WO2020139057A2 - Composition pour prévenir et traiter une maladie musculaire ou améliorer la fonction musculaire, comprenant un extrait d'illicium verum ou de l'acide shikimique - Google Patents

Composition pour prévenir et traiter une maladie musculaire ou améliorer la fonction musculaire, comprenant un extrait d'illicium verum ou de l'acide shikimique Download PDF

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Publication number
WO2020139057A2
WO2020139057A2 PCT/KR2019/018726 KR2019018726W WO2020139057A2 WO 2020139057 A2 WO2020139057 A2 WO 2020139057A2 KR 2019018726 W KR2019018726 W KR 2019018726W WO 2020139057 A2 WO2020139057 A2 WO 2020139057A2
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muscle
extract
octagonal
acid
octagonal fennel
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English (en)
Korean (ko)
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WO2020139057A3 (fr
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황재관
김창희
유지희
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Industry Academic Cooperation Foundation of Yonsei University
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Industry Academic Cooperation Foundation of Yonsei University
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Priority claimed from KR1020190076670A external-priority patent/KR20200083146A/ko
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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)
    • A61K36/79—Schisandraceae (Schisandra family)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • 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
    • A23V2200/316—Foods, ingredients or supplements having a functional effect on health having an effect on regeneration or building of ligaments or muscles

Definitions

  • the present invention relates to a composition for preventing and treating muscle disease or improving muscle function, comprising an octagonal fennel extract or shikimic acid.
  • Muscle atrophy is caused by a gradual decrease in muscle mass and refers to muscle weakness and degeneration (Cell, 119(7): 907-910, 2004). Muscle atrophy is promoted by inactivity, oxidative stress, and chronic inflammation and weakens muscle function and motor capacity (Clinical Nutrition, 26(5): 524-534, 2007). The most important factor in determining muscle function is muscle mass, which is maintained by a balance of protein synthesis and degradation. Muscular dystrophy occurs when proteolysis occurs more than synthesis (The International Journal of Biochemistry and Cell Biology, 37(10): 1985-1996, 2005).
  • Muscle size is regulated by intracellular signaling pathways that induce anabolic or catabolism in the muscle, and when there are more signaling reactions that induce synthesis rather than degradation of muscle proteins Muscle protein synthesis is increased, which results in an increase in muscle size (hypertrophy) or an increase in muscle fiber number (hyperplasia) as muscle protein increases (The Korea Journal of Sports Science, 20(3): 1551-1561, 2011).
  • PI3K phosphatidylinositol-3 kinase
  • mTOR mammalian target of rapamycin
  • mTOR contributes to muscle mass gain by inducing muscle protein synthesis by activating two factors that initiate mRNA translation, 4E-binding protein (4EBP1) and phosphorylated 70-kDa ribosomal S6 kinase (p70S6K) (The Korea Journal of Sports Science, 20(3): 1551-1561, 2011; The International Journal of Biochemistry and Cell Biology, 43(9): 1267-1276, 2011).
  • 4EBP1 4E-binding protein
  • p70S6K phosphorylated 70-kDa ribosomal S6 kinase
  • Muscle cell differentiation and muscle formation are regulated by a variety of muscle regulatory factors. Among them, MyoD initiates the expression of muscle-specific genes, and induces differentiation of muscle satellite cells into myoblasts. Induction of myogenin expression by the activity of MyoD is the most important factor in fusion of myoblasts and is involved in the formation of myotubes. The muscle fibers formed through this process form a bundle and finally form muscles (Cellular and Molecular Life Sciences, 70: 4117-4130, 2013).
  • the octagonal fennel ( Illiumium verum ) refers to the fruits of magnolia and evergreen, and is called star anise because eight pods wrapped in a hard shell are shaped like a star. It is widely used as a spice, mainly after drying and in powder form.
  • Anti-cancer Journal of Medicinal Plants Research, 4(24): 2666-2673. 2016
  • Antioxidant Food Chemistry, 104(1): 59-66, 2007
  • Anti-inflammatory activity (Journal of Ethnopharmacology, 144(1): 182-189, 2012) has been reported.
  • Shikimic acid is one of the components included in octagonal fennel, and is an important biochemical intermediate involved in the biosynthesis of alkaloids, flavonoids, and lignin, as well as amino acids.
  • Sikkim acid is an antithrombotic (Journal of Natural Medicine, 70(3): 492-501, 2016), antibacterial (Bioengineered, 4(4): 244-248, 2013), neuroprotection (Journal of Molecular Neuroscience, 56(4) : 956-965, 2015), antiviral (Journal of Agricultural and Food Chemistry, 52(17): 5391-5395, 2004).
  • the present invention provides a muscle disease prevention, for the improvement or treatment compositions comprising octagonal anise (Illicium verum) extract or fractions thereof as an active ingredient.
  • octagonal anise Illicium verum
  • the present invention provides a composition for preventing, improving or treating muscle diseases comprising shikimic acid represented by Formula 1 below or a salt thereof as an active ingredient.
  • Illicium verum extract or shikimic acid increases mTOR activity involved in muscle protein synthesis, decreases mRNA expression of MuRF-1 and atrogin-1 involved in muscle protein degradation, increases muscle mass And it has an excellent effect on improving muscle function.
  • the present invention since the present invention is a natural product, it can be safely used without side effects, and thus can be used as a pharmaceutical, food, or cosmetic material.
  • 1 is a result of measuring the activity of mTOR according to the treatment of octagonal fennel extract in L6 muscle cells.
  • 3 is a result of measuring mRNA expression levels of atrogin-1 and MuRF-1 according to treatment of octagonal fennel hot water extract, 50% ethanol extract, and ethanol extract in L6 muscle cells.
  • the present invention provides a octagonal fennel (Illicium verum) extracts or fractions muscle disorders or for the prevention and treatment of muscle function improving composition comprising as an active ingredient thereof.
  • the present invention provides a composition for preventing and treating muscle disease or improving muscle function, including shikimic acid or a salt thereof as an active ingredient.
  • the present inventors tried to develop a natural substance that improves muscle function, and found that the octagonal fennel extract or its active ingredient, shikimic acid, has an effect of preventing or treating muscle diseases by increasing the expression and activity of genes involved in muscle function. Did.
  • composition of the present invention may include an octagonal fennel extract as an active ingredient.
  • The'octagonal fennel' used in the composition of the present invention belongs to the family Illiciaceae, of course, including its subspecies and varieties.
  • the octagonal fennel of the present invention is self-evident in the art and includes a homogenous drug that can be used for the same or similar purposes as the prevention and treatment purposes of the present invention.
  • extract' means that a substance is dissolved in a solvent to separate its active ingredient or characteristic ingredient.
  • the extract includes an extract extracted by adding an extractant to a plant and a fraction fractionated by adding a fractional solvent to the extract prepared by extracting with an extractant.
  • the octagonal fennel extract of the present invention is meant to include both the extract extracted by adding a solvent to the octagonal fennel and the fractions fractionated by adding a fractional solvent thereto.
  • the octagonal fennel extract contains octagonal fennel water, an organic solvent having 1 to 6 carbon atoms, or a mixture thereof, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane, cyclohexane, petroleum ether, subcritical fluid and supercritical It may be extracted with any one or more solvents selected from the group consisting of fluids.
  • the organic solvent alcohol having 1 to 6 carbon atoms (acecohol), acetone (acetone), ether (ether), benzene (benzene), chloroform (chloroform), ethyl acetate (ethyl acetate), methylene chloride (methylene chloride), hexane It may include at least one solvent selected from the group consisting of (hexane), cyclohexane and petroleum ether.
  • the present invention may include an extraction method of the octagonal fennel extract and an octagonal extract extracted from the extraction method.
  • composition of the present invention may contain sikkim acid as an active ingredient.
  • the "shimkimic acid” is a compound extracted or purified from natural products or synthesized, and is represented by the following Chemical Formula 1.
  • the shikimic acid may be derived from octagonal fennel. At this time, it may be prepared by a method of layer separation by adding a solvent to the octagonal fennel extract.
  • the shikimic acid of the present invention may include hydrates, derivatives, and the like within a range having the same efficacy, and may also include solvent compounds or stereoisomers thereof.
  • the method for obtaining the shikimic acid is not particularly limited, and a chemically synthesized or commercially available product may be used using a known manufacturing method.
  • the octagonal fennel extract can be obtained by extracting octagonal fennel under ultra high pressure conditions of 100 MPa or more.
  • muscle refers to the tendon, muscle, tendon, and'muscle function' refers to the ability to exert power by contraction of the muscle, and the muscle exerts the greatest contractile force to overcome resistance. Includes muscle power, the ability to perform, muscle endurance, the ability to indicate how long or how many times a muscle can repeat contractions and relaxations at a given weight, and wits, the ability to exert strong power in a short period of time.
  • This muscle function is subject to the liver and is proportional to muscle mass.
  • the term'muscle function improvement' refers to improving muscle function better.
  • the octagonal fennel extract or sickimic acid which is an active ingredient according to the present invention, has an excellent ability to increase the synthesis of muscle protein from increasing the activity of mTOR in muscle cells.
  • the octagonal fennel extract or shikimic acid which is an active ingredient according to the present invention, has an excellent ability to increase muscle from increasing anterior muscle weight and improving muscle strength in musculoskeletal induced mice.
  • the composition of the present invention may be a pharmaceutical composition for preventing and treating muscle disease.
  • prophylaxis refers to all actions that inhibit or delay the onset of the administration of the composition.
  • “improvement” or “treatment” refers to all actions in which the symptoms of the disease are improved or beneficially altered by administration of the composition.
  • the composition of the present invention can be used for the prevention or treatment of muscle diseases caused by muscle wasting or degeneration.
  • Muscle wasting and degeneration are caused by genetic factors, acquired factors, aging, and the like, and muscle wasting is characterized by gradual loss of muscle mass, weakness and degeneration of muscles, especially skeletal or veterinary muscles and cardiac muscles.
  • muscle diseases due to muscle wasting or degeneration are not limited thereto, but atony, muscular atrophy, muscular dystrophy, muscle degeneration, myasthenia gravis, cachexia, and muscular dystrophy ( sarcopenia), and these diseases can be used to treat or prevent various diseases in which natural recovery of muscles is difficult.
  • the composition of the present invention has an effect of increasing muscle mass, and the muscle does not limit its type.
  • the pharmaceutical composition of the present invention may include shikimic acid or a pharmaceutically acceptable salt thereof.
  • pharmaceutically acceptable means physiologically acceptable and does not generally cause an allergic reaction or similar reaction when administered to a human being, and the salt may include a pharmaceutically acceptable free acid (free). acid) is preferred.
  • the above-mentioned acid addition salts are a) general salts that directly mix sickimic acid, or b) dissolve and mix it in a solvent or hydrous solvent, or c) place skimic acid in an acid in a solvent or a water-based solvent and mix them. It is manufactured by the manufacturing method.
  • possible salt forms include gaba salt, gabapentin salt, pregabalin salt, nicotinate salt, adipate salt, hemimalonate salt, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt or And aspartates.
  • composition for preventing and treating muscle diseases of the present invention may further include a pharmaceutically acceptable carrier.
  • Pharmaceutically acceptable carriers may further include, for example, carriers for oral administration or carriers for parenteral administration.
  • Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like.
  • carriers for parenteral administration may include water, suitable oils, saline, aqueous glucose and glycols, and the like.
  • stabilizers and preservatives may be further included. Suitable stabilizers include antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-parabens and chlorobutanol.
  • the pharmaceutical composition of the present invention can be administered by any method to mammals, including humans.
  • it can be administered orally or parenterally, and the parenteral administration method is not limited thereto, but intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal , Intranasal, intestinal, topical, sublingual or rectal administration.
  • the pharmaceutical composition of the present invention may be formulated as a formulation for oral administration or parenteral administration according to the administration route as described above.
  • one or more buffers e.g. saline or PBS
  • antioxidants e.g. saline or PBS
  • bacteriostatic agents e.g. EDTA or glutathione
  • fillers e.g. EDTA or glutathione
  • extenders e.g. EDTA or glutathione
  • binders e.g. aluminum hydroxide
  • adjuvants e.g. aluminum hydroxide
  • suspension thickener wetting agent, disintegrant or surfactant, diluent or excipient.
  • Solid preparations for oral administration include tablets, pills, powders, granules, liquids, gels, syrups, slurries, suspensions or capsules, etc. These solid preparations include at least one excipient in the pharmaceutical composition of the present invention. , Starch (including corn starch, wheat starch, rice starch, potato starch, etc.), calcium carbonate, sucrose, lactose, dextrose, sorbitol, mannitol, xylitol, erythritol maltitol, cellulose , Methyl cellulose, sodium carboxymethyl cellulose and hydroxypropyl methyl-cellulose or gelatin, and the like. For example, tablets or tablets of sugar can be obtained by mixing the active ingredient with a solid excipient and then grinding it and adding a suitable adjuvant to the granular mixture.
  • Liquid preparations for oral use include suspensions, intravenous solutions, emulsions or syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances or preservatives, in addition to water or liquid paraffin, a simple diluent commonly used. .
  • cross-linked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may be added as a disintegrant, and may further include an anti-coagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent, and a preservative. .
  • compositions of the present invention may be formulated according to methods known in the art in the form of injections, transdermal administrations and nasal inhalants, along with suitable parenteral carriers.
  • the injections must be sterile and protected from contamination of microorganisms such as bacteria and fungi.
  • suitable carriers include, but are not limited to, solvents or dispersion media including water, ethanol, polyols (eg, glycerol, propylene glycol and liquid polyethylene glycol, etc.), mixtures thereof and/or vegetable oils.
  • solvents or dispersion media including water, ethanol, polyols (eg, glycerol, propylene glycol and liquid polyethylene glycol, etc.), mixtures thereof and/or vegetable oils.
  • suitable carriers include Hanks' solution, Ringer's solution, phosphate buffered saline (PBS) containing triethanol amine or sterile water for injection, isotonic solutions such as 10% ethanol, 40% propylene glycol and 5% dextrose. Etc. can be used.
  • PBS phosphate buffered saline
  • isotonic solutions such as 10% ethanol, 40% propylene glycol and 5% dextrose. Etc. can be used.
  • it may further include various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid, thimerosal, and the like.
  • the injection may further include isotonic agents such as sugars or sodium chloride in most cases.
  • the compounds used in accordance with the present invention may be pressurized packs or, using suitable propellants, such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. It can be conveniently delivered in the form of an aerosol spray from a nebulizer.
  • the dosage unit can be determined by providing a valve that delivers a metered amount.
  • gelatin capsules and cartridges used in inhalers or insufflators can be formulated to contain a powder mixture of a compound and a suitable powder base such as lactose or starch. Formulations for parenteral administration are described in Remington's Pharmaceutical Science, 15th Edition, 1975.Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour, a prescription generally known to all pharmaceutical chemistries.
  • the pharmaceutical composition for preventing and treating muscle diseases of the present invention can provide a desirable muscle disease prevention and treatment effect when an octagonal fennel extract or shikimic acid is included in an effective amount.
  • the term'effective amount' refers to an amount that exhibits a higher response than a negative control, and preferably refers to an amount sufficient to improve muscle function.
  • the pharmaceutical composition of the present invention may include octagonal fennel extract or shikimic acid in an amount of 0.01 to 99.99%, and the remaining amount may be occupied by a pharmaceutically acceptable carrier.
  • the effective amount of the octagonal fennel extract or shikimic acid included in the pharmaceutical composition of the present invention will vary depending on the form in which the composition is commercialized.
  • the total effective amount of the pharmaceutical composition of the present invention can be administered to a patient in a single dose, and can be administered by a fractionated treatment protocol that is administered for a long time in multiple doses.
  • the pharmaceutical composition of the present invention can vary the content of the active ingredient according to the degree of disease. When administered parenterally, it is preferably administered in an amount of 0.01 to 50 mg, more preferably 0.1 to 30 mg per kg of body weight per day based on the octagonal extract or shikimic acid, and when administered orally, the octagonal extract or It may be administered in divided portions of 1 to several times to be administered in an amount of preferably 0.01 to 100 mg, more preferably 0.01 to 10 mg per kg of body weight per day, based on sikimic acid.
  • the pharmaceutical composition for preventing and treating muscle diseases of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormonal therapy, chemotherapy, or biological response modifiers.
  • composition for preventing and treating muscle diseases or improving muscle function of the present invention may contain octagonal fennel extract or shikimic acid alone.
  • additional components may further enhance the muscle function improving effect of the composition of the present invention.
  • the pharmaceutical composition of the present invention may be provided as a formulation of an external preparation containing octagonal fennel extract or shikimic acid as an active ingredient.
  • the pharmaceutical composition for preventing and treating muscle diseases of the present invention is provided as an external preparation for skin, it is not limited thereto, and may be a formulation such as ointment, patch, gel, cream or spray.
  • the composition of the present invention may be prepared as a food composition for preventing muscle disease or improving muscle function.
  • the food composition for preventing muscle disease and improving muscle function of the present invention is a food composition, it can be used to prevent or improve muscle disease due to muscle wasting or degeneration.
  • Muscle wasting and degeneration are caused by genetic factors, acquired factors, aging, and the like, and muscle wasting is characterized by gradual loss of muscle mass, weakness and degeneration of muscles, especially skeletal or veterinary muscles and cardiac muscles. Examples of related diseases include atony, muscle atrophy, muscular dystrophy, muscle degeneration, myasthenia gravis, cachexia, and sarcopenia.
  • the composition of the present invention has an effect of increasing muscle mass, and the muscle does not limit its type.
  • the food composition of the present invention includes all forms of functional foods, nutritional supplements, health foods, food additives and feeds, and includes animals including humans or livestock. Subject to eating. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
  • Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
  • Beverages including alcoholic beverages
  • fruits and processed foods thereof e.g. canned fruits, bottled foods, jams, marmalades, etc.
  • fish meat and processed foods
  • breads and noodles e.g. udon, buckwheat noodles, ramen, spagate, macaroni, etc.
  • juice various drinks
  • cookies syrup
  • dairy products e.g. butter, cheese, etc.
  • edible plant maintenance margarine
  • Plant protein, retort food, frozen food, various seasonings eg, miso, soy sauce, sauce, etc.
  • seasonings eg, miso, soy sauce, sauce, etc.
  • the nutritional supplement it is not limited to the nutritional supplement, but may be prepared by adding octagonal fennel extract to capsules, tablets, pills, and the like.
  • the health functional food is not limited to this, for example, the octagonal fennel extract itself is prepared in the form of tea, juice, and drink to be consumed by liquefaction, granulation, encapsulation, and powdering for drinking (health drink). Can.
  • the octagonal fennel extract in order to use the octagonal fennel extract as a food additive, it can be prepared and used in the form of a powder or a concentrate.
  • the octagonal fennel extract can be prepared in the form of a composition by mixing with a known active ingredient known to have an effect of preventing muscle disease and improving muscle function.
  • the food composition of the present invention may be added to a feed additive or feed composition for the purpose of preventing muscle disease or improving muscle function.
  • the feed additive of the present invention corresponds to supplementary feeds under the feed management method, and mineral preparations such as sodium hydrogen carbonate, bentonite, magnesium oxide, and complex minerals, mineral preparations such as zinc, copper, cobalt, and selenium, and keratin , Vitamin A, D, E, nicotinic acid, vitamins such as vitamin B complex, protective amino acids such as methionine and lysine, protective fatty acids such as fatty acid calcium salts, probiotics (lactic acid bacteria), yeast culture, mold fermentation, etc. Probiotics, yeasts, etc. may be further included.
  • mineral preparations such as sodium hydrogen carbonate, bentonite, magnesium oxide, and complex minerals, mineral preparations such as zinc, copper, cobalt, and selenium, and keratin , Vitamin A, D, E, nicotinic acid, vitamins such as vitamin B complex, protective amino acids such as methionine and lysine, protective fatty acids such as fatty acid calcium salts, probiotics (lactic acid bacteria
  • feed in the present invention, any natural or artificial diet for the animal to eat, eat, digest or suitable for this, or a component of the meal, or the composition of the meal, bone formation promoting composition according to the present invention
  • Feed containing as an active ingredient can be prepared in various forms of feed known in the art, and preferably may include a rich feed, forage and/or special feed, but is not limited thereto.
  • Thick feed contains seeds, wheat, oats, corn and other grains, and by-products obtained by refining and harvesting grains such as rice bran, wheat bran, barley bran, etc., rice, soybean, fluid, sesame, flaxseed, coco palm, etc.
  • Fish-soluble (fish fish) which is a concentrate of fresh liquid obtained from fish, fish meal, fish residues, fish residues, etc. soluble), meat powder, blood powder, milk powder, skim milk powder, cheese from milk, whey, which is the balance when manufacturing casein from skim milk, and animal feed materials such as dry whey, yeast, chlorella, and algae, but are not limited thereto. Does not.
  • the feed additive according to the present invention can be prepared by adding octagonal fennel extract or sickimic acid in an appropriate effective concentration range according to various methods for preparing feeds known in the art.
  • the excipients include, but are not limited to, for example, skin emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickening agents and solvents.
  • fragrances, pigments, fungicides, antioxidants, preservatives and moisturizers may be further included, and for the purpose of improving physical properties, may include thickeners, inorganic salts, synthetic polymer materials, and the like.
  • it can be easily prepared by adding an octagonal fennel extract to a conventional cleanser and soap base.
  • the use of the octagonal fennel extract or the composition containing shikimic acid represented by the formula (1) as an active ingredient may be provided for the prevention or treatment of muscle disease.
  • L6 myoblasts (ATCC; Manassas, VA, USA) 1 ⁇ in a 6-well plate with Dulbecco's modified Eagle's media (DMEM; Hyclone) with 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA) After seeding to be 10 5 cells/well, the cells were cultured for 24 hours. After incubation, the medium in the well was removed and exchanged with DMEM (Hyclone) containing 2% horse serum (HS; Hyclone) for 6 days to incubate L6 cells to differentiate into myotubes.
  • DMEM Dulbecco's modified Eagle's media
  • FBS Hyclone
  • FBS fetal bovine serum
  • each of the octagonal fennel extract prepared in Example 1 was dissolved in DMEM (Hyclone) at 10 ⁇ g/mL, and then treated with cells and cultured for 12 hours. After incubation, cells were lysed by treatment with a cell lysis buffer. The protein in the obtained cell lysate was quantified at a concentration of 1 mg/mL using Bradford (Bio-Rad Laboratories Inc., Hercules, CA, USA). Cell lysate was dispensed in 50 ⁇ L of each microwell attached with anti-mTOR antibody and left at 37°C for 2 hours. After washing a total of 4 times with a washing buffer, treated with a detection antibody, and allowed to stand for 1 hour at 37°C.
  • DMEM Hyclone
  • the anti-rabbit secondary antibody (Bethyl Laboratories, Inc., Montgomery, TA, USA) conjugated with horseradish peroxidase recognizing the primary antibody was diluted to 1:5000 in 2.5% BSA with nitrocellulose membrane 2 The mixture was reacted at room temperature for an hour, and washed three times with 10 minutes using TBST. Protein bands were developed using ECL western blotting detection reagents (Amersham, Tokyo, Japan), and protein bands developed using a G;BOX EF imaging system (Syngene, Cambridge, UK) were identified. The results are shown in FIG. 2.
  • the muscle cell L6 myoblast was placed in a 6-well plate with DMEM (Hyclone) containing 10% FBS (Hyclone) to 1 ⁇ 10 5 cells/mL.
  • DMEM Hyclone
  • FBS Hyclone
  • RNA isolated was quantified using a nanodrop (NanoDrop 1000; Thermo Fisher Scientific Inc., Waltham, MA, USA). Quantitative 16 ⁇ L of RNA using Reverse Transcriptase Premix (ELPIS-Biotech) and PCR machine (Gene Amp PCR System 2700; Applied Biosystems, Foster City, CA, USA) at 42°C, 55 minutes and 70°C for 15 minutes. It was synthesized with cDNA under conditions.
  • Reverse primer 5'-CCGTATGAGTCTTATGTTTTGCTGG-3' (SEQ ID NO: 2)
  • Reverse primer 5'-AGCCTGGAAGATGTCGTTGG-3' (SEQ ID NO: 4)
  • Reverse primer 5'-TAAAACGCAGCTCAGTAACAGTC-3' (SEQ ID NO: 6)
  • the amplified cDNA was separated by electrophoresis with a 1.5% agarose gel, and the cDNA band was confirmed using a G;BOX EF imaging system (Syngene). The results are shown in FIG. 3.
  • Reverse primer 5'-GGTGTAACAACCATACCCCACT-3' (SEQ ID NO: 8)
  • Reverse primer 5'-GGGAGTTTGCGTTCCTCTGA-3'
  • the amplified cDNA was separated by electrophoresis with a 1.5% agarose gel, and the cDNA band was confirmed using a G;BOX EF imaging system (Syngene). The results are shown in FIG. 4.
  • the muscle strength of the rats was measured using a muscle strength meter (Panlab, Barcelona, Spain).
  • the rat's tail was pulled with constant force until the rat placed the youngest of the muscular strength tester, and a total of 5 consecutive tests were performed per head.
  • the octagonal hot water extract of the present invention has an excellent effect of increasing the weight of muscles reduced due to muscular atrophy.
  • muscle strength was significantly decreased ( ## p ⁇ 0.01) in the atrophy group compared to the normal group, but muscle strength was significantly increased ( ** p ⁇ 0.01) as treated with shikimic acid. was confirmed.
  • a powder was prepared by filling in an airtight fabric according to a conventional powder manufacturing method.
  • tablets After mixing the octagonal fennel extract or 50 mg of sikkim acid, 400 mg of crystalline cellulose, and 5 mg of magnesium stearate, tablets were prepared by tableting according to a conventional tablet manufacturing method.
  • the present invention relates to a composition for preventing and treating muscle disease or improving muscle function, comprising an octagonal fennel extract and shikimic acid.
  • the octagonal fennel extract and shikimic acid according to the present invention have the effect of increasing the activity of mTOR involved in muscle protein synthesis and reducing the mRNA expression of MuRF-1 and atrogin-1 involved in muscle protein degradation, increasing muscle mass and muscle function It is useful for preventing, treating or improving various muscle diseases such as atony, muscle atrophy, muscle dystrophy, muscle degeneration, myasthenia, cachexia, and sarcopenia. As it can be used, it has industrial applicability.

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Abstract

La présente invention concerne une composition permettant de prévenir et de traiter une maladie musculaire ou d'améliorer la fonction musculaire, comprenant un extrait d'Illicium verum et de l'acide shikimique. L'extrait d'Illicium verum et l'acide shikimique selon la présente invention ont pour effet d'augmenter l'activité mTOR impliquée dans la synthèse de protéines musculaires et de réduire l'expression d'ARNm de MuRF-1 et d'atrogine-1 impliquées dans la dégradation des protéines musculaires, et d'augmenter la masse musculaire et d'améliorer la fonction musculaire, ce qui est utile pour prévenir, traiter ou soulager diverses maladies musculaires telles que l'atonie, l'atrophie musculaire, la dystrophie musculaire, la dégénérescence musculaire, la myasthénie, la cachexie et la sarcopénie.
PCT/KR2019/018726 2018-12-28 2019-12-30 Composition pour prévenir et traiter une maladie musculaire ou améliorer la fonction musculaire, comprenant un extrait d'illicium verum ou de l'acide shikimique Ceased WO2020139057A2 (fr)

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KR20180172731 2018-12-28
KR1020190076670A KR20200083146A (ko) 2018-12-28 2019-06-26 팔각회향 또는 시킴산을 함유하는 근육 질환 예방 및 치료용 또는 근 기능 개선용 조성물
KR10-2019-0076670 2019-06-26

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KR102105532B1 (ko) * 2013-10-17 2020-04-29 (주)아모레퍼시픽 만능 줄기세포의 유도 방법 및 상기 방법에 의해 제조된 만능줄기세포

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