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WO2021118080A1 - Composition pharmaceutique de prévention ou de traitement des maladies musculaires comprenant des ginsenosides rg2, rg4, rg6, rh1, et rh4 comme principes actifs - Google Patents

Composition pharmaceutique de prévention ou de traitement des maladies musculaires comprenant des ginsenosides rg2, rg4, rg6, rh1, et rh4 comme principes actifs Download PDF

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Publication number
WO2021118080A1
WO2021118080A1 PCT/KR2020/016007 KR2020016007W WO2021118080A1 WO 2021118080 A1 WO2021118080 A1 WO 2021118080A1 KR 2020016007 W KR2020016007 W KR 2020016007W WO 2021118080 A1 WO2021118080 A1 WO 2021118080A1
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Prior art keywords
muscle
ginsenoside
ginsenosides
preventing
mixture
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Korean (ko)
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송규용
안병희
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Arez Co Ltd
Industry and Academy Cooperation In Chungnam National University
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Arez Co Ltd
Industry and Academy Cooperation In Chungnam National University
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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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/316—Foods, ingredients or supplements having a functional effect on health having an effect on regeneration or building of ligaments or muscles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention relates to a pharmaceutical composition for preventing or treating muscle disease comprising ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 as active ingredients.
  • Muscle is the tissue with the largest amount of composition in the human body, and in order to maintain the functional ability of the human body and prevent metabolic diseases, it is essential to secure an appropriate muscle mass.
  • Muscles are largely divided into smooth muscles, cardiac muscles, and skeletal muscles. Skeletal muscle occupies a significant portion of our entire body, and facilitates skeletal movement. These skeletal muscles do not divide, and consist of multinucleated muscle fibers, which are created during embryogenesis. After the embryonic process is completed, muscle is formed by the process of postnatal growth or myogenesis. In particular, when muscles are damaged by frostbite, sprains, bruises, etc., muscle differentiation occurs.
  • myogenesis process first, satellite cells are activated, and the activated satellite cells are differentiated into myoblasts (Morgan, JE et al., Int J Biochem Cell Biol., 35(8)). , 1151-1156, 2003).
  • the differentiated myoblasts divide and fusion of myoblasts occurs to develop into a myotube to form a muscle fiber.
  • the muscle fibers formed through this process are bundled to finally form a muscle.
  • Ginseng (Panax ginseng C. A. Meyer) is a plant of the Araliaceae family, and the root is mainly used as a medicinal part, and the fine root of the root is removed and dried or the whole plant is used.
  • white ginseng (white ginseng: raw), red ginseng ( ⁇ : steamed), and fine ginseng ( ⁇ : thin root) are used according to medicinal effects, and wild ginseng is also classified into camphor and wild ginseng in folklore.
  • it refers to the root and rhizome of ginseng and is divided into raw ginseng (cultivated ginseng), red ginseng, and wild ginseng (wild ginseng).
  • Ginseng has a peculiar smell, is sweet and slightly bitter, and is known to be slightly warm in nature. Ginseng is known for its vitality, body weakness, malaise, fatigue, anorexia, vomiting, and diarrhea. is known to increase As pharmacological actions of ginseng, various activities such as nourishing tonic, immune-enhancing, central nervous system, cardiovascular, and blood sugar lowering have been reported (Choi, J. et al., PLoS One, 8(4), e59978, 2013). ; Alraek, T. et al., BMC Complement Altern Med., 11(87), 1-11, 2011).
  • Ginsenoside is a compound word of ginseng and glycoside, and is known to have a unique chemical structure and pharmacological effect unlike saponins found in other plants.
  • Ginsenoside is a neutral glycoside in which glucose, arabinose, xylose, rhamnose, etc. are bonded to the triterpenoid-type dammarane skeleton.
  • PPD protopanaxadiol
  • PPT protopanaxatriol
  • oleic acid It is classified as oleanane (type 1).
  • the main ginsenosides present in fresh ginseng or white ginseng are Rg1, Re, Rf, Rh1, Rb1, Rb2, Rc, Rd, etc., accounting for more than 80-90% of the total ginsenosides.
  • Rg1, Re, Rf, Rh1, Rb1, Rb2, Rc, Rd, etc. accounting for more than 80-90% of the total ginsenosides.
  • some of the sugars are separated from the ginsenosides present in a large amount or are produced by dehydration, but when ginseng is extracted with water and alcohol, it is present in a trace amount.
  • ginsenosides The pharmacological activity of ginsenosides is shown by rare ginsenosides resulting from the ginsenosides present in large amounts, and strengthens immunity, anti-inflammatory, anti-allergy, anti-cancer, blood pressure lowering, anti-cholesterol, anti-thrombosis, anti-aging, antioxidant , brain activity promotion, and skin beautification effects are known as major effects (Kim, YS et al., Arch Pharm Res., 23(5), 518-524, 2000; Shibata, S., J Korean Med Sci., 16(suppl), S28-37, 2001; Tachikawa, E. et al., Biochem Pharmacol., 66(11), 2213-2221, 2003; Tsai, SC et al., Chin J Physiol., 46(1) , 1-7, 2003).
  • Korean Patent No. 10-1120996 discloses a composition containing ginsenoside Rg3 and Rg2.
  • a composition for promoting exercise capacity and fatigue recovery has been disclosed, and
  • Korean Patent No. 10-1966117 discloses a composition for promoting muscle differentiation of a processed ginseng extract containing ginsenosides Rh2 and Rg3 as active ingredients.
  • 10-2019-0108777 disclose a composition for muscle regeneration comprising ginsenoside Rg1, ginsenoside Rh2, ginsenoside Rb1 and Rb2. has been disclosed.
  • ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 have therapeutic effects on muscle diseases, particularly muscle diseases caused by decreased muscle function, muscle wasting or muscle degeneration.
  • one or more ginsenosides selected from the group consisting of the ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 inhibit muscle loss and improve muscle regeneration
  • An object of the present invention relates to a composition for the prevention or treatment of muscle diseases comprising one or more ginsenosides selected from the group consisting of ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 as an active ingredient, and more specifically
  • An object of the present invention is to provide a composition for preventing or treating muscle disease due to decreased muscle function, muscle wasting or muscle degeneration.
  • the present invention relates to a pharmaceutical composition for the prevention or treatment of muscle diseases comprising, as an active ingredient, one or more ginsenosides selected from the group consisting of ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4. It relates to a pharmaceutical composition for preventing or treating muscle diseases caused by decreased function, muscle wasting or muscle degeneration.
  • a mixture (RGX 365) in which all of the ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 are mixed (RGX 365) is used as a pharmaceutical composition for preventing or treating muscle diseases, wherein the mixture is ginsenoside Rg2 ((S )-Rg2 and (R)-Rg2) 30-40% by weight, ginsenoside Rg4 30-40% by weight, ginsenoside Rg6 13-23% by weight, ginsenoside Rh1 ((S)-Rh1 and (R) -Rh1) 1-5% by weight and ginsenoside Rh4 2.5-5% by weight is effective for preventing or treating muscle disease.
  • the mixture is ginsenoside Rg2 ((S )-Rg2 and (R)-Rg2) 30-40% by weight, ginsenoside Rg4 30-40% by weight, ginsenoside Rg6 13-23% by weight, ginsenoside Rh1 ((S)-Rh1 and (R
  • the one or more ginsenosides selected from the group consisting of Rg2, Rg4, Rg6, Rh1 and Rh4 are pharmaceutically acceptable salts as well as any method that can be prepared according to a conventional method in the art.
  • 100 to 300 parts by weight of distilled water is mixed with 100 parts by weight of ginsenoside Re, and then for 4 to 8 hours, in a temperature range of 110 to 140 °C and a pressure condition of 0.11 to 0.16 MPa at high temperature and high pressure. It is preferably obtained by treatment and column separation.
  • the muscle disease relates to a muscle disease caused by a decrease in muscle function, muscle wasting or muscle degeneration, more preferably sarcopenia, atony, muscular atrophy, myopathy, It is selected from the group consisting of muscle injury, muscular dystrophy, myasthenia, diabetic amyotrophy and amyotrophic lateral sclerosis (ALS).
  • a muscle disease caused by a decrease in muscle function, muscle wasting or muscle degeneration, more preferably sarcopenia, atony, muscular atrophy, myopathy, It is selected from the group consisting of muscle injury, muscular dystrophy, myasthenia, diabetic amyotrophy and amyotrophic lateral sclerosis (ALS).
  • ALS amyotrophic lateral sclerosis
  • compositions according to the present invention may be formulated in a suitable form together with a commonly used pharmaceutically acceptable carrier.
  • “Pharmaceutically acceptable” refers to a composition that is physiologically acceptable and does not normally cause allergic reactions such as gastrointestinal disorders, dizziness, or similar reactions when administered to humans.
  • the composition may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions according to conventional methods, respectively.
  • Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl paraoxybenzoate, propyl paraoxybenzoate, talc, magnesium stearate, and mineral oil, but is not limited thereto.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient, for example, starch, microcrystalline cellulose, sucrose or the ginsenoside of the present invention. It is prepared by mixing lactose, low-substituted hydroxypropyl cellulose, hypromellose, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
  • Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc.
  • various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
  • Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • the base of the suppository As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerol, gelatin, etc. may be used.
  • the ginsenoside or a pharmaceutically acceptable salt thereof is sterilized or an adjuvant such as a preservative, a stabilizer, a wetting agent or an emulsification accelerator, a salt or buffer for regulating osmotic pressure, and other therapeutically It may be mixed with useful substances in water to prepare solutions or suspensions, which may be prepared in ampoules or vial unit dosage form.
  • the pharmaceutical composition may be administered to mammals such as mice, livestock, and humans by various routes. Any mode of administration can be envisaged, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebrovascular injection.
  • the dosage may vary depending on the age, sex, weight, specific disease or pathology to be treated, the severity of the disease or pathology, administration time, administration route, absorption, distribution and excretion rate of the drug, the type of other drugs used, and the prescriber's It will depend on judgment, etc. Dosage determination based on these factors is within the level of the skilled artisan, and dosages generally range from 0.01 mg/kg/day to approximately 2000 mg/kg/day. A more preferred dosage is 1 mg/kg/day to 500 mg/kg/day. Administration may be administered once a day, or may be administered in several divided doses. The above dosage does not limit the scope of the present invention in any way.
  • the present invention provides a health functional food for preventing or improving muscle disease, comprising one or more ginsenosides selected from the group consisting of ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 as an active ingredient do.
  • the health functional food refers to food manufactured or processed using raw materials or ingredients having useful functionality, and includes, for example, health supplements, functional foods, nutritional supplements, supplements, and the like.
  • the ginsenoside is preferably added in an amount of 0.001% to 50% by weight, more preferably 0.001% to 40% by weight, and most preferably 0.001% to 30% by weight based on the total weight of the health functional food. can be
  • the health functional food of the present invention includes the form of tablets, capsules, pills, and liquids, and the food to which ginsenoside of the present invention can be added includes, for example, various foods, beverages, gum, tea, vitamins. Combination drugs, etc.
  • the present invention relates to a composition for preventing or treating a muscle disease comprising at least one selected from ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 as an active ingredient.
  • ginsenoside When the ginsenoside is treated in cells induced by muscle atrophy or in mice induced by aging, the effect of promoting differentiation into the root canal and the regeneration of muscle tissue are excellent, so that muscle diseases, particularly muscle diseases caused by decreased muscle function, muscle wasting, or muscle degeneration It can be usefully used to treat diseases.
  • 1 is a graph confirming the cell viability according to the treatment of single ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 in myoblasts and a mixture (RGX 365) containing them all.
  • Figure 2A is a fluorescence microscope measurement result confirming the myosin expression level of the differentiation degree of the root canal according to the treatment by concentration of the ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365),
  • Figure 2B is the diameter of the number of root canals It is the result of checking by size.
  • Figure 3A is a fluorescence microscopic measurement of the myosin expression level according to the treatment of the single ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 and a mixture (RGX 365) containing all of the differentiation degree of myotubes induced by dexamethasone.
  • Figure 3B is the result of confirming the number of root canals by diameter size.
  • Figure 4 is the result of confirming the degree of muscle tissue damage according to the intramuscular injection and oral administration of single ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 and a mixture (RGX 365) including all of them to aging mice by H&E staining.
  • C.S.A. muscle fiber cross-sectional area
  • FIG. 6A is a result of measuring the change in grip strength according to intramuscular injection and oral administration of a single ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 and a mixture (RGX 365) containing all of them to an aging mouse
  • FIG. 6B is a total muscle This is the result of measuring the change in weight.
  • FIG. 7A to 7D show Atrogin-1, Murf-1, MyoD, and MyoG expression levels in muscle tissue following intramuscular injection and oral administration of ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) to aging mice. It is the result of confirming the change.
  • ginsenoside Rg2 30-40 wt%, ginsenoside Rg4 30-40 wt%, ginsenoside Rg6 13-23 wt%, ginsenoside Rg2 30-40 wt% of the present invention by concentrating the fraction obtained using 35-70% fermentation alcohol solvent under reduced pressure A mixture (RGX 365) containing 1 to 5% by weight of side Rh1 and 2.5 to 5% by weight of ginsenoside Rh4 was obtained. In addition, it was separated and purified to obtain single ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4.
  • C2Cl2 is a myoblast cell line obtained from C3H mice, and is widely used in myocyte differentiation studies.
  • Normal cell culture medium (GM, growth media) is DMEM (Dulbecco's Modified Eagle's Medium; Invitrogen, OR, USA) supplemented with 10% fetal bovine serum, 50 U/ml penicillin and 50 ⁇ g/ml streptomycin.
  • DMEM Dulbecco's Modified Eagle's Medium
  • a medium was used, and DMEM containing 2% horse serum was used as a differentiation medium (DM).
  • the setting of the incubator used for cell culture was maintained at a temperature of 37° C. and a concentration of CO 2 of 5%.
  • the MTT assay was performed to confirm cell viability.
  • C2C12 cells cultured under the conditions of Experimental Example 1 were seeded in a 96-well tissue culture plate (BD Falcon, NJ, USA) at a concentration of 2000 cells/well and cultured for 24 hours. After 24 hours, single ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 were at 20 ⁇ g/ml, and ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 mixtures (RGX 365) were concentrated at different concentrations (0, 1.25, 2.5).
  • single ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 and a mixture containing them all (RGX 365) treated C2C12 mouse myoblast survival rate was similar to the control group not treated with anything. Therefore, it can be seen that the present invention single ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 and a mixture (RGX 365) including all of them is a composition that does not exhibit cytotoxicity.
  • differentiated myoblasts divide and fusion between myoblasts develops into myotubes to form muscle fibers.
  • the formed muscle fibers form bundles and finally form a muscle.
  • the differentiation activity into myotubes was confirmed.
  • the degree of differentiation into the root canal was confirmed by measuring the expressed amount of myosin, a major structural protein of the muscle, and the size of the root canal.
  • C2C12 cells cultured under the conditions of Experimental Example 1 were aliquoted in a 6-well tissue culture plate (BD Falcon, NJ, USA) at a concentration of 30000 cells/well and cultured for 24 hours. After culturing until the cells are about 90% full, add DMEM (Dulbecco's Modified Eagle's Medium, Gibco) medium containing 2% horse serum (HS) and 1% penicillin/streptomycin (P/S) to the root canal for 3 days. After inducing differentiation into ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) was further cultured for 2 days in a medium treated with each concentration (1.25, 2.5, 5, 10 ⁇ g / ml) .
  • DMEM Dulbecco's Modified Eagle's Medium, Gibco
  • HS horse serum
  • P/S penicillin/streptomycin
  • muscle atrophy is inhibited by measuring the expression amount of myosin and the size change of the myosin according to the treatment of the ginsenoside Rg2, Rg4, Rg6 and Rh1 mixture (RGX 365) in the root canal induced by dexamethasone. The effect was checked.
  • C2C12 cells cultured under the conditions of Experimental Example 1 were dispensed in a 6-well tissue culture plate at a concentration of 30000 cells/well and cultured for 24 hours. After inducing differentiation into myotube cells for 5 days, by adding DMEM medium containing 2% horse serum (HS) and 1% penicillin/streptomycin (P/S) to the cells in culture until the cells are about 90% full, Dexamethasone (50 ⁇ M) was diluted in serum-free DMEM medium and treated for 24 hours.
  • HS horse serum
  • P/S penicillin/streptomycin
  • single ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 or a mixture of ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4 (RGX 365) at a concentration of 10 ⁇ g/ml was further cultured for 2 days in DMEM medium containing
  • mice of C57BL/6 male mice of 2 months of age and 22-23 months of age were used. 10 mice of similar body weight were assigned to two-month-old mice without administration, a control group (22-23 month-old mice) administered with the same amount of solvent diluted in saline, and single ginsenosides Rg2, Rg4, Rg6, Rh1 and Rh4
  • the administered group (22-23 month old mouse) and the ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) administered group (22-23 month old mouse) were used for the experiment.
  • composition of the present invention administered to the mice of the experimental group was diluted in saline to prepare 0.5 mg/ml, and then administered by intramuscular injection once every 2 days for 30 days, or orally administered daily for 90 days.
  • the muscle tissue was separated, put into a mold containing the OCT compound, and lyophilized using liquid nitrogen, and then the muscle tissue was sectioned into 10 ⁇ m using a microtome device.
  • the cut muscle tissue (Tibialis anterior muscle, TA) was attached to a microscope slide and fixed with 4% paraformaldehyde.
  • the fixed sample was H&E stained (hematoxylin eosin staining) and imaged with a digital camera (IMTcam3_Plus, P/NUP900310A), as shown in FIG. 4 .
  • composition of the present invention when the composition of the present invention was administered by oral administration or intramuscular injection to aged mice, the degree of muscle damage was reduced compared to the control group (aged mice treated only with solvent), and the size of the muscle fibers was 2 months old. It was found to be an effective composition for the treatment of sarcopenia caused by aging, as it increased by the level of young mice.
  • the grip force was measured with a grip force meter for a mouse of BIOSEB company.
  • the mouse was placed on the wire mesh attached to the instrument panel to monitor the strength of the force, and the mouse gripped the wire mesh while grabbing the tail and dragging it down. It is shown in FIG. 6A using the average value shown repeatedly 5 times in succession.
  • the specific nucleotide sequence of the primer used in the above process is as follows.
  • Atrogin-1 and Murf-1 having muscle proteolytic activity increased in the control group, aged mice (old), while the present invention ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX) 365) by oral administration or intramuscular injection to aging mice, the expression of Atrogin-1 and Murf-1 decreased to a similar extent to that of a 2-month-old mouse (young), and it was found that muscle protein degradation was not promoted. .
  • the ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) of the present invention can treat damaged muscles by regulating muscle control factors increased or decreased by aging.
  • ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) was mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid, respectively. After adding a 10% gelatin solution to this mixture, it was ground and passed through a 14 mesh sieve. This was dried, and 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate were added thereto, and the resulting mixture was made into tablets.
  • ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) of the present invention 100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate, the above ingredients according to a conventional capsule preparation method was mixed and filled in gelatin capsules to prepare capsules.
  • the present invention ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) 1g, sodium chloride 0.6g and ascorbic acid 0.1g was dissolved in distilled water to make 100ml. This solution was placed in a bottle and sterilized by heating at 20° C. for 30 minutes.
  • the present invention ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) 20g, vitamin mixture appropriate amount, vitamin A acetate 70 ⁇ g, vitamin E 1.0mg, vitamin B1 0.13mg, vitamin B2 0.15mg, vitamin B6 0.5mg , vitamin B12 0.2 ⁇ g, vitamin C 10mg, biotin 10 ⁇ g, nicotinic acid amide 1.7mg, folic acid 50 ⁇ g, calcium pantothenate 0.5mg, mineral mixture appropriate amount, ferrous sulfate 1.75mg, zinc oxide 0.82mg, magnesium carbonate 25.3mg, Although it was prepared as granules by mixing 15 mg of potassium monophosphate, 55 mg of dibasic calcium phosphate, 90 mg of potassium citrate, 100 mg of calcium carbonate, and 24.8 mg of magnesium chloride, it can be prepared by modifying it into various formulations depending on the use. In addition, the composition ratio of the vitamin and mineral mixture may be arbitrarily modified,
  • ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) of the present invention Mix 1 g of ginsenoside Rg2, Rg4, Rg6, Rh1 and Rh4 mixture (RGX 365) of the present invention, 0.1 g of citric acid, 100 g of fructooligosaccharide, and 900 g of purified water, and stir, heat, filter, sterilize, and refrigerate according to a conventional beverage preparation method to prepare a beverage.

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition de prévention ou de traitement des maladies musculaires, la composition comprenant au moins un ginsenoside sélectionné parmi les ginsenosides Rg2, Rg4, Rg6, Rh1, et Rh4 comme principe actif. Lorsqu'utilisés pour traiter les cellules induites d'atrophie musculaire ou des souris à vieillissement induit, les ginsenosides présentent un excellent effet de promotion de la différenciation dans les myotubes, et un excellent effet de régénération du tissu musculaire, et ainsi les ginsenosides peuvent être efficacement utilisés pour traiter les maladies musculaires, en particulier, les maladies musculaires causées par l'atrophie musculaire, la dégénérescence musculaire, ou la fonction musculaire réduite.
PCT/KR2020/016007 2019-12-12 2020-11-13 Composition pharmaceutique de prévention ou de traitement des maladies musculaires comprenant des ginsenosides rg2, rg4, rg6, rh1, et rh4 comme principes actifs Ceased WO2021118080A1 (fr)

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KR1020190166045A KR102291748B1 (ko) 2019-12-12 2019-12-12 진세노사이드 Rg2, Rg4, Rg6, Rh1 및 Rh4를 유효성분으로 포함하는 근육 질환 예방 또는 치료용 약학 조성물
KR10-2019-0166045 2019-12-12

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CN115317588B (zh) * 2022-09-26 2024-04-05 东阿阿胶股份有限公司 保元汤、保元浸膏、保元固体制剂的制备方法
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CN118489625A (zh) * 2024-04-01 2024-08-16 中国农业大学 人参皂苷在制备药品、试剂中的应用

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