WO2018217009A1 - Composition pour prévenir ou traiter des maladies liées aux muscles, contenant un extrait d'angelica keiskei ou un composé isolé à partir de celui-ci, et son utilisation - Google Patents

Composition pour prévenir ou traiter des maladies liées aux muscles, contenant un extrait d'angelica keiskei ou un composé isolé à partir de celui-ci, et son utilisation Download PDF

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WO2018217009A1
WO2018217009A1 PCT/KR2018/005840 KR2018005840W WO2018217009A1 WO 2018217009 A1 WO2018217009 A1 WO 2018217009A1 KR 2018005840 W KR2018005840 W KR 2018005840W WO 2018217009 A1 WO2018217009 A1 WO 2018217009A1
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compound
xanthoangelol
hydroxy
hydroxyphenyl
cancer
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Korean (ko)
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류재하
권민선
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숙명여자대학교산학협력단
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Publication of WO2018217009A1 publication Critical patent/WO2018217009A1/fr

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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
    • 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
    • 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
    • A61K31/66—Phosphorus compounds
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • 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
    • 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
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
    • 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
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/316—Foods, ingredients or supplements having a functional effect on health having an effect on regeneration or building of ligaments or muscles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to a composition for the prevention and treatment of muscle-related diseases containing fresh vinegar extract or a compound isolated therefrom and its use.
  • Muscle regeneration includes atony, muscular atrophy, muscular dystrophy, muscle degeneration, myopathy, muscular atrophy, ataxia, cachexia and sarcopenia It has been noted for the purpose of overcoming skeletal muscle degenerative diseases such as. ( J Cachexia Sarcopenia Muscle. 2015 , 6 , 197)
  • muscle loss can also be caused by the progression of aging and various chronic diseases. As aging progresses, some of the newly created skeletal muscles are replaced with fibrous tissues, resulting in sarcopenia, which reduces the body's skeletal muscle mass and strength. In addition, muscle loss also occurs in chronic diseases in which the incidence increases with age, such as hypertension, impaired glucose tolerance, and diabetes, obesity, dyslipidemia, atherosclerosis, and cardiovascular disease. ( Pharmacol Res. 2015 , 99 , 86).
  • muscle In muscle, assimilation and catabolism are balanced and regulate muscle production. In this context, many biological signaling processes are regulated in muscle cells. If the signaling response that induces synthesis is activated rather than the degradation of muscle proteins, the synthesis of muscle proteins is increased, leading to increased muscle size (hypertrophy) or increased muscle fiber (hyperplasia) resulting in excessive muscle production ( Br) J Pharmacol. 2008 , 154, 557).
  • Muscle induction factors induce muscle protein synthesis by activating the phosphatidylinositol-3 kinase (PI3K) / Akt pathway in muscle cells and thereby phosphorylating downstream proteins.
  • PI3K phosphatidylinositol-3 kinase
  • the activity of mTOR (mammalian target of rapamycin) by PI3K / Akt signaling is recognized as a central growth signaling mechanism that integrates various growth signals in cells.
  • Activation of mTOR activates two subtargets, 4EBP1 (4E-binding protein) and p70S6K (phosphorylated 70-kDa ribosomal S6 kinase), which induce muscle protein synthesis to increase muscle mass ( Br J Pharmacol. 2008 , 154, 557; J Biol. Chem. 2003 , 278, 40717).
  • myoD initiates the expression of specific genes related to muscle differentiation, inducing mesenchymal stem cells to differentiate into myoblasts.
  • Myogenin and myosin heavy chain (MHC) which are regulated by MyoD, induce fusion of myoblasts, leading to the formation of myotubes and muscle fibers. Muscle fibers formed through this process are bundled to form muscles finally ( Cell Mol. Life Sci. 2013, 70, 4117; Brain Dev. 2013 , 35, 349).
  • myo D myogenic factor
  • myogenin myogenin
  • Mrf-4 myogenin and Mrf-4.
  • MyoD and Myf-5 are transcription factors specifically expressed in myogenic lineage and play an important role in initiating myoblast differentiation.
  • Myo D induces the expression of myogenic proteins such as MHC and myogenin through binding to non-muscular specific factors such as E protein, Mef-2 family proteins and transcriptional cofactors.
  • Angelica keiskei is a dicotyledonous plant, 4-hydroxyderricin, xanthoangelol, xanthoangelol E, xanthoangelol D, and xanthoangelol D.
  • Ingredients such as xanthoangelol F, xanthoangelol B, xanthokeismin A, and isobavachalcone are known, and are known to be effective in treating diseases such as colds, asthma and diabetes. It is called the Japanese ashitaba, the Japanese name Ashitaba, and includes Angelica keiskei , Angelica kiusina , and the like.
  • the present inventors have conducted MyoD transcriptional activity through a myogenic cell differentiation efficacy evaluation method (Experimental Example 1) to measure myoD transcriptional activity in fresh vinegar extract as part of a study to develop an effective prophylactic and therapeutic agent for muscle-related diseases. Whether significantly increased, or increased MHC expression in differentiated C2C12 cells by Western blotting analysis, and (2) the sample through the experiment to induce myoblast differentiation (Experimental Example 2) Treatment induced concentration-dependent differentiation into cylinder-shaped multinucleated myotubes. In addition, the number of multinuclear myotubes was increased.
  • the results of the above experiments showed that the extract of the fresh vinegar of the present invention and the compound 4-hydroxyderricin, xanthoangelol, xanthoangelol E, xanthoangelol D, xanthoangelol F, xanthoangelol B, xanthokeismin A, isobavachalcone, strains, muscular dystrophy, muscular dystrophy, muscle degeneration,
  • the present invention was completed after confirming that it can be used as a therapeutic agent or an adjuvant for muscle diseases such as myocardiomyopathy, muscular dystrophy, ataxia, myasthenia, cachexia and senile muscular dystrophy.
  • the present invention aims to develop a natural product therapeutic agent that is more excellent for improving muscle diseases.
  • An object of the present invention to provide a pharmaceutical composition for the prevention and treatment of muscle-related diseases containing fresh vinegar extract or a compound isolated therefrom as an active ingredient.
  • the present invention provides a functional food for the prevention and improvement of muscle-related diseases containing fresh vinegar extract or a compound isolated therefrom as an active ingredient.
  • Fresh vines as defined herein are characterized by comprising roots, stems, outpost leaves, preferably roots or outposts of the same plant, such as Angelica keiskei , Angelica kiusina , and the like.
  • Fresh vinegar extract as defined herein is characterized in that it comprises a fresh vinegar crude extract, a polar solvent soluble extract or a non-polar solvent soluble extract purified from the crude vinegar extract.
  • the crude extract as defined herein is a solvent selected from water including purified water, lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, butanol, or a mixed solvent thereof, preferably water or a mixed water and ethanol solvent, more preferably Characterized in that the extract is soluble in ethanol.
  • Non-polar solvent soluble extracts as defined herein include extract fractions soluble in non-polar solvents purified only of the extracts soluble in hexane, methylene chloride, chloroform, or ethyl acetate solvents from the crude extracts herein.
  • the polar solvent soluble extract as defined herein includes an extract soluble in a solvent selected from water, methanol, butanol, or a mixed solvent thereof after removing the non-polar solvent soluble extracts from the crude extract.
  • Compounds isolated from fresh vinegar extract as defined herein are isobavachalcone (compound 1), 4-hydroxyderricin (compound 2), xanthoangelol E (compound 3), xantho Angelol D (xanthoangelol D, Compound 4), xanthoangelol (Compound 5), xanthoangelol F, (xanthoangelol F, Compound 6), xanthokesamine A (Xanthokeismin A, Compound 7), 1 -[2,4-dihydroxy-3- (6,7-dihydroxy-3,7-dimethyl-2-octenyl) phenyl] 3- (4-hydroxyphenyl-2-prefen-1- Onconcon (1- [2,4-dihydroxy-3- (6,7-dihydroxy-3,7-dimethyl-2-octenyl) phenyl] 3- (4-hydroxyphenyl-2-prepen-1-onechalcone compound 8) , 1- [
  • High performance liquid chromatography (HPLC) analysis of fresh vinegar extracts and compounds as defined herein is performed under conditions of mixing an acidic solvent with a nonpolar solvent such as methanol or acetenitrile.
  • Muscle-related disorders as defined herein include atony, muscular atrophy, muscular dystrophy, muscle degeneration, myopathy, muscular atrophy, ataxia, cachexia and sarcopenia At least one muscle disease selected from the group consisting of muscle specific diseases caused by senile muscular atrophy or cancer, more specifically, muscular atrophy due to senile muscular atrophy or cancer, muscular dystrophy, Muscle degeneration, myopathy, muscular dystrophy, ataxia, ataxia, cachexia, sarcopenia and muscular loss.
  • the present invention also provides a prophylactic and anticancer adjuvant therapy or a therapeutic agent for muscle-related diseases caused by cancer containing fresh vinegar extract or a compound isolated therefrom.
  • the present invention also provides a pharmaceutical composition for preventing and treating muscle-related diseases caused by cancer, comprising a combination of Sinchocho extract or a compound separated therefrom and an existing anticancer agent, an anticancer adjuvant or a health functional food.
  • Existing anticancer agents as defined herein include cyclophosphamide, methotrexate, 5-fluorouracil, doxorubicin, mustine, vicristine, procarba Procarbazine, prednisolone, bleomycin, vinblastine, dacarbazine, etoposide, cisplatin, epirubicin, cispool Cisplatin, capecitabine, oxaliplatin and the like.
  • lung cancer non-small cell Sex lung cancer, small cell lung cancer
  • thymic cancer kidney cancer, bladder cancer, prostate cancer, testicular cancer, ovarian cancer, cervical cancer, sarcoma, gastrointestinal stromal tumor (
  • Extracts of the present invention can be obtained by the preparation method as follows.
  • Fresh vinegar extract of the present invention can be prepared as follows. After washing and rinsing the dried fresh vinegar, a solvent selected from water including purified water, lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol and butanol, or a mixed solvent thereof, preferably a mixed solvent of water and ethanol, more preferably 30 ⁇ 100% ethanol several times and then ultrasonic extraction, hydrothermal extraction, room temperature extraction for 30 minutes to 48 hours, preferably 24 to 36 hours at a temperature of 30 °C to 150 °C, preferably 50 °C to 100 °C or
  • the crude extract of the present invention can be obtained by filtering, concentrating under reduced pressure, and drying the extract obtained by reflux extraction, preferably at room temperature extraction, about 1 to 20 times, preferably 2 to 10 times.
  • the polar or non-polar solvent soluble extract of the present invention is added to the water of about 0.0005 to 500 times, preferably 0.05 to 5 times the volume (v / w%) of the crude extract obtained above, n-hexane,
  • a conventional fractionation process using methylene chloride, ethyl acetate and butanol was performed to prepare a non-polar solvent soluble extract available in non-polar solvents such as n-hexane, methylene chloride, ethyl acetate, and a polar solvent soluble in polar solvents such as butanol and water. Extraction fractions can be obtained respectively.
  • the compounds of the present invention can be prepared as follows.
  • the crude fresh extract obtained above is fractionated with ethyl ether.
  • Purification using chromatography or chromatography such as Diaion HP-20 column chromatography may be performed several times selectively to purify and obtain the compounds of the present invention, respectively.
  • the present inventors pay attention to MyoD transcriptional activity (Experimental Example 1) through the differentiation promoting efficacy evaluation method (Experimental Example 1) of measuring the myoD transcriptional activity of the extract obtained by the above production method (Experimental Example 1). It was confirmed that MHC expression was increased in the C2C12 cells, and (2) the effect of myoblast differentiation on the myoblast differentiation (Experimental Example 2). shaped) increased the number of multinucleated myotubes, and proved to promote myotube formation through myoblast differentiation, confirming that the composition is useful as a pharmaceutical composition or health functional food for the prevention and treatment of muscle diseases.
  • the present invention provides a pharmaceutical composition or health functional food for preventing and treating muscle-related diseases containing the fresh vinegar extract obtained by the above method or a compound isolated therefrom as an active ingredient.
  • the compounds of the present invention can be prepared with pharmaceutically acceptable salts and solvates according to methods conventional in the art.
  • Acid addition salts formed by free acid are useful.
  • Acid addition salts are prepared by conventional methods, for example by dissolving a compound in an excess of aqueous acid solution and precipitating the salt using a water miscible organic solvent such as methanol, ethanol, acetone or acetonitrile. Equal molar amounts of the compound and acid or alcohol (eg, glycol monomethylether) in water can be heated and the mixture can then be evaporated to dryness or the precipitated salts can be suction filtered.
  • acid or alcohol eg, glycol monomethylether
  • organic acids and inorganic acids may be used as the free acid
  • hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid, and the like may be used as the inorganic acid
  • methanesulfonic acid, p -toluenesulfonic acid, acetic acid, and trifluoroacetic acid may be used as the organic acid.
  • Citric acid maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid (gluconic acid), galacturonic acid, glutamic acid, glutaric acid (glutaric acid), glucuronic acid (glucuronic acid), aspartic acid, ascorbic acid, carbonic acid, vanic acid and hydroiodic acid may be used.
  • Bases can also be used to make pharmaceutically acceptable metal salts.
  • An alkali metal or alkaline earth metal salt is obtained by, for example, dissolving a compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the non-soluble compound salt, and then evaporating and drying the filtrate.
  • the metal salt it is particularly suitable to prepare sodium, potassium or calcium salt, and the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (for example, silver nitrate).
  • Pharmaceutically acceptable salts of the compounds of the invention include salts of acidic or basic groups which may be present in the compounds of the invention, unless otherwise indicated.
  • pharmaceutically acceptable salts include sodium, calcium and potassium salts of the hydroxy group
  • other pharmaceutically acceptable salts of the amino group include hydrobromide, sulfate, hydrogen sulphate, phosphate, hydrogen phosphate, dihydrogen Phosphate, acetate, succinate, citrate, tartrate, lactate, mandelate, methanesulfonate (mesylate) and p -toluenesulfonate (tosylate) salts. It can be prepared through.
  • composition of the present invention comprises 0.01 to 99% by weight of the extract or compound relative to the total weight of the composition.
  • 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.
  • compositions comprising extracts or compounds of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
  • compositions comprising extracts or compounds according to the invention, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, external preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods
  • Carriers, excipients and diluents that may be included in the formulation 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, magnesium stearate and mineral oil.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one or more excipients in at least one of the excipients, cotton, starch, calcium carbonate, sucrose ( It is prepared by mixing sucrose or lactose, gelatin and the like.
  • 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.
  • Preferred dosages of the extracts or compounds 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 extract or compound is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. 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.
  • composition of the present invention can be administered to mammals such as mice, live mice, livestock, humans, etc. by various routes. All modes of administration can be anticipated, for example, by oral and rectal or intravenous methods.
  • the present invention also provides a therapeutic agent for senile muscular dystrophy or cachexia containing the fresh vinegar extract or a compound isolated therefrom as an active ingredient, and the therapeutic agent is for improving the effect of weight change or appetite recovery in combination therapy with senile muscular atrophy or cachexia.
  • the present invention provides a combination therapy using the composition of the present invention rather than an anticancer agent alone in cachexia treatment.
  • the present invention provides a therapeutic method for treating a patient with muscle-related diseases, comprising administering to the patient with muscle-related diseases.
  • the present invention also provides the use of fresh vinegar extract or a compound isolated therefrom for the manufacture of a medicament for the treatment of muscle-related diseases.
  • the present invention provides a health functional food for the prevention and improvement of muscle-related diseases containing a fresh vinegar extract or a compound isolated therefrom as an active ingredient.
  • health functional food refers to physical or mental functionality by adding the extract of the present invention to a conventional specimen for preventing or ameliorating a target disease in a human body or a mammal according to Korean Health Functional Food Act No. 6723. It includes a functional food to improve the functionality such as.
  • the dietary supplement for the prevention and improvement of the muscle-related diseases of the present invention comprises the extract or compound in an amount of 0.01 to 95%, preferably 1 to 80% by weight, based on the total weight of the composition.
  • composition of the present invention may be a dietary supplement or dietary supplement for the purpose of treating and improving muscle-related diseases.
  • a health functional food in the form of a pharmaceutical dosage form such as powders, granules, tablets, capsules, pills, suspensions, emulsions, syrups or tea bags, leaching tea, health drinks for the purpose of preventing and improving muscle-related diseases. Manufacturing and processing are possible.
  • the extract comprises 0.01 to 95% by weight, preferably 1 to 80% by weight relative to the total weight of the composition.
  • composition of the present invention can be used as a major component or additive and adjuvant in the manufacture of various dietary supplements and dietary supplements for the purpose of preventing or treating muscle-related diseases.
  • a health functional food in the form of a pharmaceutical dosage form such as powders, granules, tablets, capsules, pills, suspensions, emulsions, syrups or tea bags, leaching tea, health drinks for the purpose of preventing and improving muscle-related diseases. Manufacturing and processing are possible.
  • the present invention also provides a dietary supplement for the prevention and improvement of muscle-related diseases containing fresh vinegar extract or a compound isolated therefrom as an active ingredient.
  • the health functional beverage composition of the present invention is not particularly limited to other ingredients except for containing the extract as an essential ingredient in the indicated proportions, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, 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 the natural carbohydrate is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.
  • the present invention also provides a food or food additive for the prevention and improvement of muscle-related diseases containing fresh vinegar extract or a compound isolated therefrom as an active ingredient.
  • the extract or compound according to the present invention When used as a food additive, the extract may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method.
  • the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, etc., includes all of the health food in the conventional sense.
  • 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, chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
  • the compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages 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 extract or compound of the present invention may be added to food or beverages for the purpose of preventing muscle-related diseases.
  • the amount of the extract in the food or beverage can be added in 0.01 to 15% by weight of the total food weight
  • the health beverage composition is added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml Can be.
  • 1 is a diagram showing an HPLC chromatogram for determining the content of compound 2 and compound 5 contained in the extract of the present invention.
  • 3L of 100% ethanol was added to 3 kg of dried fresh vinegar (Saengdong Nongsan, Seoul Korea, medicinal herb sample storage room, Sookmyung Women's University, SPH 1502), extracted at room temperature for 24 hours, filtered and concentrated under reduced pressure.
  • the concentrated ethanol extract was lyophilized with a freeze dryer (ScanVac, Labogene) under reduced pressure to obtain 300 g of fresh ethanol extract powder (hereinafter referred to as AKCE) and used for the next experiment.
  • Example 2 To 300 g of dried fresh ethanol extract obtained in Example 1, 500 mL of purified water was added and suspended. The suspension was added with 500 mL of n-hexane and fractionated into n-hexane soluble fractions. The remaining water suspension was diluted with 600 mL of ethyl acetate and 600 mL of butanol.
  • AKH n-hexane soluble fraction
  • AKE ethyl acetate soluble fraction
  • AKB butanol soluble fraction
  • HPLC analysis was performed to determine the contents of Compound 2 and Compound 5 of the fresh ethanol extract of the Example.
  • Example 1 The fresh ethanol extract of Example 1 and the compound 2 and 5 obtained in Example were 360 nm using a column (C18 4.6 mm x 150 mm, 5 ⁇ m, cat. 5020-01124, GL sciences Inc.) under 80% methanol conditions. It was analyzed at the wavelength of. Through this analysis, the content of Compound 2 and Compound 5 contained in the extract was analyzed.
  • HPLC HPLC was measured at 360 nm using a 4.6 x 150 mm, 5um column at 80% methanol.
  • Samples of fresh ethanol extract and compounds 2 and 5 were prepared at 1 mg / ml, 0.1 mg / ml, and 0.01 mg / ml, respectively, and 5 ⁇ l, 2 ⁇ l, and 3 ⁇ l were injected to obtain chromatograms. The contents of the included compounds 2 and 5 were obtained.
  • reporter vector MyoD-responsive
  • myoD-reactive gene and luciferase were fused to C2C12 cells, a mouse myoblast cell line, to investigate the effect on the myogenic effect of ethanol extract of fresh ethanol extract of the above example.
  • reporter 4RTK-luc was inserted and myoD transcriptional activity was analyzed by measuring luciferase activity change according to extract treatment to evaluate the differentiation-promoting efficacy of myoblasts ( J. Biol. Chem 2004, 279 , 52643).
  • a self-made reporter vector (MyoD-responsive reporter 4RTK-luciferase construct) comprising four E-box sites fused to a thymidine kinase promoter was used to assess MyoD transcriptional activity.
  • a myoD expression vector and a reporter vector (MyoD-responsive reporter 4RTK-luc) (provided by Prof. Kyu-Woon Bae, College of Pharmacy, Sookmyung Women's University) Transfection was performed by the method described in ( Eur J Histochem . 2004, 48 , 223).
  • cells were treated with fresh vinegar extract (10, 100, 1000 ng / mL), and then cultured further for 24 hours.
  • the cultured cells were washed twice with phosphate buffered saline solution, lysed with reporter lysis buffer (Cat #. E1941, Promega), and then 5 ⁇ l of the cell lysate was taken into a 96-well plate for luciferase analysis (Cat # 31196, SPL) and absorbance was measured by adding 30 ⁇ L of Luciferase Substrate (Dual Luciferase Reporter Assay System, Cat # E1910, Promega).
  • ⁇ -galactosidase activity was measured by adding 30 ⁇ L of Stop and Glo reagent (Cat # E1910, Promega) to cell lysates. Data are expressed as relative luciferase activity (RLU) divided by ⁇ -galactosidase activity and expressed as mean ⁇ SD.
  • RLU relative luciferase activity
  • myoblasts In the process of differentiation of myoblasts into myotubes, mononucleated myoblasts are elongated and transformed into cylinder-shaped myocytes. In activated myocytes, the expression of MyoD, myogenic factor (Myf) -5, myogenin, and myogenic regulatory factor (Mrf) -4 is increased to activate genes involved in different muscle differentiation and promote differentiation into myotube fibers. . The resulting myocytes fuse together to form multinucleated myotubes, which increase the expression of Mrf-4, myogenin or MHC, a muscle differentiation marker ( Histochem . Cell Biol . 2012 , 138 , 187; J. Cell Physiol . 2010 , 224 , 7).
  • MHC is known as a marker of late stage of muscle differentiation, and the level of myogenic differentiation ability of myoblasts can be predicted by analyzing the level of MHC expression in terminally differentiated myotubes.
  • MHC protein expression was measured and used as an indicator of the differentiation of myoblasts into myotubes.
  • C2C12 myoblasts were treated with fresh vinegar extract (10, 100, 1000 ng / mL) to induce differentiation by treatment on differentiation medium (2% horse serum-containing DMEM, Cat # 11965-084, Gibco) for 3 days. .
  • MHC protein was evaluated by Western blot, and immunized with mouse anti-MHC (Santa Cruze) and anti mouse (anti-mouse IgG2b Alexa-fluor 568). Staining was performed to evaluate MHC expression.
  • the source cells were differentiated in the differentiation medium to which each sample was added, and immunofluorescence staining was performed.
  • Each differentiation medium was removed, washed twice with phosphate buffered saline, and fixed for 20 minutes with 4% paraformaldehyde. Again washed with phosphate buffered saline twice, and treated with 0.1% tritonX-100 for 20 minutes. After washing twice with phosphate buffered saline, blocking in 5% horse serum solution, mouse anti-MHC (MAB4470, R & D systems) was added and reacted at 4 ° C for 12 hours.
  • MAB4470 mouse anti-MHC
  • the cells were washed with phosphate buffered saline at least three times, and then MHC expression was analyzed using Alexa Flouor 568-bound secondary anti-mouse (A-21144, MicoProbes) and DAPI (D9542, Sigma).
  • the effect on MHC expression of fresh vinegar extract was measured.
  • the differentiation medium of myoblasts was treated with 10, 100 and 1000 ng / mL concentrations to differentiate into myotube fibers for 3 days, and the cells were harvested.
  • the protein expression of MHC, a marker of differentiation into myotubes, was analyzed by Western blotting. .
  • the fresh vinegar extract was increased three times when treated with 10 ng / mL, four times when treated with 100 ng / mL, and five times when treated with 1000 ng / mL.
  • increased red-fluorescence means that fresh herb extracts promote MHC expression in C2C12 cells in a concentration dependent manner, and the cylindrical form of MHC expressed through DAPI counter staining. (cylinder-shaped) root canal cells were confirmed to be multinucleated (multinucleated).
  • Myoblast differentiation in this experiment was expressed as a percentage of multinucleated MHC-positive cells. As a result, it was found that S. extract increased MHC expression and number of cylinder-shaped multinucleated myotubes in myotubes even at low concentrations of 1000 ng / mL and activated muscle cell differentiation. Proved.
  • MHC protein expression was measured and used as an indicator for the differentiation of myoblasts into myotubes.
  • Table 5 shows the effect of MHC expression of the compounds contained in fresh vinegar.
  • the differentiation medium of myoblasts was treated at a concentration of 0.1 nM to differentiate into myotube fibers for 3 days, and the cells were harvested.
  • the protein expression of MHC, a differentiation marker into myotube fibers, was analyzed by Western blotting analysis.
  • MHC protein expression was measured and used as an indicator for the differentiation of myoblasts into myotubes.
  • Table 6 and Table 7 show the effect on the expression of MHC of several chalcone compounds contained in fresh vinegar.
  • the differentiation medium of myoblasts was treated at a concentration of 0.1 nM to differentiate into myotube fibers for 3 days, and the cells were harvested.
  • the protein expression of MHC, a differentiation marker into myotube fibers, was analyzed by Western blotting analysis.
  • 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).
  • each component is added to the purified water to dissolve it, the lemon flavor is added appropriately, the above components are mixed, purified water is added, the whole is adjusted to 100 ml by the addition of purified water, and then filled in a brown bottle.
  • the solution is prepared by sterilization.
  • Vitamin A Acetate 70 ⁇ g
  • Vitamin E 1.0 mg
  • Vitamin B1 0.13 mg
  • Vitamin B2 0.15 mg
  • Vitamin B6 0.5 mg
  • Vitamin B12 0.2 ⁇ g
  • Vitamin C 10 mg
  • Nicotinamide 1.7 mg
  • composition ratio of the said vitamin and mineral mixture was mixed and comprised in the preferable embodiment the component suitable for a healthy food, you may change arbitrarily the compounding ratio considered that it does not deviate from the mind and range of this invention.
  • Citric Acid 1000 mg
  • Plum concentrate 2 g
  • the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilized and refrigerated and then Used to prepare the healthy beverage composition of the invention.
  • composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment
  • compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

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Abstract

La présente invention concerne une composition pour prévenir ou traiter des maladies liées aux muscles, contenant, à titre de principe actif, un extrait d'Angelica keiskei ou un composé isolé à partir de celui-ci, et qui s'est avérée utilisable à titre de composition pharmaceutique, aliment fonctionnel de santé, aliment complémentaire de santé, et autres, pour la prévention et le traitement des maladies musculaires.
PCT/KR2018/005840 2017-05-25 2018-05-23 Composition pour prévenir ou traiter des maladies liées aux muscles, contenant un extrait d'angelica keiskei ou un composé isolé à partir de celui-ci, et son utilisation WO2018217009A1 (fr)

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KR1020170064440A KR102040119B1 (ko) 2017-05-25 2017-05-25 신선초 추출물로부터 분리된 화합물을 함유하는 근육관련 질환의 예방 및 치료용 조성물
KR10-2017-0064440 2017-05-25

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111638299A (zh) * 2020-07-06 2020-09-08 广西中医药大学 一种明日叶高效液相色谱指纹图谱的建立方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20060106065A (ko) * 2005-04-06 2006-10-12 주식회사풀무원 신선초 뿌리 추출물, 하이드록시데리신(4-hydroxyderricin)및 잔소안제롤(xanthoangelol)의 간보호 효과
KR20120042092A (ko) * 2010-10-22 2012-05-03 대한민국(농촌진흥청장) 항산화 활성을 가지는 신선초 분말을 포함하는 건강보조식품 및 이의 제조방법
KR20120128854A (ko) * 2011-05-18 2012-11-28 (주)풀무원홀딩스 대황 추출물 및 신선초 추출물을 유효성분으로 함유하는 피로회복 또는 운동능력 증강용 또는 항산화용 식품조성물
KR20160017223A (ko) * 2014-08-01 2016-02-16 주식회사 풀무원 진공건조 홍삼농축액 및 신선초 추출물을 유효성분으로 함유하는 운동피로회복, 운동수행능력 증강용 또는 근감소증 예방 식품조성물
KR20160067225A (ko) * 2013-10-24 2016-06-13 유니버시티 오브 테네시 리서치 파운데이션 암 환자에서 근육 소모를 치료하는 선택적 안드로겐 수용체 조절물질 및 화학치료제

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20060106065A (ko) * 2005-04-06 2006-10-12 주식회사풀무원 신선초 뿌리 추출물, 하이드록시데리신(4-hydroxyderricin)및 잔소안제롤(xanthoangelol)의 간보호 효과
KR20120042092A (ko) * 2010-10-22 2012-05-03 대한민국(농촌진흥청장) 항산화 활성을 가지는 신선초 분말을 포함하는 건강보조식품 및 이의 제조방법
KR20120128854A (ko) * 2011-05-18 2012-11-28 (주)풀무원홀딩스 대황 추출물 및 신선초 추출물을 유효성분으로 함유하는 피로회복 또는 운동능력 증강용 또는 항산화용 식품조성물
KR20160067225A (ko) * 2013-10-24 2016-06-13 유니버시티 오브 테네시 리서치 파운데이션 암 환자에서 근육 소모를 치료하는 선택적 안드로겐 수용체 조절물질 및 화학치료제
KR20160017223A (ko) * 2014-08-01 2016-02-16 주식회사 풀무원 진공건조 홍삼농축액 및 신선초 추출물을 유효성분으로 함유하는 운동피로회복, 운동수행능력 증강용 또는 근감소증 예방 식품조성물

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111638299A (zh) * 2020-07-06 2020-09-08 广西中医药大学 一种明日叶高效液相色谱指纹图谱的建立方法

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