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WO2022030719A1 - Composition pour améliorer, traiter ou prévenir une maladie musculaire, ou améliorer la fonction musculaire, contenant du cynorrhodon comme ingrédient actif - Google Patents

Composition pour améliorer, traiter ou prévenir une maladie musculaire, ou améliorer la fonction musculaire, contenant du cynorrhodon comme ingrédient actif Download PDF

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Publication number
WO2022030719A1
WO2022030719A1 PCT/KR2021/003055 KR2021003055W WO2022030719A1 WO 2022030719 A1 WO2022030719 A1 WO 2022030719A1 KR 2021003055 W KR2021003055 W KR 2021003055W WO 2022030719 A1 WO2022030719 A1 WO 2022030719A1
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WIPO (PCT)
Prior art keywords
muscle
rosehip
improving
extract
preventing
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Ceased
Application number
PCT/KR2021/003055
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English (en)
Korean (ko)
Inventor
황재관
이혜린
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Aat Costech Co Ltd
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Aat Costech Co Ltd
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Priority to JP2023507679A priority Critical patent/JP2023536936A/ja
Publication of WO2022030719A1 publication Critical patent/WO2022030719A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • 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
    • 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)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/738—Rosa (rose)
    • 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

Definitions

  • the present invention relates to a composition for improving, treating or preventing muscle disease, or to a composition for improving muscle function, and more particularly, to improve or treat muscle disease containing rose hips such as pulverized rosehip or rosehip extract as an active ingredient Or for prevention, or relates to a composition for improving muscle function.
  • Muscle atrophy is caused by a gradual decrease in muscle mass, and refers to muscle weakness and degeneration (Cell, 119(7):907-910, 2004). Muscular atrophy is promoted by inactivity, oxidative stress, and chronic inflammation, and weakens muscle function and athletic performance (Clinical Nutrition, 26(5):524-534, 2007). The most important factor that determines muscle function is muscle mass, which is maintained by a balance between protein synthesis and breakdown. Muscular dystrophy occurs when protein degradation 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 anabolism or catabolism within the muscle.
  • a signal transduction reaction that induces synthesis rather than degradation of muscle protein occurs, muscle protein synthesis is increased, which appears as an increase in muscle size (hypertrophy) or an increase in the number of muscle fibers (hyperplasia) according to an increase in muscle protein (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 increase 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 cells and muscle formation are regulated by various muscle regulatory factors. Among them, the induction of myogenin expression by the activity of MyoD is the most important factor in the fusion of myoblasts, and is involved in the formation of myotubes. The muscle fibers formed through this process are bundled to finally form a muscle (Cellular and Molecular Life Sciences, 70:4117-4130, 2013).
  • Rose hip is a plant belonging to the family Rosaceae, and the scientific name is known as Rosa canina L. So far, in relation to rosehip, anti-aging effects (Clinical Interventions in Aging, 19(10): 1849-1856, 2015), antioxidant effects (Antioxidants, 8(4): 92, 2019), anti-cancer effects (Journal of Pharmaceutical Analysis 8 , 8(6): 394-399, 2018), antidiabetic effect (Journal of Evidence-Based Complementary & Alternative Medicine, 21(4): 25-30, 2016), anti-obesity effect (Preventive Nutrition and Food Science, 18) (2): 85-91, 2013) has been reported to have the activity.
  • the present inventors have searched for natural substances that have excellent muscle function control activity and can be safely applied.
  • rose hips such as pulverized rosehip or rosehip extract are used for improving, treating or preventing muscle disease, or improving muscle function.
  • an object of the present invention is to provide a food composition for improving or preventing muscle disease, or for improving muscle function, containing rosehip as an active ingredient.
  • Another object of the present invention is to provide a pharmaceutical composition for treating or preventing muscle disease containing rosehip as an active ingredient.
  • Another object of the present invention is to provide a cosmetic composition for improving or preventing muscle disease, or for improving muscle function, containing rosehip as an active ingredient.
  • Another object of the present invention is to provide a feed additive for improving or preventing muscle disease, or for improving muscle function, containing rosehip as an active ingredient containing rosehip as an active ingredient.
  • the present invention provides a food composition for improving or preventing muscle disease, or for improving muscle function, containing rose hip, such as pulverized rosehip or rosehip extract, as an active ingredient.
  • the present invention also provides a pharmaceutical composition for treating or preventing muscle disease containing rosehip as an active ingredient.
  • the present invention provides a cosmetic composition for improving or preventing muscle disease or improving muscle function containing rosehip as an active ingredient.
  • the present invention provides a feed additive for improving or preventing muscle disease or improving muscle function containing rosehip as an active ingredient.
  • the present invention provides the use of a pharmaceutical composition comprising rosehip as an active ingredient for the manufacture of a medicament for the prevention or treatment of muscle disease.
  • the present invention also provides a method for treating muscle disease, comprising administering to a patient with a muscle disease a pharmaceutical composition comprising rosehip as an active ingredient.
  • Rosehip according to the present invention has an excellent effect in increasing the activity of mTOR involved in muscle protein synthesis and inhibiting the mRNA expression of MuRF1 and atrogin-1 involved in muscle protein degradation.
  • the present invention is a natural product, it can be safely used without side effects and can be used as a pharmaceutical, food, cosmetic or feed additive.
  • 5 is a result confirming the effect of increasing the protein expression level of p-mTOR, p-p70S6K and p-4EBP-1 according to the treatment with hot water extract of rosehip in muscle atrophy-induced mice.
  • the present invention relates to a food composition for improving or preventing muscle disease, or for improving muscle function, containing rosehip, such as a pulverized rosehip or a rosehip extract; a pharmaceutical composition for treating or preventing a muscle disease containing rosehip, such as a pulverized rosehip or a rosehip extract; Or a cosmetic composition for improving or preventing muscle disease, or for improving muscle function, containing rosehip, such as a pulverized rosehip or a rosehip extract; or a feed additive for improving or preventing muscle disease or improving muscle function containing rosehip, such as rosehip pulverized or rosehip extract; Or it provides a method for treating a muscle disease comprising applying a rosehip, such as a pulverized rosehip or a rosehip extract, to a human or non-human mammal.
  • 'rose hip' is a plant of the Rosaceae family, a fruit of Rosa canina L., and a crushed rosehip or a rosehip extract may be used.
  • 'pulverized rosehip' refers to a method that can be easily performed by a person of ordinary skill in the art to which the present invention pertains to dried rosehip fruit, and ingested while being easily ingested by mammals, including humans.
  • the active ingredient is easily released from the dry pulverized material in the intestine, and as a result, it can be prepared and used in a form that can be easily absorbed into the body of a mammal.
  • the shape or size of the dry pulverized particles is not limited, but as the surface of the particles is maximized, it is easier to release the active ingredient described above, so it is preferable to prepare it in the form of a fine powder as much as possible.
  • 'rosehip extract' is obtained by extracting dried rosehip fruit using a suitable solvent, and is obtained in the form of an extract, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or a prepared or purified product thereof.
  • the method for preparing the rosehip extract may be obtained by extracting from the rosehip with one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, and ultra-high pressure, subcritical or supercritical fluid, but is not limited thereto.
  • the rosehip extract of the present invention can be prepared using conventional extraction methods in the art, such as heat extraction, cold-chill extraction, ultrasonic extraction, filtration, and reflux extraction. Cultivated ones can be used.
  • the rosehip extract according to the present invention can be separated using a conventional solvent according to a conventional method known in the art for preparing an extract from a natural product, that is, under conditions of conventional temperature and pressure.
  • the term 'fraction' refers to a result obtained by a fractionation method for separating a specific component or a specific group from a mixture containing various components. In the present invention, it refers to a result obtained by a fractionation method for separating a specific component or a specific group from the rosehip extract prepared as described above.
  • a conventional fractionation solvent known in the art, for example, a polar solvent such as anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms such as water, ethanol, and methanol, and hexane, butanol, ethyl
  • a non-polar solvent such as acetate, chloroform, dichloromethane, or a mixed solvent thereof may be used, but is not limited thereto.
  • the rosehip fraction of the present invention may include those obtained by additionally applying a purification process.
  • 'muscle' refers to tendons, muscles, and tendons comprehensively
  • 'muscular function' means the ability to exert force by contraction of the muscle, It includes muscle strength, which is the ability to perform, muscular endurance, which is the ability to repeat contractions and relaxations for how long or how many times a muscle can repeat contractions and relaxations with a given weight, and instantaneous power, which is the ability to exert strong force in a short period of time.
  • the term 'improving muscle function' refers to improving muscle function by increasing muscle mass.
  • the present invention relates to a food composition for improving and preventing muscle disease, or for improving muscle function, containing rosehip as an active ingredient, such as a pulverized rosehip or a rosehip extract; pharmaceutical compositions for preventing and treating muscle diseases; A cosmetic composition for improving and preventing muscle disease, or improving muscle function; It provides a feed additive for improving or preventing muscle disease, or for improving muscle function.
  • the rosehip extract may be a hot water extract, an ethanol extract, an ethyl acetate extract, a hexane extract, an ultra-high pressure extract, a subcritical extract, or a supercritical extract, but is not limited thereto.
  • the rosehip extract can be obtained by extracting the fruit of rosehip with one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, and subcritical and supercritical fluids. It can also be obtained by extracting rosehip under ultra-high pressure conditions of 100 MPa or more. If necessary, it may be prepared by additionally including filtration and concentration steps according to methods known in the art.
  • the organic solvent having 1 to 6 carbon atoms is alcohol, acetone, ether, benzene, chloroform, ethyl acetate, It may be at least one selected from the group consisting of methylene chloride, hexane, cyclohexane, and petroleum ether.
  • the present inventors repeatedly extract the dried rosehip fruit pulverized product using ethanol, ethyl acetate and hexane as solvents at room temperature, respectively, hot water extraction, ultra-high pressure extraction, subcritical fluid extraction, supercritical A rosehip extract was prepared using fluid extraction.
  • the food composition for preventing and improving muscle disease or improving muscle function of the present invention can be used for preventing or improving muscle disease due to muscle wasting or degeneration.
  • Muscle wasting and degeneration occurs due to genetic factors, acquired factors, aging, etc., and muscle wasting is characterized by a gradual loss of muscle mass, weakness and degeneration of muscles, particularly skeletal or voluntary muscles and cardiac muscles.
  • Examples of related diseases include sarcopenia, muscular atrophy, muscular dystrophy, atony, muscle degeneration, myasthenia gravis, cachexia, and the like.
  • the composition of the present invention has an effect of increasing muscle mass, and the type of muscle is not limited.
  • the food composition of the present invention includes all forms such as functional food, nutritional supplement, health function food, food additives and feed, including humans or livestock Animals are intended for food.
  • 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.
  • Common foods include, but are not limited to, beverages (including alcoholic beverages), fruits and their processed foods (eg, canned fruit, bottled, jam, marmalade, etc.), fish, meat and their processed foods (eg, ham, sausages) Corned beef, etc.), breads and noodles (eg udon noodles, soba noodles, ramen, spagate, macaroni, etc.), fruit juice, various drinks, cookies, syrup, dairy products (eg butter, cheese, etc.), edible vegetable oils and fats, margarine , vegetable protein, retort food, frozen food, various seasonings (eg, soybean paste, soy sauce, sauce, etc.) can be prepared by adding crushed rosehip or rosehip extract.
  • the nutritional supplement is not limited thereto, but may be prepared by adding crushed rosehip or rosehip extract to capsules, tablets, pills, and the like.
  • the pulverized rosehip or rosehip extract itself is prepared in the form of tea, juice, and drink, and liquefied, granulated, encapsulated and powdered so that it can be consumed (health drink). can be ingested.
  • the pulverized rosehip or rosehip extract in the form of a food additive, it may be prepared and used in the form of a powder or concentrate.
  • it can be prepared in the form of a composition by mixing the pulverized rosehip or rosehip extract with an active ingredient known to be effective in preventing and improving muscle disease, or improving muscle function.
  • the health drink composition may contain various flavoring agents or natural carbohydrates as additional ingredients like a conventional drink.
  • the above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrin and cyclodextrin; It may be a sugar alcohol such as xylitol, sorbitol, or erythritol.
  • Sweeteners include natural sweeteners such as thaumatin, stevia extract; A synthetic sweetener such as saccharin or aspartame may be used.
  • the proportion of the natural carbohydrate is generally about 0.01 to 5.0 g, preferably about 0.1 to 1.0 g per 100 mL of the composition of the present invention.
  • the pulverized rosehip or rosehip extract may be contained as an active ingredient in a food composition for preventing and improving muscle disease or improving muscle function, the amount of which is effective to achieve the action for preventing and improving muscle disease or improving muscle function.
  • the amount is not particularly limited, but is preferably 0.01 to 100% by weight based on the total weight of the total composition.
  • the food composition of the present invention may be prepared by mixing with other active ingredients known to be effective in preventing and improving muscle disease or improving muscle function together with pulverized rosehip or rosehip extract.
  • the composition for preventing and treating muscle disease of the present invention may also be a pharmaceutical composition.
  • the composition for preventing and treating muscle disease of the present invention is a pharmaceutical composition, it may be used for the prevention or treatment of muscle disease caused by muscle wasting or degeneration.
  • Muscle wasting and degeneration occurs due to genetic factors, acquired factors, aging, etc., and muscle wasting is characterized by a gradual loss of muscle mass, weakness and degeneration of muscles, particularly skeletal or voluntary muscles and cardiac muscles.
  • related diseases include sarcopenia, muscular atrophy, muscular dystrophy, atony, muscle degeneration, myasthenia gravis, cachexia, and the like.
  • the composition of the present invention has an effect of increasing muscle mass, and the type of muscle is not limited.
  • the 'pharmaceutical composition for preventing and treating muscle disease of the present invention may include a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier may further include, for example, a carrier for oral administration or a carrier 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 also include water, suitable oils, saline, aqueous glucose and glycols, and the like.
  • it may further include a stabilizer and a preservative. Suitable stabilizers include antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid.
  • Suitable preservatives are benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol.
  • reference may be made to those described in the following literature Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).
  • the pharmaceutical composition of the present invention may be administered to mammals including humans by any method.
  • it may be administered orally or parenterally, and parenteral administration methods include, but are not limited to, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal. , intranasal, enteral, 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 eg, saline or PBS
  • antioxidants e.g, bacteriostatic agents, chelating agents (eg, EDTA or glutathione), fillers, bulking agents, binders, adjuvants (eg, aluminum hydroxide) side), suspending agents, thickening agents, wetting agents, disintegrating agents or surfactants, diluents or excipients.
  • bacteriostatic agents eg, EDTA or glutathione
  • fillers eg, bulking agents, binders, adjuvants (eg, aluminum hydroxide) side), suspending agents, thickening agents, wetting agents, disintegrating agents or surfactants, diluents or excipients.
  • Solid preparations for oral administration include tablets, pills, powders, granules, liquids, gels, syrups, slurries, suspensions or capsules, and such solid preparations include at least one excipient in the pharmaceutical composition of the present invention, for example , 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 hydroxypropylmethyl-cellulose or gelatin may be mixed and prepared.
  • tablets or sugar tablets can be obtained by blending the active ingredient with a solid excipient, grinding it, adding a suitable adjuvant, and processing it into a granule mixture.
  • Liquid formulations for oral use include suspensions, solutions, emulsions, or syrups.
  • various excipients for example, wetting agents, sweeteners, flavoring agents, or preservatives may be included. .
  • cross-linked polyvinylpyrrolidone, agar, alginic acid or sodium alginate may be added as a disintegrant, and an anti-aggregating agent, a lubricant, a wetting agent, a flavoring agent, an emulsifier, and a preservative may be additionally included. .
  • the pharmaceutical composition of the present invention may be formulated according to methods known in the art in the form of injections, transdermal administrations and nasal inhalants together with suitable parenteral carriers.
  • suitable parenteral carriers include, but are not limited to, solvents or dispersion media containing 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, PBS (phosphate buffered saline) with triethanolamine or isotonic solutions such as sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose. etc. can be used.
  • PBS phosphate buffered saline
  • isotonic solutions such as sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose. etc.
  • it may further include various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like.
  • the injection may further contain an isotonic agent such as sugar or sodium chloride.
  • transdermal administration forms such as ointment, cream, lotion, gel, external solution, pasta, liniment, and air are included.
  • 'transdermal administration' means that an effective amount of the active ingredient contained in the pharmaceutical composition is delivered into the skin by topically administering the pharmaceutical composition to the skin.
  • the compounds for use according to the invention may be administered in pressurized packs or using a suitable propellant, for example, dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. It can be conveniently delivered in the form of an aerosol spray from the nebulizer.
  • the dosage unit may be determined by providing a valve to deliver a metered amount.
  • gelatin capsules and cartridges for use in inhalers or insufflators may be formulated to contain a powder mixture of the 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 recipe commonly known to all pharmaceutical chemistry.
  • the pharmaceutical composition for preventing and treating muscle disease of the present invention contains an effective amount of a rosehip extract, it is possible to provide a desirable preventive and therapeutic effect on muscle disease.
  • the term 'effective amount' refers to an amount that exhibits a higher response than that of the negative control group, and preferably refers to an amount sufficient to improve muscle function.
  • the pharmaceutical composition of the present invention may contain 0.01 to 99.99% of the rosehip extract, and the remaining amount may be occupied by a pharmaceutically acceptable carrier.
  • the effective amount of the rosehip extract contained 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 may be administered to a patient as a single dose, or may be administered by a fractionated treatment protocol in which multiple doses are administered for a long period of time.
  • the pharmaceutical composition of the present invention may vary the content of the active ingredient depending on the severity of the 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 1 kg of body weight per day based on the rosehip extract, and when administered orally, the body weight per day based on the rosehip extract It may be administered in 1 to several divided doses so as to be administered in an amount of preferably 0.01 to 100 mg, more preferably 0.1 to 50 mg per 1 kg.
  • the dosage of the rosehip extract is determined by considering various factors such as the age, weight, health status, sex, severity of the disease, diet and excretion rate of the patient, as well as the administration route and number of treatments of the pharmaceutical composition, and the effective dosage for the patient is determined. Therefore, in consideration of this point, those of ordinary skill in the art will be able to determine an appropriate effective dosage according to the specific use of the rosehip extract for the prevention and treatment of muscle diseases.
  • the pharmaceutical composition according to the present invention is not particularly limited in its formulation, administration route and administration method as long as the effect of the present invention is exhibited.
  • the pharmaceutical composition for preventing and treating muscle disease of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, or biological response modifiers.
  • the pharmaceutical composition for preventing and treating muscle disease of the present invention may also be provided in the form of an external preparation containing a rosehip extract as an active ingredient.
  • the pharmaceutical composition for the prevention and treatment of muscle diseases of the present invention is used as an external preparation for skin, additionally, a fatty substance, an organic solvent, a solubilizer, a thickening agent and a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, and a foaming agent (foaming agent) ), fragrance, surfactant, water, ionic emulsifier, nonionic emulsifier, filler, sequestering agent, chelating agent, preservative, vitamin, blocker, wetting agent, essential oil, dye, pigment, hydrophilic active agent, lipophilic active agent Or it may contain adjuvants commonly used in the field of dermatology, such as any other ingredients commonly used in external preparations for skin, such as lipid vesicles. In addition, the above ingredients may be introduced in an amount generally used in the field of dermatology.
  • the pharmaceutical composition for preventing and treating muscle disease of the present invention is provided as an external preparation for skin, it may be in the form of an ointment, patch, gel, cream or spray, but is not limited thereto.
  • the composition for preventing and improving muscle disease or for improving muscle function of the present invention may also be a cosmetic composition.
  • the cosmetic composition of the present invention contains rosehip extract as an active ingredient, and a basic cosmetic composition (toilet water, cream, essence, face wash such as lotion, cream, essence, cleansing foam and cleansing water, pack, body oil), color cosmetic composition together with a dermatologically acceptable excipient (foundation, lipstick, mascara, makeup base), hair product compositions (shampoo, conditioner, hair conditioner, hair gel), and soap.
  • a basic cosmetic composition toilet water, cream, essence, face wash such as lotion, cream, essence, cleansing foam and cleansing water, pack, body oil
  • color cosmetic composition together with a dermatologically acceptable excipient (foundation, lipstick, mascara, makeup base), hair product compositions (shampoo, conditioner, hair conditioner, hair gel), and soap.
  • the excipient is not limited thereto, but may include, for example, an emollient, a skin penetration enhancer, a colorant, a fragrance, an emulsifier, a thickening agent, and a solvent.
  • fragrances, dyes, bactericides, antioxidants, preservatives and moisturizing agents may be additionally included, and for the purpose of improving physical properties, thickeners, inorganic salts, synthetic polymer materials, and the like may be included.
  • a face wash and soap with the cosmetic composition of the present invention it can be easily prepared by adding a rosehip extract to a conventional face wash and soap base.
  • a cream it can be prepared by adding rosehip extract to a general oil-in-water type (O/W) cream base.
  • synthetic or natural materials such as proteins, minerals and vitamins for the purpose of improving physical properties such as fragrances, chelating agents, pigments, antioxidants, and preservatives may be additionally added.
  • the content of the rosehip extract contained in the cosmetic composition of the present invention is not limited thereto, but is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight, based on the total weight of the composition. If the content is less than 0.001% by weight, the desired effect cannot be expected, and if it exceeds 10% by weight, there may be difficulties in safety or formulation.
  • composition of the present invention may be added to a feed additive or a feed composition comprising the same for the purpose of preventing or improving muscle disease.
  • the term 'feed additive' refers to a substance added to feed for various effects such as nutrient supplementation and weight loss prevention, enhancement of digestibility of fiber in feed, oil quality improvement, reproductive disorder prevention and fertility improvement, and prevention of high temperature stress in summer includes
  • the feed additive of the present invention corresponds to an auxiliary feed under the Feed Management Act, and mineral preparations such as sodium bicarbonate, bentonite, magnesium oxide, and complex minerals, and trace minerals such as zinc, copper, cobalt, selenium, and kerotene.
  • vitamins AD, E, nicotinic acid, vitamin B complex, etc. protective amino acids such as methionine and lysine, protective fatty acids such as fatty acid calcium salts, probiotics (lactic acid bacteria), yeast cultures, live bacteria such as mold fermented products, Yeast agents and the like may be further included.
  • the term 'feed' refers to any natural or artificial diet, one-meal meal, etc. or a component of the one-meal meal for animals to eat, ingest and digest, or to prevent or improve muscle disease according to the present invention.
  • the feed containing the composition for use as an active ingredient can be prepared in various types of feed known in the art, and preferably, a concentrated feed, roughage and/or special feed may be included, but is not limited thereto.
  • seed fruits containing grains such as wheat, oats, and corn, bran containing rice bran, bran, barley bran, etc.
  • Fish Soluble is a concentrated fish meal, fish waste, and fresh liquid obtained from fish, fish meal, fish waste, and residual starch, which is the main component of starch residue, which is a by-product obtained by subtracting starch from sweet potatoes and potatoes.
  • animal feeds such as dried whey, yeast, chlorella, and seaweed, which are dried whey, which is the remainder of the production of soluble), meat meal, blood meal, cow meal, powdered skim milk, cheese from skim milk, and casein from skim milk. It is not limited thereto.
  • raw grass feed such as wild grasses, grasses, and green cuttings, turnips for feed, beets for feed, root vegetables such as rutherbearers, a type of turnip, raw herbs, green crops, grains, etc.
  • silage which is stored feed fermented with lactic acid after filling, wild grass, hay obtained by cutting and drying grass, straw of crops for breeding purposes, and leaves of legumes.
  • Special feed includes mineral feed such as oyster shells and rock salt, urea feed such as urea or its derivative diureide isobutane, supplementing ingredients that are easily lacking when only natural feed raw materials are mixed, or added to formulated feed to increase feed storage.
  • feed additives and dietary supplements which are substances added in trace amounts, but are not limited thereto.
  • the feed additive for preventing or improving muscle disease according to the present invention can be prepared by adding ground rosehip or rosehip extract in an appropriate effective concentration range according to various feed preparation methods known in the art.
  • the feed additive according to the present invention can be applied without limitation as long as it is an individual for the purpose of preventing or improving muscle disease.
  • non-human animals such as cattle, horses, pigs, goats, sheep, dogs, cats, rabbits, etc., birds and fish can be applied to any object.
  • the dried rosehip fruit was crushed with a mixer, and 10 g of the crushed rosehip fruit was charged into a sample cartridge and extracted using a supercritical fluid extraction device (SFX 3560, Isco Inc., Lincoln, NE, USA).
  • the supercritical extraction conditions were an extraction pressure of 300 bar, an extraction temperature of 50° C., a flow rate of supercritical carbon dioxide of 60 mL/min, and an extraction time of 2 hours.
  • the supercritical fluid state was released by lowering the pressure of the extraction device to obtain a rosehip fruit supercritical extract.
  • Example 2 Effect of increasing mTOR activity, a biomarker for muscle protein synthesis of rosehip hot water extract and ethanol extract
  • mTOR protein when mTOR protein is phosphorylated and activated, it can induce activation of proteins involved in muscle protein synthesis and increase in muscle mass in the PI3K/Akt signaling pathway in muscle cells. Therefore, in order to confirm the muscle-generating activity of the rosehip extract, the activity of mTOR was confirmed using the mTOR Sandwich ELISA kit (Cell Signaling Technology, Beverly, MA, USA).
  • L6 myoblasts ATCC; Manassas, VA, USA
  • DMEM Dulbecco's modified Eagle's media
  • FBS fetal bovine serum
  • HS horse serum
  • the hot water extract of rosehip of Example 1-1 was dissolved in DMEM (Hyclone) at a concentration of 40 ⁇ g/mL
  • the ethanol extract of rosehip of Example 1-2 was dissolved in DMEM (Hyclone) at a concentration of 5.0 ⁇ g/mL
  • the cells were treated and Incubated for 12 hours.
  • cells were lysed by treatment with cell lysis buffer. Proteins in the obtained cell lysate were quantified at a concentration of 1 mg/mL using Bradford (Bio-Rad Laboratories Inc., Hercules, CA, USA). 50 ⁇ L of cell lysate was dispensed into microwells to which anti-mTOR antibody was attached and left at 37° C.
  • the experiment was repeated a total of three times, and the measured values obtained for each were calculated as a percentage (%) relative to the control and expressed as the mean ⁇ standard deviation. Differences between groups were confirmed through Duncan multi-range analysis by one-way analysis of variance using the SPSS25.0 statistical package (SPSS Inc., Chicago, IL, USA). At this time, when the p value was less than 5%, it was marked as statistically significant.
  • mTOR activity was measured in the same manner as in Example 2, except that 5.0 ⁇ g/mL of each of the rosehip extracts of Examples 1-3 to 1-7 was treated.
  • the rosehip extract of the present invention has an excellent ability to promote muscle protein synthesis in muscle cells.
  • L6 myoblast (ATCC), a muscle cell, was placed in a 6-well plate with DMEM (Hyclone) containing 10% FBS (Hyclone) at a concentration of 1 ⁇ 10 5 cell/mL.
  • DMEM Hyclone
  • FBS Hyclone
  • the medium in the well was removed and the cells were treated with DMEM (Hyclone) containing 2% HS (Hyclone) to induce myotube differentiation. Differentiation was performed for a total of 6 days by replacing the medium with a new medium once every 2 days.
  • the rosehip hot water extract prepared in Example 1-1 was added to DMEM (Hyclone) containing 50 ng/mL tumor necrosis factor alpha (TNF- ⁇ ; PeproTech, Rocky Hills, NJ, USA). After dissolving at a concentration of 80 ⁇ g/mL, the cells were treated and incubated for 12 hours. After incubation, the cells were lysed with a NP-40 buffer (ELPIS-Biotech, Daejeon, Korea) containing a protease inhibitor cocktail (Sigma-Aldrich St. Louis, MO, USA) to obtain a cell lysate. The obtained cell lysate was centrifuged at 13,000 rpm for 10 minutes to obtain a supernatant.
  • DMEM Hyclone
  • TNF- ⁇ tumor necrosis factor alpha
  • the protein concentration in the supernatant was quantified with a Bradford (Bio-Rad Laboratories Inc.), and then the protein was heated for 5 minutes, and then the protein was separated by running on a 10% sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) gel. The separated protein was transferred to a nitrocellulose membrane.
  • p-mTOR, mTOR, p-p70S6K, p70S6K, p-4EBP1, 4EBP1, or ⁇ -tubulin antibody (Cell Signaling Technology) was diluted 1:1000 in 2.5% bovine serum albumin (BSA) at a ratio of 1:1000 to nitro
  • BSA bovine serum albumin
  • the protein transferred to the cellulose membrane was reacted at room temperature for 20 hours. After reacting with the primary antibody, the nitrocellulose membrane was washed 3 times for 10 minutes using Tris-buffer Saline Tween20 (TBST).
  • a secondary antibody (Bethyl Laboratories, Inc., Montgomery, TA, USA) conjugated with horseradish peroxidase (HRP), which recognizes the primary antibody, was diluted 1:5000 in 2.5% BSA, and then placed with a nitrocellulose membrane at room temperature for 2 hours. , and washed 3 times for 10 minutes each using TBST.
  • the protein band was developed using ECL Western Blot detection reagent (GE Healthcare, Piscataway, NJ, USA), and the colored protein band was confirmed using the G;BOX EF imaging system (Syngene, Cambridge, UK).
  • the protein expression levels of p-mTOR, p-p70S6K and p-4EBP-1 involved in muscle protein synthesis by TNF- ⁇ were significantly ( ## p ⁇ 0.01) decreased.
  • the protein expression levels of p-mTOR, p-p70S6K, and p-4EBP-1 were significantly increased ( ** p ⁇ 0.01) as the rosehip hot water extract was treated. This means that the hot water extract of rosehip of the present invention has excellent ability to increase the expression of biomarkers involved in muscle protein synthesis in muscle cells.
  • L6 myoblast (ATCC), a muscle cell, was placed in a 6-well plate with DMEM (Hyclone) containing 10% FBS (Hyclone) at a concentration of 1 ⁇ 10 5 cell/mL.
  • DMEM Hyclone
  • FBS Hyclone
  • the medium in the well was removed and the cells were treated with DMEM (Hyclone) containing 2% HS (Hyclone) to induce myotube differentiation. Differentiation was performed for a total of 6 days by replacing the medium with a new medium once every 2 days.
  • Example 1-1 After differentiation, the hot water extract of Example 1-1 was mixed with 40 ⁇ g/mL of the rosehip hot water extract of Example 1-1 in DMEM (Hyclone) containing 50 ng/mL tumor necrosis factor alpha (TNF- ⁇ ; PeproTech, Rocky Hills, NJ, USA). After dissolving in DMEM (Hyclone) at a concentration of 80 ⁇ g/mL, the cells were treated. After 12 hours, total RNA was isolated using TRIzol reagent (Takara, Otsu, Japan). The isolated total RNA was quantified using a nanodrop (NanoDrop 1000; Thermo Fisher Scientific Inc., Waltham, MA, USA).
  • RNA 16 ⁇ L of quantified RNA was analyzed using Reverse Transcriptase Premix (ELPIS-Biotech) and a 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 as cDNA under conditions. Out of 16 ⁇ L of the generated cDNA, 1 ⁇ L of cDNA, the following specific primers (Bioneer, Daejeon, Korea) and PCR premix (ELPIS-Biotech) were used for 30 seconds at 95°C, 1 minute at 60°C, and 1 minute at 72°C. PCR was performed by repeating 30 times.
  • EPIS-Biotech Reverse Transcriptase Premix
  • Reverse primer 5'-AGCCTGGAAGATGTCGTTGG-3' (SEQ ID NO: 2)
  • Reverse primer 5'-CCGTATGAGTCTTATGTTTTGCTGG-3' (SEQ ID NO: 4)
  • Reverse primer 5'-TAAAACGCAGCTCAGTAACAGTC-3' (SEQ ID NO: 6)
  • the amplified cDNA was separated by electrophoresis on 1.5% agarose gel, and the cDNA band was confirmed using the G;BOX EF imaging system (Syngene).
  • the hot water extract of rosehip of the present invention has excellent ability to suppress the expression of biomarkers involved in muscle protein degradation in muscle cells.
  • Example 5 In the same manner as in Example 5, except that 5 ⁇ g/mL of the rosehip ethanol, ethyl acetate, hexane, ultra-high pressure, subcritical, and supercritical extracts of Examples 1-2 to 1-7 were treated, respectively. This was repeated 3 times in total. Next, the band density of MuRF1 and atrogin-1 mRNA was measured using the Image J program (National Institute of Health, Bethesda, MD, USA), and then each measured value was calculated as a percentage (%) for the control group and the mean ⁇ It is expressed as standard deviation.
  • mice 7-week-old male mice (C57BL/6J; DBL, Korea) were purchased and the experiment was carried out.
  • the breeding room environment of all animals was maintained at a temperature of 23 ⁇ 2 °C and a relative humidity of 55 ⁇ 10%.
  • a total of 20 rats were randomly divided into 5 rats per group.
  • anesthesia was induced by intraperitoneal injection of 325 mg/kg of tribromoethanol (Sigma-Aldrich).
  • the right hindlimb gastrocnemius muscle and right sole of the rats in the muscle atrophy group and the sample administration group were cut with a stapler seam using a skin stapler (Unidus, Chungcheongbuk-do, Korea).
  • the damage resulted in immobilization of the right hind leg, which was maintained for a week.
  • the stapler shim fixed to the calf muscles and the soles of the feet was removed, and dried rosehips 500 mg/kg for another week; 200 mg/kg of hot water extract of rosehip of Example 1-1; 200 mg/kg of rosehip ethanol extract of Example 1-2; 200 mg/kg of the rosehip supercritical extract of Example 1-7 was orally administered daily for 7 days.
  • the normal group and the muscular atrophy group were orally administered with saline instead of the sample.
  • the muscle strength of the rats was measured using a muscle strength meter (Panlab, Barcelona, Spain).
  • the rat's tail was pulled with a constant force until the rat released the youngest member of the muscle strength meter, and a total of five consecutive tests were performed per rat.
  • muscle strength was significantly ( # p ⁇ 0.05) decreased in the muscle atrophy group compared to the normal group, but when treated with the crushed rosehip powder and rosehip extract, the muscle strength was significantly reduced compared to the muscle atrophy group ( * * p ⁇ 0.01) was confirmed.
  • mice were respiratory anesthetized with isoflurane and the volume and density of the right hind limb muscle were measured using positron emission tomography/computed tomography/single photon emission tomography (microPET/CT/SPECT; Siemens Inveon, Knoxville, TN, USA). did
  • the muscle volume of the muscle atrophy group was significantly reduced ( ## p ⁇ 0.01) compared to the normal group. It was confirmed that the muscle volume increased significantly ( ** p ⁇ 0.01). This means that the pulverized rosehip and the rosehip extract of the present invention are excellent in increasing the muscle volume reduced due to muscle atrophy.
  • the experimental animals were sacrificed through deep blood sampling after anesthesia by intraperitoneal injection of 325 mg/kg of tribromethanol (Sigma-Aldrich). After confirming that the heartbeat has stopped, the uninjured tibialis anterior muscle was removed from the right hind leg and the weight was measured.
  • the weight of the tibialis anterior muscle in the muscular atrophy group was significantly ( ## p ⁇ 0.01) decreased compared to the normal group, but when treated with the crushed rosehip and rosehip extract, the weight was increased compared to the muscle atrophy group. It was confirmed that it increased significantly ( ** p ⁇ 0.01). This means that the pulverized rosehip and the rosehip extract of the present invention are excellent in increasing the muscle weight reduced due to muscle atrophy.
  • the tissue was crushed with NP-40 buffer (ELPIS-Biotech, Daejeon, Korea) containing a protease inhibitor cocktail (Sigma-Aldrich St. Louis, MO, USA) to the tibialis anterior muscle extracted in Example 7-3. After obtaining a muscle tissue lysate, centrifuged at 13,000 rpm for 10 minutes to obtain a supernatant. Next, the expression level of the muscle protein synthesis biomarker was measured in the same manner as in Example 4 using the supernatant.
  • the capsules were prepared by filling in gelatin capsules according to a conventional capsule preparation method.
  • vitamin A acetate 70 ug 1000 mg of crushed rosehip or rosehip extract of the present invention, vitamin A acetate 70 ug, vitamin E 1.0 mg, vitamin B1 0.13 mg, vitamin B2 0.15 mg, vitamin B6 0.5 mg, vitamin B12 0.2 ug, vitamin C 10 mg, biotin 10 ug, nicotinic acid amide 1.7 mg, folic acid 50 ug, calcium pantothenate 0.5 mg, ferrous sulfate 1.75 mg, zinc oxide 0.82 mg, magnesium carbonate 25.3 mg, potassium monobasic 15 mg, dibasic calcium phosphate 55 mg, potassium citrate 90 mg, calcium carbonate 100 mg, and magnesium chloride 24.8 mg can be mixed to prepare the mixture, and the mixing ratio may be arbitrarily modified, and the above ingredients are mixed according to the usual health food manufacturing method, and then granules are prepared, , it can be used to prepare a health food composition according to a conventional method.
  • the above ingredients After adding purified water to 1000 mg of rosehip extract of the present invention, 1000 mg of citric acid, 100 g of oligosaccharide, 2 g of plum concentrate, and 1 g of taurine, the above ingredients are mixed according to the general method for preparing a total 900 mL health drink, and then about 1 hour After stirring and heating at 85 for a while, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, and then stored in a refrigerator, and then it can be used in the manufacture of health beverage compositions.
  • Chewing gum was prepared in a conventional manner by mixing 20% by weight of gum base, 76.9% by weight of sugar, 1% by weight of flavoring and 2% by weight of water and 0.1% by weight of rosehip extract of the present invention.
  • Nutrient lotion was prepared according to a conventional method by using the rosehip extract of the present invention according to the formulation ratio of the nutrient lotion in Table 3 below.
  • Softening lotion (skin lotion) A softening lotion was prepared according to a conventional method by using the rosehip extract of the present invention according to the ratio of the softening lotion formulation in Table 4 below.
  • Nutrient Cream A nourishing cream was prepared according to a conventional method by using the rosehip extract of the present invention according to the formulation ratio of the nourishing cream in Table 5 below.
  • a massage cream was prepared according to a conventional method by using the crushed rosehip powder or rosehip extract of the present invention according to the massage cream formulation ratio shown in Table 6 below.
  • Pack A pack was prepared according to a conventional method by using the pulverized rosehip powder or rosehip extract of the present invention according to the pack formulation ratio in Table 7 below.
  • 'appropriate amount' means that an appropriate amount can be added according to preference, and 'to 100' is the weight% remaining after subtracting the sum of the weight% of the remaining ingredients except for purified water from 100% by weight of purified water. It means that it can be done in weight %.
  • the present invention provides a composition for improving, treating or preventing muscle disease, or for improving muscle function, containing rose hips such as pulverized rosehips or rosehip extracts. More specifically, the rose hip of the present invention improves muscle mass and muscle strength by increasing the activity of mTOR and reducing the mRNA expression levels of MuRF1 and atrogin-1, thereby improving, treating or preventing muscle diseases, or improving muscle function. indicates. Accordingly, the present invention has high industrial applicability because it can provide a composition showing an excellent effect for improving, treating or preventing muscle disease, or improving muscle function.

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Abstract

La présente invention concerne une nouvelle utilisation du cynorrhodon sous la forme de cynorrhodon moulu ou d'un extrait de cynorrhodon, et une composition pour améliorer, traiter ou prévenir une maladie musculaire, ou améliorer la fonction musculaire, contenant du cynorrhodon tant que principe actif. La composition de la présente invention a pour effet d'augmenter l'activité de mTOR impliquée dans la synthèse de protéines musculaires et de réduire l'expression d'ARNm de MuRF -1 et d'atrogine-1 impliquée dans la dégradation des protéines musculaires, et augmente la masse musculaire et améliore la fonction musculaire de telle sorte que la composition de la présente invention peut être utilisée efficacement pour prévenir, améliorer ou traiter diverses maladies musculaires telles que la sarcopénie, l'atrophie musculaire, la dystrophie musculaire, l'atonie, la dégénérescence musculaire, la myasthénie, la cachexie, etc.
PCT/KR2021/003055 2020-08-03 2021-03-11 Composition pour améliorer, traiter ou prévenir une maladie musculaire, ou améliorer la fonction musculaire, contenant du cynorrhodon comme ingrédient actif Ceased WO2022030719A1 (fr)

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Citations (4)

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US20110097427A1 (en) * 2009-10-27 2011-04-28 Shyam Ramakrishnan Molecular Targets and Dietary Modulators of Exercise-Induced Muscle Damage
WO2014005597A1 (fr) * 2012-07-06 2014-01-09 Axellus A/S Composition de cynorrhodon, procédé pour la fabrication de la composition de cynorrhodon et ladite composition destinée à être utilisée dans un procédé pour l'entretien d'articulations souples et d'une inflammation réduite
JP2019517470A (ja) * 2016-05-27 2019-06-24 スマートフィッシュ・アーエス 筋肉の性能を改善するための、海洋性油及びジュースを含む組成物の使用
KR20200071363A (ko) * 2018-12-11 2020-06-19 주식회사 엘리바이오 로즈힙을 함유하는 연골손상방지 내지 재생용 조성물

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BR112013016230B1 (pt) * 2010-12-23 2022-02-08 Amazentis Sa Composições e métodos para melhora da função mitocondrial e tratamento de doenças neurodegenerativas e transtornos cognitivos

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WO2014005597A1 (fr) * 2012-07-06 2014-01-09 Axellus A/S Composition de cynorrhodon, procédé pour la fabrication de la composition de cynorrhodon et ladite composition destinée à être utilisée dans un procédé pour l'entretien d'articulations souples et d'une inflammation réduite
JP2019517470A (ja) * 2016-05-27 2019-06-24 スマートフィッシュ・アーエス 筋肉の性能を改善するための、海洋性油及びジュースを含む組成物の使用
KR20200071363A (ko) * 2018-12-11 2020-06-19 주식회사 엘리바이오 로즈힙을 함유하는 연골손상방지 내지 재생용 조성물

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