WO2021125733A1 - Composition pharmaceutique pour la prévention ou le traitement de la perte de cheveux - Google Patents
Composition pharmaceutique pour la prévention ou le traitement de la perte de cheveux Download PDFInfo
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- WO2021125733A1 WO2021125733A1 PCT/KR2020/018308 KR2020018308W WO2021125733A1 WO 2021125733 A1 WO2021125733 A1 WO 2021125733A1 KR 2020018308 W KR2020018308 W KR 2020018308W WO 2021125733 A1 WO2021125733 A1 WO 2021125733A1
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- WIPO (PCT)
- Prior art keywords
- hair loss
- tansinone
- preventing
- tanshinone
- pharmaceutical composition
- Prior art date
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- 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
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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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- 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
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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
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
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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
- 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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- 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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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
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- A—HUMAN NECESSITIES
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Definitions
- the present invention relates to a pharmaceutical composition for preventing or treating hair loss.
- Hair is an important indicator of health, and when health deteriorates, hair becomes coarse or falls out. On average, there are 100,000 hairs on the human scalp, and they repeat generation and extinction with periodic changes in the anagen, catagen, telogen, and exogen phases. Hair is composed of 90% keratin composed of 18 amino acids and 10% water, and is mainly composed of carbon, oxygen, nitrogen, hydrogen, and sulfur. About 80 to 100 hairs fall out a day normally, and new hairs are formed in the places where they fall out.
- Hair loss refers to a condition in which the number of hairs falling out is greater than the number of new hairs.
- the causes of hair loss vary from person to person, but the degeneration of scalp cells due to aging including genetic factors, lack of nutrients supplied to the hair roots, and scalp fat Examples include insufficient oxygen supply due to excess, inflammation and pore clogging caused by fat or foreign substances or scalp disease, and stress.
- the blood circulation is good, nutrients and oxygen are smoothly supplied to the hair roots, so that the hair grows healthy.
- the blood circulation is not smooth due to a high fat diet or smoking, hair loss is promoted. Alopecia occurred only in the middle-aged in the past, but recently, it is also occurring frequently in young people in their 20s and 30s.
- An object of the present invention is to provide a pharmaceutical composition for preventing or treating hair loss.
- An object of the present invention is to provide a cosmetic composition for preventing or alleviating hair loss.
- An object of the present invention is to provide a food composition for preventing or alleviating hair loss.
- a pharmaceutical composition for preventing or treating hair loss comprising at least two or more of tanshinone I (Tanshinone I), tanshinone IIA (Tanshinone IIA), and cryptotanshinone.
- composition for preventing or treating hair loss according to the above 1, comprising tansinone I and tansinone IIA.
- composition for preventing or treating hair loss according to the above 4, wherein the composition prevents or treats hair loss by lowering the active oxygen level in testosterone.
- a method for preventing or treating hair loss comprising administering to a subject a therapeutically effective amount of at least two or more of Tanshinone I, Tanshinone IIA, and cryptotanshinone.
- a cosmetic composition for preventing or alleviating hair loss comprising at least two of tanshinone I, tanshinone IIA, and cryptotanshinone.
- Food composition for preventing or alleviating hair loss comprising at least two or more of tanshinone I (Tanshinone I), tanshinone IIA (Tanshinone IA), and cryptotanshinone.
- the present invention relates to a pharmaceutical composition for preventing or treating hair loss, which can effectively prevent or treat hair loss by inhibiting NOX expression and reducing active oxygen production.
- composition according to the present invention contains two or more compounds of tansinone I, tansinone IA, and cryptotansinone, and has excellent efficacy in preventing or treating hair loss compared to the case of using a single compound.
- 1 is a view confirming the reduction in active oxygen production according to the inhibition of NOX expression.
- Figure 2 is a view confirming the reduction of apoptosis (apoptosis) according to the inhibition of NOX expression.
- 3 is a view confirming the restoration of hair growth according to the inhibition of NOX expression.
- FIGS. 8 and 9 are diagrams confirming the inhibition of active oxygen production of tansinone I and tansinone IIA in vitro.
- FIGS. 10 and 11 are diagrams confirming the inhibition of active oxygen production according to the content of tansinone I and tansinone IIA in vitro.
- 16 and 17 are diagrams confirming hair follicle length growth by tansinone I and tansinone IIA.
- the present invention provides a pharmaceutical composition for preventing or treating hair loss comprising at least two or more of tansinone I, tansinone IA, and cryptotansinone.
- tansinone I may be represented by the following formula (1).
- tansinone IA may be represented by the following formula (2).
- cryptotansinone may be represented by the following formula (3).
- composition according to the present invention comprises at least two compounds selected from tansinone I, tansinone IA and cryptotansinone.
- the composition according to the present invention comprises tansinone I and tansinone IA.
- the content of tansinone I and tansinone IA included in the composition may be included in, for example, a molar ratio of 5:1 to 1:5, a molar ratio of 3:1 to 1:3, or a molar ratio of 1:1. It is not limited.
- the hair loss of the present invention may include androgenetic hair loss, telogen hair loss, anagen phase hair loss, alopecia areata, drug telogen hair loss, and postpartum telogen hair loss.
- it may include all kinds of hair loss that forms an abnormal hair loss pattern such as vellus hair growth of terminal hair, short hair growth of group hair, and atrophy of hair follicles due to a series of other factors.
- hair loss may be androgenic alopecia.
- Androgenetic alopecia is due to hyperandrogen stimulation caused by excessive accumulation of testosterone or androgen hormone in the metabolic system.
- Androgenetic alopecia is known to cause hair loss due to an increase in the level of free radicals caused by testosterone.
- testosterone increases calcium production by binding to the GPRC6A receptor, thereby increasing the activity of NOX to generate reactive oxygen species.
- Reactive oxygen generated in hair follicle cells can induce hair follicle cell death and cause hair loss (Eunbi Ko et al., Testosterone stimulates Duox1 activity through GPRC6A in skin keratinocytes. Journal of Biol Chem. 2014 oct 17;289(42)) :28835-45.).
- NOX or NADPH oxidase is a protein that mediates reactive oxygen production and includes NOX1, NOX2, NOX4, NOX5, DUOX1 and DUOX2.
- Reactive oxygen or reactive oxygen species are chemically reactive molecules containing oxygen atoms. As a compound of oxygen produced in living organisms, it has strong oxidative power that attacks living tissue and damages cells. When active oxygen increases, cells die, and when antioxidants such as NAC (N-acetylcysteine) or BHA (butylated hydroxyanisole) are treated in the cells with increased active oxygen, apoptosis is inhibited (Sang Won Kang, Role of Reactive) Oxygen Species in Cell Death Pathways, Hanyang Med Rev, 2013;33:77-82).
- NAC N-acetylcysteine
- BHA butylated hydroxyanisole
- hair loss may be caused by an increase in the level of active oxygen due to overexpression of NOX in hair follicle cells, and when the composition of the present invention is administered, it inhibits the expression of NOX in hair follicle cells to lower the level of active oxygen, and apoptosis
- the present invention was completed by confirming that it is possible to prevent or treat hair loss by inhibiting.
- TUNEL asssy Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling assay
- TdT Terminal deoxynucleotidyl transferase
- Figs. 12 to 15 the 'TUNEL assay' is a method for confirming the number of dead cells, and is performed using the property of TdT that labels the blunt end of the double-stranded DNA fragment regardless of the template (Kateryna Kyrylkova et al. ., Detection of apoptosis by TUNEL assay, Methods Mol Biol, 2012;887:41-7), can be visualized according to the introduced label.
- DHT dihydrotestosterone
- 5 ⁇ -reductase an enzyme that reduces the double bond between the 4th and 5th carbons of testosterone
- DHT dihydrotestosterone
- 5 ⁇ -reductase an enzyme that reduces the double bond between the 4th and 5th carbons of testosterone
- composition of the present invention may further comprise a 5 ⁇ -reductase inhibitor.
- a 5 ⁇ -reductase inhibitor that inhibits the action of this enzyme to inhibit the production of dihydrotestosterone
- compounds such as finasteride and dutasteride may be used, but the present invention is not limited thereto.
- composition of the present invention includes two or more compounds selected from tansinone I, tansinone IA and cryptotansinone and a 5 ⁇ -reductase inhibitor, it is possible to inhibit each mechanism by NOX and 5 ⁇ -reductase, It may have excellent efficacy in preventing or treating hair loss.
- the pharmaceutical composition for preventing or treating hair loss of the present invention is formulated in the form of oral dosage forms such as powders, granules, tablets, capsule suspensions, emulsions, syrups and aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods.
- oral dosage forms such as powders, granules, tablets, capsule suspensions, emulsions, syrups and aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods.
- the composition of the present invention is for external use, and it is possible to prepare any formulation that can make the composition come into contact with the skin, such as a liquid or gel type.
- it may be formulated in the form of ointments, creams, packs and gels such as liniments, patches, or sprays.
- the liniment agent may be used by applying it to a body part in need of hair growth, and the patch may be used by attaching it to the body part in need of hair growth.
- the spray can be used in a manner of spraying a body part in need of hair growth.
- Carriers, excipients and diluents that may be contained in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, 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 commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations include at least one excipient in the compound, for example, starch, calcium carbonate, sucrose or lactose. , gelatin, etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
- Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. may be included. .
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
- Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
- injectable esters such as ethyl oleate.
- As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.
- the usage amount of the pharmaceutical composition of the present invention may vary depending on the age, sex, and weight of the patient, but may be administered at 0.1 to 100 mg/kg, preferably 1 to 10 mg/kg, once or several times a day.
- the dosage may be increased or decreased according to the route of administration, the degree of disease, sex, weight, age, and the like. Therefore, the above dosage does not limit the scope of the present invention in any way.
- the part where the composition of the present invention can be included can be applied to any part of the body that requires hair growth as well as the scalp.
- it can be used to improve the condition of hair or hair damaged by trauma or a wide forehead or M-shaped forehead, eyelashes or eyebrows for the purpose of simple cosmetic effect, and alopecia.
- the present invention provides a method for preventing or treating hair loss comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition.
- the pharmaceutical composition administered to a subject in the method for preventing or treating hair loss according to the present invention may have the characteristics as described above herein.
- the pharmaceutical composition of the present invention may be administered in a pharmaceutically effective amount.
- pharmaceutically effective amount means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, drug activity, and type of the patient's disease; Sensitivity to the drug, administration time, administration route and excretion rate, duration of treatment, factors including concurrent drugs, and other factors well known in the medical field may be determined.
- the pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple.
- an amount that can obtain the maximum effect with a minimum amount without side effects which can be easily determined by those skilled in the art.
- the exact therapeutically effective dose of an active ingredient may vary depending on the relative amount of each active ingredient used, the drug used, and the synergistic ratio.
- the present invention provides a method for preventing or treating hair loss, comprising administering to a subject a therapeutically effective amount of at least two or more of tanshinone I, tanshinone IA, and cryptotanshinone do.
- the present invention provides a method for preventing or treating hair loss, comprising administering to a subject a therapeutically effective amount of tansinone I and tansinone IIA.
- the tansinone I and the tansinone IIA may be administered in a molar ratio of 3:1 to 1:3.
- the present invention provides a method for preventing or treating androgenetic alopecia.
- hair loss by can be prevented or treated.
- a therapeutically effective amount of at least two or more of the tanshinone I, Tanshinone IIA, and cryptotanshinone and a 5 ⁇ -reductase inhibitor is further administered to the subject. It can be administered to prevent or treat hair loss.
- the present invention provides the use of the pharmaceutical composition for preventing or treating hair loss.
- composition for this use according to the present invention may have the characteristics as described hereinabove.
- the present invention provides a cosmetic composition for preventing or alleviating hair loss comprising the composition.
- the cosmetic composition is a softening lotion, astringent lotion, nourishing lotion, nourishing cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, body lotion, body cream, body oil, body It may be formulated as an essence, makeup base, foundation, hair dye, shampoo, conditioner or body cleaner, but is not limited thereto.
- a substance When used as a cosmetic composition, a substance may be further added according to the formulation of an external preparation for skin or cosmetics.
- an external preparation for skin or cosmetics For example, but not limited thereto, when the formulation is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or Zinc oxide and the like may be used, and when the formulation is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In particular, in the case of a spray, additionally propellants such as chlorofluorohydrocarbons, propane/butane or dimethyl ether.
- propellants such as chlorofluorohydrocarbons, propane/butane or dimethyl ether.
- a solvent, solubilizer or emulsifier is used as a carrier component, preferably water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 ,3-Butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan may be used, but is not limited thereto.
- the formulation is a suspension
- a liquid diluent such as ethanol or propylene glycol
- a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, Aluminum metahydroxide, bentonite, agar or tracanth
- a surfactant containing cleansing agent aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivatives, methyltaurate, sarcosinate, fatty acid amide ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative or ethoxylated glycerol fatty acid ester may be, but is not
- the present invention provides the use of a cosmetic composition for preventing or treating hair loss.
- composition for this use according to the invention may have the characteristics as described hereinabove.
- the present invention provides a food composition for preventing or alleviating hair loss comprising the composition.
- the food composition of the present invention includes beverages (including alcoholic beverages), fruits and processed foods thereof (eg, canned fruit, bottled, jam, marmalade, etc.), fish, meat, and processed foods thereof (eg, ham, corned sausage). etc.), breads and noodles (e.g. udon, soba, ramen, spaghetti, macaroni, etc.), fruit juice, various drinks, cookies, syrup, dairy products (e.g. butter, cheese, etc.), edible vegetable oils and fats, margarine, vegetable protein, It may be retort food, frozen food, various seasonings (eg, miso, soy sauce, sauce, etc.).
- beverages including alcoholic beverages
- fruits and processed foods thereof eg, canned fruit, bottled, jam, marmalade, etc.
- fish, meat, and processed foods thereof eg, ham, corned sausage.
- breads and noodles e.g. udon, soba, ramen, spaghetti, macaroni, etc.
- fruit juice
- the food composition of the present invention may be formulated in tablets, pills, powders, granules, powders, capsules, liquid formulations, and the like. They may be formulated to further include one or more of carriers, diluents, excipients and additives.
- the food composition may further include an additive.
- Additives include natural carbohydrates, flavoring agents, nutrients, vitamins, minerals (electrolytes), flavoring agents (synthetic flavoring agents, natural flavoring agents, etc.), coloring agents, fillers (cheese, chocolate, etc.), lactic acid and its salts, alginic acid and its salts.
- At least one component selected from the group consisting of salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, antioxidants, glycerin, alcohols, carbonation agents, and pulp may be used.
- the food composition includes various nutrients, vitamins, minerals (electrolytes), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
- the food composition of the present invention may contain the pulp for the production of natural fruit juice and vegetable beverage. These components may be used independently or in combination.
- the present invention provides the use of a food composition for preventing or treating hair loss.
- composition for this use according to the invention may have the characteristics as described hereinabove.
- composition according to the present invention can be usefully used as a raw material for the development of a pharmaceutical (external) product capable of preventing or treating hair loss or promoting hair growth.
- HBSS Hanks' balanced salt solution
- DCF-DA 10 ⁇ M 2',7'-dichlorofluorescin diacetate
- FIG. 1 The results are shown in FIG. 1 .
- FIG. 1 it was confirmed that active oxygen production was reduced in Duox1 knockout mice.
- FIG. 2 The results are shown in FIG. 2 . As shown in FIG. 2 , it was confirmed that apoptosis was reduced as the TUNEL-positive cells of the Duox1 knockout mice were decreased.
- mice of wild type and Duox1 knockout were depilated using wax to synchronize the mouse hair cycle. After depilation, 200 ⁇ g/100 ⁇ l of testosterone was applied to the back skin of mice for 7 days from the 8th day. After that, mice were sacrificed to obtain skin tissues, and H&E (hematoxylin & eosin) staining was performed to analyze the number of hairs per unit length.
- H&E hematoxylin & eosin
- FIG. 3 The results are shown in FIG. 3 . It was found that the inhibition of hair growth by testosterone in Duox1 knockout mice was restored ( FIG. 3A ). In addition, it was confirmed that Duox1 knockout mice had a higher number of hair follicles per unit length ( FIG. 3B ). This suggests that inhibition of NOX expression is effective in treating hair loss.
- ROS scavenging ability of Nox inhibitor was confirmed by adding tansinone I and tansinone IIA to 1X PBS at concentrations of 1 and 10 ⁇ M and reacting with H 2 O 2 500 mM and lucigenin 400 ⁇ M. Chemiluminescence was measured with a Promega GloMax 20/20 Luminometer at 10-second intervals for 1 minute. The average values were compared with NAC (N-Acetylcysteine) 500 ⁇ M and 1 mM as positive controls. In all experiments, the measured values obtained by reacting only the Nox inhibitor with lucigenin without adding H 2 O 2 were subtracted.
- Amplex red glucose/glucose oxidase assay kit and Amplex red xanthine/xanthine oxidase assay kit were used for glucose oxidase activity and xanthine oxidase activity.
- tanshinone I and tanshinone IIA were treated at concentrations of 1 and 10 ⁇ M, fluorescence values were measured at absorbance at a wavelength of 560 nm. This was compared with the case of NAC 500 ⁇ M, 1 mM treatment.
- FIGS. 5 to 7 The results are shown in FIGS. 5 to 7 .
- tansinone I and tansinone IA are not substances that directly reduce active oxygen.
- tansinone I and tansinone IA have no inhibitory activity of glucose oxidase (Fig. 6), and no or very low inhibitory activity of xanthine oxidase (Fig. 7), it is known that they are compounds having specific inhibitory activity on NOX.
- the level of reactive oxygen production according to the concentration of tansinone I and tanshinone IIA was measured in Ker-CT cells in the same manner as in Experiment 6. Tansinone I and Tanshinone IIA were treated with 10 nM, 100 nM, 1 ⁇ M, and 10 ⁇ M, respectively.
- Wild type primary mouse keratinocytes were cultured and treated with 100 and 500 nM of tansinone I and tansinone IIA in serum free medium, respectively. Then, it was incubated for 24 hours after treatment with 70% ethanol or testosterone. After that, it was fixed with 3.5% paraformaldehyde at room temperature for one hour, and permeabilized in 0.5% triton X-100 for 10 minutes. Apoptotic cells were stained for 1 hour using an in situ cell death detection kit (Roche). Then, it was stained with DAPI for 10 minutes. Wash with 1X PBS between each step. The stained cells were analyzed by measuring the fluorescence through a confocal microscope, and the number of apoptotic cells compared to DAPI was analyzed using the Image J program.
- mice The back hairs of 8-week-old C57BL/6J mice were shaved, and the hairs were completely removed by applying an appropriate amount of depilatory cream. Mice without a back wound were selected, divided into groups, and 200 ⁇ g/100 ⁇ l of testosterone was applied to the back for 3 days from the day after hair removal. After 3 days, the final concentrations of tansinone I and tansinone IIA were diluted in 70% ethanol to 50 and 100 ⁇ M and applied together with testosterone for 12 days. In the control group, DMSO in the same amount as tansinone was diluted in 70% ethanol and applied. On the 12th day after drug application, mice were sacrificed to obtain dorsal skin tissue, which was frozen section and H&E stained. The length of hair follicles in each group was analyzed using Image J program.
- Tanshinone I Tanshinone IIA Cryptotansinone Example 1 10 ⁇ M 10 ⁇ M - Example 2 10 ⁇ M - 10 ⁇ M Example 3 - 10 ⁇ M 10 ⁇ M Comparative Example 1 20 ⁇ M - - Comparative Example 2 - 20 ⁇ M - Comparative Example 3 - - 20 ⁇ M
- mice The back hairs of 8-week-old C57BL/6J mice were shaved, and the hairs were completely removed by applying an appropriate amount of depilatory cream. Mice without a back wound were selected, divided into groups, and 200 ⁇ g/100 ⁇ l of testosterone was applied to the back for 3 days from the day after hair removal.
- tansinone I and tansinone IIA (Example 1), tanshinone I and cryptotansinone (Example 2), tansinone IIA and cryptotansinone (Example 3) , tansinone I (Comparative Example 1), tanshinone IIA (Comparative Example 2), and cryptotansinone (Comparative Example 3) were prepared by diluting in 70% ethanol so that the final concentration of 20 ⁇ M.
- Each Example and Comparative Example was applied to the back from the 4th day (day 0 of drug treatment) after hair removal, and the control group was applied by diluting DMSO in the same amount as tancinone in 70% ethanol.
- mice were sacrificed 12 days after drug treatment.
- the hair condition of the mice was confirmed by photographing once every 2 days from the 0th day of the drug treatment to the 12th day.
- the ratio of the hair growth area to the total hair removal area was measured using the Image-Pro Analyzer 7.0 program. The results are shown in FIGS. 18 and 19 .
- tansinone I and tansinone IIA were mixed, the synergistic effect of hair growth was excellent compared to when each compound was used alone.
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Abstract
La présente invention concerne une composition pharmaceutique pour prévenir ou traiter la perte de cheveux qui peut prévenir ou traiter efficacement la perte de cheveux en inhibant l'expression de NOX et en réduisant la génération d'oxygène réactif. Selon la présente invention, la composition comprend deux composés ou plus parmi les composés suivants : tanshinone I, tanshinone IIA et cryptotanshinone. En outre, la composition améliore la prévention ou le traitement de la perte de cheveux comparativement aux cas où un seul composé est utilisé.
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CN102127037A (zh) * | 2011-01-11 | 2011-07-20 | 上海交通大学 | 丹参酮类化合物及其应用 |
KR20120053248A (ko) * | 2010-11-17 | 2012-05-25 | 경희대학교 산학협력단 | 탄시논 ⅱa의 신규 용도 |
CN103193860A (zh) * | 2013-03-11 | 2013-07-10 | 常州大学 | 丹参酮类化合物、制备方法及其用途 |
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CN101254156A (zh) * | 2007-03-01 | 2008-09-03 | 段亚东 | 一种化妆品组合物及其用途 |
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CN102127037A (zh) * | 2011-01-11 | 2011-07-20 | 上海交通大学 | 丹参酮类化合物及其应用 |
CN103193860A (zh) * | 2013-03-11 | 2013-07-10 | 常州大学 | 丹参酮类化合物、制备方法及其用途 |
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