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WO2012173382A2 - Composition à usage externe pour l'épiderme, contenant du tanshinone ii a en tant que principe actif - Google Patents

Composition à usage externe pour l'épiderme, contenant du tanshinone ii a en tant que principe actif Download PDF

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Publication number
WO2012173382A2
WO2012173382A2 PCT/KR2012/004644 KR2012004644W WO2012173382A2 WO 2012173382 A2 WO2012173382 A2 WO 2012173382A2 KR 2012004644 W KR2012004644 W KR 2012004644W WO 2012173382 A2 WO2012173382 A2 WO 2012173382A2
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WIPO (PCT)
Prior art keywords
skin
composition
acid
active ingredient
tanshinone iia
Prior art date
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Ceased
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PCT/KR2012/004644
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English (en)
Korean (ko)
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WO2012173382A3 (fr
Inventor
이옥찬
염명훈
조가영
이진영
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Amorepacific Corp
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Amorepacific Corp
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Publication of WO2012173382A2 publication Critical patent/WO2012173382A2/fr
Publication of WO2012173382A3 publication Critical patent/WO2012173382A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0208—Tissues; Wipes; Patches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
    • A61Q1/02—Preparations containing skin colorants, e.g. pigments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
    • A61Q1/02—Preparations containing skin colorants, e.g. pigments
    • A61Q1/04—Preparations containing skin colorants, e.g. pigments for lips
    • A61Q1/06—Lipsticks

Definitions

  • the present invention relates to an external preparation composition for skin containing tanshinone IIA as an active ingredient.
  • Human skin is changed by a number of internal and external factors as it ages. That is, internally, the secretion of various hormones that regulate metabolism decreases, and the function of immune cells and the activity of cells decreases, thereby reducing the biosynthesis of immune proteins and constituent proteins necessary for living organisms. Due to the increase in the amount of ultraviolet rays reaching the surface of the sun's rays and further increase environmental pollution, free radicals and free radicals, such as free radicals, skin thickness, wrinkles, elasticity is reduced only In addition, skin problems frequently occur, causing a variety of changes, including increasing blemishes, freckles, and blotch. In addition, as the skin ages, capillaries are reduced or deformed, resulting in poor skin circulation, resulting in dull skin color, and rough skin.
  • melanin which is produced by the action of various enzymes such as tyrosinase in melanocytes in the human body.
  • melanin pigment is influenced by genetic factors, physiological factors related to hormone secretion, stress, and environmental factors such as ultraviolet irradiation.
  • Melanin pigment which is produced from melanocytes of the skin of the body, is a phenolic polymer material having a complex form of black pigment and protein.
  • melanin produced by stress stimulation inside and outside the skin is a stable substance that does not disappear until it is discharged to the outside through skin keratinization even if the stress disappears.
  • melanin causes hyperpigmentation such as blemishes, freckles, and spots, resulting in cosmetically bad results.
  • Asian women prefer white and clean skin like white jade, and this is an important standard of beauty, increasing the demand for treatment and cosmetic problems for hyperpigmentation.
  • the most important function of the outermost epidermis of the skin is to protect the skin from various external stimuli (chemicals, air pollutants, dry environment, physical and chemical stimulating factors such as ultraviolet rays). It is a protective function that prevents excessive divergence of moisture through the body, and this protective function can be maintained only when the stratum corneum composed of keratinocytes is normally formed.
  • the outermost stratum corneum (horney layer) of the epidermis is formed from keratinocytes and is composed of the differentiated keratinocytes and the surrounding lipid layer. Keratinocytes are characteristic cells whose basal cells, which continuously proliferate in the epidermal layer, undergo morphological and functional changes in stages and rise to the surface of the skin.
  • keratinization Exfoliated and new keratinocytes take over their functions. This repetitive sequence of changes is called “epidermal differentiation” or “keratinization.” During the keratinization process, keratinocytes form the stratum corneum by generating natural moisturizing factor (NMF) and intercellular fat (ceramide, cholesterol, fatty acid), making the stratum corneum firm and flexible. It has a function as).
  • NMF natural moisturizing factor
  • ceramide, cholesterol, fatty acid intercellular fat
  • the turnover rate of the stratum corneum is slowed, the lipid synthesis ability of the keratinocytes is degraded, or the epidermis is normal in the epidermis. Due to poor cell division, maturation and differentiation, the amount of moisturizing factors and lipids in the stratum corneum is reduced, so that humans with skin with a condition that is unable to maintain normal stratum corneum function, that is, the skin barrier function is degraded There is a growing trend.
  • the skin Due to the abnormal division and differentiation of epidermal cells, the skin causes various skin diseases such as dry skin, atopy and psoriasis, and these diseases can alleviate the symptoms slightly by using a conventional moisturizer having only water retention function. However, it is difficult to expect radical healing.
  • the present invention aims to provide a skin external preparation composition having a skin whitening effect, a skin moisturizing effect, a skin color improving effect, and a skin clarifying effect while being able to safely use without side effects on the skin to solve the above problems.
  • an embodiment of the present invention is an external preparation composition for skin containing tanshinone IIA represented by the following formula (1), an isomer thereof, a precursor thereof, a salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
  • tanshinone IIA represented by the following formula (1), an isomer thereof, a precursor thereof, a salt thereof, a hydrate thereof, or a solvate thereof as an active ingredient.
  • the content of the tanshinone IIA may be from 0.0001 to 10% by weight based on the total weight of the composition.
  • the composition may be an external skin composition for skin whitening having an effect of inhibiting melanin production.
  • the composition may be a skin external preparation composition for moisturizing the skin having an effect of promoting differentiation of keratinocytes.
  • the composition may be a skin external preparation composition for moisturizing the skin having the effect of increasing the expression of transglutaminase (transglutaminase) of the skin cell line.
  • the composition may be a skin external preparation composition for improving skin color and improving skin transparency having an effect of increasing nitric oxide (Nitric Oxide, NO) production in vascular endothelial cells.
  • Nitric Oxide Nitric Oxide
  • the composition may be a skin external preparation composition for improving skin color and improving skin clarity having an effect of improving peripheral blood circulation.
  • the composition may be a pharmaceutical composition.
  • the pharmaceutical composition may be a formulation selected from the group consisting of drops, ointments, lotions, gels, creams, patches, sprays, suspensions and emulsions.
  • the composition may be a cosmetic composition.
  • the cosmetic composition is a softening lotion, nourishing lotion, lotion, body lotion, nutrition cream, massage cream, moisturizing cream, hand cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, It may be a formulation selected from the group consisting of gels, patches, lipsticks, makeup bases and foundations.
  • composition of the present invention may have a skin whitening effect, a skin moisturizing effect, a skin color improving effect, and a skin transparency improving effect.
  • One embodiment of the present invention provides a topical skin composition containing tanshinone IIA, an isomer thereof, a precursor thereof, a salt thereof, a hydrate thereof or a solvate thereof as an active ingredient.
  • Said “isomers” include in particular optical isomers, form isomers, positional isomers (particularly tautomers) or geometric isomers.
  • the precursor refers to a chemical change of a compound to control physical and chemical properties.
  • the precursor itself does not exhibit physiological activity, but may be converted to the original compound by the action of chemical or enzymes in the body after administration, thereby exerting an effect. .
  • the salts refer to pharmaceutically acceptable salts, wherein the "pharmaceutically acceptable” is generally useful for preparing safe, nontoxic, biologically or otherwise desirable pharmaceutical compositions, and is useful for humans as well as for veterinary use. It is also useful for pharmaceutical use.
  • salts refers to salts that are pharmaceutically acceptable and have the desired pharmacological activity as defined above.
  • Such salts include (1) inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like, or organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, stone Sinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3- (4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-n
  • hydrate means “pharmaceutically acceptable hydrate”.
  • the "hydrate” is present when the compound of the present invention contains water.
  • Hydrates may contain one or more water molecules per molecule of the compounds of the invention. Exemplary non-limiting examples include monohydrates, dihydrates, trihydrates, and tetrahydrates. Hydrates may contain one or more compound molecules of the invention per one water molecule. Exemplary non-limiting examples include semihydrates.
  • water may be retained in the crystal in a variety of ways such that water molecules may occupy lattice positions within the crystal, or may form bonds with salts of the compounds described above.
  • a luggage must be "acceptable” in the sense that it is not harmful to its reception.
  • solvate means “pharmaceutically acceptable solvate” and “solvate” means that the compound of the present invention contains one or more pharmaceutically acceptable solvents.
  • the solvate may contain one or more solvent molecules for one molecule of the compound of the present invention, or may contain one molecule of the compound of the present invention for one molecule of the solvent.
  • the solvent may be retained in the crystal in various ways such that water molecules may occupy a lattice position in the crystal, or may form bonds with salts of the compounds described above.
  • Tanshinone IIA may be represented by the following [Formula 1].
  • the content of the tanshinone IIA may be 0.0001 to 10% by weight based on the total weight of the composition. When the content is less than 0.0001% by weight, the efficacy is weak, and when it exceeds 10% by weight, there is no apparent increase in efficacy due to the increase in content, which is not economical.
  • the content of tanshinone IIA is 0.0005 to 9.5% by weight, 0.001 to 9% by weight, 0.005 to 8.5% by weight, 0.01 to 8% by weight, 0.05 to 7.5% by weight, 0.1 based on the total weight of the composition. It may be from 7% by weight or 0.5 to 6.5% by weight.
  • the tanshinone IIA can also be produced by organic synthesis, or can be obtained from the extract of Salvia.
  • Dansam is a perennial herbaceous plant of Lamiaceae (Sun-Hyun, Labiatae), which has tinnitus such as red ginseng, powdered horseweed, and sheep oil. Root stocks are short and coarse and usually have stem marks at their ends. Roots are long cylindrical, divided into several, the outer side is reddish brown or dark reddish brown with rough and vertical wrinkles.
  • Salvia mimics blood circulation, removes blood, and relieves limb pain. Pharmacological actions include increased cardiovascular blood flow, decreased serum lipids, improved microcirculation, antithrombotic action, sedative action, antimicrobial action, immune enhancement, anticancer action, and hypoglycemic effect.
  • Salvia extract can be obtained, for example, from the root.
  • the extract as defined in the present invention is characterized in that the crude extract, polar solvent soluble extract or non-polar solvent soluble extract.
  • the crude extract includes water containing purified water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably a water and ethanol mixed solvent, and more preferably 75 to 100% ethanol extract.
  • the polar solvent soluble extract is an extract selected from water, methanol, butanol or a mixed solvent thereof, preferably n-butanol, and the non-polar solvent soluble extract is hexane, chloroform, methylene chloride, ethyl acetate, glycerin, Extracts soluble in propylene glycol, butylene glycol or ether, preferably methylene chloride or ethyl acetate.
  • the extract is more preferably, after primary extraction using any one or more of a polar solvent containing anhydrous and hydrous lower alcohols having 1 to 4 carbon atoms, acetone and butylene glycol, and then sequentially ethyl acetate, diethyl acetate Extraction may be performed through secondary extraction using any one or more of a low polar solvent including diethyl ether, benzene, chloroform and hexane.
  • an extraction solvent water, anhydrous and hydrous lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, normal propanol, normal butanol), a mixture of water and lower alcohol, acetone, 1,3-butylene glycol, isopropanol 5 to 20 times the volume of the polar solvent and their mixed solvent to be added, based on the dry weight of the pulverized product of the red ginseng root, immersion extraction and filtration, and the filtrate is concentrated under reduced pressure.
  • an extraction solvent water, anhydrous and hydrous lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, normal propanol, normal butanol), a mixture of water and lower alcohol, acetone, 1,3-butylene glycol, isopropanol 5 to 20 times the volume of the polar solvent and their mixed solvent to be added, based on the dry weight of the pulverized product of the red ginseng root, immersion extraction and filtration, and the filtrate is concentrated under reduced pressure.
  • Extraction method is carried out for about 12 to 96 hours in the case of cold needle, or left for 3 to 20 days at room temperature of 4 to 25 °C using an anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms, ethyl acetate or diethyl ether as a solvent
  • the active ingredient can be extracted by aging.
  • warm needle it is different depending on the type and temperature of the extraction solvent, but it is preferably performed at a temperature close to the reflux temperature of the solvent for about 5 to 24 hours.
  • the extraction is subjected to filtration
  • the filtration is a process of removing the suspended solid particles from the extract, by filtering the particles using cotton, nylon, or the like, ultrafiltration, cryofiltration, centrifugation, etc. This is not restrictive.
  • the step of drying the filtrate includes, but is not limited to, freeze drying, vacuum drying, hot air drying, spray drying, reduced pressure drying, foam drying, high frequency drying, infrared drying and the like. If desired, a process of grinding the final dried extract may be added.
  • the external preparation composition for skin generally is a concept encompassing the overall composition used for external application of the skin, and may be, for example, a pharmaceutical composition or a cosmetic composition.
  • the pharmaceutical composition may be formulated as a parenteral dosage form in solid, semi-solid or liquid form by adding a commercially available inorganic or organic carrier, excipient and diluent with tanshinone IIA as an active ingredient.
  • the preparation may be a transdermal dosage form selected from the group consisting of drops, ointments, lotions, gels, creams, patches, sprays, suspensions and emulsions, but is not limited thereto.
  • Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, oligosaccharides, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • composition according to the present invention when used as a pharmaceutical composition, it may further contain pharmaceutical supplements and other therapeutically useful substances such as preservatives, stabilizers, hydrating or emulsifiers, salts or buffers for controlling osmotic pressure. And may be formulated in parenteral dosage forms according to conventional methods.
  • the actual dosage of the active ingredient should be determined in light of several relevant factors such as the severity of the symptom, the route of administration chosen, the age, sex, weight and health of the subject.
  • the dosage of the active ingredient ranges from 0.001 ⁇ g / kg / day to approximately 2000 ⁇ g / kg / day. More preferred dosages are 0.5 ⁇ g / kg / day to 2.5 ⁇ g / kg / day.
  • Topical administration may be administered once a day or may be divided several times.
  • the cosmetic composition may include, for example, a basic cosmetic, makeup cosmetics, cosmetics for the body, the formulation is not particularly limited and may be appropriately selected as desired.
  • the cosmetic composition is formulated into solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, sprays, and the like. It may be, but is not limited thereto.
  • a cosmetic composition such as (O / W) type, basic cosmetics such as water-in-oil (O / W) type, color cosmetics such as lipstick, makeup base or foundation, shampoo, rinse, body cleanser and the like.
  • the cosmetic composition contains a cosmetically acceptable medium or base.
  • a cosmetically acceptable medium or base for example emulsions, suspensions, microemulsions, microcapsules, microgranules or ionic (liposomes) obtained by dispersing an oil phase in a solution, gel, solid or pasty anhydrous product, aqueous phase, and / or It may be provided in the form of a nonionic vesicle dispersant or in the form of a cream, skin, lotion, powder, ointment, spray or cone stick.
  • These compositions can be prepared according to conventional methods in the art.
  • a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.
  • liquid carrier diluents such as water, ethanol or propylene glycol
  • suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
  • the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide
  • cellulose derivatives polyethylene glycols
  • silicones bentonites
  • silicas talc or zinc oxide
  • lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.
  • the carrier component is 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 or ethoxylated glycerol fatty acid esters and the like can be used.
  • the cosmetic composition may further contain a thickener.
  • the thickener included in the cosmetic composition of the present invention is methyl cellulose, carboxy methyl cellulose, carboxy methyl hydroxy guanine, hydroxy methyl cellulose, hydroxyethyl cellulose, carboxy vinyl polymer, polyquaternium, cetearyl alcohol, stearic acid, Carrageenan and the like can be used, and preferably, at least one of carboxy methyl cellulose, carboxy vinyl polymer and polyquaternium can be used, and most preferably, carboxy vinyl polymer.
  • the cosmetic composition may contain a variety of suitable bases and additives as necessary, the type and amount of these components can be easily selected by the inventors. If necessary, it may contain an acceptable additive, for example, may further include components such as preservatives, pigments, additives and the like conventional in the art.
  • Preservatives may be specifically phenoxyethanol (Phenoxyethanol) or 1,2-hexanediol (1,2-Hexanediol) and the like, fragrance may be artificial flavors and the like.
  • the cosmetic composition may include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids, and seaweed extracts.
  • Other components that may be added include fats and oils, moisturizers, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, fungicides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, flavorings, Blood circulation accelerators, cooling agents, restriction agents, purified water and the like.
  • the compounding component which may be added other than this is not limited to this, Moreover, any of the above components can be mix
  • Salvia roots were washed with purified water, dried and triturated. 200 g of granulated salvia root powder was added to 1 liter of an aqueous 70% ethanol solution, and extracted by boiling in an extractor equipped with a cooling condenser for 12 hours, followed by filtration with a 300 mesh filter cloth. The filtrate was left to mature at 4-15 ° C. for 7 days and then filtered through Whatman No. 2 filter paper. Thereafter, the extract was added to a 3-liter separatory funnel, and 1 liter of ethyl acetate was added thereto, shaken well, the mixture was thoroughly separated, and the upper layer (ethyl acetate layer) was taken. The lower layer (water layer) was again extracted twice with a separatory funnel. The combined upper layers were combined, concentrated under reduced pressure at 50 ° C. using a distillation apparatus equipped with a cooling condenser, and dried to obtain a dry weight 45.5 g of Dansam root extract.
  • mice derived from C57BL / 6 mice (Dooley, TP et al, Skin pharmacol, 7, pp 188-200) were placed in DMEM (Dulbeccos modified Eagles media) in 10% fetal placental serum, 100 nM 2-O-tetradecanoylphorbol-13-ate and 1 nM cholera toxin were incubated at 37 ° C. and 5% CO 2.
  • the cultured Mel-Ab cells were separated with 0.25% trypsin-EDTA, the cells were incubated at a concentration of 105 cells / well in a 24-well plate, and 1 ppm, 10 ppm of tanshinone IIA for 3 consecutive days from the second day. Culture was added.
  • the tanshinone IIA of the present invention showed an excellent melanin production inhibition rate, and showed a melanin production inhibition rate similar to that of hydroquinone. Through this it was found that the tanshinone IIA of the present invention has an excellent whitening effect.
  • UVB ultraviolet light
  • the difference in skin color ( ⁇ L *) between the start point of application and the end point of application of each test substance was calculated according to the following equation, which is shown in Table 3 below.
  • the whitening effect is determined by comparing ⁇ L * between the sample application site and the control site. When ⁇ L * value is about 2, the whitening effect of the deposited pigment is clear, and when it is about 1.5 or more, the whitening effect is determined. Can be.
  • the tanshinone IIA of the present invention shows a similar degree of skin color brightness as hydroquinone. This is because the tanshinone IIA improves the pigmentation produced by ultraviolet light, thereby brightening the skin color.
  • the amount of Cornified Envelop (CE) produced during the differentiation of keratinocytes and human skin cell lines (HaCaT) was measured and tested by absorbance to see the effect of promoting the differentiation of tanshinone IIA.
  • the human keratinocytes (Human Epidermal Keratinocytes, catalog # C-020-25P, Cascade Biologics Inc., Portland, Oregon (OR) USA) were cultured in the flask and attached to the bottom.
  • the test substances of Table 4 were added to the culture solution at the concentrations shown in Table 4, and the cells were incubated for 5 days until the cells grew to 70-80% of the floor area.
  • the cells were harvested and washed with PBS (phosphate buffered saline), followed by 10 mM Tris-HCl (Tris-HCl) containing 2% Sodium Dodecyl Sulfate (SDS) and 20 mM Dithiothreitol (DTT).
  • PBS phosphate buffered saline
  • Tris-HCl Tris-HCl
  • SDS 2% Sodium Dodecyl Sulfate
  • DTT Dithiothreitol
  • tanshinone IIA As shown in Table 4, tanshinone IIA according to the present invention can be seen to promote differentiation in keratinocytes. Therefore, tanshinone IIA has a skin moisturizing effect.
  • Transglutaminase is a kind of skin differentiation indicator, which helps to form the formed corneal envelope (CE) produced by the differentiation of the human skin cell line (HaCaT) and cell differentiation.
  • CE corneal envelope
  • HaCaT Human skin cell lines (HaCaT) (prepared from Dr. NE Fusenig, Deutsches Krebsforschungstechnik, Heidelberg, Germany) were placed 5 ⁇ 10 4 into each well of a 96 well cell culture plate and attached for 24 hours. After treatment with the test substance to the attached skin cell line, after 2 days, the medium was removed, and stored in a -20 °C refrigerator. After freeze-thawing was repeated twice, the cells treated with material were destroyed, and then treated with acetone: ethanol (1: 1, v / v) stored at -20 ° C and left at 4 ° C for 30 minutes. Fix the cells.
  • tanshinone IIA according to the present invention showed a two-fold increase compared to the control, it can be seen that the amount is expressed more than the control. Therefore, it was found that tanshinone IIA according to the present invention improves the expression of transglutaminase.
  • Example 1 containing tanshinone IIA
  • Comparative Example 1 were applied to the face twice daily for 4 weeks in each group.
  • Table 6 shows the compositions of Example 1 and Comparative Example 1.
  • the test result is a percentage of the increase of the measured value after a certain period of treatment based on the Koniometer value measured immediately before the test was started.
  • a conniometer is a skin moisture meter that measures the amount of moisture present on the skin by measuring the conductivity of the epidermis. As shown in Table 7, in the group to which the material of Example 1 containing tanshinone IIA was applied, the amount of skin moisture was further increased compared to the control to which Comparative Example 1 was applied. Also, two weeks after the application of the test substance was stopped, the value after 6 weeks of skin moisture measurement was similar to that after 1 to 2 weeks. It was found that the skin moisture is maintained continuously.
  • Nitric Oxide Formation of Tanshinone IIA in Human UVB (Human umbilical vein endothelial cell)
  • Endothelial nitric oxide synthase is present in human vascular endothelial cells, and its activity is increased to produce nitric oxide (NO), which expands blood vessels and promotes blood circulation.
  • eNOS Endothelial nitric oxide synthase
  • NO nitric oxide
  • Table 8 shows the generation of nitrogen monoxide (Nitric Oxide, NO) by the tanshinone IIA.
  • tanshinone IIA showed an excellent ability to form nitric oxide (Nitric Oxide, NO) in vascular endothelial cells.
  • Nitric Oxide Nitric Oxide
  • the excellent Nitric Oxide (NO) -producing ability of tanshinone IIA can eventually expand capillaries and promote blood circulation, so that it can smoothly supply nutrients to skin, inhibit skin aging, and improve skin color. Contribute to efficacy. It also contributes to improving skin clarity.
  • LDPI Laser Doppler Perfusion Imager
  • the initial values were measured using an IRPI (Infrad) camera, an LDPI and skin temperature measuring instrument.
  • LDPI was used to measure the initial blood flow in the lower part of the forehead
  • the IR camera was used to measure the initial skin temperature of the forehead, eyes, and cheeks.
  • Example 1 having the composition shown in Table 6 above was prepared and the blood flow and skin temperature after using Example 1 for one week were compared with the initial measurements.
  • LDPI results before and after the use of Example 1 are shown in Table 9 below, and IR results before and after use are shown in Table 10.
  • Example 1 containing tanshinone IIA as described above, it was shown that the color of blood was improved as a peripheral blood circulation improving effect of the face, which ultimately effectively delivers the skin's nutrients and contributes to inhibiting and delaying skin aging. do.
  • Table 12 ingredient Content (% by weight) Tanshinone IIA 1.0 glycerin 3.0 Butylene glycol 3.0 Propylene glycol 3.0 Carboxy Vinyl Polymer 0.2 Beeswax 4.0 Polysorbate 60 1.5 Caprylic / Capric Reglycerides 5.0 Squalane 5.0 Sorbitassquioleate 1.5 Cetearyl Alcohol 1.0 Triethanolamine 0.2 Preservatives, spices Quantity Purified water Remaining amount system 100
  • Table 13 ingredient Content (% by weight) Tanshinone IIA 1.0 glycerin 3.5 Butylene glycol 3.0 Liquid paraffin 7.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / Capric Reglycerides 3.0 Squalane 5.0 Cetearyl Glucoside 1.5 Sorbitan stearate 0.4 Polysorbate 60 1.2 Triethanolamine 0.1 Preservatives, spices Quantity Purified water Remaining amount system 100
  • Table 14 ingredient Content (% by weight) Tanshinone IIA 1.0 glycerin 8.0 Butylene glycol 3.0 Liquid paraffin 45.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / Capric Triglycerides 3.0 Beeswax 4.0 Cetearyl Glucoside 1.5 Sesqui oleic acid sorbitan 0.9 paraffin 1.5 Preservative, coloring, flavoring Quantity Purified water Remaining amount system 100
  • the composition of the present invention may have a skin whitening effect, a skin moisturizing effect, a skin color improving effect, and a skin transparency improving effect. Through this, it can be variously used in the cosmetic and medical field.

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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Public Health (AREA)
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Abstract

La présente invention concerne une composition à usage externe pour l'épiderme, contenant en tant que principe actif du tanshinone II A, un isomère, un précurseur, un sel, un hydrate ou un solvate de ce dernier. La composition selon la présente invention a pour effets de blanchir, d'hydrater et d'améliorer la teinte et la transparence de la peau.
PCT/KR2012/004644 2011-06-17 2012-06-13 Composition à usage externe pour l'épiderme, contenant du tanshinone ii a en tant que principe actif Ceased WO2012173382A2 (fr)

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KR20110058902A KR101509848B1 (ko) 2011-06-17 2011-06-17 탄시논ⅱａ를 유효성분으로 함유하는 피부 외용제 조성물
KR10-2011-0058902 2011-06-17

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Cited By (3)

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CN106420387A (zh) * 2016-11-03 2017-02-22 浙江大学 一种中药化合物靶向脂质纳米球组合物及其制备方法
CN110787152A (zh) * 2019-12-10 2020-02-14 宁夏医科大学 一种促进皮肤吸收能力低药物的透皮凝胶贴剂及制备方法
CN117487154A (zh) * 2023-10-31 2024-02-02 暨南大学 一种丹参酮衍生物及其制备方法和应用

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KR102611023B1 (ko) * 2018-11-21 2023-12-08 (주)아모레퍼시픽 탈수소 아비에틱산을 포함하는 피부 장벽 강화용 또는 보습용 피부 외용제 조성물
JP7395637B2 (ja) * 2022-03-28 2023-12-11 株式会社ナリス化粧品 ヒアルロニダーゼ阻害剤

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KR100853377B1 (ko) * 2006-10-31 2008-08-21 (주)아모레퍼시픽 피부세포의 프로테아솜 활성을 촉진시키는 항노화 조성물
GB2453807A (en) 2007-10-15 2009-04-22 Botan Century Purified tanshinone extracts from Salvia spp and their antibacterial effects
JP2010106001A (ja) 2008-10-31 2010-05-13 Theravalues Corp Ｐｐａｒ活性化剤

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106420387A (zh) * 2016-11-03 2017-02-22 浙江大学 一种中药化合物靶向脂质纳米球组合物及其制备方法
CN110787152A (zh) * 2019-12-10 2020-02-14 宁夏医科大学 一种促进皮肤吸收能力低药物的透皮凝胶贴剂及制备方法
CN110787152B (zh) * 2019-12-10 2023-11-21 宁夏医科大学 一种促进皮肤吸收能力低药物的透皮凝胶贴剂及制备方法
CN117487154A (zh) * 2023-10-31 2024-02-02 暨南大学 一种丹参酮衍生物及其制备方法和应用

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