WO2015199516A1 - Composition pour améliorer la fonction musculaire ou augmenter la performance d'exercice physique, contenant du kirenol ou un extrait de hui chum - Google Patents

Composition pour améliorer la fonction musculaire ou augmenter la performance d'exercice physique, contenant du kirenol ou un extrait de hui chum Download PDF

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WO2015199516A1
WO2015199516A1 PCT/KR2015/006655 KR2015006655W WO2015199516A1 WO 2015199516 A1 WO2015199516 A1 WO 2015199516A1 KR 2015006655 W KR2015006655 W KR 2015006655W WO 2015199516 A1 WO2015199516 A1 WO 2015199516A1
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Prior art keywords
extract
exercise performance
muscle function
siegesvecchia
rare
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PCT/KR2015/006655
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English (en)
Korean (ko)
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황재관
김미보
김창희
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연세대학교 산학협력단
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Priority to JP2017520846A priority Critical patent/JP6524222B2/ja
Priority claimed from KR1020150092315A external-priority patent/KR101778365B1/ko
Priority claimed from KR1020150092336A external-priority patent/KR101759779B1/ko
Publication of WO2015199516A1 publication Critical patent/WO2015199516A1/fr
Priority to US15/390,800 priority patent/US10507224B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • 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
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates

Definitions

  • the present invention relates to a composition for improving muscle function or enhancing exercise performance, containing a kyrenol, Sigesbeckia spp. Extract or a fraction thereof as an active ingredient.
  • PGC-1 ⁇ peroxisome proliferator-activated receptor-gamma coactivator 1 alpha
  • SIRT1 sirtulin
  • NRF nuclear respiratory factor
  • AMPK, p-AMPK, PPAR ⁇ ERR ⁇ and Tfam are known as factors related to the improvement of exercise performance.
  • muscle atrophy is caused by a gradual decrease in muscle mass and refers to muscle weakness and degeneration (Cell 119: 90710, 2004). Muscular atrophy is promoted by inactivity, oxidative stress and chronic inflammation, weakening muscle function and motor capacity (Clin. Nutr. 26: 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 (Cell Biol. 37: 1985-1996, 2005).
  • Muscle size is controlled by intracellular signaling pathways that induce anabolism or catabolism in the muscle, leading to more signaling reactions that induce synthesis than muscle protein degradation. In this case, muscle protein synthesis is increased.
  • An increase in muscle protein synthesis may be attributed to an increase in muscle size (hypertrophy) or muscle fiber number (hyperplasia) as muscle protein increases (The Korea Journal of Sports Science 30: 1551-1561, 2011).
  • Muscle hypertrophy inducers induce protein synthesis by phosphorylating downstream proteins from the stimulation of the phosphatidylinositol-3 kinase (PI3K) / Akt pathway in myocytes.
  • PI3K phosphatidylinositol-3 kinase
  • the activity of mTOR (mammalian target of rapamycin) by PI3K / Akt signaling is recognized as a central growth signaling mechanism that integrates various growth signals in cells.
  • Activation of mTOR contributes to muscle mass gain by inducing muscle protein synthesis by activating two downstream targets, 4E-BP1 (4E-binding protein) and p70S6K (phosphorylated 70-kDa ribosomal S6 kinase). Korea Journal of Sports Science 30: 1551-1561, 2011, J Biol Chem 278: 40717-40722, 2003).
  • muscle cells are regulated by various muscle regulatory factors (cell Mol Life Sci 70: 4117-4130, 2013).
  • myoD initiates the expression of genes specific for muscle differentiation and induces mesenchymal stem cells to differentiate into myoblasts (myoblasts).
  • Myogenin regulated by 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 finally form muscles (Cell Mol Life Sci 70: 4117-4130, 2013; Sci Signal 6: re2, 2013).
  • Huicheom is Shige's Becky Ashok plants (Siegesbeckia spp.) Of the Asteraceae in Shige's Becky Oh Mugla Brenna sense (Siegesbeckia glabrescens Mak.), Shigeru's Becky Oh Mfuwe sense (Siegesbeckia pubescens Mak.) Or Shige's Becky Ah The ground part of the Orientalis ( Siegesbeckia orientalis L.) is dried.
  • Siegesvecchia glabreense called Jindukchal, is an antibacterial agent (Int. J. Food Microbiol. 160: 260-266, 2013), anticancer (Oncol. Rep.
  • Kirenol is a diterpenoid mainly found in rapeseed and has anti-inflammatory and analgesic effects (J. Ethnopharmacol. 137: 1089-1094, 2011), antibacterial effect (Pharmacogn. Mag. 8: 149-155 , 2012), arthritis therapeutic effects (Phytomedicine 19: 882-889, 2012), anti-obesity effects (BBRC 445, 433-438, 2014) and the like.
  • the present inventors have superior oblique modulating activity or superior physical performance result of browsing the natural substances that can have an active safely applied, Kastrup play (kirenol) or huicheom (Hui Chum, Siegesbeckia spp.) Extracts or fractions thereof containing the same
  • Kastrup play kirenol
  • huicheom Human Chum, Siegesbeckia spp. Extracts or fractions thereof containing the same
  • the present invention was completed by confirming that there are muscle function improving activity and exercise performance enhancing activity.
  • compositions for improving muscle function or enhancing exercise performance including a rare extract as an active ingredient.
  • Still another object of the present invention is to provide a composition for improving muscle function or enhancing exercise performance, comprising the compound of Formula 1 as an active ingredient:
  • the present invention As a means for solving the above problems, the present invention
  • It provides a pharmaceutical composition and food composition for improving muscle function or enhancing exercise performance, including a rare extract or a fraction thereof as an active ingredient.
  • compositions and food compositions for improving muscle function or enhancing exercise performance, comprising the compound represented by the formula (1) as an active ingredient:
  • Kirenol according to the present invention or a rare extract containing the same or fractions thereof increases the protein expression of p-mTOR, a major gene involved in improving muscle function, and has an excellent effect on increasing muscle mass.
  • the kyrenol (kirenol), or a rare extract containing the same or a fraction thereof according to the present invention by increasing the protein expression of PGC-1 ⁇ , a major gene involved in exercise performance, and excellently enhance the exercise performance It is effective.
  • the present invention is a natural product can be used safely without side effects, it can be used as a medicine or food.
  • 1 is a protein of p-mTOR according to the treatment of chirenol or Sigebexkia glabressenth ethanol extract, Sigebexkia fuvesense ethanol extract, Sigebexchia orientalis ethanol extract in L6 muscle cells The result of measuring the expression level is shown.
  • Figure 2 shows the results of measuring the protein expression level of p-mTOR according to the treatment of Sigebek Beckia orientalis ultra-high pressure extract containing the chilenol in L6 muscle cells.
  • Figure 3 shows the results of measuring the mRNA expression level of muscle differentiation regulating genes (myogenin and MyoD) according to the treatment of the Siegesvekchia orientalis ethanol extract containing chilenol in L6 muscle cells.
  • Figure 4 shows the results of measuring the mRNA expression level of muscle differentiation regulating genes (myogenin and MyoD) according to the chilenol treatment in L6 muscle cells.
  • FIG. 5 shows the major genes involved in protein catabolism (Atrogin-1 and MuRF1) in L6 muscle cells following the treatment of Shigeresvecchia orientalis ethanol extract containing chilenol. The result of measuring mRNA expression is shown.
  • Figure 6 shows the results of measuring the mRNA expression level of the major genes (Atrozine-1 and MuRF1) involved in the protein catabolism in muscle following the chilenol treatment in L6 muscle cells.
  • Figure 7 shows the results of measuring the level of muscle mass increase according to administration of Shigeresvecchia orientalis ethanol extract containing chilenol in a normal diet animal model.
  • Figure 8 shows the results of measuring the muscle volume increase level according to the administration of Sigestescchia orientalis ethanol extract containing chilenol in the normal diet animal model (left: PET / CT results, right: muscle volume measurement results).
  • Figure 9 shows the results of measuring the level of muscle mass increase according to administration of Shigeresvecchia orientalis ethanol extract containing chilenol in a high-fat diet animal model.
  • Figure 10 shows the results of measuring the muscle volume increase level according to the administration of Shigeresvecchia orientalis ethanol extract containing chilenol in a high-fat diet animal model (left: PET / CT results, right: muscle volume measurement results) .
  • FIG. 11 is a protein of PGC-1 ⁇ according to the treatment of chirenol or Sigestesevikia glabressenth ethanol extract, Sigestesevikia fuvesens ethanol extract, Sigestesevichia orientalis ethanol extract in L6 muscle cells The result of measuring the expression level is shown.
  • Figure 12 shows the results of measuring the protein expression level of PGC-1 ⁇ in accordance with the treatment of Sigebek Beckia orientalis ultra-high pressure extract containing chilenol in L6 muscle cells.
  • Figure 13 shows the results of measuring the change in exercise performance by administration of Shigeresvecchia orientalis ethanol extract containing chilenol in a normal diet animal model (a: exercise distance, b: exercise time).
  • Figure 14 shows the results of measuring the change in exercise performance by administration of Shigeresvecchia orientalis ethanol extract containing chilenol in a high fat diet-induced obese animal model (a: exercise distance, b: exercise time ).
  • FIG. 15 shows the results of measuring the expression levels of p-AMPK, SIRT1, PGC-1 ⁇ , and PPAR ⁇ proteins, which are genes related to improvement of exercise ability, by administration of Shigeresvecchia orientalis ethanol extract containing chilenol in an animal model calf muscle. Shows.
  • FIG. 16 shows the results of measuring mRNA expression levels of PGC-1 ⁇ , NRF-1, ERR ⁇ , and Tfam, genes related to mitochondrial biosynthesis by administration of Shigeresvecchia orientalis ethanol extract containing chilenol in an animal model calf muscle Shows.
  • the present invention is a rare extract or fractions thereof, or the use of the compounds represented by the formula (1) to improve muscle function or enhance the performance of exercise; Rare extract or fractions thereof, or a composition for improving muscle function or enhancing exercise performance, including a compound represented by the following formula (1); Or a rare extract or a fraction thereof, or a compound represented by the following Formula 1 is provided to a subject, thereby improving muscle function or enhancing exercise performance.
  • the ⁇ extracted extract '' or the ⁇ development extract '' is used interchangeably, and refers to an extract obtained by extracting the rare (excreted).
  • the preparation method of the rare extract may be used without limitation conventional extraction methods known in the art, for example, water, organic solvents having 1 to 6 carbon atoms, and children from rare plants or parts of plants (leaves or roots) It can be obtained by extraction with one or more solvents selected from the group consisting of critical fluids and supercritical fluids.
  • 'fraction' means a result obtained by the fractionation method of separating a specific component or a specific group from a mixture comprising various components.
  • Methods for preparing fractions are well known in the art, and known methods can be used without limitation.
  • a specific fraction in which the active substance is concentrated can be prepared using a technique such as solvent fractionation, silica gel chromatography, and prep-HPLC.
  • the fraction of the rare extract may be obtained by fractionating the rare extract with ethyl acetate, methanol or a mixed solvent thereof.
  • 'muscle' refers to tendons, muscles, and tendons
  • 'muscle function' refers to the ability to exert strength by contraction of muscles, and muscles can exert maximum contraction force to overcome resistance.
  • Muscle strength which is the ability to be present
  • muscle endurance which is how long or how many times a muscle can repeat contraction and relaxation
  • quickness which is the ability to exert a strong force in a short time.
  • This muscle function is controlled by the liver and is proportional to muscle mass.
  • the term 'improving muscle function' refers to improving muscle function better.
  • composition for improving muscle function' refers to a composition containing a substance having an effect on improving muscle function as an active ingredient, and includes a pharmaceutical composition or a food composition.
  • the 'exercise performance ability' is a fast, strong, accurate, long, skillfully when the physical movements seen in daily life or sports are divided into running, running, throwing, swimming, etc.
  • the exercise performance is defined as factors such as muscle strength, agility and endurance.
  • the term 'enhancing athletic performance' refers to improving or improving athletic performance.
  • the 'exercise performance enhancing composition' refers to a composition containing a substance having an athletic performance enhancing effect as an active ingredient, and includes a pharmaceutical composition or a food composition.
  • the composition for improving muscle function or enhancing exercise performance of the present invention may further contain at least one active ingredient exhibiting the same or similar function, in addition to the rare extract or fractions thereof.
  • it may include a known muscle function improving component or exercise performance enhancing component. Including the additional components will be able to further enhance the muscle function improvement effect or exercise performance enhancing effect of the composition of the present invention.
  • the composition is a muscle function improving component or exercise performance enhancing component known in the art, the extract of Camperia Fabiflora extract, Piperretrofractum Vahl.
  • Fruit, mycetin , cooker It may further comprise at least one component selected from the group consisting of bitine extract, panduratata extract, grape root extract, root root extract and red ginseng extract. Additional components may be included in at least 0.0001% and up to 10% by weight relative to the total composition weight.
  • the content range may be adjusted according to requirements such as skin safety, ease of formulating the compound of Formula 1, and the like.
  • composition for improving muscle function or enhancing exercise performance including the rare extract or fractions thereof of the present invention as an active ingredient may be a pharmaceutical composition or a food composition.
  • composition for improving muscle function or enhancing exercise performance comprising the compound represented by Formula 1 of the present invention as an active ingredient, may be a pharmaceutical composition or a food composition:
  • the compound of Formula 1 may include all possible isomers, for example, may include a compound of Formula 2 below.
  • the compound of Formula 2 is referred to as kirenol.
  • the compound of Formula 1 or the compound of Formula 2 may be used by separating or synthesizing from a plant extract or using a commercially available compound.
  • the compound represented by Formula 1 or the compound represented by Formula 2 may be isolated from the rare extract.
  • the rare extract may be an extract of one or more plants selected from the group consisting of Siegesvecchia glabresense, Siegesvecchia fubesense, and Siegesvecchia orientalis.
  • Siegesvecchia glabresense Siegesvecchia fubesense
  • Siegesvecchia orientalis For example, ethanol extract, hot water extract, hexane extract, ethyl acetate extract, ultra high pressure extract using dried leaves and stems of Siegesvecchia glabresense, Sigebesvecchia fubense or Siegesvecchia orientalis have.
  • the rare extract may be obtained by extracting the rare extract 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.
  • solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, a subcritical fluid and a supercritical fluid.
  • rare plants may be obtained by extraction under ultrahigh 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 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 rare extract of the present invention can be obtained by extracting and purifying the dried rare extract using purified water, ethanol, subcritical water or supercritical carbon dioxide suitable for food processing, or extracted and purified using an ultra-high pressure extraction device
  • the rare plant can be obtained by separation and purification from oil obtained by direct compression.
  • the extract can be obtained by extracting the rare oil under ultra-high pressure conditions of 100 MPa or more.
  • the fraction of the rare extract may be obtained by fractionating the rare extract with ethyl acetate, methanol or a mixed solvent thereof.
  • the composition of the present invention is a pharmaceutical composition, in order to improve muscle function, 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.
  • Examples of related diseases include 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 type of muscle is not limited.
  • the pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable salt of chilenol or a rare extract or fraction thereof containing it.
  • ⁇ 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.
  • Pharmaceutically acceptable salts of the chilenol or rare extracts or fractions thereof containing the same may be acid addition salts formed using organic or inorganic acids, 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.
  • organic or inorganic acids for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, Iso
  • 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 prepared by a) chirenol or its rare extracts or fractions containing them and acids, or b) by dissolving and mixing one of them in a solvent or a hydrous solvent, or c) Knoll or a rare extract containing the same or a fraction thereof is prepared by a general method for preparing a salt, which is placed in an acid in a solvent or an aqueous solvent and mixed with 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 of the present invention may further comprise 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
  • Formulations for oral administration include tablets, pills, powders, granules, solutions, gels, syrups, slurries, suspensions or capsules and the like, and such solid preparations may be used in the pharmaceutical compositions of the present invention at least one excipient, 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 can 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 formulations may include various excipients, such as wetting agents, sweeteners, fragrances or preservatives, in addition to the commonly used simple diluents, water or liquid paraffin.
  • 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 administrations In the case of transdermal administrations, ointments, creams, lotions, gels, external preparations, pasta preparations, linen preparations, air rolls and the like are included.
  • '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 of the present invention may provide a desirable muscle function improving effect or exercise performance enhancing effect when it contains an effective amount of chilenol or a rare extract or a fraction thereof.
  • 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 or improve exercise performance.
  • the pharmaceutical composition of the present invention may contain 0.01 to 99.99% of chilenol or a rare extract containing the same, and the remaining amount may be occupied by a pharmaceutically acceptable carrier.
  • the effective amount of the chilenol or rare extract or fractions thereof included in the pharmaceutical composition of the present invention will vary depending on the form in which the composition is commercialized and the like.
  • the total effective amount of the pharmaceutical composition of the present invention may be administered to a patient in a single dose, or may be administered by a fractionated treatment protocol that is administered in multiple doses for long periods of time.
  • the pharmaceutical composition of the present invention may vary the content of the active ingredient depending on the extent of the disease.
  • the amount is preferably administered in an amount of 0.01 to 50 mg, more preferably 0.1 to 30 mg per kg of body weight per day based on the kyrenol or the rare extract containing the same, and on oral administration It may be administered in portions of 1 to several times so as to be administered in an amount of preferably 0.01 to 100 mg, more preferably 0.01 to 10 mg per kg of body weight per day, based on the knol or the rare extract containing the same.
  • the dose of the kyrenol or the rare extract containing the same is determined in consideration of various factors such as the age, weight, health condition, sex, severity of the disease, diet and excretion rate, as well as the route of administration and the number of treatments.
  • 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.
  • composition 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 of the present invention may also be provided in the formulation of a topical preparation containing chilenol or a rare extract or a fraction thereof as an active ingredient.
  • the pharmaceutical composition of the present invention is used as an external preparation for skin, it is additionally used for fatty substances, organic solvents, solubilizers, thickening and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants.
  • Skin external preparations such as water, ionic emulsifiers, nonionic emulsifiers, fillers, metal ion sequestrants, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic active agents, lipophilic active agents or lipid vesicles It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients commonly used in the art. The ingredients may also be introduced in amounts generally used in the field of dermatology.
  • the pharmaceutical composition of the present invention when provided as an external preparation for skin, it may be a formulation such as, but not limited to, an ointment, a patch, a gel, a cream, or a spray.
  • the composition of the present invention may also be a food composition.
  • the composition for improving muscle function or enhancing exercise performance of the present invention is a food composition, it may be used for preventing or improving 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. Examples of related diseases include 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 type of muscle is not limited.
  • 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 including 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.
  • 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 vegetable protein, retort food, frozen food, various seasonings may be prepared by adding the above-mentioned chilenol or a rare extract containing the same.
  • the nutritional supplements are not limited thereto, and may be prepared by adding the chilenol or a rare extract containing the same to capsules, tablets, pills, and the like.
  • a health functional food but is not limited to, for example, the liquefied, granulated, encapsulated so that the chilenol or a rare extract containing the same itself is produced in the form of tea, juice and drinks for drinking (health drink) And it can be prepared by powdering.
  • the chilenol or a rare extract containing the same may be prepared and used in the form of a powder or a concentrate for use in the form of a food additive.
  • it can be prepared in the form of a composition by mixing with the Jerusalemol or a rare extract containing the same and known active ingredients known to have an effect of improving muscle function or enhancing exercise performance.
  • the health beverage composition may contain various flavors or natural carbohydrates, etc. as additional ingredients, 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 said 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.
  • Kirenol or a rare extract containing the same may be contained as an active ingredient of a food composition for improving muscle function or enhancing exercise performance, the amount of which is particularly limited to an amount effective to achieve the effect of improving muscle function or enhancing exercise performance. It is preferably, but it is preferably from 0.01 to 100% by weight relative to the total weight of the composition.
  • 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 present invention also provides a method for improving muscle function or improving exercise performance, comprising administering to a subject a composition comprising a rare extract or a fraction thereof as an active ingredient.
  • the subject refers to a subject in need of improving muscle function or enhancing exercise performance, but may be, but is not limited to, a mammal including a human.
  • the rare extract may be one or more selected from the group consisting of Siegesvecchia glabresense, Siegesvecchia fubesense, and Siegesvecchia orientalis.
  • the rare extract may be obtained by extracting the rare extract 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 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 rare extract may be obtained by extracting the rare earth under ultra-high pressure conditions of 100 MPa or more.
  • the fraction of the rare extract may be obtained by fractionating the rare extract with ethyl acetate, methanol or a mixed solvent thereof.
  • the method of improving muscle function or enhancing motor performance consists of atony, muscular atrophy, muscular dystrophy, muscle degeneration, work sickness, cachexia and sarcopenia.
  • treating, preventing or ameliorating one or more diseases selected from the group By treating, preventing or ameliorating one or more diseases selected from the group.
  • the present invention also provides a method for improving muscle function or improving exercise performance, comprising administering to a subject a composition comprising a compound represented by Formula 1 as an active ingredient:
  • the compound represented by Formula 1 may be a chilenol represented by Formula 2:
  • the subject refers to a subject in need of improving muscle function or enhancing exercise performance, but may be, but is not limited to, a mammal including a human.
  • the compound represented by Formula 1 may be isolated from one or more extracts or fractions thereof selected from the group consisting of Siegesvecchia glabresense, Siegesvecchia fubesense, and Siegesvecchia orientalis. have.
  • the method of improving muscle function or enhancing motor performance consists of atony, muscular atrophy, muscular dystrophy, muscle degeneration, work sickness, cachexia and sarcopenia.
  • treating, preventing or ameliorating one or more diseases selected from the group By treating, preventing or ameliorating one or more diseases selected from the group.
  • composition for improving muscle function or improving exercise performance may be applied or mutatis mutandis to a method for improving muscle function or a method for enhancing exercise performance.
  • Kirenol Kirel; (1R, 3S, 4aS, 4bS, 7S, 10aS) -1,2,3,4,4a, 4b, 5,6,7,9,10,10a-Dodecahydro-3-hydroxy-7-[(R) -1,2-dihydroxyethyl] -1,4a, 7-trimethylphenanthrene-1-methanol
  • the dried leaves and stems of Siegesvecchia glabresense were pulverized with a mixer, and then 100 g of the ground Siegesvecchia glabresense sample was placed in 1 L of ethanol and extracted with stirring at 50 ° C. for 60 minutes.
  • the extracted sample was filtered using Whatman No. 2 filter paper, and the filtered extract was concentrated using a vacuum rotary concentrator to remove the solvent component, thereby obtaining an extract of Sigebexkia glabressen ethanol.
  • the dried leaves and stems of Siegesvecchia glabresense were ground with a mixer, and then 100 g of the ground Siegesvecchia glabresense sample was put in 1 L of water and extracted with stirring at 100 ° C. for 4 hours.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the filtrate was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Sigebexkia glabresense hydrothermal extract.
  • the dried leaves and stems of Siegesvecchia glabresense were pulverized with a mixer, and then 100 g of the ground Siegesvecchia glabresense sample was placed in 1 L of hexane and extracted with stirring at 50 ° C. for 60 minutes.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Sigebexkia glabresense hexane extract.
  • the dried leaves and stems of Siegesvecchia glabresense were pulverized with a mixer, and 100 g of the ground Siegesvecchia glabresense sample was placed in 1 L of ethyl acetate and extracted with stirring at 50 ° C. for 60 minutes.
  • the extracted sample was filtered using Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Sigebexkia glabressen ethyl acetate extract.
  • the dried leaves and stems of Siegesvecchia glabresense were pulverized with a mixer, and then 1 g of the ground Siegesvecchia glabresense sample and 76 mL of 18% ethanol were put in a polyethylene pack and sealed, followed by ultra high pressure Extraction was performed using an extractor (Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan).
  • the ultrahigh pressure extraction conditions were 320 MPa extraction time and 5 min extraction time.
  • the extracted sample was filtered using Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Sigebexkia glabresense ultrahigh pressure extract.
  • the dried leaves and stems of Siegesvecchia glabresense were ground with a mixer, and then 1 g of the ground Siegesvecchia glabresense sample was charged into a sample cartridge and a supercritical fluid extraction device (SFX 3560, Isco Inc. , Lincoln, NE, USA).
  • Supercritical fluid extraction conditions were 20 MPa extraction pressure, 60 ° C extraction temperature, 60 mL / min flow rate of supercritical carbon dioxide, 60 min extraction time.
  • the pressure of the extraction device was lowered to release the supercritical fluid state to obtain a Siegesvecchia glabresense supercritical fluid extract.
  • the dried leaves and stems of Siegesvecchia glabresense were ground with a mixer, and then 1 g of the ground Siegesvecchia glabresense sample was placed in 10 mL of distilled water, and a subcritical fluid extraction device (DIONEX Accelerated Solvent Extractor 100, DIONEX co., USA). Subcritical fluid extraction conditions were performed under the conditions of extraction pressure 0.5 MPa, extraction temperature 240 °C, extraction time 20 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was freeze-dried at -40 ° C to obtain a Siegesvecchia glabresense subcritical fluid extract.
  • DIONEX Accelerated Solvent Extractor 100 DIONEX co.
  • the dried leaves and stems of Siegesvecchia glabresense were pulverized with a mixer, and then 100 g of the ground Siegesvecchia glabresense sample was placed in 1 L of ethanol and extracted with stirring at 50 ° C. for 60 minutes.
  • the extracted sample was filtered using Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining an extract of Sievesbeckia fuvesense ethanol.
  • the leaves and stems of dried Siegesvecchia fuveycens were ground with a mixer, and then 100 g of the ground Siegesvecchia fuveysense sample was placed in 1 L of water and extracted with stirring at 100 ° C for 4 hours.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Sigebexkia fuvacense hot water extract.
  • the leaves and stems of dried Siegesvecchia fuveycens were pulverized with a mixer, and then 100 g of the ground Siegesvecchia fuveysense sample was placed in 1 L of hexane and extracted with stirring at 50 ° C. for 60 minutes.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Sigebexkia fuvacense hexane extract.
  • the leaves and stems of dried Siegesvecchia fuveycens were pulverized with a mixer, and 100 g of the ground Siegesvecchia fuveysense sample was put in 1 L of ethyl acetate and extracted with stirring at 50 ° C. for 60 minutes.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated using a vacuum rotary concentrator to remove the solvent component, thereby obtaining Sigebexkia fuvacense ethyl acetate extract.
  • the dried leaves and stems of Siegesvecchia fuveysense were pulverized with a mixer, and then 1 g of ground Siegesvecchia fuescens samples and 76 mL of 18% ethanol were put in a polyethylene pack and sealed, and then the ultra-high pressure extractor Extracted using (Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan).
  • the ultrahigh pressure extraction conditions were 320 MPa extraction time and 5 min extraction time.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining a Siegesvecchia fuvacense ultrahigh pressure extract.
  • the dried leaves and stems of Siegesvecchia fuveysense are ground with a mixer, and then 1 g of the ground Siegesvecchia fuveysense sample is charged into a sample cartridge and a supercritical fluid extraction device (SFX 3560, Isco Inc., Lincoln , NE, USA).
  • Supercritical fluid extraction conditions were 50 MPa extraction pressure, 40 °C extraction temperature, 60 mL / min flow rate of supercritical carbon dioxide, 60 min extraction time.
  • the pressure of the extraction device was lowered to release the supercritical fluid state to obtain a Siegesvecchia fuvesense supercritical fluid extract.
  • the dried leaves and stems of Siegesvecchia orientalis were ground with a mixer, and then 100 g of the Siegesvecchia orientalis sample was put in 1 L of ethanol and extracted with stirring at 50 ° C. for 60 minutes.
  • the extracted sample was filtered using Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining an extract of Siegesvecchia orientalis ethanol.
  • the dried leaves and stems of Siegesvecchia orientalis were ground with a mixer, and then 100 g of the ground Siegesvecchia orientalis sample was added to 1 L of water and extracted with stirring at 100 ° C for 4 hours.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the filtrate was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining Sigebexkia orientalis hydrothermal extract.
  • the leaves and stems of dried Siegesvecchia orientalis were ground with a mixer, and then 100 g of the Siegesvecchia orientalis sample was added to 1 L of hexane and extracted with stirring at 50 ° C. for 60 minutes.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining an extract of Sigebecia orientalis hexane.
  • the dried leaves and stems of Siegesvecchia orientalis were ground with a mixer, and then 100 g of the Siegesvecchia orientalis sample was added to 1 L of ethyl acetate and extracted with stirring at 50 ° C. for 60 minutes.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the filtrate was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining an extract of Sigestescchia orientalis ethyl acetate.
  • the dried leaves and stems of Siegesvecchia orientalis were ground with a mixer, and then 1 g of the ground Siegesvecchia orientalis sample and 76 mL of 18% ethanol were put in a polyethylene pack and sealed, and then the ultra-high pressure extractor Extracted using (Frescal MFP-7000; Mitsubishi Heavy Industries, Tokyo, Japan).
  • the ultrahigh pressure extraction conditions were 320 MPa extraction time and 5 min extraction time.
  • the extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was concentrated with a vacuum rotary concentrator to remove the solvent component, thereby obtaining an extract of Sigesvecchia orientalis ultrahigh pressure.
  • the dried leaves and stems of Siegesvek orientalis are pulverized with a mixer, and then 1 g of the ground Siegesvecchia orientalis sample is filled into a sample cartridge and a supercritical fluid extraction device (SFX 3560, Isco Inc., Lincoln) , NE, USA).
  • Supercritical fluid extraction conditions were 40 MPa extraction pressure, 50 °C extraction temperature, 60 mL / min flow rate of supercritical carbon dioxide, 60 min extraction time.
  • the pressure of the extraction device was lowered to release the supercritical fluid state to obtain a Siegesvecchia orientalis supercritical fluid extract.
  • the leaves and stems of the dried Sigestescchia orientalis were ground using a mixer, and then 1 g of the ground Sigesvecchia orientalis sample was added to 10 mL of distilled water, and a subcritical fluid extraction unit (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 °C, extraction time 15 minutes. The extracted sample was filtered through Whatman No. 2 filter paper, and the filtered extract was lyophilized at -40 ° C to obtain a Siegexvek orientalis subcritical fluid extract.
  • DIONEX Accelerated Solvent Extractor 100 DIONEX co , USA
  • the concentrated Sigestescchia orientalis ethanol extract obtained in Example 3-1 was loaded on a column filled with silica gel, and ethyl acetate and methanol were mixed at a ratio of 10: 0.5 (v / v) using a solvent system. Aliquoted. The fractions were divided into a total of seven fractions according to the aliquots and concentrated to dry each fraction. Fraction 6 of 7 fractions (fraction 6) were aliquoted into 10% ethylacetate of developing solvent using RP-18 reverse phase column chromatography (Lichroprep RP-18 25-40um, Merck & Co., Whitehouse Station, NJ, USA). . Each fraction was concentrated to dryness by dividing into a total of two fractions according to the aliquot sequence.
  • Fraction 2 of the two fractions (fraction 6-2) was concentrated to dryness and again fractionated with 20% ethyl acetate in developing solvent using RP-18 reverse phase column chromatography. Each fraction was concentrated to dryness by dividing into a total of three fractions according to the preparative sequence. Finally fraction 2 of the three fractions (fraction 6-2-2) was concentrated to dryness to separate a single pure active substance.
  • 1 H-NMR spectrum and 13 C-NMR spectrum were measured at 500 MHz and 125 MHz (solvent: MeOH), respectively.
  • the 1 H 1 H COSY spectrum and 1 H 13 C HSQC spectra in order to obtain the 1 H-NMR measurement of correlation between the spectrum and the 13 C-NMR correlation of the 1 H 1 H on the basis of the result of the spectrum related to the 1 H 13 C relationships
  • Each carbon signal was distinguished by the wavelength emitted through the carbon resonance, and the result was measured.
  • FAB-MS was measured for the mass spectrometry of the isolated single material.
  • This compound had a molecular weight of 338.48 as [M] was observed at m / z 338.48 in FAB-MS, and has the molecular formula C 20 H 34 O 4 .
  • Example 5-1 Effects of improving the muscle function of chirenol or Sigestesevikia glabressenth ethanol extract, Siegesbeckia fuvecens ethanol extract, Sieves Beckia orientalis ethanol extract
  • Muscle cells L6 myoblast (American Type Culture Collection, Manassas, VA, USA), were treated with 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA) and 100 U / mL penicillin, 100 ⁇ g / mL streptomycin. Cultured in Dulbecco's modified Eagle's media (DMEM; Hyclone) containing (Gibco, Grand Island, NY, USA). Sigebexkia glabracens ethanol extract prepared in Example 1-1, Sigebexkia fuvesense ethanol extract prepared in Example 2-1, Sigebexki prepared in Example 3-1 on L6 cells Orientalis ethanol extract was treated to 10 ppm concentration.
  • FBS fetal bovine serum
  • DMEM Dulbecco's modified Eagle's media
  • L6 cells were treated with the chilenol prepared in Example 4 at a concentration of 10 ⁇ M. At this time, the group treated with 0.01% DMSO instead of the sample was used as a control. After 24 hours, L6 cells were lysed with RIPA (ELPIS-Biotech, Daejeon, Korea) buffer solution containing a proteinase inhibitor cocktail (Sigma-Aldrich, St. Louis, MO, USA). After boiling the sample for 5 minutes, the same amount of protein (20 ⁇ g) was separated by electrophoresis with 10% SDS-PAGE. After electrophoresis, the separated proteins were transferred to nitrocellulose membrane and Western blot was performed.
  • RIPA EPIS-Biotech, Daejeon, Korea
  • the type and dilution ratio of the primary antibody used in the present invention is 1: 1000.
  • a secondary antibody anti-rabbit horseradish
  • the dilution ratio of the secondary antibody was 1: 5000.
  • the protein band was developed using ECL western blotting detection reagents (Amersham, Tokyo, Japan) to confirm the protein expression of the major gene p-mTOR involved in muscle function, and ⁇ -tubulin. It is shown that the protein loading is constant.
  • Sigebexchia orientalis ultra-high pressure extract prepared in Example 3-5 was treated to muscle cells in the same manner as in Example 5-1 at a concentration of 10, 20, 40 ppm.
  • 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 (%).
  • the Siege Beckia glabreense ethyl acetate extract, the Siege Beckia fuvesense ethyl acetate extract, and the Siege Beckia orientalis ethyl acetate extract are proteins of the main gene p-mTOR involved in muscle function improvement. It was found to increase the amount of expression.
  • the cells were treated. Next, the density of the control protein band was 100% in the same manner as in Example 5-3, and the density of the relative protein band of the experimental group treated with the sample was expressed as a percentage (%).
  • the Siege Beckia glabreense, Siege Beckia fuubesense, Siege Beckia orientalis supercritical and subcritical extracts express the protein expression level of the main gene p-mTOR involved in muscle function improvement. It was found to increase.
  • the fraction 6 of the 10: 0.5 (v / v) mixed solvent of ethyl acetate and methanol of the Siegesvecchia orientalis ethanol extract prepared in Example 4-1 was the same as Example 5-1 at 20 ppm. Muscle cells were treated by the method. Next, the density of the control protein band was 100% in the same manner as in Example 5-3, and the density of the relative protein band of the experimental group treated with the sample was expressed as a percentage (%).
  • Muscle cells L6 myoblasts (American Type Culture Collection, Manassas, VA, USA) were cultured in DMEM (10% FBS, 100 U / mL penicillin, 100 g / mL streptomycin). When the cell density reached about 80-85%, the cell medium was replaced with DMEM growth medium containing 2% FBS, followed by differentiation for 6 days, and then experimented. After treatment with TNF- ⁇ for 24 hours in order to induce muscle reduction in differentiated L6 cells, Siegesvecchia orientalis ethanol extract (10, 40 ppm) prepared in Example 3-1 and Example 4 The prepared chilenol (10, 40 ⁇ M) was treated.
  • RT-PCR was performed to determine the mRNA expression levels of myogenin and myoD, which are muscle differentiation regulators.
  • Total RNA was harvested and reverse-transcribed using TRIzol reagent (Invitrogen, Carlsbad, Calif., USA) from differentiated cells, followed by RT-PCR analysis. The RNA was first reverse transcribed with reverse transcriptase for cDNA synthesis.
  • RT-PCR was performed with the following specific primers, indicating that mRNA loading was constant with ⁇ -actin.
  • kyrenol of the present invention a rare extract containing the same or a fraction thereof inhibits the muscle catabolism involved in muscle loss, thereby contributing to the maintenance of muscle mass.
  • mice Four-week-old C57BL / 6 male mice were acclimated for 1 week and fed with a high-fat diet (Research Diets D12492, 60% kcal from fat) for 6 weeks to induce obesity. In the same manner as in Example 7-1 was administered orally to the obese animal model.
  • Example 8-1 The high-fat diet of Example 8-1 was used to measure muscle volume in the same manner as in Example 7-3.
  • Example 9-1 Effect of Enhancing Exercise Performance of Cyrenol or Sigestesckkia Glabressenth Ethanol Extract, Sievesbeckia Fuvesense Ethanol Extract, Siesbekschia Orientalis Ethanol Extract
  • Muscle cells L6 myoblast (American Type Culture Collection, Manassas, VA, USA), were treated with 10% fetal bovine serum (FBS; Hyclone, Logan, UT, USA) and 100 U / mL penicillin, 100 ⁇ g / mL streptomycin. Cultured in Dulbecco® modified Eagle® media (DMEM; Hyclone) containing (Gibco, Grand Island, NY, USA). Sigebexkia glabracens ethanol extract prepared in Example 1-1, Sigebexkia fuvesense ethanol extract prepared in Example 2-1, Sigebexki prepared in Example 3-1 on L6 cells Orientalis ethanol extract was treated to 10 ppm concentration.
  • FBS fetal bovine serum
  • DMEM Dulbecco® modified Eagle® media
  • L6 cells were treated with the chilenol prepared in Example 4 at a concentration of 10 ⁇ M. At this time, the group treated with 0.01% DMSO instead of the sample was used as a control. After 24 hours, L6 cells were lysed with RIPA (ELPIS-Biotech, Daejeon, Korea) buffer solution containing a proteinase inhibitor cocktail (Sigma-Aldrich, St. Louis, MO, USA). After boiling the sample for 5 minutes, the same amount of protein (20 ⁇ g) was separated by electrophoresis with 10% SDS-PAGE. After electrophoresis, the separated proteins were transferred to nitrocellulose membrane and Western blot was performed.
  • RIPA EPIS-Biotech, Daejeon, Korea
  • the primary antibody After reacting with the primary antibody, it was washed three times for 10 minutes using Tris-buffered saline containing 0.1% Tween 20 (TBST). At this time, the type and dilution ratio of the primary antibody used in the present invention is 1: 1000.
  • a secondary antibody anti-rabbit horseradish
  • the dilution ratio of the secondary antibody was 1: 5000.
  • Protein bands were developed using ECL western blotting detection reagents (Amersham, Tokyo, Japan) to confirm the protein expression of the major gene PGC-1 ⁇ involved in motor performance, and ⁇ -tubulin ( ⁇ - tubulin) showed a constant protein loading.
  • Sigebexkia orientalis ultra-high pressure extract prepared in Example 3-5 was treated to muscle cells in the same manner as in Example 9-1 at a concentration of 10, 20, 40 ppm.
  • the PGC-1 ⁇ 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 (%).
  • the Siege Beckia glabreense ethyl acetate extract, the Siege Beckia fuvesense ethyl acetate extract, and the Siege Beckia orientalis ethyl acetate extract are involved in the exercise performance of PGC-1 ⁇ . It was found to increase the amount of protein expression.
  • the cells were treated. Next, the density of the control protein band was 100% in the same manner as in Example 9-3, and the density of the relative protein band of the experimental group treated with the sample was expressed as a percentage (%).
  • the fraction 6 of the 10: 0.5 (v / v) mixed solvent of ethyl acetate and methanol of the Siegesvecchia orientalis ethanol extract prepared in Example 4-1 was the same as Example 5-1 at 20 ppm. Muscle cells were treated by the method. Next, the density of the control protein band was 100% in the same manner as in Example 5-3, and the density of the relative protein band of the experimental group treated with the sample was expressed as a percentage (%).
  • the chilenol of the present invention a rare extract containing the same or a fraction thereof has the activity to enhance the exercise performance through the increase in the amount of PGC-1 ⁇ protein expression.
  • the exercise performance was evaluated using a treadmill.
  • the performance evaluation was performed 20 minutes at a speed of 25 cm / sec at a slope of 5 °, 20 minutes at a speed of 30 cm / sec, 20 minutes at a speed of 33 cm / sec, 20 minutes at a speed of 36 cm / sec, 36 cm / sec.
  • the maximum exercise performance of the test animals was measured by running 15 minutes at a slope of 10 °, 15 minutes at a speed of 38 cm / sec, and 41 cm / sec.
  • the point of determination of the maximum exercise performance was defined as the time when the experimental animals could not catch up with the treadmill speed for more than 10 seconds after the start of exercise, or the cumulative number of electric shocks exceeded 100 times in 5 minutes.
  • Sigebexkia glabresense hydrothermal extract prepared in Example 1-2 in the same manner as in Example 10-1 and Example 10-2, Sigebexkia fuvacense prepared in Example 2-2
  • the exercise time for the hydrothermal extract, Siegesvecchia orientalis hydrothermal extract prepared in Example 3-2 was measured.
  • mice Four-week-old C57BL / 6 male mice were acclimated for 1 week and fed with a high-fat diet (Research Diets D12492, 60% kcal from fat) for 6 weeks to induce obesity. Divided into and administered orally to the obese animal model in the same manner as in Example 10-1.
  • Example 10-2 The exercise performance was evaluated in the same manner as in Example 10-2 using the obese animal model induced by the high fat diet.
  • the experimental results were tested by the t-test of the high-fat diet control group and the high-fat diet Siegesvecchia orientalis ethanol extract group, and the significance was verified (** p ⁇ 0.01).
  • Calf muscles were extracted from the normal diet mouse of Example 10-1 and the high-fat diet mouse of Example 11-1, and then, p-AMPK, SIRT1, PGC-1 ⁇ , Protein expression of PPAR ⁇ was confirmed, indicating that protein loading was constant with ⁇ -tubulin.
  • Sigesvecchia orientalis extract increased the protein expression levels of p-AMPK, SIRT1, PGC-1 ⁇ , and PPAR ⁇ , which are genes related to the improvement of exercise ability in both the normal diet model and the high-fat diet model. Sikkim was known.
  • Sigebecia orientalis extract increased the mRNA expression levels of mitochondrial biosynthetic genes PGC-1 ⁇ , NRF-1, ERR ⁇ , Tfam in the normal diet and high-fat diet model could.
  • the above ingredients are mixed according to a conventional health food manufacturing method, and then granulated. It can be prepared and used in the manufacture of health food compositions according to conventional methods.
  • Example 1 to 3 of the rare extract or Kirenol 1000 mg, citric acid 1000 mg, oligosaccharide 100 g, plum concentrate 2 g, taurine 1 g of purified water was added to the above ingredients according to the general 900 ml conventional health beverage production method After mixing and heating at 85 for about 1 hour after stirring, the resulting solution is filtered, obtained in a sterilized 2 L container, sealed and sterilized, and then refrigerated and then used for preparing a healthy beverage composition.
  • Chewing gum was prepared in a conventional manner by combining 20% by weight of gum base, 76.9% by weight of sugar, 1% by weight of perfume, and 2% by weight of water, and 0.1% by weight of the rare extract or chilenol of Examples 1 to 3.
  • 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 the rare extract or chilenol of Examples 1 to 3.
  • Powders were prepared by mixing the rare extracts of Examples 1 to 3 or 50 mg of chilenol and 2 g of crystalline cellulose and then filling them in airtight cloths according to a conventional powder preparation method.
  • the tablets were prepared by mixing the rare extracts of Examples 1 to 3 or 50 mg of chilenol, 400 mg of crystalline cellulose, and 5 mg of magnesium stearate, followed by compression according to a conventional tablet preparation method.
  • Example 1 To prepare a capsule by mixing the rare extract of Example 1 to 3 or 30 mg of wheyol, 100 mg of whey protein, 400 mg of crystalline cellulose, 6 mg of magnesium stearate and filling it into gelatin capsules according to a conventional capsule preparation method It was.
  • the active ingredient was dissolved in distilled water for injection according to a conventional injection method, and the pH was adjusted to about 7.5. Then, 100 mg of chilenol, distilled water for injection, and a pH adjusting agent of Example 3-5 were mixed to prepare an ampoule of 2 ml. Injections were made by filling and sterilizing.

Abstract

La présente invention concerne une composition améliorant une fonction musculaire ou augmentant une performance d'exercice physique, la composition contenant, en tant que principe actif, kirenol, un extrait de Hui Chum (Siegesbeckia spp.) le contenant, ou une fraction de ce dernier. Le kirenol, l'extrait de Hui Chum (Siegesbeckia spp. ) le contenant, ou la fraction de ce dernier, selon la présente invention, augmente l'expression protéique de p-mTOR, qui est un gène principal mis en jeu dans la fonction musculaire, ce qui permet d'augmenter considérablement la fonction musculaire. Le kirenol, l'extrait de Hui Chum (Siegesbeckia spp.) le contenant, ou la fraction de ce dernier, selon la présente invention, augmente l'expression protéique de PGC -1α, qui est un gène principal mis en jeu dans la performance d'exercice physique, ce qui permet d'augmenter significativement la performance d'exercice physique. En outre, la présente invention peut être utilisée en toute sécurité sans effets secondaires étant donné qu'il s'agit d'un matériau naturel, et peut donc être utilisée en tant que produit médicinal ou aliment.
PCT/KR2015/006655 2014-06-27 2015-06-29 Composition pour améliorer la fonction musculaire ou augmenter la performance d'exercice physique, contenant du kirenol ou un extrait de hui chum WO2015199516A1 (fr)

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