooperation Foundation of Wonkwang University
Publication of WO2019143197A1 publication Critical patent/WO2019143197A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • 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
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin

Definitions

  • the present invention relates to a method for the production of cimicifuga dahurica extract or a fraction thereof as an active ingredient.
  • the present invention also relates to a cosmetic composition, a pharmaceutical composition or a food additive composition for skin whitening.
  • melanocyte melanocyte
  • melanocyte is a biopolymer of phenol that determines hair color and skin color. It synthesizes melanin which is a complex of black protein and secretes it to prevent skin damage by ultraviolet But also the absorption of toxic drugs.
  • melanin causes skin diseases such as spots and freckles, and it is reported that it is also related to the induction of skin cancer in severe cases.
  • skin color is determined by the content and distribution of melanin, and is related to the number and distribution of melanosomes released from the melanocytes and released to the outside of the cells.
  • Melanin is produced in the organelle of melanocytes called melanosomes of skin cells and moves to epidermal cells called keratinocytes.
  • Melanin is produced by oxidizing tyrosine by tyrosinase, which oxidizes tyrosine with tyrosine as a substrate.
  • the hyperpigmentation of the skin can be caused by various factors such as hormonal disorders, genetic diseases, and ultraviolet irradiation after the inflammation reaction of the skin, and the main factor is the abnormal synthesis and distribution of melanin pigment.
  • Cimicifuga dahurica is a perennial plant belonging to the family Ranunculaceae. It is also known as an endosperm, and the horse riding and rootstock of the same plant are used for medicinal purposes.
  • the mountains are Korea, China and Japan.
  • the rootstock is uneven in the shape of thick nodule, 6 ⁇ 8cm in length and 10 ⁇ 25cm in diameter.
  • the outer surface is brown or black, with several large stem marks on the top of the rootstock, with many root residues attached.
  • the horse riding extract regulates insulin secretion, and visnazin, which is known as an effective ingredient of horse riding, suppresses vascular smooth muscle contraction by inhibiting the inflow of calcium It is known.
  • the inventors of the present invention have made intensive studies to utilize eye riding as a natural cosmetic composition as a cosmetic composition, and as a result, they have completed the present invention by confirming skin rash extract, fractions and skin whitening effect of active ingredients isolated therefrom.
  • an object of the present invention is to provide a cosmetic composition for whitening skin, which comprises an eye riding extract, a fraction thereof, or an active ingredient isolated therefrom as an active ingredient.
  • the present invention relates to a method for the production of cimicifuga dahurica extract or a fraction thereof as an active ingredient.
  • the eye-riding horse-riding extract may be an eye ridge-root extract.
  • the eyes riding extract can be extracted with water, 1- C 4 alcohol or mixtures thereof.
  • the horse riding extract may be a 30-70% ethanol aqueous solution extract.
  • the eye riding extract may be a dichloromethane fraction obtained by fractionating an aqueous solution of 30 to 70 vol% ethanol aqueous solution of horse riding with hexane and water, and fractionating the obtained water fraction with dichloromethane.
  • the whitening active ingredient of the eye riding extract may be a compound represented by the following general formulas (1) to (4).
  • the present invention relates to a method for the production of cimicifuga
  • the present invention provides a pharmaceutical composition for the treatment or prevention of a disease associated with tyrosinase overexpression or melanosis hyperalgesia comprising an extract of dahurica or a fraction thereof as an active ingredient and further comprising a Cimicifuga dahurica extract, The active ingredient is as previously described.
  • diseases associated with tyrosinase overexpression or melanin overproduction may be selected from the group consisting of skin cancer, melanoma, hypercholesterolemia, skin pigmentation, freckles, nevi, ectopic mongolian spots, have.
  • the present invention relates to a method for the production of cimicifuga dahurica extract or an active ingredient isolated therefrom as an active ingredient.
  • the present invention also provides a skin whitening food additive composition comprising the Cimicifuga dahurica extract, fractions thereof, or active ingredients thereof are as set forth above.
  • the present invention relates to a method for the production of cimicifuga tyrosinase overexpression or melanin, comprising administering a compound selected from the group consisting of dahurica extract, a fraction thereof, or a compound represented by any one of Chemical Formulas 1 to 4 to a subject having a disease associated with tyrosinase overexpression or melanin overproduction, A method for treating diseases associated with hyperplasia.
  • the disease associated with tyrosinase overexpression or melanin overproduction is selected from the group consisting of skin cancer, melanoma, hypercholesterolemia, skin pigmentation, freckles, nevus, ectopic mongolian spots, .
  • the present invention relates to a method for the production of cimicifuga a composition for use in the prevention or treatment of tyrosinase overexpression or a disease associated with melanin overgrowth, comprising a compound selected from the group consisting of dahurica extract, a fraction thereof, and a compound represented by any one of Chemical Formulas 1 to 4.
  • the present invention relates to the use of Cimicifuga dahurica extract, a fraction thereof or a compound represented by any one of Chemical Formulas 1 to 4 for the manufacture of a medicament for the prevention or treatment of diseases associated with tyrosinase overexpression or melanin excess production to provide.
  • the present invention relates to a method for the production of cimicifuga a composition for inhibiting tyrosinase activity comprising a compound selected from the group consisting of dahurica extract, fractions thereof, and compounds represented by formulas (1) to (4).
  • the present invention relates to a method for the production of cimicifuga dahurica extract, a fraction thereof, or a compound represented by any one of formulas (1) to (4).
  • the extract or its fraction according to the present invention inhibits tyrosinase activity and inhibits melanin production in melanin-producing cells, and thus has excellent skin whitening effect. Therefore, it is possible to prevent, improve and treat skin whitening and skin pigmentation diseases Cosmetics for pharmacy, external preparation for skin, quasi-drugs and food compositions.
  • Fig. 1 shows the tyrosinase activity inhibition results of the horse riding extract of Example 1.
  • Fig. 2 shows the result of inhibition of tyrosinase activity of the horse ridoe extract fraction of Example 2.
  • Figure 3 shows the results of inhibition of tyrosinase activity of the active ingredients 1 to 4 isolated from the dichloromethane fraction of the horse riding extract.
  • Example 4 is a cytotoxicity evaluation result of the horse riding extract of Example 1.
  • Fig. 5 shows the cytotoxicity evaluation results of the horse ridoe extract fraction of Example 2.
  • Figure 6 shows the cytotoxicity results of the active ingredients 1 to 4 isolated from the dichloromethane fraction of the horse riding extract.
  • Fig. 7 shows the results of inhibition of melanin production in the untreated group of the horse riding extract of the eye of Example 1.
  • Fig. 8 shows the results of inhibition of melanin production in the non-treated group of the horse ridoe extract fraction of Example 2.
  • FIG. 9 shows the results of inhibition of melanin production relative to the untreated group of the active ingredients 1 to 4 isolated from the dichloromethane fraction of the horse riding extract.
  • the present invention relates to a method for the production of cimicifuga dahurica extract or a fraction thereof as an active ingredient.
  • Cimicifuga dahurica in the present invention is also called perennial herbaceous perennial plant belonging to the butterfly family, and has origins in Korea, China and Japan.
  • horse riding uses roots for medicinal purposes.
  • the rootstock is uneven in the shape of thick nodule, 6 ⁇ 8cm in length and 10 ⁇ 25cm in diameter.
  • the outer surface is brown or black with several large streaks on the top of the rootstock.
  • the above-mentioned eye riding horse can be used without limitation such as cultivated or marketed, and can be used as it is, or can be used by drying. Examples of the drying method include a blanket, shade, hot air drying, Can be used.
  • horse riding horse extract in the present invention means an extract obtained by extracting horse riding horse with water, an organic solvent or a combination thereof.
  • extract used in the present invention refers to an extract obtained by extracting a natural substance, a diluted solution or a concentrate of the extract, a dried product obtained by drying the extract, a preparation or a purified product of the extract, , The extract itself and extracts of all the formulations that can be formed using the extract.
  • the method for producing the extract is not particularly limited, and may be extracted according to a method commonly used in the art.
  • the extraction method include hydrothermal extraction method, ultrasonic extraction method, filtration method, reflux extraction method, immersion extraction method, high temperature and high pressure steam extraction method, etc. These methods can be performed alone or in combination of two or more methods have.
  • the kind of the extraction solvent used for extracting the natural substance in the present invention is not particularly limited, and any solvent known in the art can be used.
  • Particular examples of the extraction solvent is water, alcohol or the like, and mixed solvents of the foregoing, when using an alcohol as a solvent is preferably 1- C 4 alcohol, more preferably to extraction with methanol or ethanol And most preferably water, extracts from 30% to 80% methanol (v / v), and 30% to 80% ethanol (v / v).
  • the most preferable extraction solvent is preferably 2 to 20 times the dry weight of the horse riding horse.
  • eyes riding extract sejeol to the eyes of riding into the extraction vessel, water, 1- C 4 alcohol or mixtures thereof, preferably from 30 to 70% by volume aqueous ethanol solution into a constant temperature . ≪ / RTI >
  • the above method is not limited to the method of manufacturing the horse riding extract as an example, and the horse riding extract of the present invention includes all the horse riding extracts manufactured according to the methods known in the art or similar technical fields .
  • an aqueous solution of 30 to 70% by volume ethanol is used as an extraction solvent for eye riding, an ingredient having excellent skin whitening, specifically tyrosinase inhibiting activity and melanin pigment formation inhibiting activity desired by the present invention is obtained So that it is particularly preferable.
  • fraction in the present invention means a product obtained by a fractionation method of separating a specific component or a group of specific components from a mixture containing various components.
  • the fractionation method for obtaining the fraction in the present invention is not particularly limited and may be carried out according to a method commonly used in the art.
  • a method in which a fraction obtained from the above extract is obtained by treating a predetermined substance with an extract obtained by extracting a natural substance there can be mentioned a method in which a fraction obtained from the above extract is obtained by treating a predetermined substance with an extract obtained by extracting a natural substance
  • the kind of the fraction solvent used for obtaining the fraction in the present invention is not particularly limited, and any solvent known in the art can be used.
  • Non-limiting examples of the fraction solvent include polar solvents such as water, alcohol and the like; And non-polar solvents such as hexane, ethyl acetate, chloroform and dichloromethane. These may be used alone or in combination of two or more.
  • polar solvents such as water, alcohol and the like
  • non-polar solvents such as hexane, ethyl acetate, chloroform and dichloromethane. These may be used alone or in combination of two or more.
  • C 1-4 alcohol is preferably used.
  • the fractions according to the present invention are obtained by dissolving the horse riding extract in water and then fractionating the mixture using a nonpolar organic solvent and a solvent with an increased polarity.
  • a nonpolar organic solvent and a solvent with an increased polarity For example, hexane, dimethylformamide, ethyl acetate and butanol are dissolved in an organic solvent ≪ / RTI >
  • the eye-riding horse-riding extract may be a dichloromethane fraction obtained by fractionating an aqueous solution of an aqueous ethanol solution of 30 to 70% by volume of horse riding horse race with hexane and water, and fractionating the obtained water fraction with dichloromethane.
  • the dichloromethane fraction has superior tyrosinase inhibitory effect than the crude extract of ethanol aqueous solution or other fractions thereof.
  • the horse riding extract, fraction, and compounds represented by Chemical Formulas 1 to 4 inhibit tyrosinase activity in tyrosinase enzyme experiments. Furthermore, it has an excellent effect of inhibiting melanin production in melanin accumulation-induced cell models and inhibiting tyrosinase activity in melanocytes. And can be usefully used as a cosmetic composition for skin whitening.
  • the compound selected from the compounds represented by formulas (1) to (4) may be a single compound or at least one compound.
  • the present invention provides a cosmetic composition for skin whitening comprising a compound selected from the compounds represented by Formulas (1) to (4) as an active ingredient.
  • the eye-sight equine horse extract, fraction or active ingredient isolated therefrom is preferably contained in an amount of 0.01 to 95% by weight, more preferably 1 to 80% by weight, based on the total weight of the cosmetic composition.
  • the content is less than 0.01% by weight, the effect of improving skin whitening may be insignificant.
  • the rate of effect increase relative to the usage amount is low, which may be uneconomical.
  • the cosmetic composition of the present invention may further contain conventional auxiliary agents and carriers such as antioxidants, stabilizers, solubilizers, vitamins, pigments, fragrances and the like which are conventionally used in cosmetic compositions, in addition to the above-mentioned effective ingredients.
  • the cosmetic composition may further contain an auxiliary component such as glycerin, butylene glycol, polyoxyethylene hardened castor oil, tocopheryl acetate, citric acid, panthenol, squalane, sodium citrate, allantoin and the like .
  • the cosmetic composition of the present invention is basically applied to the skin, it can be prepared into any formulation conventionally produced by referring to the cosmetic composition of the related art.
  • they may be formulated as solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations and sprays, But is not limited thereto. More specifically, it can be manufactured in the form of a soft lotion, a nutritional lotion, a nutritive cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a mask pack, a spray or a powder.
  • the carrier component may include an animal oil, vegetable oil, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, have.
  • the carrier component may include lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder and the like. Particularly in the case of a spray, a mixture of chlorofluorohydrocarbons, propane / Propane, dimethyl ether, and the like.
  • the carrier component may include a solvent, a solubilizing agent, an emulsifying agent, and the like.
  • a solvent e.g., water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, Glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, fatty acid esters of sorbitan, and the like.
  • the formulation of the present invention is a suspension
  • a liquid diluent such as water, ethanol, propylene glycol or the like as a carrier component
  • Suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester
  • the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, and the like.
  • the present invention relates to a method for the production of cimicifuga dahurica extract or fractions thereof as an active ingredient for the treatment or prevention of a disease associated with tyrosinase overexpression or melanin overgrowth.
  • diseases associated with tyrosinase overexpression or melanin overproduction may be selected from the group consisting of skin cancer, melanoma, hypercholesterolemia, skin pigmentation, freckles, nevi, ectopic mongolian spots, have.
  • the eye-riding horse-riding extract may be an eye ridge-root extract.
  • the eyes riding extract may be water, alcohol or a C 1- 4 can be extracted with a mixed solvent thereof, and, preferably, riding eyes 30 to 70% by volume ethanol aqueous solution extract.
  • the eye-riding horse-drawn fraction may be a dichloromethane fraction obtained by fractionating a 30-70 vol% ethanol aqueous solution extract of horse riding horse race with hexane and water, and fractionating the obtained water fraction with dichloromethane.
  • the active ingredient effective for treating or preventing diseases associated with over-expression of tyrosinase or melanin over-production of eye-sight equine extract may be a compound represented by the following general formula (1): ## STR1 ## wherein the dichloromethane fraction .
  • the present invention provides a pharmaceutical composition for the treatment or prevention of a disease associated with tyrosinase overexpression or melanin excess production comprising a compound selected from the compounds represented by Chemical Formulas 1 to 4 as an active ingredient.
  • the pharmaceutical composition according to the present invention may be formulated into various forms according to conventional methods.
  • it can be formulated into oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions and syrups, and can be formulated in the form of external preparations, suppositories, and sterilized injection solutions.
  • the composition of the present invention may be most preferably provided in the form of an external preparation for skin. Specifically, it can be used in the form of a liquid preparation, an ointment, a cream, a lotion, a spray, a patch, a gel or an aerosol.
  • each formulation may further comprise a pharmaceutically acceptable carrier, excipient and diluent.
  • a pharmaceutically acceptable carrier such as syrups and aerosols
  • it may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, external preparations such as syrups and aerosols, and sterilized injection solutions according to a conventional method, and preferably used in the form of creams, gels, patches, An ointment preparation, an oral preparation, a lotion preparation, a liniment preparation, a pasta preparation or a cataplasma formulation.
  • conventional additives such as a preservative, a solvent for assisting drug penetration, a softening agent for ointment and cream, and the like, May contain conventional carriers.
  • Suitable agents known in the art are preferably, but not limited to, those disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA).
  • Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like.
  • the pharmaceutical composition When the pharmaceutical composition is formulated or formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used.
  • Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, , Lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate talc are also used.
  • liquid formulations for oral use include suspensions, solutions, emulsions and syrups.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like.
  • the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.
  • the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
  • the ingredients may be added to the active ingredient, either alone or in combination, with the ruminal extract or the active ingredient isolated therefrom.
  • the pharmaceutical composition of the present invention is useful as an effective ingredient or amount of a pharmaceutical composition that induces a biological or medical response in a tissue system, an animal or a human, as considered by a researcher, veterinarian, physician or other clinician, Or a therapeutically effective amount which is sufficient to induce relief. It will be apparent to those skilled in the art that the therapeutically effective dose and frequency of administration for the pharmaceutical compositions of the present invention will vary with the desired effect.
  • the optimal dosage to be administered can be readily determined by those skilled in the art, and can be readily determined by those skilled in the art and will vary depending upon factors such as the type of disease, the severity of the disease, the amount of active and other ingredients contained in the composition, the type of formulation, Sex and diet of the patient, the time of administration, the route of administration and the rate of administration of the composition, the duration of the treatment, the drugs used concurrently, and the like.
  • the pharmaceutical compositions of the present invention can be administered to a subject in a variety of routes. But are not limited to, intravenous, intraperitoneal, intramuscular, intraarterial, oral, intracardiac, intramedullary, intradermal, transdermal, intestinal, subcutaneous, sublingual or topical administration.
  • the pharmaceutical composition of the present invention may be administered in an amount of 1 to 10,000 mg / kg / day, preferably 1 to 200 mg / kg / day, and may be administered once a day or divided into several doses .
  • the present invention provides a quasi-drug for preventing or ameliorating diseases associated with over-expression of tyrosinase or production of melanin overgrowth, which comprises an active ingredient as an active ingredient separated from the horse's eye horse extract or an extract thereof.
  • quadsi-drug in the present invention means a fiber, a rubber product or the like used for the purpose of treating, alleviating, treating or preventing a disease of a human or an animal, Or products similar to those that are not machinery, preparations used for sterilization, insecticides and similar uses for the prevention of infectious diseases, for the purpose of diagnosing, treating, alleviating, treating, or preventing diseases of human beings or animals Means goods, machinery, or apparatus other than the apparatus, machinery or equipment of the commodity being used and used for the purpose of giving pharmacological effects to the structure and function of humans or animals.
  • composition of the present invention When used as a quasi-drug additive, the composition may be added as it is or may be used together with other quasi-drugs or quasi-drugs, and may be appropriately used according to a conventional method.
  • the amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use.
  • the present invention relates to a method for the production of cimicifuga dahurica extract or a fraction thereof as an active ingredient.
  • the eye ridoe extract or its fraction of the present invention can be used as a health functional food, a food additive or a dietary supplement.
  • the horse riding extract or its fraction is as described above.
  • the active ingredient of the eye-sight equine horse extract or its fraction effective for skin whitening may be a compound selected from the compounds represented by formulas (1) to (4).
  • a skin whitening food additive composition comprising, as an active ingredient, a compound selected from the compounds represented by Formulas (1) to (4).
  • the horse riding extract or its fraction When the above-mentioned horse riding extract or its fraction is used as a food additive, it may be suitably used according to a conventional method such that the horse riding extract or its fraction is added as it is or mixed with other foods or food ingredients.
  • the mixing amount of the above-mentioned horse riding extract or its fraction may suitably be changed according to the intended use (prevention, health or therapeutic treatment), and it is preferably 0.01 to 95% by weight based on the total weight of the food composition By weight, more preferably 1 to 80% by weight.
  • the content is less than 0.01% by weight, the skin whitening action may be insignificant.
  • the rate of effect increase relative to the usage amount is low, which may be uneconomical.
  • the eye-sight equine extract of the present invention or the active ingredient isolated therefrom is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material.
  • the active ingredient can be used in an amount exceeding the above range have.
  • examples of the food to which the horse riding extract of the present invention or its fractions can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, , Dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, vitamin complexes, and the like.
  • the food composition of the present invention When the food composition of the present invention is prepared as a beverage, it may contain additional ingredients such as various flavors or natural carbohydrates such as ordinary beverages.
  • natural carbohydrate include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweetening agents such as dextrin and cyclodextrin; Synthetic sweetening agents such as saccharin and aspartame, and the like can be used.
  • the natural carbohydrate is contained in an amount of 0.01 to 10% by weight, preferably 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.
  • the food composition of the present invention can be used as a food composition containing various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, Carbonation agents used in beverages, etc., and may include, but is not limited to, natural fruit juices, fruit juice beverages, and flesh for the manufacture of vegetable beverages. These components may be used independently or in combination.
  • the proportion of the above additives is not particularly limited, but is preferably within the range of 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.
  • the food composition of the present invention has no problem in terms of safety and can be taken for a long period of time.
  • the present invention exemplifies a method for producing a horse riding extract.
  • the eye riding extract according to the present invention can be prepared by incorporating horse riding in an aqueous solution of 30 to 70% by volume ethanol and extracting the mixture at 30 to 110 ° C.
  • the extraction temperature may be preferably 50 to 100 DEG C, and when extracted in the above range, a large amount of components effective for tyrosinase overexpression or inhibition of melanin overproduction can be extracted.
  • a method for preparing an extract which comprises fractionating the above-mentioned horse riding extract with hexane and water to obtain hexane fraction and water fraction; And a step of adding dichloromethane to the water fraction and fractionating to obtain a dichloromethane fraction.
  • the extracted horse ridoe extract is dissolved in water, and then hexane, dichloromethane , Ethyl acetate and butanol may be fractionated using a solvent whose polarity gradually increases in a non-polar solvent.
  • a particularly effective component for inhibiting tyrosinase overexpression or melanin overproduction is particularly preferred Do.
  • the present invention also relates to an active ingredient of an eye rumble extract or its fraction effective for skin whitening, comprising the steps of: separating the dichromate fraction of the eye rumberry extract, preferably the eye rumberry extract, into a single component; And a step of obtaining a compound represented by the following general formula (1) to (4).
  • the separation into a single component may be carried out by conventional methods known in the art, for example, silica gel column chromatography, thin layer chromatography, high performance liquid chromatography chromatography, and the like can be used.
  • the present invention also relates to a method for the treatment of hyperlipidemia, comprising administering to a subject having a disease associated with tyrosinase overexpression or melanin hyperreactivity, a compound selected from the above-mentioned eye rumberry extract, a fraction thereof or a compound represented by any one of Chemical Formulas 1 to 4, A method for treating diseases associated with overexpression of synechia or melanin overgrowth.
  • diseases associated with tyrosinase overexpression or melanin overproduction may be selected from the group consisting of skin cancer, melanoma, hypercholesterolemia, skin pigmentation, freckles, nevi, ectopic mongolian spots, have.
  • administering means providing a pharmaceutical composition of the present invention to a subject in any suitable manner.
  • the compound selected from the eye ridoe extract of the present invention, a fraction thereof, or a compound represented by any one of Chemical Formulas 1 to 4 is useful as an agent for inducing a biological or medicinal response in a tissue system, an animal, or a human by a researcher, a veterinarian, Effective amount of the active ingredient or pharmaceutical composition, that is, a therapeutically effective amount which is an amount that induces the reduction of symptoms of the disease or disorder being treated. It will be apparent to those skilled in the art that the therapeutically effective dose and the number of administrations of the compound selected from the eye ridin extract of the present invention, its fractions or the compounds represented by Formulas 1 to 4 will vary depending on the desired effect.
  • the optimal dosage to be administered can be readily determined by those skilled in the art, and can be readily determined by those skilled in the art and will vary depending upon factors such as the type of disease, the severity of the disease, the amount of active and other ingredients contained in the composition, the type of formulation, Sex and diet of the patient, the time of administration, the route of administration and the rate of administration of the composition, the duration of the treatment, the drugs used concurrently, and the like.
  • the compound selected from the above-mentioned eye ridoe extract of the present invention, a fraction thereof or a compound represented by any one of Chemical Formulas 1 to 4 may be administered to a subject in various routes. But are not limited to, intravenous, intraperitoneal, intramuscular, intraarterial, oral, intracardiac, intramedullary, intradermal, transdermal, intestinal, subcutaneous, sublingual or topical administration.
  • the compound selected from the eye ridoe extract of the present invention, the fraction thereof or the compound represented by any one of Chemical Formulas 1 to 4 is administered in an amount of 1 to 10,000 mg / kg / day, preferably 1 to 200 mg / kg / day It can be administered once a day or divided into several doses.
  • the present invention relates to a method for the production of cimicifuga a composition for use in the prevention or treatment of tyrosinase overexpression or a disease associated with melanin overgrowth, comprising a compound selected from the group consisting of dahurica extract, a fraction thereof, and a compound represented by any one of Chemical Formulas 1 to 4.
  • the invention also tyrosinase over expression or eyes for the manufacture of a medicament for the prevention or treatment of diseases which are associated with melanin excessive generation of riding (Cimicifuga dahurica) extract, its fractions or formulas (1) to use of a compound of the formula (4) Lt; / RTI >
  • the present invention relates to a method for the production of cimicifuga dahurica extract, a fraction thereof, or a compound represented by any one of Chemical Formulas (1) to (4) for inhibiting tyrosinase activity.
  • the present invention relates to a method for the production of cimicifuga dahurica extract, a fraction thereof, or a compound represented by any one of Chemical Formulas (1) to (4).
  • the inhibitory effect of tyrosinase activity was measured using the extract of Example 1. Specifically, the eye-riding extracts of Example 1 were prepared at concentrations of 8, 40, and 200 ⁇ g / ml, respectively, and used as a control group.
  • the tyrosinase enzyme from mushroom was dissolved in 50 mM phosphate buffer at a concentration of 250 U / ml and the substrate L-DOPA was used at 5 mM in the experiment. 20 ⁇ l of the tyrosinase enzyme, 100 ⁇ l of the prepared sample, 40 ⁇ l of the phosphate buffer solution and 40 ⁇ l of L-DOPA were added to a 96-well plate and incubated at 37 ° C. for 10 minutes, and the absorbance was measured at 475 nm. Respectively.
  • the untreated group did not inhibit tyrosinase enzyme, and the extract of Example 1 inhibited tyrosinase activity in a concentration-dependent manner.
  • the fraction was fractionated by the method of Example 2, and the obtained fraction was evaluated for inhibition of tyrosinase activity.
  • the dichloromethane fraction, ethyl acetate fraction, butanol fraction and water fraction of Example 2 were dissolved in 5% DMSO at concentrations of 4, 20 and 100 ⁇ g / ml, respectively, to prepare samples.
  • As a control group no treatment group was used.
  • the tyrosinase enzyme from mushroom was dissolved in 50 mM phosphate buffer at a concentration of 250 U / ml and the substrate L-DOPA was used at 5 mM in the experiment.
  • the untreated group did not inhibit the tyrosinase enzyme, and tyrosinase activity inhibition was particularly excellent in the dichloromethane fraction, and the inhibitory activity tended to increase in a concentration-dependent manner .
  • the fractions obtained were purified by silica gel column chromatography (Kieselgel 60, 70-230, and 230-400 mesh, Merck , Darmstadt, Germany) and YMC RP-18 resins column chromatography to isolate the active components from each fraction.
  • the tyrosinase inhibitory activity was evaluated using the substances separated from each fraction.
  • the active ingredient having excellent tyrosinase inhibitory activity was identified as four single components separated from the dichloromethane fraction.
  • Fig. 3 it was confirmed that the active ingredients 1 to 4 isolated from the dichloromethane fraction were superior in tyrosinase inhibitory activity to arbutin, which is a positive control group.
  • Mouse melanin cell lines were purchased from American Cell Bank and cultured in Dulbecco's Modified Eagle's Medium medium supplemented with 10% fetal bovine serum and 1% penicillin. The cells were cultured at 37 ° C and 5% CO 2 and were used for experiments when the cells were stabilized by subculturing at least two times.
  • MTT (3- (4,5-dimethylthiazol-2-yl) -2, 3-diol, 5-diphenyl tetrazolium bromide) assay.
  • the cultured B16F10 cells were inoculated into a 48-well plate at a concentration of 5 ⁇ 10 4 cells / ml using DMEM medium, cultured in an incubator for 24 hours, and then the culture medium was changed.
  • the extracts of Example 1 were treated at concentrations of 8, 40 and 200 ⁇ l / mL, respectively, and the fractions of Example 2 were treated at concentrations of 4, 20 and 100 ⁇ l / mL, respectively.
  • Components 1 to 4 isolated from the dichloromethane fraction were treated at a concentration of 0.4, 2, 10 ⁇ M, and cell viability was measured using MTT buffer after 48 hours.
  • the control group was the untreated group.
  • the experiment was performed three times, and the cell viability was calculated according to the following formula 1, and the results are shown in FIGS. 4 to 6.
  • Cell survival rate (%) (absorbance of sample treated group / absorbance of control group) x 100
  • the extract of Example 1 and the fraction of Example 2 showed no cytotoxicity even at a high concentration.
  • the dichloromethane fraction of Example 2 showed a cell survival rate of 90% at a high concentration (100 ⁇ l / mL), whereas the components 1 to 4 isolated from the dichloromethane fraction had a high concentration (10 ⁇ M as a single component) It is expected that the toxicity is not toxic by the active ingredient according to the present invention.
  • the amount of melanin produced in the B16F10 cells cultured in Test Example 3 was analyzed . Specifically, after the inoculation of B16F10 cells in 6-well plates in density of 1 ⁇ 10 5 cell / well and cultured for 24 hours.
  • Example 1 After the incubation, the extracts of Example 1 were treated at a concentration of 8, 40 and 200 ⁇ l / mL, the fractions of Example 2 were treated at concentrations of 4, 20 and 100 ⁇ l / mL, respectively, and the dichloromethane Components 1 to 4 isolated from the fractions were co-treated with 100 nM of? -MSH at a concentration of 2, 10 ⁇ M and cultured for 48 hours. MSH and ⁇ -MSH + ⁇ -MSH + 10-mM arbutin-treated groups were compared. Then, the cells were separated and centrifuged at 4 ° C and 1,000 rpm for 10 minutes to collect only the cells.
  • Cells were inoculated with 1 M NaOH 300 containing 10% DMSO and incubated at 80 ° C for 2 hours. Then, 200 ⁇ l of the culture was added to a 96-well plate, and the absorbance at 400 nm was measured.
  • the active ingredient isolated from the eye-riding extract of Example 1, the fraction of Example 2 and the dichloromethane fraction according to the present invention was induced from? -MSH in B16F10 cells Melanin production was inhibited in a concentration-dependent manner and statistically significant.
  • the compounds represented by formulas (1) to (4) as the active ingredients exhibited excellent melanin production inhibitory effect even in comparison with arbutin, which is a positive control.
  • the horse riding extract according to the present invention and the active ingredient isolated therefrom inhibit tyrosinase activity, inhibit melanin production in melanin-producing cells, are superior to water extracts, Compounds represented by Formulas (1) to (4), which are the active ingredients isolated, exhibit remarkably improved inhibition of tyrosinase activity and inhibition of melanin formation even in comparison with arbutin. Therefore, the eye riding extract and the fractions thereof according to the present invention are effective as a skin whitening cosmetic composition or a pharmaceutical composition for preventing or treating skin pigmentation diseases.
  • 0.5% by weight of an active ingredient for eye riding or an active ingredient in eye rinse 4.0% by weight of glycerin, 3.5% by weight of petroleum jelly, 2.1% by weight of triethanolamine, 5.3% by weight of liquid paraffin, 3.0% by weight squalane, 2.6% by weight of beeswax, 3.2% by weight of polysorbate 60, 1.0% by weight of a carboxyl vinyl polymer, 3.1% by weight of sorbitan sesquioleate, a small amount of fragrance, a small amount of preservative and a remaining amount of purified water are mixed to prepare a nutritional cream by a conventional method.
  • a cleansing body cleanser is prepared by a conventional method.
  • the tablets are prepared by mixing 10 mg of the horse riding extract or eye-sight-riding active ingredient, 100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate, followed by tableting according to the usual preparation method of tablets.
  • capsules were prepared by mixing 10 mg of the horse riding extract or eye riding active ingredient, 3 mg of crystalline cellulose, 14.8 mg of lactose and 0.2 mg of magnesium stearate, and filling the mixture in gelatin capsules.
  • liquid preparations 20 mg of the horse riding extract or eye riding active ingredient, 10 g of isomerized sugar, and 5 g of mannitol were added to purified water and dissolved, and the lemon flavor was added in an appropriate amount. Then, purified water was further added thereto, adjusted to a total volume of 100 mL, filled in a brown bottle, and sterilized to prepare a liquid preparation.
  • Vitamin B acetate, vitamin E, vitamin E, vitamin E, vitamin E, vitamin E, vitamin E, vitamin E, vitamin B, vitamin B, vitamin B, 10 g of biotin, 1.7 mg of nicotinic amide, 50 g of folic acid, 0.5 mg of calcium pantothenate, 1.75 mg of ferrous sulfate, 0.82 mg of zinc oxide, 25.3 mg of magnesium carbonate, 15 mg of potassium phosphate, 55 mg of calcium, 90 mg of potassium citrate, 100 mg of calcium carbonate, and 24.8 mg of magnesium chloride were mixed and granules were prepared, and a health food was prepared according to a conventional method. At this time, although the composition ratio of the vitamin and mineral mixture is relatively mixed with the ingredient suitable for health food, it may be arbitrarily modified.
  • the extract or its fraction according to the present invention inhibits tyrosinase activity and inhibits melanin production in melanin-producing cells, and thus has excellent skin whitening effect. Therefore, it is possible to prevent, improve and treat skin whitening and skin pigmentation diseases Cosmetics for pharmacy, external preparation for skin, quasi-drugs and food compositions.

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Abstract

La présente invention concerne une composition de blanchiment de la peau contenant un extrait de Cimicifuga dahurica ou une fraction associée en tant que principe actif et son utilisation.
PCT/KR2019/000789 2018-01-22 2019-01-18 Composition de blanchiment de la peau contenant un extrait de cimicifuga dahurica ou une fraction associée Ceased WO2019143197A1 (fr)

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KR20180007708 2018-01-22
KR10-2018-0007708 2018-01-22
KR10-2018-0071735 2018-06-22
KR1020180071735A KR20190089696A (ko) 2018-01-22 2018-06-22 눈빛승마 추출물 또는 이로부터 분리된 활성성분을 유효성분으로 포함하는 피부미백용 조성물

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Publication number Priority date Publication date Assignee Title
KR20090050856A (ko) * 2007-11-16 2009-05-20 학교법인 동의학원 승마 추출물의 분획추출물을 함유하는 미백화장료와 이의제조방법
KR20110002198A (ko) * 2009-07-01 2011-01-07 학교법인 동의학원 미백 활성성분을 포함하는 승마 추출물 및 그의 추출방법
KR20140145278A (ko) * 2013-06-12 2014-12-23 (주)하이메디코스 피부 수렴 및 탄력 효과를 갖는 승마 추출물, 산수유 추출물 및 현초 추출물을 함유하는 화장료 조성물.
KR20150019574A (ko) * 2013-08-14 2015-02-25 주식회사 엘지생활건강 피부 재생, 주름 개선, 항산화, 항염증 및 피부 미백용 조성물

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KR20110002198A (ko) * 2009-07-01 2011-01-07 학교법인 동의학원 미백 활성성분을 포함하는 승마 추출물 및 그의 추출방법
KR20140145278A (ko) * 2013-06-12 2014-12-23 (주)하이메디코스 피부 수렴 및 탄력 효과를 갖는 승마 추출물, 산수유 추출물 및 현초 추출물을 함유하는 화장료 조성물.
KR20150019574A (ko) * 2013-08-14 2015-02-25 주식회사 엘지생활건강 피부 재생, 주름 개선, 항산화, 항염증 및 피부 미백용 조성물

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