WO2016190689A2 - Composition permettant de prévenir, de soulager ou de traiter les maladies musculaires ou d'améliorer la fonction musculaire - Google Patents

Composition permettant de prévenir, de soulager ou de traiter les maladies musculaires ou d'améliorer la fonction musculaire Download PDF

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WO2016190689A2
WO2016190689A2 PCT/KR2016/005597 KR2016005597W WO2016190689A2 WO 2016190689 A2 WO2016190689 A2 WO 2016190689A2 KR 2016005597 W KR2016005597 W KR 2016005597W WO 2016190689 A2 WO2016190689 A2 WO 2016190689A2
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extract
sargassum
muscle
fucosterol
preventing
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PCT/KR2016/005597
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English (en)
Korean (ko)
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WO2016190689A3 (fr
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황재관
김창희
김미보
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연세대학교 산학협력단
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Priority to JP2018514759A priority Critical patent/JP6818018B2/ja
Priority to US15/577,098 priority patent/US10646498B2/en
Priority claimed from KR1020160064917A external-priority patent/KR101809156B1/ko
Publication of WO2016190689A2 publication Critical patent/WO2016190689A2/fr
Publication of WO2016190689A3 publication Critical patent/WO2016190689A3/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • 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
    • A61K36/02—Algae
    • A61K36/03—Phaeophycota or phaeophyta (brown algae), e.g. Fucus

Definitions

  • the present invention relates to a composition for preventing, improving or treating muscle diseases or improving muscle function. More specifically, the present invention relates to fucosterol and sargassum. fulvellum), Sargassum pulverized Sargassum extract Chop (Sargassum fusiforme ), ⁇ pulverized powder or ⁇ extract, and relates to a composition for preventing, improving or treating muscle diseases or 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, weakening 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 the balance of protein synthesis and degradation. Muscular atrophy occurs when proteolysis occurs more than synthesis (The International Journal of Biochemistry and Cell Biology, 37 (10): 1985-1996, 2005).
  • Muscle size is controlled by intracellular signaling pathways that induce anabolism or catabolism in the muscle, and when there are more signaling reactions that induce synthesis than muscle protein degradation Muscle protein synthesis is increased, which is manifested as an increase in muscle size (hypertrophy) or muscle fiber number (hyperplasia) (The Korea Journal of Sports Science, 20 (3): 1551-1561, 2011).
  • PI3K phosphatidylinositol-3 kinase
  • mTOR mammalian target of rapamycin
  • mTOR induces muscle protein synthesis by activating two factors that initiate mRNA translation, 4E-binding protein (4E-BP1) and phosphorylated 70-kDa ribosomal S6 kinase (p70S6K), contributing to muscle mass gain (The Korea Journal of Sports) Science, 20 (3): 1551-1561, 2011; The International Journal of Biochemistry and Cell Biology, 43 (9): 1267-1276, 2011).
  • 4E-BP1 4E-binding protein
  • p70S6K phosphorylated 70-kDa ribosomal S6 kinase
  • the transfer of the transcription factor forhead box (FoxO) from the cytoplasm into the nucleus increases the expression of the E3 ubiquitin ligase factors atrogin-1 and MuRF-1, which are involved in proteolysis (Disease Models and Mechanisms, 6: 25). -39, 2013).
  • Increased expression of these proteins promotes protein breakdown in muscles, thereby reducing muscle mass. Therefore, promoting the
  • MyoD initiates the expression of muscle specific genes and induces the differentiation of muscle satellite cells into myoblasts. 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. Muscle fibers formed through this process are bundled to form muscles finally (Cellular and Molecular Life Sciences, 70: 4117-4130, 2013).
  • Sargassum fulvellum is a marine algae belonging to the genus Sargassum (Sargassum).
  • the activities of mother-in-law include antimicrobial (Korean Journal of Food Science and Technology, 42 (2): 155-159, 2010), anti-inflammatory (Journal of Ethnopharmacology, 116 (1): 187-190, 2008), antioxidant of Food Science and Nutrition, 12 (2): 65-73, 2007), Chemotherapy (32 (12): 1004-1009, 1984), Evidence-based Complementary and Alternative Medicine, 2013: 747 846, 2013 ), Antidiabetic (Natural Product Sciences, 18 (2): 130-136, 2012) and the like have been reported.
  • Sargassum fusiforme is an algae belonging to Sargassum.
  • activity against ⁇ includes anti-acid and anti-inflammatory (Tropical Journal of Pharmaceutical Research, 14 (3): 463-468, 2015), antidiabetic (Food Science and Biotechnology, 23 (3): 2037-2044, 2014), Antiviral (Natural Medicines, 48 (3): 173-179, 1994), Journal of Medicinal Food, 12 (4): 782-787, 2009), Journal of Medicinal Food, 15 (4): 384-390, 2012) and the like have been reported.
  • Fucosterol is a substance found in algae, including maban and mud, and is found in seaweeds in coastal areas of Asia such as Korea, China, and Japan. To date, the activity of fucosterol has been shown to be anticancer (Pharmacognosy Magazine, 8 (29): 60-64, 2012), antidiabetic (Archives of Pharmacal Research, 27 (11): 1120-1122, 2004), antioxidant (Bioorganic and Medicinal) Chemistry, 17 (5): 1963-1973, 2009), improving blood lipid content (Biochemical and Biophysical Research Communications, 369 (2): 363-368, 2008), improving cholesterol metabolism (New Phytologist, 183 (2): 291 -300, 2009), Journal of Pharmaceutical and Biomedical Analysis, 51 (2): 450-4555, 2010), Antifungal (Natural Product Research, 24 (15): 1481-1487, 2010), Anti-aging (Photochemistry and Photobiology, 89 (4): 911-918, 2013).
  • the present inventors have searched for a natural substance having excellent muscle function control activity and can be safely applied.
  • the fucosterol, hatban, hatban mill, millban extract, ⁇ , ⁇ mill or ⁇ extract are used for preventing, improving or
  • the present invention was completed by confirming the therapeutic or muscle function improving activity.
  • Sargassum which formula fucose cholesterol (fucosterol) represented by the compound or it (Sargassum fulvellum ) extract or Sargassum fusiforme ) to provide a pharmaceutical composition for the prevention or treatment of muscle diseases containing the extract as an active ingredient:
  • Another object of the present invention is a sargassum fulvellum ), a pulverized product thereof or an extract thereof as an active ingredient to provide a pharmaceutical composition for preventing or treating muscle diseases.
  • Another object of the present invention is Sar ( sum) fusiforme ), a pulverized product thereof or an extract thereof as an active ingredient to provide a preventive or therapeutic muscle disease or a pharmaceutical composition.
  • Yet another object of the present invention is a sargassum fulvellum ), to provide a health functional food composition for preventing or improving muscle diseases comprising a pulverized product or extract thereof as an active ingredient.
  • Another object of the present invention is Sar ( sum) fusiforme ), to provide a health functional food composition for preventing or improving muscle diseases comprising a pulverized product or extract thereof as an active ingredient.
  • Another object is to include Sargassum which formula fucose cholesterol (fucosterol) represented by the compounds of the present invention or (Sargassum fulvellum ) extract or Sargassum fusiforme ) to provide a cosmetic composition for improving muscle function comprising the extract as an active ingredient:
  • Another object of the present invention is a sargassum fulvellum ), to provide a cosmetic composition for improving muscle function comprising a pulverized product or extract thereof as an active ingredient.
  • Another object of the present invention is Sar ( sum) fusiforme ), a pulverized product thereof or an extract thereof to provide a cosmetic composition for improving muscle function comprising as an active ingredient.
  • Yet another object of the present invention is a sargassum fulvellum ), its pulverized product or extract thereof as an active ingredient to provide a feed additive for preventing or improving muscle diseases.
  • Another object of the present invention is Sar ( sum) fusiforme ), its pulverized product or extract thereof as an active ingredient to provide a feed additive for preventing or improving muscle diseases.
  • the present invention relates to fucose cholesterol (fucosterol) Sargassum (Sargassum fulvellum) a compound comprising the same or represented by the general formula (1) extracts or fusiforme (Sargassum fusiforme ) provides a pharmaceutical composition for preventing or treating muscle diseases comprising the extract as an active ingredient:
  • the invention also relates to Sargassum fulvellum), Sargassum pulverized Sargassum extract Chop (Sargassum fusiforme ), ⁇ pulverized powder or ⁇ extract provides a pharmaceutical composition for preventing or treating muscle diseases.
  • the invention also to include Sargassum which fucose cholesterol (fucosterol) compound, or it is represented by the following formula 1 (Sargassum Provided is a nutraceutical composition for preventing or improving muscle diseases comprising fulvellum ) extract or Sargassum fusiforme extract as an active ingredient:
  • the invention also relates to Sargassum fulvellum), Sargassum pulverized Sargassum extract Chop (Sargassum fusiforme ), ⁇ pulverized powder or ⁇ extract provides a health functional food composition for preventing or improving muscle diseases.
  • the invention also to include Sargassum which fucose cholesterol (fucosterol) compound, or it is represented by the following formula 1 (Sargassum Provided is a cosmetic composition for improving muscle function, comprising fulvellum ) extract or Sargassum fusiforme extract as an active ingredient:
  • the invention also relates to Sargassum fulvellum), Sargassum pulverized Sargassum extract Chop (Sargassum fusiforme ), ⁇ pulverized powder or ⁇ extract provides a cosmetic composition for improving muscle function comprising as an active ingredient.
  • the invention also to include Sargassum which fucose cholesterol (fucosterol) compound, or it is represented by the following formula 1 (Sargassum Provided are feed additives for preventing or improving muscle diseases, including fulvellum ) extract or Sargassum fusiforme extract as an active ingredient:
  • the invention also relates to Sargassum Provided is a feed additive for preventing or improving muscle diseases, including fulvellum ) extract or Sargassum fusiforme extract as an active ingredient.
  • the fucosterol represented by the formula (1) can be separated from the mother and child extract.
  • the extract may be obtained by extracting the maban or ⁇ with any one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, a subcritical fluid and a supercritical fluid. have.
  • the organic solvent having 1 to 6 carbon atoms is 1 to 6 carbon atoms (alcohol), acetone (acetone), ether (ether), benzene (benzene), chloroform (chloroform), Ethyl acetate, methylene chloride, methylene chloride, hexane, hexane, cyclohexane, and any one selected from the group consisting of petroleum ether.
  • the extract may be obtained by extracting the mother board or ⁇ under ultra-high pressure conditions of 100 MPa to 1000 MPa.
  • the muscle disease is atony, muscular atrophy, muscular dystrophy, muscle degeneration, ataxia, cachexia and sarcopenia It may be any one or more selected from the group consisting of.
  • Fucosterol, moss, moss, moss extracts, moss, moss, or muss extracts according to the present invention are muRF-1 and the protein expression of p-mTOR involved in muscle protein synthesis, muRF-1 and Inhibiting mRNA expression of atrogin-1 and increasing the mRNA expression of MyoD and myogenin, which are involved in muscle differentiation, have an excellent effect on increasing muscle mass.
  • the composition of the present invention is a natural product and can be safely used without side effects, it can be used as a medicine, food, cosmetics or livestock feed or feed additives.
  • Figure 1 shows the results of measuring the protein expression of p-mTOR according to the treatment of Maban ethanol extract, ⁇ ethanol extract or fucosterol in L6 muscle cells.
  • Figure 2 shows the results of measuring the protein expression of p-4EBP1 and p-p70S6K following the treatment of fucosterol in L6 muscle cells.
  • Figure 3 shows the results of measuring the mRNA expression of myoD and myogenin in accordance with the treatment of fucosterol in L6 muscle cells.
  • Figure 4 shows the results of measuring the mRNA expression of MyoD and myogenin myognin according to the treatment of Maban hexane extract, ethyl acetate extract, ethanol extract, hot water extract in L6 muscle cells.
  • Figure 5 shows the results of measuring the mRNA expression of MyoD and myogenin according to the treatment of hexane extract, ethyl acetate extract, ethanol extract, hydrothermal extract in L6 muscle cells.
  • Figure 6 shows the results of measuring the mRNA expression of atrogin-1 and MuRF-1 according to the treatment of fucosterol in L6 muscle cells.
  • Figure 7 shows the results of measuring the mRNA expression of atrogin-1 and MuRF-1 according to the treatment of Maban hexane extract, ethyl acetate extract, ethanol extract, hydrothermal extract in L6 muscle cells.
  • Figure 8 shows the results of measuring the mRNA expression of atrogin-1 and MuRF-1 according to the treatment of hexane extract, ethyl acetate extract, ethanol extract, hydrothermal extract in L6 muscle cells.
  • the present invention is for the prevention, improvement or treatment of muscle diseases or muscle function improvement of the fucosterol, Maban extract or ⁇ extract represented by the formula (1);
  • it provides a method for preventing, improving or treating muscle diseases or muscle function improvement comprising applying to the mammal, including humans, the fucosterol, Maban extract or ⁇ extract represented by the following formula (1):
  • ' hatzaban fulvellum s is a seaweed belonging to Sargassum spp. of the Helotiaceae family.
  • Sargassum fusiforme is an algae belonging to Sargassum spp. Of Helotiaceae.
  • Sargassum pulverized “or" Chop pulverized “is the dried Sargassum (Sargassum fulvellum) or fusiforme (Sargassum fusiforme ) can be easily ingested by a person skilled in the art according to the present invention, so that the active ingredient is easily released from the dry ground in the intestine after ingestion while being easily ingested by mammals including humans. And as a result can be prepared and used in a form that can be readily absorbed into the mammalian body.
  • the shape and size of the dry pulverized particles for this purpose is not limited, but as the surface of the particles is maximized, the glass of the active ingredient described above is easier to be prepared, preferably in the form of fine powder. In one embodiment of the present invention by milling the dried mother board or pan with a mixer to prepare a pulverized product.
  • 'capillary extract' is a moth ( Salgassum) fulvellum ) is obtained by extracting with a suitable solvent, and includes both extracts, dilutions or concentrates of the extracts, dried products obtained by drying the extracts, or modifiers or purified products thereof.
  • the preparation method of the mother and child extract may be obtained by extracting from the mother and child with one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, and a subcritical or supercritical fluid, but is not limited thereto.
  • ' ⁇ extract' is ⁇ ( Sargassum fusiforme ) obtained by extracting with a suitable solvent, and includes both extracts, dilutions or concentrates of the extracts, dried products obtained by drying the extracts, or modifiers or purified products thereof.
  • the method of preparing the extract may be obtained by extracting water from one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, and a subcritical or supercritical fluid, but is not limited thereto.
  • Hatban extract or ⁇ extract of the present invention can be prepared using conventional extraction methods such as heat extraction, cold soak extraction ultrasonic extraction, filtration and reflux extraction method, and banban and ⁇ purchased commercially available or It may be used for harvesting or cultivation in nature.
  • the mother or child extract according to the present invention can be separated according to conventional methods known in the art for preparing extracts from natural products, i.e. using conventional solvents under the conditions of conventional temperature, pressure.
  • the term "fraction” means the result obtained by the fractionation method of separating a specific component or a specific group from a mixture comprising various components. In the present invention, it means a result obtained by the fractionation method for separating a specific component or a specific group from the mother or ⁇ extract prepared as described above.
  • polar solvents such as anhydrous or hydrous lower alcohols having 1 to 4 carbon atoms, such as water, ethanol and methanol, and hexane, butanol
  • Non-polar solvents such as ethyl acetate, chloroform, dichloromethane, or a mixed solvent thereof may be used, but are not limited thereto.
  • the mother or child fraction of the present invention may also include those obtained by further applying the purification process.
  • fractions obtained by passing a mother or worm extract according to the present invention through an ultrafiltration membrane having a constant molecular weight cut-off value and subjected to various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity).
  • Fractions obtained through various purification methods additionally carried out, such as by separation, are also included in the mother or son fraction of the present invention.
  • 'muscle' refers to tendons, muscles, and tendons in general, and 'muscle function' means the ability to exert strength by contraction of muscles, and the muscles exert maximum contraction force to overcome resistance.
  • Muscle endurance the ability to express how long or how many times a muscle can repeat contraction and relaxation at a given weight, and quickness, the ability to exert a strong force in a short time. This muscle function is dominated by the liver and is proportional to muscle mass. The term “improving muscle function” refers to improving muscle function better.
  • the composition for preventing, improving or treating muscle diseases of the present invention or for improving muscle function may contain only acupuncture, acupuncture millus, acupuncture extracts, or a millet, a millet millet or a millet extract alone, or It may contain a mixture of ⁇ , ⁇ pulverized product or ⁇ extract at a ratio of 1 to 100, or at least one active ingredient exhibiting a similar function thereof. Inclusion of additional components may further enhance the muscle function improving effect of the composition of the present invention. When the ingredient is added, skin safety, ease of formulation, and stability of the active ingredients may be considered.
  • the present invention is a pharmaceutical composition for the prevention or treatment of muscle diseases, including mabanban, mabanban crushed, Mabanban extract, ⁇ , ⁇ crushed or ⁇ extract as an active ingredient; Health functional food composition for preventing or improving muscle diseases; Cosmetic composition for improving muscle function; And it provides a feed additive for preventing or improving muscle diseases.
  • the present invention also provides a pharmaceutical composition for preventing or treating muscle diseases, which comprises a compound represented by the formula (1), and a mother extract or ⁇ extract containing the same as an active ingredient; Health functional food composition for preventing or improving muscle diseases; Cosmetic composition for improving muscle function; And feed additives for preventing or ameliorating muscle diseases:
  • the compound of Formula 1 is called fucosterol.
  • the compound of Formula 1 may be used by separating or synthesizing from seaweeds and plant extracts or fractions thereof, or may use a commercially available compound.
  • the fucosterol represented by the formula (1) may be isolated from Maban extract or ⁇ extract.
  • the mother and child extract may be, but is not limited to, ethanol extract, hydrothermal extract, hexane extract, ethyl acetate extract, ultrahigh pressure extract, supercritical fluid extract or subcritical fluid extract.
  • the moss extract can be obtained by extracting the mop with one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, a subcritical fluid and a supercritical fluid.
  • the mother board may be obtained by extracting under ultra-high pressure conditions of 100 MPa or more, preferably 100 MPa to 1000 MPa. 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 may be selected from alcohols having 1 to 6 carbon atoms, 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 mother and child extract of the present invention can be obtained by extracting and purifying the dried mother and child using purified water, ethanol and subcritical water or supercritical carbon dioxide suitable for food processing, or by extracting and purifying using an ultrahigh pressure extraction device.
  • it can be obtained by separating and purifying the oil obtained by directly compressing the mother board.
  • an extract may be obtained by extracting hatban under ultra-high pressure conditions of 100 MPa or more, preferably 100 MPa to 1000 MPa.
  • ⁇ extract may be, but is not limited to, ethanol extract, hydrothermal extract, hexane extract, ethyl acetate extract, ultrahigh pressure extract, supercritical fluid extract or subcritical fluid extract.
  • the murine extract can be obtained by extracting murine with at least one solvent selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, a subcritical fluid and a supercritical fluid.
  • the char may be obtained by extraction under ultra-high pressure conditions of 100 MPa or more, preferably 100 MPa to 1000 MPa. 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 may be selected from alcohols having 1 to 6 carbon atoms, 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.
  • ⁇ extract of the present invention can be obtained by extracting and purifying dried ⁇ using purified water, ethanol and subcritical water or supercritical carbon dioxide suitable for food processing, or extracted and purified using an ultra-high pressure extraction device Alternatively, it can be obtained by separating and purifying oil from the oil obtained by directly compressing the char.
  • the extract may be obtained by extracting the charcoal under ultra-high pressure conditions of 100 MPa or more, preferably 100 MPa to 1000 MPa.
  • the present inventors are repeatedly extracted at room temperature with a dried mother board or millet pulverized product as methanol, ethanol, ethyl acetate and hexane as a solvent, hot water extraction, ultra-high pressure extraction, supercritical fluid extraction, Extract was prepared by subcritical fluid extraction.
  • mabanban, mabanban crushed, Mabanban extract, ⁇ , ⁇ crushed, ⁇ extract, or fucosterol isolated from the extract shows an excellent effect to increase muscle mass, preventing muscle disease Or therapeutic pharmaceutical compositions; Health functional food composition for preventing or improving muscle diseases; Feed additives for preventing or improving muscle diseases; Cosmetic composition for improving muscle function; And it can be usefully used as an active ingredient of a feed additive or a feed additive comprising the same.
  • the composition for preventing or treating muscle diseases of the present invention is a pharmaceutical composition
  • it may be used for the prevention or treatment of muscle diseases due to muscle wasting or degeneration.
  • Muscle depletion and degeneration occur due to genetic factors, acquired factors, aging, etc., muscle depletion is characterized by a gradual loss of muscle mass, weakening and degeneration of muscles, especially skeletal or veterinary and cardiac muscles.
  • related diseases include, but are not limited to, atony, muscular atrophy, muscular dystrophy, muscle degeneration, myasthenia, cachexia and sarcopenia.
  • the composition of the present invention has an effect of increasing muscle mass, the muscle does not limit its kind.
  • the pharmaceutical composition of the present invention may include pharmaceutically acceptable salts of fucosterol, moth, moth, moth, moth extract, moth, moth moth, or moth extract.
  • pharmaceutically acceptable refers to a physiologically acceptable and typically does not cause an allergic or similar reaction when administered to a human, wherein the salt is a pharmaceutically acceptable free acid. Acid addition salts formed by acid) are preferred.
  • the pharmaceutically acceptable salt of the fucosterol, hatban, hatban mill, millban extract, ⁇ , ⁇ mill or ⁇ extract may be an acid addition salt formed using an organic acid or an inorganic acid, the organic acid may be, for example, formic acid , Acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid , Benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxy acetic acid, benzenesulfonic acid, p-toluenesulfonic acid or methanesulfonic acid.
  • the organic acid may be, for example, formic acid , Acetic
  • Inorganic acids include, for example, hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid or boric acid.
  • the acid addition salt may preferably be in the form of hydrochloride or acetate, more preferably in the form of hydrochloride.
  • the above-mentioned acid addition salts can be a) directly mixed with fucosterol, hatban, hatban mill, hattan extract, ⁇ , ⁇ mill or ⁇ extract and acid, or b) dissolving one of them in a solvent or hydrous solvent.
  • the fucosterols, moths, moths, moths, moths extracts, moths, moths, or moths extracts are prepared in the usual salt preparation process by placing them in an acid in a solvent or submerged solvent and mixing them.
  • salts that can be additionally salted are gabar salt, gabapentin salt, pregabalin salt, nicotinate, adipate salt, hemimalonate, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt or Aspartate.
  • composition for preventing or 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 also include water, suitable oils, saline, aqueous glucose, 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-paraben and chlorobutanol.
  • Other pharmaceutically acceptable carriers may be referred to those described in the following documents (Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).
  • composition of the present invention can be administered to any mammal, including humans.
  • parenteral administration methods include, but are not limited to, intravenous, intramuscular, intraarterial, intramedullary, intradural, intracardiac, transdermal, subcutaneous, intraperitoneal , Intranasal, intestinal, topical, sublingual or rectal administration.
  • the pharmaceutical composition of the present invention may be formulated into a preparation for oral or parenteral administration according to the route of administration 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., extenders, binders, adjuvants (e.g. aluminum hydroxide) Side)
  • suspending agents e.g. aluminum hydroxide
  • Solid form preparations for oral administration include tablets, pills, powders, granules, solutions, gels, syrups, slurries, suspensions or capsules, and the like, and the solid form may 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 carboxymethylcellulose and hydroxypropylmethyl-cellulose or gelatin may be prepared by mixing.
  • tablets or dragees can be obtained by combining the active ingredients with solid excipients and then grinding them and adding suitable auxiliaries and then processing them into granule mixtures.
  • Liquid preparations for oral use include suspensions, solutions, emulsions, or syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, or preservatives, in addition to water or liquid paraffin, which are commonly used simple diluents. .
  • crosslinked polyvinylpyrrolidone, agar, alginic acid or sodium alginate may be added as a disintegrant, and may further include an anticoagulant, a lubricant, a humectant, a perfume, an emulsifier, a preservative, and the like.
  • compositions of the present invention may be formulated according to methods known in the art in the form of injections, transdermal and nasal inhalants with suitable parenteral carriers.
  • suitable parenteral carriers include, but are not limited to, solvents or dispersion media comprising water, ethanol, polyols (e.g., glycerol, propylene glycol and liquid polyethylene glycols, etc.), mixtures thereof and / or vegetable oils Can be.
  • suitable carriers include Hanks solution, Ringer's solution, phosphate buffered saline (PBS) containing triethanol amine or sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose Etc. can be used.
  • PBS phosphate buffered saline
  • various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like may be further included.
  • the injection may in most cases further comprise an isotonic agent such as sugar or sodium chloride.
  • transdermal administration means that the pharmaceutical composition is locally administered to the skin so that an effective amount of the active ingredient contained in the pharmaceutical composition is delivered into the skin.
  • the compounds used according to the invention may be pressurized packs or by means of suitable propellants, for example dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. It can be delivered conveniently from the nebulizer in the form of an aerosol spray. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to deliver a metered amount.
  • gelatin capsules and cartridges for use in inhalers or blowers can be formulated to contain a 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 prescription generally known in all pharmaceutical chemistries.
  • the pharmaceutical composition for preventing or treating muscle diseases of the present invention may provide a desirable muscle disease prevention or treatment effect when it contains an effective amount of fucosterol, moths, moths, moths, moths, moths, moths, or moths.
  • the 'effective amount' refers to an amount that exhibits a higher response than the negative control, 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 fucosterol, hatban, hatban mill, mill extract, ⁇ , ⁇ mill or ⁇ extract, the remaining amount may be occupied by a pharmaceutically acceptable carrier.
  • the effective amount of fucosterol, moths, moths, moss extracts, moths, moths, or moths extracts included in the pharmaceutical compositions of the present invention will vary depending on the form in which the composition is formulated.
  • the total effective amount of the pharmaceutical composition of the present invention may be administered to a patient in a single dose, and may be administered by a fractionated treatment protocol that is administered in multiple doses for a long time.
  • the pharmaceutical composition of the present invention may vary the content of the active ingredient depending on the extent of the disease. For parenteral administration, preferably from 0.01 to 50 mg per kg of body weight per day, more preferably from 0.1 to 30 mg per day, based on fucosterol, moth, moth, moth, moth extracts, moths, moths, or moth extracts.
  • the fucosterol, moth, moth, moth, moth, moth, moth, or moth extracts Preferably, it may be administered one to several times so as to be administered in an amount of 0.01 to 10 mg.
  • the doses of the fucosterol, mabanban, mabanban crushed, mabanban extract, ⁇ , ⁇ crushed or ⁇ extracts are determined by the age, weight, health condition, sex and disease of the patient as well as the route of administration and frequency of treatment of the pharmaceutical composition.
  • the effective dosage for the patient is determined in consideration of various factors such as severity, diet, and excretion rate, those having ordinary knowledge in the art, such as fucosterol, banban, banban crushed, banban extract
  • the effective dose may be determined according to the specific use for the prevention or treatment of muscle diseases.
  • the pharmaceutical composition according to the present invention is not particularly limited to its formulation, route of administration and method of administration as long as the effect of the present invention is shown.
  • the pharmaceutical composition for preventing or treating muscle diseases of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy or biological response modifiers.
  • the pharmaceutical composition for preventing or treating muscle diseases of the present invention may also be provided in the form of an external preparation including fucosterol, moths, moths, moths, moths, moths, moths, moths, or moths as an active ingredient.
  • the pharmaceutical composition for preventing or treating muscle diseases of the present invention is used as an external preparation for skin, it is additionally used as a fatty substance, an organic solvent, a dissolving agent, a thickening agent and a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, and a foaming agent.
  • Fragrance surfactant, water, ionic emulsifier, nonionic emulsifier, filler, metal ion sequestrant, chelating agent, preservative, vitamin, blocking agent, wetting agent, essential oil, dye, pigment, hydrophilic active agent, lipophilic active agent Or any other ingredient commonly used in external preparations for skin, such as lipid vesicles.
  • the ingredients may also be introduced in amounts generally used in the field of dermatology.
  • the pharmaceutical composition for preventing or treating muscle diseases of the present invention may be a formulation such as, but not limited to, ointment, patch, gel, cream or spray.
  • the composition for preventing muscle diseases or improving muscle function of the present invention may also be a food composition.
  • the food composition for preventing or improving muscle function of the present invention is a food composition, it may be used for preventing or improving muscle disease due to muscle wasting or degeneration. Muscle depletion and degeneration occur due to genetic factors, acquired factors, aging, etc., muscle depletion is characterized by a gradual loss of muscle mass, weakening and degeneration of muscles, especially skeletal or veterinary and cardiac muscles. Examples of related diseases include atony, muscular atrophy, muscular dystrophy, muscle degeneration, myasthenia gravis, cachexia and sarcopenia.
  • the composition of the present invention has an effect of increasing muscle mass, the muscle does not limit its kind.
  • the food composition of the present invention includes all forms such as functional food, nutritional supplement, health food, food additives and feed, and includes animals such as humans or livestock. It is for 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.
  • General foods include, but are not limited to, beverages (including alcoholic beverages), fruits and processed foods (e.g. canned fruit, canned foods, jams, marmalade, etc.), fish, meat and processed foods (e.g. hams, sausages) Cornbread, etc.), breads and noodles (e.g. udon, soba noodles, ramen, spagate, macaroni, etc.), fruit juices, various drinks, cookies, malts, dairy products (e.g.
  • the nutritional supplements are not limited thereto, and may be prepared by adding fucosterol, maban, maban flour, maban extract, Mabu, Mabu, or Mama extract to capsules, tablets and pills.
  • a health functional food but is not limited to, for example, the mother extract or ⁇ extract itself in the form of tea, juice and drinks to be liquefied, granulated, encapsulated and powdered to drink (health drink) Can be consumed.
  • mabanban, mabanban crushed, Mabanban extract, ⁇ , ⁇ crushed or ⁇ extract in the form of food additives can be prepared in powder or concentrate form.
  • it can be prepared in the form of a composition by mixing with fucosterol, mabanban, mabanban crushed, Mabanban extract, ⁇ , ⁇ pulverized or ⁇ extract with active ingredients known to prevent muscle disease or improve muscle function have.
  • the health beverage composition may contain various flavors or natural carbohydrates, etc. as additional components, as in general beverages.
  • the above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Polysaccharides such as dextrin, cyclodextrin; Sugar alcohols such as xylitol, sorbitol, and erythritol.
  • Sweeteners include natural sweeteners such as taumartin, stevia extract; Synthetic sweeteners such as saccharin and aspartame;
  • the proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.
  • Fucosterol, mabanban, mabanban crushed, Mabanban extract, ⁇ , ⁇ crushed or ⁇ extract may be contained as an active ingredient in the food composition for preventing or improving muscle diseases, the amount of which is to prevent muscle disease or improve muscle function It is not particularly limited to the amount effective to achieve the above, but preferably 0.01 to 100% by weight based on the total weight of the total composition.
  • the food composition of the present invention is mixed with fucosterol, mabanban, mabanban powder, Mabanban extract, ⁇ , ⁇ crushed or ⁇ extract with other active ingredients known to be effective in the composition for preventing muscle diseases or improving muscle function. Can be prepared.
  • the health food of the present invention is various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, Glycerin, alcohol or carbonation agent, and the like.
  • the health food of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage or vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
  • the composition for improving muscle function of the present invention may also be a cosmetic composition.
  • the cosmetic composition of the present invention contains fucosterol, mabanban, mabanban mashed, Mabanban extract, Mabu, Mabu mamulma or Mama extract as an active ingredient, and with a dermatologically acceptable excipient, a basic cosmetic composition (cosmetic water, cream, essence)
  • a basic cosmetic composition cosmetic water, cream, essence
  • facial cleansing agents such as cleansing foams and cleansing water, packs, body oils, color cosmetic compositions (foundations, lipsticks, mascara, makeup bases), hair product compositions (shampoos, rinses, hair conditioners, hair gels) and soaps.
  • facial cleansing agents such as cleansing foams and cleansing water, packs, body oils, color cosmetic compositions (foundations, lipsticks, mascara, makeup bases), hair product compositions (shampoos, rinses, hair conditioners, hair gels) and soaps.
  • cosmetic cleansing agents such as cleansing foams and cleansing water, packs, body oils, color cosmetic compositions (foundations, lipsticks, mascara
  • the excipients include, but are not limited to, emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickeners and solvents.
  • fragrances, pigments, fungicides, antioxidants, preservatives and moisturizing agents may be further included, and may include thickeners, inorganic salts, synthetic polymer materials and the like for the purpose of improving the properties.
  • thickeners inorganic salts, synthetic polymer materials and the like for the purpose of improving the properties.
  • the cream When the cream is prepared, it can be prepared by adding fucosterol, hatban, hatban mill, millban extract, ⁇ , ⁇ mill,, extract or salt thereof to the cream base of general oil-in-water type (O / W). .
  • fucosterol hatban, hatban mill, millban extract, ⁇ , ⁇ mill,, extract or salt thereof
  • synthetic or natural materials such as proteins, minerals, vitamins, etc., for the purpose of improving physical properties, such as flavors, chelating agents, pigments, antioxidants, and preservatives, may be added.
  • the content of the fucosterol, hatban, hatban mill, millban extract, ⁇ , ⁇ mill or ⁇ extract contained in the cosmetic composition of the present invention is not limited thereto, but is preferably 0.001 to 10% by weight based on the total weight of the composition. It is more preferable that it is 0.01 to 5 weight%. If the content is less than 0.001% by weight can not be expected to improve the desired muscle function, more than 10% by weight may be difficult to manufacture 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 diseases.
  • the term "feed additive” is a substance added to the feed for the purpose of various effects, such as supplementation of nutrients and weight loss prevention, improving the digestive availability of the fiber in the feed, improving the quality, prevention of reproductive disorders and improving conception, prevention of high temperature stress in summer It includes.
  • the feed additive of the present invention corresponds to a feed supplement under the Feed Control Act, and includes mineral preparations such as sodium bicarbonate, bentonite, magnesium oxide, and composite minerals, mineral preparations such as trace minerals such as zinc, copper, cobalt, and selenium, and keratin.
  • Vitamins AD, E, nicotinic acid, vitamin B complexes, protective amino acids such as methionine, lysine, protective fatty acids such as fatty acid calcium salts, probiotics (lactic acid bacteria), yeast culture, fungi fermentation products, Yeasts and the like may further be included.
  • the term “feed” is any natural or artificial diet, one meal, or the like or a component of the one meal for the animal to eat, ingest, and digest, and to prevent or improve muscle diseases according to the present invention.
  • the feed containing the composition for the active ingredient can be prepared in various forms of feed known in the art, and preferably include, but is not limited to, rich feed, forage and / or special feed.
  • the rich feed includes seed fruits containing grains such as wheat, oats and corn, and by-products obtained by refining grains, bran, beans, fluids, sesame seeds, linseed, coco, etc., including rice bran, bran and barley bran.
  • Fish soluble which is a concentrate of fresh liquids obtained from fish residues, fish residues, and fish residues such as by-products such as seaweed, sweet potatoes, and potatoes, which are the remaining components of starch residue. soluble), meat meal, blood meal, milk powder, skim milk powder, milk from cheese, and whey, the balance of manufacturing casein from skim milk, dried foods such as dried whey, yeast, chlorella, and seaweed. This is not restrictive.
  • raw vegetables such as grasses, grasses, and green grass, fodder turnips, fodder beets, and root vegetables such as Lutherbearger, a type of turnip, raw grass, green grass crops, and grains Silage (silage), grasses, grasses, and dried hay, straws of breeders, and leaves of legumes, which are filled and fermented by lactic acid fermentation, are not limited thereto.
  • Special feeds are supplemented with mineral feeds such as oyster shells and rock salts, urea feeds such as urea and its derivatives such as diureide isobutane, and natural feed ingredients.
  • Feed additives and dietary supplements which are substances added in small amounts, are not limited thereto.
  • Feed additives for the prevention or improvement of the muscle diseases according to the present invention is fucosterol, maban, mabanban maize, mabanban extract, majapan, mashed maize or the like in an appropriate effective concentration range according to various feed preparation methods known in the art.
  • ⁇ can be prepared by adding the extract.
  • 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 diseases.
  • it can be applied to any individual such as non-human animals such as monkeys, dogs, cats, rabbits, marmots, rats, mice, cows, sheep, pigs, goats, birds and fish.
  • the dried mother board was pulverized with a mixer, and 100 g of the milled mother board sample was put in 1 L of 100% methanol, and extracted three times at room temperature for 24 hours.
  • the extracted sample was filtered under reduced pressure with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Maban methanol extract.
  • the dried mother board was pulverized with a mixer, and 100 g of the milled mother board sample was put in 1 L of 100% ethanol, and extracted three times at room temperature for 24 hours.
  • the extracted sample was filtered under reduced pressure with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Maban ethanol extract.
  • the dried mother board was pulverized with a mixer, and 100 g of the milled mother board sample was put in 1 L of 100% ethyl acetate, and extracted three times at room temperature for 24 hours.
  • the extracted sample was filtered under reduced pressure with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Maban ethyl acetate extract.
  • the dried mother board was ground with a mixer, and 100 g of the milled mother board sample was put in 1 L of 100% hexane, and extracted three times at room temperature for 24 hours.
  • the extracted sample was filtered under reduced pressure with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Maban hexane extract.
  • the dried mother board was ground with a mixer, and then 100 g of the milled mother board sample was put in 1 L of water and extracted with stirring at 80 hours.
  • the extracted sample was filtered under reduced pressure with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a maban hot water extract.
  • the dried mother board was pulverized with a mixer, and then 1 g of the milled mother board and 76 mL of 18% ethanol were put in a polyethylene pack, sealed, and extracted using an ultra-high pressure extractor (Frescal MFP-7000; Mitsubishi Heavy Industries).
  • the ultrahigh pressure extraction conditions were 320 MPa extraction time and 5 min extraction time.
  • the extracted sample was filtered with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component to obtain a Maban ultra-high pressure extract.
  • the dried mother board was pulverized with a mixer, and then 1 g of the milled mother board sample was filled into a sample cartridge and extracted using a supercritical fluid extraction device (SFX 3560, Isco Inc., Lincoln, NE, USA).
  • the supercritical fluid extraction conditions were 40 MPa extraction pressure, 50 extraction temperature, 60 mL / min flow rate of supercritical carbon dioxide, and 60 min extraction time.
  • the pressure of the extraction device was lowered to release the supercritical fluid state, thereby obtaining a mother and child supercritical fluid extract.
  • the dried mother board was pulverized with a mixer, and then 1 g of the ground mother board was put in 10 mL of distilled water and extracted using a subcritical fluid extraction device (DIONEX Accelerated Solvent Extractor 100, DIONEX co., USA). Subcritical fluid extraction conditions were carried out under the conditions of 2.5 MPa, extraction temperature 150, extraction time 15 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was lyophilized at -40 to obtain a mother-ban subcritical fluid extract.
  • DIONEX Accelerated Solvent Extractor 100 DIONEX co.
  • the dried Soybean was pulverized with a mixer, and 100 g of the crushed Soybean sample was added to 1 L of 100% methanol, and extracted three times at room temperature for 24 hours.
  • the extracted sample was filtered under reduced pressure with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a methanol extract.
  • the dried Soybean was pulverized by a mixer, and 100 g of the Soybean pulverized sample was put into 1 L of 100% ethanol and extracted three times at room temperature for 24 hours.
  • the extracted sample was filtered under Whatman No. 2 filter paper, and the filtrate was concentrated with a vacuum rotary concentrator to remove the solvent component.
  • the dried Soybean was pulverized by a mixer, and 100 g of the Soybean pulverized sample was put into 1 L of 100% ethyl acetate and extracted three times at room temperature for 24 hours.
  • the extracted sample was filtered under reduced pressure with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining ethyl acetate extract.
  • the dried Soybean was pulverized with a mixer, and 100 g of the crushed Soybean sample was added to 1 L of 100% hexane, and extracted three times at room temperature for 24 hours.
  • the extracted sample was filtered under reduced pressure with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a hexane extract.
  • the dried clay was pulverized with a mixer, and then 100 g of the ground char sample was put in 1 L of water and extracted with stirring at 80 hours for 2 hours.
  • the extracted sample was filtered under Whatman No. 2 filter paper, and the filtrate was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a hot water extract.
  • the dried mill was ground with a mixer, and then 1 g of the ground mill and 76 mL of 18% ethanol were put in a polyethylene pack, sealed, and extracted using an ultra-high pressure extractor (Frescal MFP-7000; Mitsubishi Heavy Industries). It was.
  • the ultrahigh pressure extraction conditions were 320 MPa extraction time and 5 min extraction time.
  • the extracted sample was filtered with Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component.
  • the dried char was ground with a mixer, and then 1 g of the ground char was charged into a sample cartridge and extracted using a supercritical fluid extraction device (SFX 3560, Isco Inc., Lincoln, NE, USA).
  • the supercritical fluid extraction conditions were 40 MPa extraction pressure, 50 extraction temperature, 60 mL / min flow rate of supercritical carbon dioxide, and 60 min extraction time.
  • the pressure of the extraction device was lowered to release the supercritical fluid state to obtain a supercritical fluid extract.
  • the dried mill was ground with a mixer, and then 1 g of the milled mill sample was placed in 10 mL of distilled water and extracted using a subcritical fluid extraction device (DIONEX Accelerated Solvent Extractor 100, DIONEX co., USA). Subcritical fluid extraction conditions were carried out under the conditions of 2.5 MPa, extraction temperature 150, extraction time 15 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was lyophilized at -40 to obtain a subcritical fluid extract.
  • DIONEX Accelerated Solvent Extractor 100 DIONEX co.
  • DMEM Dulbecco's modified Eagle's media
  • FBS fetal bovine serum
  • the well plate was added to 2 X 10 5 cell / ml. When the cell density reached about 80-85%, the medium in the well was removed, and the ethanol extract (20) prepared in Example 1-2 in DMEM (Hyclone) containing 2% horse serum (HS; Hyclone) was used.
  • Example 3 ⁇ g / mL
  • ⁇ ethanol extract (20 ⁇ g / mL) prepared in Example 2-2 and fucosterol (10 ⁇ M) isolated and purified in Example 3 were dissolved, and then treated with cells to differentiate myotube differentiation. Induced. At this time, the group treated with 0.01% DMSO instead of the sample was used as a control. This process was carried out for 6 days for 2 days to differentiate and then dissolved in NP-40 buffer solution (ELPIS-Biotech, Daejeon, Korea) containing a proteinase inhibitor cocktail. The cells dissolved in the buffer solution were transferred to a 1.5 ml tube and centrifuged at 13,000 rpm for 10 minutes to obtain only the supernatant.
  • NP-40 buffer solution EPIS-Biotech, Daejeon, Korea
  • Example 3 The fucosterol isolated and purified in Example 3 was conducted in the same manner as in Example 4 at concentrations of 1 and 10 ⁇ M, respectively. Protein bands were identified by treatment with p-p70S6K and p-4EBP1 primary antibodies (Santa Cruz Biotechnology, Santa Cruz, CA, USA) involved in the mRNA translation process instead of the p-mTOR primary antibody.
  • the protein expression levels of p-p70S6K and p-4EBP1, which are involved in the mRNA translation process, in L6 muscle cells may be increased by treatment with fucosterol.
  • the fucosterol of the present invention promotes the mRNA translation process for muscle production in muscle cells.
  • L6 myoblast (ATCC), a muscle cell, was added to 2 ⁇ 10 5 cells / ml in a 6-well plate with DMEM (Hyclone) containing 10% FBS (Hyclone).
  • DMEM Hyclone
  • FBS Hyclone
  • the fucosterols isolated and purified in Example 3 in DMEM (Hyclone) containing 2% HS (Hyclone) were 1 and 10, respectively.
  • the cells were treated to induce myotube differentiation.
  • the group treated with 0.01% DMSO instead of the sample was used as a control.
  • Reverse primer 5'-CAGAGCCTGCAGACCTTCAA-3 '(SEQ ID NO: 2)
  • Reverse primer 5'-CTTTCTTGAGCCTGCGCTTC-3 '(SEQ ID NO: 4)
  • Reverse primer 5'-CTCTCAGCTGTGGTGCTGAA-3 '(SEQ ID NO: 6)
  • the amplified cDNA was isolated by electrophoresis with 1.5% agarose gel, and cDNA band was identified using G; BOX EF imaging system (Syngene). The results are shown in FIG.
  • Mabanban extract of the present invention has an excellent ability to promote muscle differentiation in muscle cells.
  • L6 myoblast (ATCC) in the same manner as in Example 6, ⁇ prepared in Examples 2-2 to 2-5 in DMEM (Hyclone) containing 2% HS (Hyclone) Ethanol extract, ethyl acetate extract, hexane extract and hot water extract were dissolved at a concentration of 10 ⁇ g / mL, and then treated with cells to induce myotube differentiation. At this time, the group treated with 0.01% DMSO instead of the sample was used as a control. This process was carried out for 2 days and 6 days to differentiate and RT-PCR was performed in the same manner as in Example 6.
  • L6 myoblast (ATCC), a muscle cell, was added to 2 ⁇ 10 5 cells / ml in a 6-well plate with DMEM (Hyclone) containing 10% FBS (Hyclone).
  • DMEM Hyclone
  • FBS Hyclone
  • the media in the wells were removed and myotube differentiation was induced by treating DMEM (Hyclone) containing 2% HS (Hyclone) to the cells. Once every two days, the cells were replaced with fresh medium for a total of six days of differentiation.
  • DMEM fetal calf serum
  • EPIS-Biotech Reverse Transcriptase Premix
  • Reverse primer 5'-AGGTCCCGCCCATCGCTCA-3 '(SEQ ID NO: 8)
  • Reverse primer 5'-ATTCCTGCTTGTAGATGTCG-3 '(SEQ ID NO: 10)
  • Reverse primer 5'-CTCTCAGCTGTGGTGCTGAA-3 '(SEQ ID NO: 6)
  • the amplified cDNA was isolated by electrophoresis with 1.5% agarose gel, and cDNA band was identified using G; BOX EF imaging system (Syngene). The results are shown in FIG.
  • Muscle cells were treated with DMEM (Hyclone) containing 2% HS (Hyclone) in the same manner as in Example 9, followed by myotube differentiation, and then in DMEM (Hyclone) containing 50 ng / mL TNF- ⁇ (PeproTech). After dissolving Maban ethanol extract, ethyl acetate extract, hexane extract and hot water extract prepared in Examples 1-2 to 1-5 at a concentration of 10 ⁇ g / mL, RT-PCR was performed in the same manner as in Example 9.
  • Mabanban extract of the present invention has an excellent ability to inhibit muscle protein degradation in muscle cells.
  • Muscle cells were treated with DMEM (Hyclone) containing 2% HS (Hyclone) in the same manner as in Example 9, followed by myotube differentiation, and then in DMEM (Hyclone) containing 50 ng / mL TNF- ⁇ (PeproTech).
  • DMEM Hexane extract
  • TNF- ⁇ TNF- ⁇
  • the p-mTOR protein band was developed using ECL western blotting detection reagents (Amersham, Tokyo, Japan) and the protein band developed using G; BOX EF imaging system (Syngene, Cambridge, UK). The density was measured. In this case, the density of the control protein band was 100%, and the density of the relative protein band of the experimental group treated with the sample was expressed as a percentage (%).
  • Table 1 The results are shown in Table 1 below.
  • Example 1-6 Increased p-mTOR Protein Expression by High Pressure Extracts Experimental group Relative density ( % ) Control 100
  • Example 1-6 131
  • Example 1-7 129
  • Example 1-8 143
  • Example 2-6 128 Example 2-7 140
  • Example 2-8 133
  • mice Five-week-old Wistar rats (Daehan Biolink, Korea) were acclimated for 1 week and TNF- ⁇ 100 ng / g was supplied for 2 weeks to induce muscular atrophy. Divided into six groups and used in the experiment. Experimental group 500 mg / kg body weight dry powder 500 mg / kg body weight, 500 mg / kg body weight ethanol extract prepared in Example 1-2, 500 mg / kg body weight dry powder ⁇ ethanol extract 500 prepared in Example 2-2 mg / kg body weight, suspended in 0.25% carboxymethylcellulose at a concentration of 300 mg / kg body weight of the fucosterol prepared in Example 3 and administered once a day for 8 weeks at a constant time. In this case, a control group was used to administer TNF- ⁇ to the same amount of 0.25% carboxymethyl cellulose ingested by the experimental group.
  • the powder of the present invention was prepared by mixing the fucosterol, mabanban pulverum, mabanban extract, ⁇ crushed or ⁇ extract 50 mg, and 2 g of crystalline cellulose in a hermetic bag according to a conventional powder preparation method.
  • the tablets were prepared by mixing the fucosterol, maban crushed, maban extract, ⁇ crushed or ⁇ extract 50 mg, 400 mg of crystal cellulose, 5 mg of magnesium stearate, and then tableting according to a conventional tablet preparation method of the present invention.
  • Gelatin according to the conventional method for preparing capsules after mixing the fucosterol, maban crushed, maban extract, ⁇ crushed or ⁇ extract 30 mg, whey protein 100 mg, crystalline cellulose 400 mg, magnesium stearate 6 mg of the present invention Capsules were prepared by filling the capsules.
  • the active ingredient is dissolved in distilled water for injection according to a conventional injection method, and the pH is adjusted to about 7.5. Then, 100 mg of fucosterol of Example 3, distilled water for injection, and a pH adjuster are mixed in a 2 ml ampoule. Injections were prepared by filling and sterilization.
  • Fucosterol, morus pulverum, morus pulverum, pulverulent pulverum or pulverulent extract of the present invention 1000 mg, 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, Nicotinamide 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 Phosphate 15 mg , 55 mg of dibasic calcium phosphate, 90 mg of potassium citrate, 100 mg of calcium carbonate, 24.8 mg of magnesium chloride may be prepared, and the compounding ratio may be arbitrarily modified, and according to the conventional health food manufacturing method. After mixing the components of the granules are prepared, it can be used for preparing a health food composition according to a conventional
  • Purified water is added to the fucosterol, maban crushed, maban extract, ⁇ crushed or ⁇ extract 1000 mg, citric acid 1000 mg, oligosaccharide 100 g, plum concentrate 2 g, 1 g of taurine of the present invention, the total 900 ml normal health drink
  • the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized and stored in refrigerated and then used in the manufacture of a healthy beverage composition.
  • Candy was prepared in a conventional manner by combining 60% by weight of sugar, 39.8% by weight of starch syrup, and 0.1% by weight of fragrance, and 0.1% by weight of fucosterol, hatban powder, hatpan extract, beet flour or beet extract of the present invention.
  • the nutrient cosmetics according to the conventional method was prepared by the fucosterol, maban crushed mash, maban crushed extract, ⁇ crushed crushed extract or ⁇ extract according to the nutrient lotion formulation ratio of Table 3 below.
  • the fucosterol of the present invention was prepared according to the conventional method.
  • Nutrients cream was prepared according to a conventional method by the fucosterol, hatban grinds, hatban extracts, millet extracts or millet extracts of the present invention according to the nutrition cream formulation ratio of Table 5.
  • Massage cream was prepared according to a conventional method by the fucosterol, mabanban crushed, mabanban extract, ⁇ crushed or ⁇ extract of the present invention according to the massage cream formulation ratio of Table 6.
  • the pack was prepared according to a conventional method using the fucosterol, hatban grinds, hatban extracts, jam mills, or millet extracts of the present invention in the pack formulation ratios of Table 7 below.
  • the gel was prepared according to a conventional method according to the fucosterol, mabanban pulverized, mabanban extract, ⁇ crushed or ⁇ extract of the present invention according to the gel formulation ratio of Table 8.
  • the fucosterol of the present invention mash crushed mash, mash mash extract, mash crushed or mash extract was mixed with the ingredients of Table 9 to prepare a feed additive according to a conventional method.
  • the feed of the present invention was prepared according to a conventional method by mixing the fucosterol, mabanban crushed, Mabanban extract, ⁇ crushed or ⁇ extract the ingredients of the following Table 10.
  • the present invention provides a composition for preventing or treating muscle diseases or improving muscle function, including fucosterol, hatban, hatban grind, moth extract, ⁇ , ⁇ crush or ⁇ extract.
  • the fucosterol, hatban, hatban mill, millban extract, ⁇ , ⁇ mill or ⁇ extract of the present invention is involved in the increase in protein expression of the major gene p-mTOR involved in muscle protein synthesis, muscle protein degradation Inhibition of mRNA expression of MuRF-1 and atrogin-1 and increase of mRNA expression of MyoD and myogenin, which are involved in muscle differentiation, have an excellent effect on preventing, improving or treating muscle diseases or improving muscle function.
  • the composition of the present invention is a natural product, it can be safely used without side effects, and it is highly industrially available because it can provide a composition showing an excellent effect on preventing, improving or treating muscle diseases or improving muscle function.

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Abstract

La présente invention concerne une composition permettant de prévenir ou traiter des maladies musculaires ou d'améliorer la fonction musculaire, contenant du fucostérol, du Sargassum fulvellum, un produit broyé de Sargassum fulvellum, un extrait de Sargassum fulvellum, du Sargassum fusiforme, un produit broyé de Sargassum fusiforme ou un extrait de Sargassum fusiforme . Selon la présente invention, le fucostérol, le Sargassum fulvellum, un produit broyé de Sargassum fulvellum, un extrait de Sargassum fulvellum, le Sargassum fusiforme, un produit broyé de Sargassum fusiforme ou un extrait de Sargassum fusiforme augmente l'expression de la protéine de p-mTOR, qui est un gène principal impliqué dans la synthèse des protéines musculaires, inhibe l'expression de mARN de MuRF-1 et de l'atrogine-1 impliqués dans la dégradation des protéines musculaires, et augmente l'expression de mARN de MyoD et de myogénine impliqués dans la différenciation musculaire, ce qui a pour effet d'accroître considérablement la fonction musculaire. En outre, étant donné que la composition selon la présente invention est un produit naturel, la composition peut être utilisée en toute sécurité sans effet secondaire, ce qui la rend utilisable en médecine, dans les aliments, les produits cosmétiques, les aliments pour bétail, en tant qu'additif alimentaire et analogue.
PCT/KR2016/005597 2015-05-26 2016-05-26 Composition permettant de prévenir, de soulager ou de traiter les maladies musculaires ou d'améliorer la fonction musculaire WO2016190689A2 (fr)

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JP2018514759A JP6818018B2 (ja) 2015-05-26 2016-05-26 筋肉疾患の予防、改善または治療用または筋機能改善用組成物
US15/577,098 US10646498B2 (en) 2015-05-26 2016-05-26 Composition for preventing, alleviating or treating muscle diseases or improving muscular function

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KR20150072740 2015-05-26
KR10-2015-0072740 2015-05-26
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KR1020160064917A KR101809156B1 (ko) 2015-05-26 2016-05-26 퓨코스테롤을 포함하는 근육 질환 예방, 개선 또는 치료용 또는 근 기능 개선용 조성물

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Cited By (2)

* Cited by examiner, † Cited by third party
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CN107298696A (zh) * 2017-06-22 2017-10-27 舟山富晟食品科技有限公司 羊栖菜活性蛋白的提取方法
WO2019022263A1 (fr) * 2017-07-24 2019-01-31 강릉원주대학교 산학협력단 Préparation pharmaceutique pour traiter la dermatite atopique

Family Cites Families (6)

* Cited by examiner, † Cited by third party
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KR100397531B1 (ko) * 2000-07-26 2003-09-13 주식회사 선진애드 한국산 갈조류 유래의 면역증강용 추출물 및 그 제조방법
KR20050006533A (ko) * 2003-07-09 2005-01-17 이재화 해조류로부터 항암 및 면역활성 추출물을 추출하는 방법
JP2009191008A (ja) * 2008-02-14 2009-08-27 South Product:Kk 褐藻類由来機能性成分の抽出方法
KR101559483B1 (ko) * 2012-11-09 2015-10-12 한국생명공학연구원 해조류 추출물 또는 이의 분획물을 유효성분으로 함유하는 신경보호용 조성물
KR20140081339A (ko) * 2012-12-21 2014-07-01 부경대학교 산학협력단 푸코스테롤을 유효성분으로 포함하는 퇴행성 신경질환 예방 또는 치료용 약제학적 조성물
KR20140131100A (ko) * 2013-05-03 2014-11-12 경희대학교 산학협력단 푸코스테롤을 포함하는 피부 주름 개선 식품, 의약품 및 화장품, 의약품 및 화장품의 조성물

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107298696A (zh) * 2017-06-22 2017-10-27 舟山富晟食品科技有限公司 羊栖菜活性蛋白的提取方法
WO2019022263A1 (fr) * 2017-07-24 2019-01-31 강릉원주대학교 산학협력단 Préparation pharmaceutique pour traiter la dermatite atopique
US11497782B2 (en) 2017-07-24 2022-11-15 Gangneung-Wonju National University Industry Academy Cooperation Group Composition for treating atopic dermatitis

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