WO2020256397A1 - Composition for preventing or treating muscular diseases, containing, as active ingredient, glycyrrhiza uralensis extract or compound isolated therefrom - Google Patents
Composition for preventing or treating muscular diseases, containing, as active ingredient, glycyrrhiza uralensis extract or compound isolated therefrom Download PDFInfo
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- WO2020256397A1 WO2020256397A1 PCT/KR2020/007826 KR2020007826W WO2020256397A1 WO 2020256397 A1 WO2020256397 A1 WO 2020256397A1 KR 2020007826 W KR2020007826 W KR 2020007826W WO 2020256397 A1 WO2020256397 A1 WO 2020256397A1
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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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- 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
- A61K31/12—Ketones
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- 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
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/484—Glycyrrhiza (licorice)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
Definitions
- the present invention relates to a composition for preventing or treating muscle diseases containing a licorice extract or a compound isolated therefrom as an active ingredient.
- Muscle is an important component of the human body, and is a tissue expressed in stem cells of the mesoderm. Muscles are responsible for 40% of our body, and they are located by supporting bones and tendons, and consist of bundles of muscle fibers that move with each other and change the size of cells, causing contraction. Muscles are divided into skeletal muscle, heart muscle, and visceral muscle, and they create force at each location, induce movement, and protect body organs such as bones, joints, and internal organs. In addition, the muscle has a regenerative ability, and when the muscle is damaged, it can be regenerated into a muscle with the original contraction and relaxation ability after being denatured by satellite cells and its surrounding environment.
- Muscle diseases are caused by congenital inheritance or environmental causes, and diseases related to muscle loss are increasing with the trend of recent aging society and life span extension. Human muscles decrease by more than 1% every year from the age of 40, and by the age of 80, the level of maximum muscle mass decreases by 50%, and thus, muscle loss in old age is recognized as the most important cause of lowering overall physical function. These muscle diseases are on the rise worldwide compared to the past.
- the present invention provides a pharmaceutical composition for preventing or treating muscle diseases containing licorice extract or a fraction thereof as an active ingredient.
- the present invention provides a health functional food composition for preventing or improving muscle diseases containing licorice extract or a fraction thereof as an active ingredient.
- the present invention provides a pharmaceutical composition for preventing or treating muscle diseases containing a compound represented by any one of the following Formulas 1 to 3 or a pharmaceutically acceptable salt thereof as an active ingredient.
- the present invention provides a health functional food composition for preventing or improving muscle diseases containing the compound or a pharmaceutically acceptable salt thereof as an active ingredient.
- Licorice extract or a fraction thereof according to the present invention proliferates myoblasts, forms myotubes, and promotes the differentiation of myoblasts into muscle cells.
- various muscles as a pharmaceutical composition or health functional food composition containing the licorice extract or its fraction according to the present invention, a compound isolated therefrom, or a salt thereof as an active ingredient. Disease can be effectively prevented, ameliorated, or treated.
- composition has few side effects and is safe by using natural products.
- FIG. 1 is a schematic diagram of a method for preparing a licorice extract or a fraction thereof according to an embodiment of the present invention.
- a is an image and graph confirming the cell proliferation according to the concentration of the licorice hot water extract by the MTT method
- b is a scratch on the cell surface
- c is a fusion index
- real-time PCR which can confirm whether myoblasts differentiate into muscle cells.
- Figure 3 is a result of analyzing the muscle of the mouse according to the intake of licorice hot water extract
- a is a table showing the weight and muscle reduction rate of the mouse
- b is a Western blot result
- c is a specific strength of the band from the Western blot It is a graph that was quantified and d is an image showing protein expression changes through immunostaining.
- a is an MTT analysis image and graph of myoblasts
- b is an image showing the change according to the treatment of the fraction after applying a scratch to the cell surface.
- a is a graph showing an image of root canal formation and a fusion index
- b and c are muscle differentiation/expression of muscle atrophy genes and proteins according to the fraction treatment It shows change.
- FIG. 6 shows the chemical structure of the final single substances separated from the ethyl acetate (EtOAc) fraction according to an embodiment of the present invention.
- a is a graph showing the change in cell proliferation according to the treatment of 10 final substances isolated according to an embodiment of the present invention
- b is a root canal formation It is a graph showing the image and the melting index
- c is a graph showing the change in cell proliferation according to the treatment of the three final substances purchased
- d is a graph showing the root canal formation image and the melting index.
- a is a graph showing body weight, muscle weight and muscle reduction rate
- b is a result of H&E staining
- c is a graph showing the muscle diameter ( ⁇ m).
- the present invention provides a pharmaceutical composition for preventing or treating muscle diseases containing licorice extract or a fraction thereof as an active ingredient.
- the licorice Glycyrrhiza uralensis Fischer is a medicinal plant belonging to the dicotyledonous rosewood legume family, and may be obtained by harvesting or cultivating in nature, and may be purchased commercially.
- the licorice roots or rhizomes can be used as they are, or can be used by removing the perilla, preferably, dried roots of licorice can be used.
- extract refers to a substance obtained by extracting a component of a natural substance regardless of the extraction method, extraction solvent, extracted component, or form of the extract, and after extracting the substance obtained by extracting the component of a natural substance, Any material that can be obtained by processing or processing by a method may be included.
- the licorice extract may be extracted according to a method commonly used in the art, for example, hot water extraction, ultrasonic extraction, filtration, reflux extraction, etc., and these are performed alone or by using two or more methods in combination. Can be done.
- the licorice extract may be extracted with water, C1 to C4 alcohol or a mixed solvent thereof, preferably 15 to 25 times the weight of the licorice, more preferably 20 times of distilled water It may be a hot water extract extracted by heating at 110 to 120°C, more preferably 115°C, 2 to 4 hours, more preferably 3 hours, but is not limited thereto.
- the fraction of the licorice extract is selected from the group consisting of the licorice extract, preferably the hot water extract of the licorice, dichloromethane, ethyl acetate and n-buthanol It may be fractionated with one or more solvents, and more preferably, it may be an ethyl acetate fraction of the licorice hot water extract fractionated with ethyl acetate.
- dichloromethane, ethyl acetate, and n-butanol are sequentially distributed, and each solution is evaporated to form a dichloromethane fraction, an ethyl acetate fraction, and n The -butanol fraction was obtained.
- the licorice extract or a fraction thereof can proliferate myoblasts, form a myotube, and promote differentiation of myoblasts into muscle cells.
- the licorice extract or a fraction thereof inhibits muscle protein degradation and muscle atrophy, and can regenerate damaged muscles.
- the licorice extract or a fraction thereof may increase the expression of one or more genes or proteins selected from the group consisting of MYOG, MYOD, MYL2 and Pax7, which are factors related to muscle differentiation or muscle regeneration, and are factors related to muscle proteolysis or muscle atrophy. It is possible to reduce the expression of one or more genes or proteins selected from the group consisting of MSTN, MuRF1, Atrogin 1, and nitrotyrosine.
- MYOD initiates the expression of muscle-specific genes and induces the differentiation of muscle satellite cells into myoblasts.
- Induction of myogenin (MYOG) expression by the activity of MYOD is the most important factor in the fusion of myoblasts, and is involved in the formation of myotubes, and the muscle fibers formed through this process are bundles. To finally form muscle.
- the present invention provides a pharmaceutical composition for preventing or treating muscle diseases containing a compound represented by any one of the following Formulas 1 to 3 or a pharmaceutically acceptable salt thereof as an active ingredient.
- the compounds of Formulas 1 to 3 are active ingredients isolated from licorice, preferably, Formula 1 is Liquiritigenin, Formula 2 is tetrahydroxy methoxychalcone, Formula 3 May be Licochalcone B.
- the compound or its salt may be directly separated or extracted from natural products by methods well known in the art, or prepared by chemical synthesis, and commercially available ones may be selected and used, but the method or material is not particularly limited.
- the compound or a salt thereof is water, a licorice extract extracted with a C1 to C4 alcohol or a mixed solvent thereof, preferably a licorice methanol extract is fractionated with dichloromethane or ethyl acetate. It may be separated from one fraction, and preferably, the licorice methanol extract may be separated from a fraction obtained by sequentially distributing the licorice methanol extract with dichloromethane and ethyl acetate, but is not limited thereto.
- the compound or a salt thereof is divided into dichloromethane by suspending the licorice methanol extract obtained by reflux extraction of the dried roots of licorice with 100% methanol in distilled water, and after removing the dichloromethane from the water fraction, to ethyl acetate. It may be separated from the ethyl acetate fraction obtained by partitioning.
- the compound of Formula 1 or a salt thereof is hexane-ethylacetate-methanol (hexane-EtOAc-MeOH, 5.5:1:0.1, 3:1:0.1, v/v), chloroform in the ethyl acetate fraction.
- -Acetone-methanol CHCl3-Acetone-MeOH, 3:1:0.1, v/v
- chloroform-methanol-water CHCl3-MeOH-H2O, 5:1:0.1, 3:1:0.1, v/v
- silica gel column chromatography to obtain five fractions (Fr.
- fraction E2 was converted into methanol-water by MPLC using a SNAP Ultra C18 cartridge. , 34-75% MeOH, v/v) to obtain 16 fractions (Fr. E2A-E2P), of which fraction E2C was used as hexane-ethylacetate-methanol (hexane-EtOAc-MeOH, 3 :1:0.1, v/v) It may be separated using silica gel column chromatography with a solvent, but is not limited thereto.
- the compound of Formula 2 or a salt thereof was prepared by MPLC using a SNAP Ultra C18 cartridge to extract fraction E3 of the five fractions (Fr. E1-E5) separated from the ethyl acetate fraction by MPLC in methanol-water (MeOH-Water, 33- After separating into 15 fractions (Fr. E3A-E3O) with a gradient of 80% MeOH, v/v), fraction E3E of these was separated into hexane-ethylacetate-methanol by MPLC using a SNAP KP-SIL cartridge.
- -EtOAc-MeOH, 28-36% EtOAc-MeOH, 1:0.1, v/v) may be separated by a gradient, but is not limited thereto.
- the compound of Formula 3 or a salt thereof was prepared by MPLC using a SNAP KP-SIL cartridge to extract the fraction E3F from the 15 fractions (Fr. E3A-E3O) by hexane-ethylacetate-methanol (hexane-EtOAc- MeOH, 20-34% EtOAc-MeOH, 1:0.1, v/v) was separated into five fractions (Fr. E3FA-E3FE), and the fraction E3FB was separated by TLC (silica gel 60 F254, hexane-EtOAc). -MeOH, 1:1:0.2, v/v) may be obtained by separating, but is not limited thereto.
- the compound can be used in the form of a pharmaceutically or food acceptable salt within a range having the same efficacy.
- pharmaceutically or food pharmaceutically acceptable means non-toxic to humans or cells exposed to the composition.
- the salt can be used in the form of either a pharmaceutically or food pharmaceutically acceptable basic salt or acid salt.
- the basic salt can be used in the form of either an organic base salt or an inorganic base salt, and a sodium salt, a potassium salt, a calcium salt, a lithium salt, a magnesium salt, a cesium salt, an aminium salt, an ammonium salt, a triethylaminium salt and a pyri It may be selected from the group consisting of dinium salts.
- Acidic salts are useful acid addition salts formed by free acids.
- Inorganic acids and organic acids can be used as free acids, hydrochloric acid, bromic acid, sulfuric acid, sulfurous acid, phosphoric acid, double phosphoric acid, nitric acid, etc. can be used as inorganic acids, and citric acid, acetic acid, maleic acid, malic acid, fumaric acid, etc. can be used as inorganic acids.
- Glucoic acid methanesulfonic acid, benzenesulfonic acid, camphorsulfonic acid, oxalic acid, malonic acid, glutaric acid, acetic acid, glycolic acid, succinic acid, tartaric acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, Glutamic acid, citric acid, aspartic acid, stearic acid, and the like may be used, but are not limited thereto, and all salts formed using various inorganic and organic acids commonly used in the art may be included.
- the compound may include all salts, hydrates, solvates, derivatives, etc. that may be prepared by conventional methods, as well as pharmaceutically or food acceptable salts.
- the addition salt can be prepared by a conventional method and dissolved in a water-miscible organic solvent, such as acetone, methanol, ethanol, or acetonitrile, to add an excessive amount of organic base, or to precipitate or crystallize after adding an aqueous base solution of an inorganic base. It can be manufactured by making it.
- the mixture may be prepared by evaporating a solvent or an excess base and drying to obtain an addition salt, or by suction filtration of the precipitated salt.
- the compound or a salt thereof can proliferate myoblasts, form root canals, and promote differentiation of myoblasts into muscle cells.
- the compound or a salt thereof inhibits muscle protein degradation and muscle atrophy, and can regenerate damaged muscles.
- the muscle disease is a muscle disease due to a decrease in muscle function, muscle wasting or muscle degeneration, for example, muscle atrophy, muscular dystrophy, sarcopenia, and myopathy ( myopathy), myasthenia, and muscle injury, but may be one or more selected from the group consisting of, but is not limited thereto.
- prevention refers to any action of inhibiting the occurrence of or delaying the onset of muscle disease, or at least one symptom thereof, by administration of the pharmaceutical composition or health functional food composition according to the present invention. In addition, it includes treatment of a subject with remission of the disease to prevent or prevent recurrence.
- treatment refers to any action that improves or beneficially changes the symptom, such as alleviating, reducing, or eliminating muscle disease, or at least one symptom thereof, by administration of the pharmaceutical composition according to the present invention. do.
- the "pharmaceutical composition” means a composition administered for a specific purpose, and for the purposes of the present invention, it is meant to be administered to prevent or treat muscle disease, or at least one symptom thereof.
- the pharmaceutical composition according to the present invention can be prepared according to a conventional method in the pharmaceutical field.
- the pharmaceutical composition may be blended with an appropriate pharmaceutically acceptable carrier according to the dosage form, and if necessary, may be prepared further including excipients, diluents, dispersants, emulsifiers, buffers, stabilizers, binders, disintegrants, solvents, etc. have.
- the appropriate carrier or the like is one that does not inhibit the activity and properties of the licorice extract or a fraction thereof, a compound isolated therefrom, or a salt thereof according to the present invention, and may be selected differently depending on the dosage form and formulation.
- the pharmaceutical composition according to the present invention may be applied in any dosage form, and more particularly, may be formulated and used in parenteral dosage forms of oral dosage forms, external preparations, suppositories and sterile injectable solutions according to conventional methods.
- the solid dosage form may be in the form of tablets, pills, powders, granules, gels, capsules, and the like, and at least one excipient such as starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, It can be prepared by mixing gelatin and the like, and in addition to simple excipients, lubricants such as magnesium stearate and talc may also be included.
- a liquid carrier such as fatty oil may be further included.
- liquid dosage forms correspond to suspensions, liquid solutions, emulsions, syrups, and the like.
- various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. may be included. have.
- the parenteral formulation may include a sterilized aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a lyophilized formulation, and a suppository.
- Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. may be used as the non-aqueous solvent and suspension.
- As a base for suppositories witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used.
- the present invention is not limited thereto, and any suitable agent known in the art may be used.
- composition according to the present invention may further add calcium or vitamins to improve therapeutic efficacy.
- the pharmaceutical composition may be administered in a pharmaceutically effective amount.
- a pharmaceutically effective amount means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and not cause side effects.
- the effective dosage level of the pharmaceutical composition is the purpose of use, the patient's age, sex, weight and health condition, the type of disease, the severity, the activity of the drug, the sensitivity to the drug, the method of administration, the administration time, the administration route and the rate of excretion, the treatment It may be determined differently depending on the duration, factors including drugs used in combination or concurrently and other factors well known in the medical field. For example, although not constant, generally 0.001 to 100 mg/kg, preferably 0.01 to 10 mg/kg may be administered once to several times a day. The above dosage does not in any way limit the scope of the present invention.
- the pharmaceutical composition according to the present invention may be administered to any animal that may cause muscle disease, and the animal may include, for example, humans and primates as well as livestock such as cattle, pigs, horses, and dogs. .
- the pharmaceutical composition according to the present invention can be administered by an appropriate route of administration according to the form of the formulation, and can be administered through various routes, either oral or parenteral, as long as it can reach the target tissue.
- the method of administration is not particularly limited, and may be administered by conventional methods such as, for example, oral, rectal or intravenous, intramuscular, skin application, inhalation in the respiratory tract, intrauterine dura mater or intracere-broventricular injection. have.
- the pharmaceutical composition according to the present invention may be used alone for the prevention or treatment of muscle diseases, or may be used in combination with surgery or other drug treatment.
- the present invention provides a health functional food composition for preventing or improving muscle diseases containing licorice extract or a fraction thereof as an active ingredient.
- the licorice extract may be a licorice hot water extract
- the fraction of the licorice extract may be an ethyl acetate fraction of the licorice hot water extract.
- the licorice extract or a fraction thereof can proliferate myoblasts and form root canals, and promote differentiation of myoblasts into muscle cells.
- the licorice extract or its fractions inhibit muscle protein decomposition and muscle atrophy, and can regenerate damaged muscles, and thus can be used as a health functional food composition for preventing or improving muscle diseases.
- the present invention provides a health functional food composition for preventing or improving muscle diseases containing a compound represented by any one of the following Chemical Formulas 1 to 3 or a pharmaceutically acceptable salt thereof as an active ingredient.
- the compound or a salt thereof may be separated from a fraction obtained by fractionating the methanol extract of licorice with dichloromethane or ethyl acetate, and Liquiritigenin, tetrahydroxy methoxy Chalcone (Tetrahydroxy methoxychalcone), or lycochalcone B (Licochalcone B) may be included.
- Liquiritigenin, tetrahydroxy methoxy Chalcone (Tetrahydroxy methoxychalcone), or lycochalcone B (Licochalcone B) may be included.
- the compound or a salt thereof can proliferate myoblasts, form a myotube, and promote differentiation of myoblasts into muscle cells.
- the compound or its salt inhibits muscle protein degradation and muscle atrophy, and can regenerate damaged muscles, and thus can be used as a health functional food composition for preventing or improving muscle diseases.
- the term “improvement” refers to any action that improves or beneficially changes the symptoms such as alleviating, reducing, or eliminating muscle diseases, or at least one symptom thereof, by ingestion of the health functional food composition according to the present invention Means.
- the term "health functional food” includes foods manufactured and processed using raw materials or ingredients having functions useful for the human body according to the Health Functional Food Act No. 6727, and in addition to supplying nutrition, the object of the present invention It refers to medicines and foods with high medical effects that have been processed to efficiently exhibit biological control functions such as prevention of upper muscle disease, body defense, immunity, and recovery.
- the health functional food according to the present invention may be prepared as a powder, granule, tablet, capsule, syrup or beverage for the purpose of preventing or improving muscle disease.
- the health functional food can take, and it can be formulated in the same manner as the pharmaceutical composition and used as a functional food, or can be added to various foods.
- the health functional food may include all foods in a conventional sense.
- beverages and various drinks, fruits and processed foods thereof canned fruit, jam, etc.
- fish, meat and processed foods thereof ham, bacon, etc.
- bread and noodles cookies and snacks
- dairy products butter, cheese, etc.
- foods used as feed for animals may also be included.
- the health functional food composition according to the present invention may be prepared by further comprising a food pharmaceutically acceptable food additive (food additive) and other appropriate auxiliary ingredients commonly used in the art.
- a food pharmaceutically acceptable food additive food additive
- other appropriate auxiliary ingredients commonly used in the art.
- the suitability as a food additive can be determined according to the standards and standards for the relevant item in accordance with the General Rules and General Test Methods of the Food Additive Code approved by the Ministry of Food and Drug Safety.
- Items listed in the'Food Additives Code' include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as reduced pigment, crystalline cellulose, high-volume pigment, and guar gum; Mixed preparations, such as a sodium L-glutamate preparation, an alkali additive for noodles, a preservative preparation, and a tar color preparation, etc. are mentioned.
- the other auxiliary ingredients are, for example, flavoring agents, natural carbohydrates, sweetening agents, vitamins, electrolytes, colorants, pectic acids, alginic acids, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents, etc. It may further contain.
- natural carbohydrates monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin
- sugar alcohols such as xylitol, sorbitol, and erythritol
- sweetener natural sweeteners such as taumatin and stevia extract, or synthetic sweeteners such as saccharin and aspartame may be used.
- the effective dose of the licorice extract or a fraction thereof, a compound isolated therefrom, or a salt thereof contained in the health functional food according to the present invention may be appropriately adjusted according to the purpose of use, such as prevention or improvement of muscle disease.
- the health functional food composition has the advantage of not having side effects that may occur when taking general medicines for a long period of time by using food as a raw material, and has excellent portability, and can be taken as an auxiliary for preventing or improving muscle diseases.
- the present invention provides a reagent composition for proliferation of myoblasts containing a licorice extract or a fraction thereof as an active ingredient.
- the present invention provides a reagent composition for promoting the differentiation of myoblasts into muscle cells containing licorice extract or a fraction thereof as an active ingredient.
- the present invention provides a reagent composition for proliferation of myoblasts containing a compound represented by any one of the following Formulas 1 to 3 or a pharmaceutically acceptable salt thereof as an active ingredient.
- the present invention provides a reagent composition for promoting differentiation of myoblasts into muscle cells containing the compound or a salt thereof as an active ingredient.
- the present invention provides a method for proliferating myoblasts comprising treating a licorice extract or a fraction thereof on animals other than humans.
- the present invention provides a method for promoting differentiation of myoblasts into muscle cells, comprising the step of treating a licorice extract or a fraction thereof on animals other than humans.
- the present invention provides a method for proliferating myoblasts comprising treating an animal other than humans with a compound represented by any one of the following Formulas 1 to 3 or a pharmaceutically acceptable salt thereof.
- the present invention provides a method for promoting differentiation of myoblasts into muscle cells, comprising the step of treating an animal other than humans with the compound or a salt thereof.
- the dried root of licorice ( Glycyrrhiza uralensis Fischer) was purchased as a dried herb from Gwangmyeong Herbal Medicine. Specimens of all plants are stored in the Herbal Medicine Bank of the KM Application Center of the Korean Institute of Oriental Medicine.
- licorice hot water extract dried licorice pieces (50.0 g) were added to 1,000 mL distilled water and extracted by heating at 115° C. for 3 hours. After extraction, it was filtered and freeze-dried using standard testing sieves (150 ⁇ m). The lyophilized extract powder was dissolved in tertiary distilled water and left at 4°C for 24 hours. After 24 hours, after centrifugation at 5000 g for 5 minutes, the supernatant was transferred to a new tube and stored at -20°C.
- FIG. 1 is a schematic diagram of a method for preparing a licorice extract or a fraction thereof according to an embodiment of the present invention.
- the ethyl acetate fraction was mixed with hexane-ethylacetate-methanol (hexane-EtOAc-MeOH, 5.5:1:0.1, 3:1:0.1, v/v), chloroform-acetone-methanol (CHCl 3 -Acetone-MeOH, 3: 1:0.1, v/v), chloroform-methanol-water (CHCl 3 -MeOH-H 2 O, 5:1:0.1, 3:1:0.1, v/v) with silica gel column chromatography Through chromatography), five fractions (Fr. E1-E5) and a semi-crystalline solid (Fr. EC) were obtained.
- hexane-EtOAc-MeOH 5.5:1:0.1, 3:1:0.1, v/v
- chloroform-acetone-methanol CHCl 3 -Acetone-MeOH, 3: 1:0.1, v/v
- chloroform-methanol-water CHCl 3
- Fraction E2 (4.9 g) was separated by a gradient of methanol-water (MeOH-Water, 34-75% MeOH, v/v) by MPLC using a SNAP Ultra C18 cartridge, and 16 fractions containing compound 1 (23.9 mg) (Fr. E2A-E2P) was obtained.
- Fraction E3 (41.6 g) was separated with a gradient of methanol-water (MeOH-Water, 33-80% MeOH, v/v) by MPLC using a SNAP Ultra C18 cartridge and 15 fractions (Fr. E3A-E3O) Was secured.
- Fraction E3E 140.0 mg was obtained by MPLC using a SNAP KP-SIL cartridge with a gradient of hexane-ethylacetate-methanol (hexane-EtOAc-MeOH, 28-36% EtOAc-MeOH, 1:0.1, v/v). It was isolated and obtained as compound 6 (35.2mg).
- Fraction E3F (410.0 mg) was obtained by MPLC using a SNAP KP-SIL cartridge at a gradient of hexane-ethylacetate-methanol (hexane-EtOAc-MeOH, 20-34% EtOAc-MeOH, 1:0.1, v/v). It was isolated and obtained as 5 fractions (Fr. E3FA-E3FE).
- Fraction E3FB (17.5 mg) was separated by TLC (silica gel 60 F254, hexane-EtOAc-MeOH, 1:1:0.2, v/v) to obtain compound 7 (5.6 mg).
- Fraction E5 (20.4 g) was sequestered with a gradient of methanol-water (MeOH-Water, 20-44% MeOH, v/v) by MPLC using a SNAP Ultra C18 cartridge and 9 fractions (Fr. E5A-E5I) Was secured.
- Fraction E5B-D was obtained with a gradient of chloroform-methanol-water (CHCl 3 -MeOH-H 2 O, 12-20% MeOH-H2O, 1:0.1, v/v) by MPLC using a SNAP KP-SIL cartridge. Combined and obtained as 5 fractions (Fr. E5BA-E5BE).
- Fraction E5BA was obtained as a compound 8 (969.0mg) by redistribution in methanol after obtaining a semi-crystalline solid.
- Fraction E5BB-C was combined using silica gel column chromatography with a solvent of chloroform-methanol-water (CHCl 3 -MeOH-H 2 O, 7:1:0.05, 6:1:0.05 and MeOH, v/v) and Separated and obtained as 6 fractions (Fr. E5BBA-E5BBF).
- Fraction E5BBD (220.0mg) is ethyl acetate-methanol-water (EtOAc-MeOH-H 2 O, 4-10% MeOH-H 2 O, 1:0.1, v/v) by MPLC using a SNAP KP-SIL cartridge. ) was isolated with a gradient of 9 (113.5mg).
- Fraction EC (3.0 g) was obtained by MPLC using a SNAP KP-SIL cartridge in chloroform-methanol-water (CHCl 3 -MeOH-H 2 O, 12-16% MeOH-H2O, 1:0.1, 100% Acetone, v After separating with a gradient of /v), it was secured as one fraction, and then re-dispersed in methanol to obtain compound 10 (22.2mg).
- Mouse myoblast cell line C2C12 cells are Dulbecco's Modified Eagle's Medium (DMEM) containing 10% Fetal bovine serum ( FBS) and 1% penicillin/streptomycin (P/S). ).
- DMEM Dulbecco's Modified Eagle's Medium
- FBS Fetal bovine serum
- P/S penicillin/streptomycin
- C2C12 cells (2 ⁇ 10 3 cells/ml) were placed in a 12 well cell culture dish and adhered for 24 hours, followed by hot water extract (0 , 50, 100, 200 ⁇ g/ml), a fraction thereof (25 ⁇ g/ml) or a final material (0.5 ng/ml) was treated for 1 day and the proliferation of cells was confirmed.
- the medium was changed every 2 days and the cells were cultured at 37°C.
- DMEM differentiation medium
- FBS FBS
- P/S hot water extract
- fraction 25 ⁇ g/ml
- the medium of the cells was removed and the cells were washed with PBS. After washing, a 1:1 volume ratio of methanol:PBS was treated and then fixed for 2 minutes. Additionally, a 2:1 volume ratio of methanol:PBS reagent was added, followed by further fixation for 2 minutes. After 2 minutes, 0.04% Giemsa reagent was added, allowed to stand for 30 minutes, washed with PBS after 30 minutes, and then the appearance of the cells was observed under a microscope, and three pictures of the cells were taken (300 ⁇ ). In the photographs taken, the number of fused nuclei in the root canal cells was counted, the total number of nuclei was counted, and the number of fused nuclei was divided by the total number of nuclei to calculate the% value.
- the cells were crushed using an ultra-high frequency pulverizer (sonicator). After centrifuging the pulverized sample (12,000 rpm, 10 minutes, 4° C.), the supernatant was transferred to a new tube, 200 ⁇ l of chloroform was added, and left at room temperature for 10 minutes. Then, centrifugation was performed (12,000 rpm, 10 minutes, 4° C.) to obtain a transparent supernatant.
- RNA pellet 500 ⁇ l was added, allowed to stand for 10 minutes, and centrifuged to obtain an RNA pellet. After washing by adding 70% ethanol (ethanol + diethylpyrocarbonate (DEPC) treated distilled water) to the RNA pellet, it was completely removed and dried. DEPC-treated distilled water was added to the dried transparent RNA and stored at -80°C. The total amount of RNA was measured by nanodrops, and 18s and 28s bands were identified on a 1.2% agarose gel. cDNA was synthesized with 2 ⁇ g of total RNA, random hexamer primer, and reverse transcriptase (25°C: 10 minutes, 37°C: 120 minutes, 85°C: 5 minutes) .
- DEPC diethylpyrocarbonate
- Real-time PCR was performed to confirm gene expression.
- gene expression was analyzed using the Power SYBR Green PCR Master Mix containing a fluorescent material of SYBR green (7500 real-time PCR system).
- PCR primers were designed with Primer 3 software (http://frodo.wi.mit.edu) according to the nucleotide sequence obtained from NCBI GenBank.
- PCR was performed 40 times at 95° C. for 10 minutes, again at 95° C. for 33 seconds, 33 seconds at the gene primer temperature (tm), and 33 seconds at 72° C.
- Gene expression values were analyzed through analysis of c(t) values obtained through real-time PCR analysis (fold change 2- ⁇ Ct formula).
- the gene expression value of the treated cells was calculated by setting the gene expression value of the untreated cell as 1.
- the GAPDH Glyceraldehyde-3-phosphate dehydrogenase
- the medium of the cultured C2C12 cells was removed and washed once with PBS. After fixing the cells for 15 minutes by treating the washed cells with 4% formaldehyde (Sigma), washing the cells with PBS, adding 0.2% trypton X-100 (Sigma), and leaving for 5 minutes I did. Wash again with PBS, add enhancer solution (enhancer sol.) and leave for 30 minutes, and then primary antibodies (MYOD, MYOG, Myosin light chain 2 (MYL2), Atrogin 1, MuRF1, Nitrothyrosine, MSTN, 1:50) ) And reacted at 4° C. for 14 hours.
- enhancer solution enhancer sol.
- the antibody was removed, washed 3 times with PBS for 10 minutes, and incubated with a secondary antibody (Alexa Fluor 488 goat anti-rabbit or mouse SFX kit) for 1 hour. After incubation, the antibody was removed, washed with PBS for 10 minutes, and then the nuclei were stained with DAP I (4′,6-diamidino-2-phenylindol), and the protein expression was observed using a fluorescence microscope.
- a secondary antibody Alexa Fluor 488 goat anti-rabbit or mouse SFX kit
- the medium of the cultured C2C12 cells was removed and washed with PBS. After adding RIPA buffer (Radioimmunoprecipitation assay buffer, Thermo) and protease inhibitor (Thermo) to the washed cells, the cells were lysed to extract proteins. Of the extracted proteins, 40 ⁇ g was electrophoresed on an 8 to 10% acrylamide gel, and then transferred to a PVDF membrane (Polyvinylidene fluoride membrane, Milipore). This was blocked with 3% skim milk or bovine serum albumin (BSA) at room temperature for 1 hour.
- RIPA buffer Radioimmunoprecipitation assay buffer, Thermo
- protease inhibitor Thermo
- the primary antibody diluted in 1% skim milk or BSA (MYOD: 1:500, MYOG: 1:400, MYL2: 1:1000, ß-actin: 1:1000, MuRF1: 1:500, Atrogin 1: 1:500, Nitrotyrosine: 1:10000, MSTN: 1:500, GAPDH: 1:1000) was added and reacted at 4°C for 16 hours or more. After 16 hours, it was washed three times with TBST (Tween 20-containing Tris-Buffered Saline), and a secondary antibody to which HRP (horseradish peroxidase) was attached was reacted at room temperature for 1 hour. This was washed 3 times with TBST and developed after adding Super Signal West Pico Chemiluminescent Substrate.
- TBST Teween 20-containing Tris-Buffered Saline
- mice were ingested with liquorice hot water extract or liquiitigenin, and Cardiotoxin (CTX) was injected into the muscle. After injection, the morphology and regeneration of the muscles were observed. C57BL/6 mice were ingested with licorice hot water extract (100mg/kg) or liquiditygenin (15mg/kg), and 100mM cardiotoxin was injected into the gastrocnemius muscle. After cardiotoxin injection, licorice hot water extract or liquiitigenin was ingested every day, and muscle tissue was sampled 7 days after cardiotoxin non-injection or injection. The diameter ( ⁇ m) of the muscle secured 7 days after cardiotoxin was not injected or injected was measured using an image J program.
- CTX Cardiotoxin
- C2C12 cells were treated with 0, 50, 100, 200 ⁇ g/ml of the hot water extract for 1 day, and then the proliferation of the cells was analyzed by the MTT method.
- FIG. 2 is a result of observation of proliferation and differentiation of myoblasts (C2C12) according to the licorice hot water extract treatment, where the degree of proliferation of myoblasts is set to 100 and the cells treated with the licorice hot water extract are Relative values were calculated, and the degree of differentiation and gene expression was expressed by calculating the relative values of cells treated with licorice hot water extract with the value of cells not treated with anything as 1. The same applies in the following experiments.
- the licorice hot water extract was ingested into the mouse, and cardiotoxin was injected into the mouse muscle to analyze the degree of regeneration of the damaged muscle.
- cardiotoxin was injected into the mouse muscle to analyze the degree of regeneration of the damaged muscle.
- the expression of related proteins was observed after feeding licorice hot water extract.
- mice injected with cardiotoxin only The expressions of MSTN, MuRF1, Atrogin 1 and Nitrotyrosine proteins related to muscle differentiation inhibition, proteolysis and muscle atrophy were decreased compared to mice injected with cardiotoxin alone in the muscles of mice injected with licorice hot water extract/cardiotoxin. Appeared to be. However, in the muscles of mice without muscle damage, differences in protein expression according to the intake of licorice hot water extract could not be observed.
- Figure 4 shows the results of myoblast proliferation according to the fraction treatment of the licorice extract, referring to this, not only the cells treated with the licorice hot water extract (EX, 10%), but also the ethyl acetate fraction of licorice (EtOAc, 12%) Alternatively, cells treated with the n-butanol fraction (BuOH, 12%) showed an increase in cell proliferation compared to cells not treated with the extract or the fraction. However, the cells treated with the dichloromethane (DCM) fraction showed a decrease in cell proliferation compared to the untreated cells (27%).
- EX the cells treated with the licorice hot water extract
- EtOAc ethyl acetate fraction of licorice
- BuOH n-butanol fraction
- the cells were treated with 2% FBS differentiation medium, and the fraction (25 ⁇ g/ml) was also treated and cultured for 4 days.
- 5 is a result of observation of differentiation of myoblasts according to the treatment of the fraction of the licorice extract. Referring to this, it was confirmed that the formation of the root canal was increased according to the treatment of the ethyl acetate (EtOAc) fraction of the licorice.
- EtOAc ethyl acetate
- MYOD, MYOG, and MYL2 genes and proteins related to muscle differentiation was increased, and the expression of Atrogin 1, MuRF1 and MSTN genes related to protein degradation, muscle atrophy and differentiation inhibition was decreased. In addition, it was confirmed that the expression of MuRF1 and MSTN proteins was decreased.
- FIG. 6 shows the chemical structure of a single substance separated from an ethyl acetate (EtOAc) fraction according to an embodiment of the present invention. After separating 10 kinds of final materials from the fractions through several stages of fractionation, structural analysis was performed.
- EtOAc ethyl acetate
- Table 2 below shows the separated 10 kinds of final materials and analysis results thereof.
- FIG. 7 is a result of observation of myoblast proliferation and differentiation according to the treatment of the final single substances.
- Liquiritigenin 10%), Tetrahydroxymethoxychalcone; 8 %) or Lycochalcone B (11%
- the proliferation of cells was increased compared to cells not treated with the substance.
- the degree of regeneration of the damaged muscle was observed by ingesting liquiitigenin into the mouse and then injecting cardiotoxin into the mouse muscle to measure the diameter of the regenerated muscle.
- FIG. 8 is a result of analyzing changes in muscle after ingesting purchased liquiritigenin into a mouse, and referring to this, the change in body weight between mice ingested and not ingested liquiitigenin in a And muscle weight was almost unchanged, but the muscle loss rate of the mice ingesting the substance was less than that of mice not ingested.
- the muscle diameter of the mice that ingested liquiitigenin was the diameter of the regenerated muscle compared to the mice that did not take it (the muscle diameter of the mouse not ingested: 78 ⁇ 4 ⁇ m, the muscle of the mouse ingested) Diameter: 91 ⁇ 3 ⁇ m) was found to be larger. Even in the muscles of mice not injected with cardiotoxin, the muscle diameter of the ingested mouse was larger than that of the non-ingested mouse (the muscle diameter of the non-ingested mouse: 124 ⁇ 4 ⁇ m, the muscle diameter of the ingested mouse: 139 ⁇ 4 ⁇ m). Was confirmed.
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Abstract
Description
GeneGene | Productsize(bp)Productsize(bp) | Tm (℃)Tm (℃) | Sequence (F)Sequence (F) | Sequence (R)Sequence (R) |
GAPDHGAPDH | 155155 | 5959 | 5'-tgctggtgctgagtatgtcg-3'(서열번호 1)5'-tgctggtgctgagtatgtcg-3' (SEQ ID NO: 1) | 5'-caagcagttggtggtacagg-3'(서열번호 2)5'-caagcagttggtggtacagg-3' (SEQ ID NO: 2) |
MYODMYOD | 213213 | 5959 | 5'-aggagcacgcacacttctct-3'(서열번호 3)5'-aggagcacgcacacttctct-3' (SEQ ID NO: 3) | 5'-tctcgaaggcctcattcact-3'(서열번호 4)5'-tctcgaaggcctcattcact-3' (SEQ ID NO: 4) |
MYOGMYOG | 185185 | 5959 | 5'-tccagtacattgagcgccta-3'(서열번호 5)5'-tccagtacattgagcgccta-3' (SEQ ID NO: 5) | 5'-caaatgatctcctgggttgg-3'(서열번호 6)5'-caaatgatctcctgggttgg-3' (SEQ ID NO: 6) |
MYL2MYL2 | 177177 | 5959 | 5'-aaagaggctccaggtccaat-3'(서열번호 7)5'-aaagaggctccaggtccaat-3' (SEQ ID NO: 7) | 5'-cctctctgcttgtgtggtca-3'(서열번호 8)5'-cctctctgcttgtgtggtca-3' (SEQ ID NO: 8) |
Atrogin1 |
160160 | 5959 | 5'-ttcagcagcctgaactacga-3'(서열번호 9) 5'-ttcagcagcctgaactacga-3' (SEQ ID NO: 9) | 5'-tgaaagcttcccccaaagta-3'(서열번호 10) 5'-tgaaagcttcccccaaagta-3' (SEQ ID NO: 10) |
MuRf1MuRf1 | 206206 | 5959 | 5'-tgaggtgcctacttgctcct-3'(서열번호 11)5'-tgaggtgcctacttgctcct-3' (SEQ ID NO: 11) | 5'-tcacctggtggctattctcc-3'(서열번호 12)5'-tcacctggtggctattctcc-3' (SEQ ID NO: 12) |
MSTNMSTN | 163163 | 5959 | 5'-acgctaccacggaaacaatc-3'(서열번호 13)5'-acgctaccacggaaacaatc-3' (SEQ ID NO: 13) | 5'-ggagtcttgacgggtctgag-3'(서열번호 14)5'-ggagtcttgacgggtctgag-3' (SEQ ID NO: 14) |
Claims (16)
- 감초 추출물 또는 이의 분획물을 유효성분으로 함유하는 근육질환 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating muscle diseases containing licorice extract or a fraction thereof as an active ingredient.
- 제 1 항에 있어서,The method of claim 1,상기 감초 추출물은,The licorice extract,상기 감초를 증류수에 넣어 110 내지 120℃에서 2 내지 4시간 가열하여 추출한 열수 추출물인 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating muscle diseases, characterized in that it is a hot water extract extracted by adding the licorice to distilled water and heating at 110 to 120°C for 2 to 4 hours.
- 제 2 항에 있어서,The method of claim 2,상기 분획물은,The fraction,상기 감초 추출물을 디클로로메탄(dichloromethane), 에틸 아세테이트(ethyl acetate) 및 n-부탄올(n-buthanol)로 이루어진 군에서 선택되는 하나 이상의 용매로 분획한 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating muscle diseases, characterized in that the licorice extract is fractionated with one or more solvents selected from the group consisting of dichloromethane, ethyl acetate, and n-buthanol.
- 제 1 항 내지 제 3 항 중 어느 한 항에 있어서,The method according to any one of claims 1 to 3,상기 감초 추출물 또는 이의 분획물은,The licorice extract or a fraction thereof,근아세포를 증식시키고 근관을 형성시키며, 근육세포로의 분화를 촉진시키는 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물. A pharmaceutical composition for preventing or treating muscle diseases, characterized in that proliferating myoblasts, forming myotubes, and promoting differentiation into muscle cells.
- 제 1 항 내지 제 3 항 중 어느 한 항에 있어서,The method according to any one of claims 1 to 3,상기 감초 추출물 또는 이의 분획물은,The licorice extract or a fraction thereof,손상된 근육을 재생시키는 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물. A pharmaceutical composition for preventing or treating muscle diseases, characterized in that to regenerate damaged muscles.
- 제 1 항 내지 제 3 항 중 어느 한 항에 있어서,The method according to any one of claims 1 to 3,상기 감초 추출물 또는 이의 분획물은,The licorice extract or a fraction thereof,근육 단백질 분해 또는 근육 위축을 억제시키는 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물. A pharmaceutical composition for preventing or treating muscle diseases, characterized in that to inhibit muscle protein degradation or muscle atrophy.
- 제 1 항 내지 제 3 항 중 어느 한 항에 있어서,The method according to any one of claims 1 to 3,상기 감초 추출물 또는 이의 분획물은,The licorice extract or a fraction thereof,근육 분화 관련 인자인 MYOG, MYOD, MYL2 및 Pax7로 이루어진 군에서 선택되는 하나 이상의 발현을 증가시키고, 근육 단백질 분해 관련 인자인 MSTN, MuRF1, Atrogin 1 및 니트로티로신(Nitrotyrosine)으로 이루어진 군에서 선택되는 하나 이상의 발현을 감소시키는 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물.One selected from the group consisting of muscle differentiation-related factors MYOG, MYOD, MYL2 and Pax7, and increasing the expression of one or more selected from the group consisting of muscle proteolysis-related factors MSTN, MuRF1, Atrogin 1 and nitrotyrosine A pharmaceutical composition for preventing or treating muscle diseases, characterized in that reducing the above expression.
- 제 1 항에 있어서,The method of claim 1,상기 근육질환은,The muscle disease,근위축증(muscular atrophy), 근이영양증(muscular dystrophy), 근육감소증(sarcopenia), 근육병증(myopathy), 근무력증(myasthenia) 및 근육 손상(muscular injury)으로 이루어진 군에서 선택되는 하나 이상인 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물.Prevention of muscle disease, characterized in that it is at least one selected from the group consisting of muscle atrophy, muscular dystrophy, sarcopenia, myopathy, myasthenia, and muscle injury. Or a pharmaceutical composition for treatment.
- 감초 추출물 또는 이의 분획물을 유효성분으로 함유하는 근육질환 예방 또는 개선용 건강기능식품 조성물.Health functional food composition for preventing or improving muscle diseases containing licorice extract or a fraction thereof as an active ingredient.
- 하기 화학식 1 내지 3 중 어느 하나로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 근육질환 예방 또는 치료용 약학 조성물. A pharmaceutical composition for preventing or treating muscle diseases containing a compound represented by any one of the following Formulas 1 to 3 or a pharmaceutically acceptable salt thereof as an active ingredient.<화학식 1><Formula 1><화학식 2><Formula 2><화학식 3><Formula 3>
- 제 10 항에 있어서,The method of claim 10,상기 화합물 또는 이의 염은,The compound or salt thereof,감초 메탄올 추출물을 디클로로메탄(dichloromethane) 또는 에틸 아세테이트(ethyl acetate)로 분획한 분획물로부터 분리된 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating muscle diseases, characterized in that the methanol extract of licorice is separated from a fraction fractionated with dichloromethane or ethyl acetate.
- 제 10 항에 있어서,The method of claim 10,상기 화합물 또는 이의 염은,The compound or salt thereof,근아세포를 증식시키고 근관을 형성시키며, 근육세포로의 분화를 촉진시키는 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물. A pharmaceutical composition for preventing or treating muscle diseases, characterized in that proliferating myoblasts, forming myotubes, and promoting differentiation into muscle cells.
- 제 10 항에 있어서,The method of claim 10,상기 화합물 또는 이의 염은,The compound or salt thereof,손상된 근육을 재생시키는 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물. A pharmaceutical composition for preventing or treating muscle diseases, characterized in that to regenerate damaged muscles.
- 제 10 항에 있어서,The method of claim 10,상기 화합물 또는 이의 염은,The compound or salt thereof,근육 단백질 분해 또는 근육 위축을 억제시키는 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물. A pharmaceutical composition for preventing or treating muscle diseases, characterized in that to inhibit muscle protein degradation or muscle atrophy.
- 제 10 항에 있어서,The method of claim 10,상기 근육질환은,The muscle disease,근위축증(muscular atrophy), 근이영양증(muscular dystrophy), 근육감소증(sarcopenia), 근육병증(myopathy), 근무력증(myasthenia) 및 근육 손상(muscular injury)으로 이루어진 군에서 선택되는 하나 이상인 것을 특징으로 하는 근육질환 예방 또는 치료용 약학 조성물.Prevention of muscle disease, characterized in that it is at least one selected from the group consisting of muscle atrophy, muscular dystrophy, sarcopenia, myopathy, myasthenia, and muscle injury. Or a pharmaceutical composition for treatment.
- 하기 화학식 1 내지 3 중 어느 하나로 표시되는 화합물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 근육질환 예방 또는 개선용 건강기능식품 조성물. A health functional food composition for preventing or improving muscle diseases containing a compound represented by any one of the following Formulas 1 to 3 or a pharmaceutically acceptable salt thereof as an active ingredient.<화학식 1><Formula 1><화학식 2><Formula 2><화학식 3><Formula 3>
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EP20826227.9A EP3811959A4 (en) | 2019-06-19 | 2020-06-17 | Composition for preventing or treating muscular diseases, containing, as active ingredient, glycyrrhiza uralensis extract or compound isolated therefrom |
AU2020296604A AU2020296604B2 (en) | 2019-06-19 | 2020-06-17 | Composition for preventing or treating muscular diseases, containing, as active ingredient, Glycyrrhiza uralensis extract or compound isolated therefrom |
CN202080004857.4A CN112739362B (en) | 2019-06-19 | 2020-06-17 | Composition for preventing or treating muscular disease comprising licorice extract or compound isolated therefrom as active ingredient |
JP2021575429A JP2022538544A (en) | 2019-06-19 | 2020-06-17 | A composition for prevention or treatment of muscle diseases containing licorice extract or a compound isolated therefrom as an active ingredient |
CN202210927644.XA CN115919924A (en) | 2019-06-19 | 2020-06-17 | Composition for preventing or treating muscular disease comprising licorice extract or compound isolated therefrom as active ingredient |
US17/266,610 US20210315957A1 (en) | 2019-06-19 | 2020-06-17 | Composition for preventing or treating muscular diseases, containing, as active ingredient, glycyrrhiza uralensis extract or compound isolated therefrom |
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KR10-2019-0072992 | 2019-06-19 | ||
KR20190072992 | 2019-06-19 | ||
KR1020200073089A KR102210500B1 (en) | 2019-06-19 | 2020-06-16 | Composition for preventing or treating muscular diseases comprising fraction of glycyrrhiza uralensis fischer extract |
KR10-2020-0073092 | 2020-06-16 | ||
KR1020200073090A KR102210501B1 (en) | 2019-06-19 | 2020-06-16 | Composition for preventing or treating muscular diseases |
KR10-2020-0073090 | 2020-06-16 | ||
KR1020200073088A KR102210499B1 (en) | 2019-06-19 | 2020-06-16 | Composition for preventing or treating muscular diseases comprising glycyrrhiza uralensis fischer extract |
KR10-2020-0073091 | 2020-06-16 | ||
KR1020200073091A KR102210502B1 (en) | 2019-06-19 | 2020-06-16 | Composition for preventing or treating muscular diseases |
KR10-2020-0073089 | 2020-06-16 | ||
KR1020200073092A KR102210503B1 (en) | 2019-06-19 | 2020-06-16 | Composition for preventing or treating muscular diseases |
KR10-2020-0073088 | 2020-06-16 |
Publications (1)
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WO2020256397A1 true WO2020256397A1 (en) | 2020-12-24 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/KR2020/007826 WO2020256397A1 (en) | 2019-06-19 | 2020-06-17 | Composition for preventing or treating muscular diseases, containing, as active ingredient, glycyrrhiza uralensis extract or compound isolated therefrom |
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WO (1) | WO2020256397A1 (en) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20060039036A (en) * | 2004-07-19 | 2006-05-08 | 경북대학교 산학협력단 | Methods for increasing liquiritigenin content in a licorice and its extracts and the method for the isolation and extraction of liquiritigenin from them |
JP2009143838A (en) * | 2007-12-13 | 2009-07-02 | Nippon Menaade Keshohin Kk | Muscle activator |
KR20100101848A (en) * | 2009-03-10 | 2010-09-20 | 한국생명공학연구원 | Composition comprising extract, fraction or compound from glycyrrhiza glabra fisch having diacyl coa:glycerol acyltransferase inhibitory activity |
KR20100135424A (en) * | 2009-06-17 | 2010-12-27 | 울산대학교 산학협력단 | Chalcone compounds as activators of ddah promoter from glycyrrhiza uralensis and compositions for prevention and treatment of islet cellular apoptosis and diabetic nephropathy containing the same as an active ingredient |
JP2012193157A (en) * | 2011-03-03 | 2012-10-11 | Kaneka Corp | Muscle builder |
-
2020
- 2020-06-17 WO PCT/KR2020/007826 patent/WO2020256397A1/en unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20060039036A (en) * | 2004-07-19 | 2006-05-08 | 경북대학교 산학협력단 | Methods for increasing liquiritigenin content in a licorice and its extracts and the method for the isolation and extraction of liquiritigenin from them |
JP2009143838A (en) * | 2007-12-13 | 2009-07-02 | Nippon Menaade Keshohin Kk | Muscle activator |
KR20100101848A (en) * | 2009-03-10 | 2010-09-20 | 한국생명공학연구원 | Composition comprising extract, fraction or compound from glycyrrhiza glabra fisch having diacyl coa:glycerol acyltransferase inhibitory activity |
KR20100135424A (en) * | 2009-06-17 | 2010-12-27 | 울산대학교 산학협력단 | Chalcone compounds as activators of ddah promoter from glycyrrhiza uralensis and compositions for prevention and treatment of islet cellular apoptosis and diabetic nephropathy containing the same as an active ingredient |
JP2012193157A (en) * | 2011-03-03 | 2012-10-11 | Kaneka Corp | Muscle builder |
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