WO2010123184A1 - 노르갈란타민 화합물을 유효성분으로 함유하는 탈모 질환의 예방 및 치료용 조성물 - Google Patents
노르갈란타민 화합물을 유효성분으로 함유하는 탈모 질환의 예방 및 치료용 조성물 Download PDFInfo
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- WO2010123184A1 WO2010123184A1 PCT/KR2009/007030 KR2009007030W WO2010123184A1 WO 2010123184 A1 WO2010123184 A1 WO 2010123184A1 KR 2009007030 W KR2009007030 W KR 2009007030W WO 2010123184 A1 WO2010123184 A1 WO 2010123184A1
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- WO
- WIPO (PCT)
- Prior art keywords
- hair
- alopecia
- compound
- acid
- composition
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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- APVVRLGIFCYZHJ-UHFFFAOYSA-N trioctyl 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCCCOC(=O)CC(O)(C(=O)OCCCCCCCC)CC(=O)OCCCCCCCC APVVRLGIFCYZHJ-UHFFFAOYSA-N 0.000 description 1
- COXJMKGEQAWXNP-UHFFFAOYSA-N tris(14-methylpentadecyl) 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CC(C)CCCCCCCCCCCCCOC(=O)CC(O)(C(=O)OCCCCCCCCCCCCCC(C)C)CC(=O)OCCCCCCCCCCCCCC(C)C COXJMKGEQAWXNP-UHFFFAOYSA-N 0.000 description 1
- RHNXTZDKMRCKKT-UHFFFAOYSA-N tris(6-methylheptyl) 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound CC(C)CCCCCOC(=O)CC(O)(C(=O)OCCCCCC(C)C)CC(=O)OCCCCCC(C)C RHNXTZDKMRCKKT-UHFFFAOYSA-N 0.000 description 1
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- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
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- 239000011735 vitamin B7 Substances 0.000 description 1
- 235000001892 vitamin D2 Nutrition 0.000 description 1
- 239000011653 vitamin D2 Substances 0.000 description 1
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
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- 235000020234 walnut Nutrition 0.000 description 1
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- CPYIZQLXMGRKSW-UHFFFAOYSA-N zinc;iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+3].[Fe+3].[Zn+2] CPYIZQLXMGRKSW-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- 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
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- 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
- A23L33/15—Vitamins
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- 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
- A23L33/16—Inorganic salts, minerals or trace elements
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
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- A—HUMAN NECESSITIES
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- A61Q5/00—Preparations for care of the hair
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/02—Preparations for cleaning the hair
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q5/00—Preparations for care of the hair
- A61Q5/12—Preparations containing hair conditioners
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
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- 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
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/91—Injection
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- A—HUMAN NECESSITIES
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- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/92—Oral administration
Definitions
- the present invention relates to a pharmaceutical composition, cosmetic composition and health functional food for the prevention and treatment of hair loss disease containing a nogalantamine compound as an active ingredient.
- Minoxidil and finasteride are well known as currently approved by the Food and Drug Administration (FDA) for promoting hair growth.
- Minoxidil was initially developed as a vasodilator for the treatment of hypertension, but it was developed as a hair growth agent due to the report of hirsutism as a side effect.
- the mechanism of action of minoxidil on the hair growth effect has not been clarified to date, but it has been shown to increase nutrient supply through vasodilation, potassium channel opening effect and inhibitory effect of apoptosis of dermal papilla cells. (Han et al . Effect of minoxodil on proliferation and apoptosis in dermal papilla cells of human hair follicle.J Dermatol Sci.
- Finasteride developed by Merck, is a substance that inhibits the activity of 5 ⁇ -reductase, an enzyme that acts on male hormone metabolism, and was developed as a treatment for prostatic hyperplasia, but it is known that it promotes hair growth.
- EGF and EGFR (Botchkarev et al . Molecular control of epithelial-mesenchymal interactions during hair follicle cycling.J Investig Dermatol Symp Proc . 2003, Vol. 8, pages 46 to 55), VEGF and VEGFR (Ozeki et al . vivo promoted growth of mice hair follicles by the controlled release of growth factors.Biomaterials. 2003, Vol .
- TGF- ⁇ and TGF- ⁇ R Hibino et al. Role of TGF- 2 in the human hair cycle. J. Dermatol. Sci. 2004, Vol.35, pages 9 to 18
- growth factors Mo It modulates the activity of the two (dermal papilla) and has been reported to influence the hair cycle.
- Wnt pathway and Bmp signaling have been found to be crucial for the proliferation or differentiation of hair follicle stem cells in the bulb region (Moore et al . Stem cells and their niches . 2006, Vol. 311, pages 1880 to 1885).
- Hair growth is caused by complex mechanisms due to the action of several genes, growth factors and their receptors, and systemic hormones.
- hair follicle cells composed of epithelial cells and hair papilla cells composed of mesenchymal cells play a pivotal role in hair formation and growth.
- Jahoda Jahoda et al. Induction of hair growth by implantation of cultured dermal papilla cells. Nature. 1984, Vol. 311, pages 560 to 562, et al., Showed that when dermal papilla cells were removed from rat's mustache follicles, hair growth temporarily stopped and the cells migrated from the dermis roots to restore the dermal papilla cells.
- the lower part of the hair follicles Removing less than one-third of the dermal papilla cells from the dermis roots and hair matrix cells from the outer root sheaths continued hair growth, but removing more than one third of the lower part of the hair follicles stopped hair growth.
- the hair growth continues, and it is thought that the dermal papilla cells play an important role in hair growth.
- Daffodil ( Crinum asiaticum var. Japonicum ) is widely distributed only in Korea and Japan.
- phenanthridine alkaloids phenanthridine alkaloids
- triterpene alcohols triterpene alcohols
- flavonoids flavonoids
- alkaloids are antiviral (Gabrielsen et al . Antiviral (RNA) activity of selected Amaryllidaceae isoquinoline constituents and synthesis of related substances.J Nat Prod. 1992, Vol .
- the present inventors searched for the components of moonju eggs showing the hair growth efficacy, and as a result of continuous research on the prevention and treatment of hair loss diseases caused by the nogalanthamine compound, one of the main ingredients of moonju eggs, rats mustache follicles (vibrissa follicles)
- the present invention was completed by confirming the growth effect and the proliferative effect of dermal papilla cells, which play an important role in hair growth.
- the present invention is to provide a pharmaceutical composition, cosmetic composition and health functional food that is effective in the prevention and treatment of hair loss disease.
- the present invention provides a pharmaceutical composition for the prevention and treatment of alopecia diseases comprising the nogalanthamine compound of formula (I) as an active ingredient.
- the present invention provides a cosmetic composition for the prevention and improvement of hair loss disease containing a nogalanthamine compound of the formula (I) as an active ingredient.
- the present invention provides a health functional food for the prevention and improvement of hair loss disease containing a nogalanthamine compound of the formula (I) as an active ingredient.
- the norgalanthamine compound according to the present invention exhibits a growth proliferation effect of dermal papilla cells, which play an important role in hair growth, it is useful for pharmaceutical compositions, cosmetic compositions, and health functional foods useful for the prevention and treatment of alopecia diseases. Can be used.
- 1 is a diagram showing the growth effect of vibrissa follicles of the norgalantamine compound (% of control),
- Figure 2 is a diagram showing the proliferative effect of the dermal papilla cells of the nogalantamine compound (% of control),
- the present invention provides a pharmaceutical composition for the prevention and treatment of alopecia diseases comprising the nogalanthamine compound of formula (I) as an active ingredient.
- the norgalantamine compound may be separated from, for example, Crinum asiaticum extracts, but is not limited thereto, and may be separated from other plant extracts or prepared by general chemical synthesis methods.
- the alopecia disease may be, but is not limited to, at least one disease selected from resting alopecia, alopecia areata, alopecia areata, traumatic alopecia, scar alopecia or non scar alopecia, preferably Resting hair loss.
- the pharmaceutical composition containing the nogalantamine compound of the present invention may comprise 0.1 to 50% by weight, 1 to 50% by weight, or 1 to 40% by weight of the compound relative to the total weight of the composition It may be included in weight percent.
- the composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient and the type and extent of the disease.
- the compound of the present invention Since the compound of the present invention has little toxicity and side effects, it is a drug that can be used safely even when taken for a long time for the purpose of prevention.
- composition of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
- Carriers, excipients and diluents that may be included in the compositions of the present invention include lactose, dextrose, sucrose, 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.
- diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose, or the like. ) Or lactose, gelatin and the like are mixed.
- lubricants such as magnesium styrate talc are also used.
- Oral liquid preparations include suspending agents, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
- the non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used.
- As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
- compositions of the present invention may be used in the form of oral dosage forms, external preparations, suppositories, and sterile injectable solutions, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., according to conventional methods, respectively.
- Preferred dosages of the compositions of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.
- the norgalantamine compound of the present invention is preferably administered at 0.5 g / kg to 5 g / kg, preferably at 1 g / kg to 3 g / kg. Administration may be administered once a day or may be divided several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
- the pharmaceutical composition for the prevention and treatment of hair loss diseases containing the nogalanthamine compound of the formula (I) as an active ingredient is a pharmaceutical composition for external application for skin, wherein the external preparation for skin is not limited to cream, gel , Patch, spray, ointment, warning, lotion, linen, pasta or cataplasma formulations can be used.
- the preferred dosage of the nogalantamine compound depends on the condition and weight of the patient, the severity of the disease, the form of the drug, the route of administration, and the duration, and may be appropriately selected by those skilled in the art. Can be. However, for the desired effect, the compound of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably at 0.001 to 10 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
- composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous injection.
- the present invention provides a cosmetic composition for the prevention and improvement of hair loss disease containing the nogalanthamine compound of Formula (I) as an active ingredient.
- Cosmetic composition according to the present invention can be used in a variety of hair cosmetics having the effect of preventing hair loss and activating hair growth.
- the cosmetic composition is not limited to hair tonic, hair conditioner, hair essence, hair lotion, hair nutrition lotion, hair shampoo, hair rinse, hair treatment, hair cream, hair nutrition cream, Hair Moisture Cream, Hair Massage Cream, Hair Wax, Hair Aerosol, Hair Pack, Hair Nutrition Pack, Hair Soap, Hair Cleansing Foam, Hair Oil, Hair Dryer, Hair Preservative, Hair Dye, Hair Wave, Hair Bleach, Hair Gel, Hair Formulations of glazes, hairdressers, hair lacquers, hair moisturizers, hair mousses or hairsprays.
- the cosmetic composition for preventing hair loss and improving hair growth of the present invention may be included in an amount of 0.1 to 50% by weight, 1 to 50% by weight, or 1 to 40% by weight based on the total weight of the composition.
- the composition as described above is not necessarily limited thereto, and may vary depending on the state and progress of the application target.
- Preferred dosages of the nogalantamine compounds according to the present invention vary depending on the condition and weight of the subject, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.
- the compound of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably at 0.001 to 10 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
- the cosmetic of the present invention may further comprise a composition selected from the group consisting of water soluble vitamins, oil soluble vitamins, polymer peptides, polymer polysaccharides, sphingolipids and seaweed extract.
- the water-soluble vitamin may be any compound that can be incorporated into cosmetics, but preferably vitamin B1, vitamin B2, vitamin B6, pyridoxine, pyridoxine, vitamin B12, pantothenic acid, nicotinic acid, nicotinic acid amide, folic acid, vitamin C, vitamin H, and the like.
- Their salts thiamine hydrochloride, sodium ascorbate salt, etc.
- derivatives ascorbic acid-2-sodium phosphate salt, ascorbic acid-2-magnesium phosphate salt, etc.
- the water-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification from microorganism culture, enzyme or chemical synthesis.
- the oil-soluble vitamin may be any compound that can be formulated into cosmetics, but preferably vitamin A, carotene, vitamin D2, vitamin D3, vitamin E (d1-alpha tocopherol, d-alpha tocopherol, d-alpha tocopherol), and the like. And derivatives thereof (ascorbic palmitate, ascorbic stearate, ascorbic acid dipalmitate, dl-alpha tocopherol acetate, dl-alpha tocopherolvitamin E, DL-pantothenyl alcohol, D-pantothenyl alcohol, pantotenylethyl Ethers, etc.) are also included in the oil-soluble vitamins used in the present invention. Oil-soluble vitamins can be obtained by conventional methods such as microbial transformation, purification of microorganism culture, enzyme or chemical synthesis.
- the polymer peptide may be any compound as long as it can be incorporated into cosmetics.
- collagen, hydrolyzed collagen, gelatin, elastin, hydrolyzed elastin, keratin, and the like can be given.
- Polymeric peptides can be purified and obtained by conventional methods such as purification from microbial cultures, enzymatic methods or chemical synthesis methods, or can be purified and used from natural products such as dermis and pig silk such as pigs and cattle.
- the polymer polysaccharide may be any compound as long as it can be incorporated into cosmetics.
- hydroxyethyl cellulose, xanthan gum, sodium hyaluronate, chondroitin sulfate or a salt thereof (sodium salt, etc.) may be mentioned.
- chondroitin sulfate or its salt, etc. can be normally purified from a mammal or fish.
- the sphingolipid may be any compound as long as it can be blended into cosmetics.
- ceramide, phytosphingosine, sphingosaccharide lipid, etc. may be mentioned.
- Sphingo lipids can usually be purified from mammals, fish, shellfish, yeasts or plants by conventional methods or obtained by chemical synthesis.
- the seaweed extract may be any compound as long as it can be blended into cosmetics.
- the seaweed extract may include brown algae extract, red algae extract, green algae extract, and the like.
- calginine, arginic acid, sodium arginate, Potassium arginate and the like are also included in the seaweed extract used in the present invention.
- Seaweed extract can be obtained by purification from seaweed by conventional methods.
- 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.
- Examples of the fat or oil component include ester fats, hydrocarbon fats, silicone fats, fluorine fats, animal fats, and vegetable fats and oils.
- ester fats and oils As ester fats and oils, glyceryl tri2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl mystinate, isopropyl palmitate, ethyl stearate, octyl palmitate, isocetyl isostearate, and stearic acid Butyl, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl acid isocetyl, isostyl acid isostearyl, isostaryl palmitate, octylate acid octyldodecyl, isostearic acid isetyl, diethyl sebacate, adipine Acid isopropyl, isoalkyl neopentane, tri (capryl, capric acid) glyceryl, tri
- Hydrocarbon-based fats and oils such as squalene, a liquid paraffin, alpha-olefin oligomer, isoparaffin, ceresin, paraffin, a liquid isoparaffin, polybutene, microcrystal wax, and a vaseline, etc. are mentioned as a hydrocarbon-type fats and oils.
- silicone-based oils and fats examples include polymethylsilicone, methylphenylsilicone, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, dimethylsiloxane, methylcetyloxysiloxane copolymer, dimethylsiloxane and methylsteoxysiloxane copolymer, and alkyl.
- Modified silicone oil amino modified silicone oil and the like.
- Perfluoro polyether etc. are mentioned as fluorine-based fats and oils.
- Animal or vegetable oils include avocado oil, almond oil, olive oil, sesame oil, rice bran oil, soybean oil, soybean oil, corn oil, rapeseed oil, almond oil, palm kernel oil, palm oil, castor oil, sunflower oil, grape seed oil. , Cottonseed oil, Palm oil, Cucumber nut oil, Wheat germ oil, Rice germ oil, Shea butter, Walnut colostrum oil, Marker demia nut oil, Meadow home oil, Egg yolk oil, Uji, Horse oil, Mink oil, Orange rape oil, Jojoba oil And animal or plant fats and oils such as candeler wax, carnava wax, liquid lanolin and hardened castor oil.
- the moisturizing agent examples include a water-soluble low molecular moisturizer, a fat-soluble molecular moisturizer, a water-soluble polymer, and a fat-soluble polymer.
- fat-soluble low molecular humectants examples include cholesterol and cholesterol esters.
- water-soluble polymer examples include carboxyvinyl polymer, polyasparaginate, tragacanth, xanthan gum, methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose, water soluble chitin, chitosan, and dextrin. Can be.
- fat-soluble polymers examples include polyvinylpyrrolidone-eicosene copolymers, polyvinylpyrrolidone-hexadecene copolymers, nitrocellulose, dextrin fatty acid esters, polymer silicones, and the like.
- emollient examples include long-chain acyl glutamic acid cholesteryl esters, hydroxy stearic acid cholesterol, 12-hydroxystearic acid, stearic acid, rosin acid, lanolin fatty acid cholesteryl esters, and the like.
- nonionic surfactant nonionic surfactant, anionic surfactant, cationic surfactant, amphoteric surfactant, etc. are mentioned.
- nonionic surfactant self-emulsifying glycerin monostearate, propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerol fatty acid ester, sorbitan fatty acid ester, POE (polyoxyethylene) sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE Glycerin Fatty Acid Ester, POE Alkyl Ether, POE Fatty Acid Ester, POE Cured Castor Oil, POE Castor Oil, POE / POP (Polyoxyethylene / Polyoxypropylene) Copolymer, POE / POP Alkyl Ether, Polyether Modified Silicone, Laurin Acid Alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, etc. are mentioned.
- anionic surfactant fatty acid soap, alpha-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate, alkylamide sulfate, alkyl phosphate, POE alkylphosphate, alkylamide Phosphates, alkyloylalkyltaurine salts, N-acylamino acid salts, POE alkyl ether carboxylate salts, alkyl sulfosuccinate salts, sodium alkyl sulfo acetates, acylated hydrolyzed collagen peptide salts, perfluoroalkyl phosphate esters, and the like. have.
- amphoteric surfactants include the carboxybetaine type, the amide betain type, the sulfobetain type, the hydroxysulfobetain type, the amide sulfobetain type, the phosphobetaine type, the aminocarboxylate type, the imidazoline derivative type, and the amideamine type.
- An amphoteric surfactant etc. are mentioned.
- Organic and inorganic pigments include silicic acid, silicic anhydride, magnesium silicate, talc, sericite, mica, kaolin, bengala, clay, bentonite, titanium film mica, bismuth oxychloride, zirconium oxide, magnesium oxide, zinc oxide, titanium oxide, aluminum oxide
- Inorganic pigments such as calcium sulfate, barium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, iron oxide, ultramarine blue, chromium oxide, chromium hydroxide, calamine and composites thereof; Polyamide, polyester, polypropylene, polystyrene, polyurethane, vinyl resin, urea resin, phenol resin, fluorine resin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, divinylbenzene, styrene copolymer, Organic pigments such as silk powder, cellulose, CI pigment yellow, CI pigment orange, and composite pigments of these inorgan
- Metal soaps such as a calcium stearate; Alkyl phosphate metal salts such as sodium cetylinate, zinc lauryl acid and calcium laurate; Acylamino acid polyvalent metal salts such as N-lauroyl beta-alanine calcium, N-lauroyl beta-alanine zinc, and N-lauroyl glycine calcium; Amide sulfonic acid polyvalent metal salts, such as N-lauroyl-taurine calcium and N-palmitoyl-taurine calcium; N-epsilon-lauroyl-L-lysine, N-epsilon-palmitolyzine, N-alpha-paratoylol nitin, N-alpha-lauroyl arginine, N-alpha-cured fatty acid acyl arginine -Acyl basic amino acid; N-acyl polypeptides, such as N-lauroyl glycyl gly
- Examples of the ultraviolet absorber include paraaminobenzoic acid, ethyl paraaminobenzoate, amyl paraaminobenzoic acid, octyl paraaminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomentyl salicylic acid and benzyl cinnamic acid.
- paraaminobenzoic acid ethyl paraaminobenzoate, amyl paraaminobenzoic acid, octyl paraaminobenzoate, ethylene glycol salicylate, phenyl salicylate, octyl salicylate, benzyl salicylate, butylphenyl salicylate, homomentyl salicylic acid and benzyl cinnamic acid.
- fungicides hinokithiol, trichloric acid, trichlorohydroxydiphenyl ether, chlorhexidine gluconate, phenoxyethanol, resorcin, isopropylmethylphenol, azulene, salicylic acid, ginxitlionone, benzalkonium chloride, photosensitive Sodium No. 301, sodium mononitrohydrol, undecylenic acid, and the like.
- antioxidants examples include butylhydroxyanisole, propyl gallic acid, and erythorbic acid.
- pH adjuster examples include citric acid, sodium citrate, malic acid, sodium malate, fmaric acid, sodium pmarate, succinic acid, sodium succinate, sodium hydroxide, sodium dihydrogen phosphate, and the like.
- Examples of the alcohol include higher alcohols such as cetyl alcohol.
- the compounding component which may be added other than this is not limited to this, although any said component can be mix
- the cosmetic of the present invention may take the form of a solution, an emulsion, a viscous mixture, or the like.
- Ingredients included in the cosmetic composition of the present invention may include components commonly used in cosmetic compositions in addition to the compound as an active ingredient, for example, conventional auxiliary agents such as stabilizers, solubilizers, vitamins, pigments and flavorings. And carriers.
- the cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, and includes, for example, milky lotion, cream, lotion, pack, foundation, lotion, essence, hair cosmetic, and the like.
- the formulation of the present invention is a paste, cream or gel, animal fibers, plant fibers, waxes, paraffins, starches, tracantes, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
- animal fibers animal fibers
- plant fibers waxes, paraffins, starches, tracantes, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide
- talc 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.
- a solvent, solvating or emulsifying agent 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, microcrystalline Cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.
- the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide.
- Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
- the present invention provides a health functional food for the prevention and improvement of hair loss disease containing the nogalanthamine compound of Formula (I) as an active ingredient.
- composition comprising a nogalantamine compound according to the present invention may be used in various ways, such as drugs, foods and beverages for the prevention and improvement of hair loss disease.
- Foods to which the compound of the present invention may be added include, but are not limited to, various foods, beverages, gums, teas, vitamin complexes, dietary supplements, and the like, and are powders, granules, tablets, capsules, or beverages. Available in form.
- the compounds of the present invention may be added to foods or beverages for the purpose of preventing and ameliorating alopecia diseases.
- the amount of the compound in the food or beverage is generally added to the health food composition of the present invention to 1 to 5% by weight of the total food weight, the health beverage composition is 0.02 to 10 g, preferably based on 100 ml Can be added in a ratio of 0.3 to 1 g.
- the health beverage composition of the present invention in addition to containing the compound as an essential ingredient in the indicated proportions, has no particular limitation on the liquid component and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
- natural carbohydrates are conventional monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and polysaccharides such as dextrin, cyclodextrin and the like.
- Sugars and sugar alcohols such as xylitol, sorbitol, and erythritol.
- natural flavoring agents such as, tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
- the proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 mL of the composition of the present invention.
- the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like.
- the compositions of the present invention may also contain pulp for the production of natural fruit juices and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
- the ground portion of Crinum asiaticum var. Japonicum native to Jeju Island was collected, and 1.5 Kg of the shaded sample was chopped, extracted three times with 2,5000 ml of methanol, and concentrated to obtain 500 g of methanol.
- This methanol extract was partitioned into 1,000 ml each of hexane, dichloromethane, ethyl acetate and butanol in order to obtain respective fractions.
- the butanol fraction was then converted into chloroform-methanol-water (13: 7: 2 (v / v / v), Silica gel column chromatography was carried out using the lower layer) as a mobile phase to obtain nine small fractions ('Fr. 1' to 'Fr. 9').
- the small fraction Fr.4 was suspended in water and dichloromethane according to the conventional method, and then treated with an acid base to obtain an alkaloid fraction. This was again carried out by silica gel column chromatography using acetone-water (2: 1 (v / v)) as a mobile phase to obtain a coarse fraction of nogalantamine, which was recrystallized from acetone to obtain 160 mg of white needle crystal nogalantamine. It was.
- Three-week-old male Wistar rats (Japan SLC, Hamamatsu, Janpan) were purchased from a central laboratory animal, anesthetized with ethyl ether and cervical slaughtered. Rat left and right mystacial pads were isolated to isolate E / P buffer [(EBSS, Earle's balanced salts solution, Sigma MO) containing 100 units / ml penicillin-100 ⁇ g / ml streptomycin (Gibco Inc, NY, USA). , USA) + (PBS, phosphate-buffered saline, Sigma MO, USA)]. The vibrissa follicles were carefully separated while observing under a dissecting microscope.
- E / P buffer ((EBSS, Earle's balanced salts solution, Sigma MO) containing 100 units / ml penicillin-100 ⁇ g / ml streptomycin (Gibco Inc, NY, USA). , USA) + (PBS, phosphate-buffered saline, Sigma
- the separated hair follicles were placed in a Petri dish containing E / P buffer and incubated at 37 ° C. in a 5% CO 2 thermostat for about 1 hour.
- 2 mM L-glutamine L-glutamine, Gibco Inc, NY, USA
- 10 ⁇ g / ml insulin insulin, Sigma MO, USA
- 50 nM hydrocortisone Sigma MO, USA
- 500 ⁇ l of William E medium (William E medium, Gibco Inc, NY, USA) containing 100 units / ml penicillin-100 ⁇ g / ml streptomycin, and put one follicle into one well at 37 ° C.
- Example 1 The norgalanthamine compound of Example 1 was treated at 0.01 and 0.1 uM concentrations, and minoxidil sulfate (minoxidil sulfate, MS, Sigma, USA), a positive control, was treated at a concentration of 1 ⁇ M.
- minoxidil sulfate minoxidil sulfate, MS, Sigma, USA
- the morphology of the cultured mustache follicle was photographed using a microscope (Olympus, Japan). Hair follicle length was measured on day 0, 7, 14 and 21 using an image analyzer (DP controller; Olympus, Japan). The average value of the hair follicle length change was calculated and compared with the average length of the control group.
- Example 1 In order to determine whether the nogalanthamine compound of Example 1 has a hair papillary proliferative effect that plays a very important role in hair growth, a method described in the literature is used using rat vibrissa immortalized dermal papilla cells. MTT assay was performed as follows (Han JH, et al ., Effect of minoxodil on proliferation and apoptosis in dermal papilla cells of human hair follicle., J Dermatol Sci , 34 , pp.91-98, 2004).
- Rat vibrissa immortalized dermal papilla cell Filsell W, et al ., Transfection of rat dermal papilla cells with a gene encoding a temperature-sensitive polyomavirus large T antigen generates cell lines a differentiated phenotype., J. Cell Sci , 107 , pp.
- the cultured dermal papilla cells (dermal papilla cells, 1.0 ⁇ 10 4 cells / ml) were put into a 96-well plate and cultured for 24 hours, and then exchanged with serum-free DMEM medium for 24 hours, followed by Example 1
- the norgalantamine compound was treated at concentrations of 0.01 and 0.1 uM, and minoxidil sulfate (minoxidil sulfate, MS, Sigma, MO, USA), a positive control, was treated at a concentration of 1 ⁇ M. After incubation for 4 days, 50 ⁇ l of MTT (Sigma, MO, USA) was added and reacted for 4 hours.
- the supernatant was removed, 200 ⁇ l of DMSO was added to dissolve the precipitate, and the absorbance was measured at 540 nm using a microplate reader (Amersham Pharmacia Biotech, NY, USA). The average absorbance value for each sample group was obtained, and the degree of proliferation was investigated by comparing with the absorbance values of the control group.
- the nogalantamine compound which is a component of Moon Ju-ran, may promote growth and proliferation of dermal papilla cells, which play an important role in hair growth, and thus act to induce the growth phase of hair follicles or maintain the growth phase.
- the nogalantamine compound can be effectively used for the prevention and treatment of hair loss.
- the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
- tablets are prepared by tableting according to a conventional method for preparing tablets.
- the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
- the amount of the above ingredient is prepared per ampoule (2 ml).
- Vitamin B6 0.5 mg
- composition ratio of the vitamin and mineral mixture is a composition suitable for a relatively healthy food in a preferred embodiment
- the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
- the granules may be prepared and used for preparing a health food composition according to a conventional method.
- composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment
- the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
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Abstract
Description
Claims (10)
- 제 1항에 있어서,상기 탈모 질환은 휴지기 탈모증, 원형 탈모증, 생장기 모발 탈모증, 외상성 탈모증, 반흔성 탈모증 또는 비반흔성 탈모증인 약학 조성물.
- 제 1항에 있어서,조성물 총 중량에 대하여 상기 화합물을 0.1 내지 50 중량% 로 포함함을 특징으로 하는 약학 조성물.
- 제1항에 있어서,상기 약학 조성물은 피부외용제용 약학 조성물.
- 제4항에 있어서,노르갈란타민 화합물의 1일 투여량이 0.0001 내지 100 mg/kg 인 피부외용제용 약학 조성물.
- 제4항에 있어서,상기 피부외용제는 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카타플라스마제 제형인 약학 조성물.
- 제1항에 기재된 화학식 Ⅰ의 노르갈란타민 화합물을 유효성분으로 함유하는 탈모 질환의 예방 및 개선용 화장료 조성물.
- 제7항에 있어서,상기 화장료 조성물은 헤어토닉, 헤어컨디셔너, 헤어에센스, 헤어로션, 헤어영양로션, 헤어샴푸, 헤어린스, 헤어트리트먼트, 헤어크림, 헤어영양크림, 헤어모이스처크림, 헤어맛사지크림, 헤어왁스, 헤어 에어로졸, 헤어팩, 헤어영양팩, 헤어비누, 헤어클렌징폼, 머릿기름, 모발건조제, 모발보존처리제, 모발염색제, 모발용 웨이브제, 모발탈색제, 헤어겔, 헤어글레이즈, 헤어드레싱어, 헤어래커, 헤어모이스처라이저, 헤어무스 또는 헤어스프레이의 제형인 화장료 조성물.
- 제 1항에 기재된 화학식 Ⅰ의 노르갈란타민 화합물을 유효성분으로 함유하는 탈모 질환의 예방 및 개선용 건강기능식품.
- 제9항에 있어서,상기 건강기능식품은 분말, 과립, 정제, 캡슐 또는 음료인 건강기능식품.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2009801589222A CN102573848A (zh) | 2009-04-24 | 2009-11-27 | 含有去甲加兰他敏化合物作为活性成分的用于预防和治疗脱发症的组合物 |
US13/265,820 US20120129838A1 (en) | 2009-04-24 | 2009-11-27 | Composition for Preventing and Treating Alopecia Disorder Containing Morgalanthamine Compounds as an Active Ingredient |
Applications Claiming Priority (4)
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KR1020090035815A KR101037235B1 (ko) | 2009-04-24 | 2009-04-24 | 노르갈란타민 화합물을 유효성분으로 함유하는 탈모 방지 및 발모 개선용 조성물 |
KR10-2009-0035815 | 2009-04-24 | ||
KR10-2009-0035814 | 2009-04-24 | ||
KR1020090035814A KR101037237B1 (ko) | 2009-04-24 | 2009-04-24 | 노르갈란타민 화합물을 유효성분으로 함유하는 탈모 질환의 예방 및 치료용 조성물 |
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WO2010123184A1 true WO2010123184A1 (ko) | 2010-10-28 |
Family
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Family Applications (1)
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PCT/KR2009/007030 WO2010123184A1 (ko) | 2009-04-24 | 2009-11-27 | 노르갈란타민 화합물을 유효성분으로 함유하는 탈모 질환의 예방 및 치료용 조성물 |
Country Status (3)
Country | Link |
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US (1) | US20120129838A1 (ko) |
CN (1) | CN102573848A (ko) |
WO (1) | WO2010123184A1 (ko) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2017003137A1 (ko) * | 2015-06-30 | 2017-01-05 | (주)아모레퍼시픽 | 속붕해형 과립환 모발 세정용 조성물 |
WO2018093370A1 (en) * | 2016-11-17 | 2018-05-24 | Follea International | System and method for preventing alopecia |
US10064816B2 (en) | 2015-06-11 | 2018-09-04 | ReJoy | Treatment of sexual dysfunction |
US10238593B2 (en) | 2014-11-14 | 2019-03-26 | Follea International | System and method for preventing alopecia |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103432958B (zh) * | 2013-08-22 | 2014-11-05 | 郑四荣 | 一种碳酸钙表面活性剂 |
KR101551891B1 (ko) | 2013-09-12 | 2015-09-09 | 삼천당제약주식회사 | 섬오가피 및 문주란의 혼합 생약 추출물의 탈모 방지 및 발모 촉진 효과를 갖는 외용 조성물 |
KR20170003414A (ko) * | 2015-06-30 | 2017-01-09 | (주)아모레퍼시픽 | 속붕해형 과립환 모발 세정용 조성물 |
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US5958903A (en) * | 1995-07-19 | 1999-09-28 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Galanthamine derivatives, and their pharmaceutical compositions |
US6358941B1 (en) * | 1996-02-19 | 2002-03-19 | Ernir Snorrason | Treatment of arthritis disorders, rheumatoid arthritis and manifestations associated with rheumatoid disorders |
US20040044023A1 (en) * | 2002-08-30 | 2004-03-04 | Marc Cantillon | Compositions and methods for treating or preventing memory impairment |
WO2004075916A1 (en) * | 2003-02-27 | 2004-09-10 | Shirankai Kyoto University Faculty Of Medicine Alumni Association Inc. | Pharmaceutical composition for treatment of drug dependence |
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EP0515301A3 (en) * | 1991-05-14 | 1993-06-16 | Ernir Snorrason | Improvements in benzodiazepine treatment by cholinesterterase inhibitors |
WO2006040688A2 (en) * | 2004-10-12 | 2006-04-20 | Ernir Snorrason | Inhibitors of acetylcholinesterase for treating skin diseases |
-
2009
- 2009-11-27 CN CN2009801589222A patent/CN102573848A/zh active Pending
- 2009-11-27 US US13/265,820 patent/US20120129838A1/en not_active Abandoned
- 2009-11-27 WO PCT/KR2009/007030 patent/WO2010123184A1/ko active Application Filing
Patent Citations (4)
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US5958903A (en) * | 1995-07-19 | 1999-09-28 | Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) | Galanthamine derivatives, and their pharmaceutical compositions |
US6358941B1 (en) * | 1996-02-19 | 2002-03-19 | Ernir Snorrason | Treatment of arthritis disorders, rheumatoid arthritis and manifestations associated with rheumatoid disorders |
US20040044023A1 (en) * | 2002-08-30 | 2004-03-04 | Marc Cantillon | Compositions and methods for treating or preventing memory impairment |
WO2004075916A1 (en) * | 2003-02-27 | 2004-09-10 | Shirankai Kyoto University Faculty Of Medicine Alumni Association Inc. | Pharmaceutical composition for treatment of drug dependence |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
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US10238593B2 (en) | 2014-11-14 | 2019-03-26 | Follea International | System and method for preventing alopecia |
US10064816B2 (en) | 2015-06-11 | 2018-09-04 | ReJoy | Treatment of sexual dysfunction |
US10357452B2 (en) | 2015-06-11 | 2019-07-23 | ReJoy | Treatment of sexual dysfunction |
WO2017003137A1 (ko) * | 2015-06-30 | 2017-01-05 | (주)아모레퍼시픽 | 속붕해형 과립환 모발 세정용 조성물 |
WO2018093370A1 (en) * | 2016-11-17 | 2018-05-24 | Follea International | System and method for preventing alopecia |
Also Published As
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US20120129838A1 (en) | 2012-05-24 |
CN102573848A (zh) | 2012-07-11 |
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