[go: up one dir, main page]

WO2025244466A1 - Composition pour la prévention ou le traitement de maladies musculaires comprenant un métabolite probiotique en tant que principe actif - Google Patents

Composition pour la prévention ou le traitement de maladies musculaires comprenant un métabolite probiotique en tant que principe actif

Info

Publication number
WO2025244466A1
WO2025244466A1 PCT/KR2025/007032 KR2025007032W WO2025244466A1 WO 2025244466 A1 WO2025244466 A1 WO 2025244466A1 KR 2025007032 W KR2025007032 W KR 2025007032W WO 2025244466 A1 WO2025244466 A1 WO 2025244466A1
Authority
WO
WIPO (PCT)
Prior art keywords
muscle
chemical formula
composition
paragraph
active ingredient
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/KR2025/007032
Other languages
English (en)
Korean (ko)
Inventor
이충환
김수현
김선여
홍성민
이은유
박진호
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Metamass Corp
University Industry Cooperation Corporation of Konkuk University
Industry Academic Cooperation Foundation of Gachon University
Original Assignee
Metamass Corp
University Industry Cooperation Corporation of Konkuk University
Industry Academic Cooperation Foundation of Gachon University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Metamass Corp, University Industry Cooperation Corporation of Konkuk University, Industry Academic Cooperation Foundation of Gachon University filed Critical Metamass Corp
Publication of WO2025244466A1 publication Critical patent/WO2025244466A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • 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

Definitions

  • the present invention relates to a composition for preventing or treating muscle disease, comprising a probiotic metabolite as an active ingredient.
  • Prebiotics, probiotics, and postbiotics are relatively new terms used to describe a variety of substances that confer health and nutritional benefits to animals.
  • the term prebiotic refers to substances that stimulate the growth or activity of bacteria in the digestive tract of animals, leading to beneficial health effects.
  • Prebiotics can be selectively fermented ingredients that induce specific changes in both the composition and activity of the gastrointestinal microflora, conferring health benefits to the host.
  • Probiotics generally refer to microorganisms that contribute to the intestinal bacterial balance and, consequently, to maintaining health.
  • Many species of lactic acid bacteria (LAB), such as Lactobacillus and Bifidobacterium are commonly considered probiotics, although some species of Bacillus and some yeasts have also been identified as suitable candidates.
  • Postbiotics refer to non-viable bacterial products or metabolic by-products derived from probiotic organisms that possess biological activity in the host.
  • probiotics to improve animal health and nutrition has been shown to be effective in a variety of diseases and health conditions.
  • prebiotics and postbiotics offer potential alternatives or adjunctive therapies to the use of live microorganisms.
  • the consumption of probiotic bacteria can potentially stabilize the immunological barrier in the gut mucosa by reducing the production of local proinflammatory cytokines.
  • alterations in the characteristics of the indigenous microbiota by probiotic therapy have been shown to reverse some immunological disturbances in human conditions such as Crohn's disease, food allergy, and atopic eczema.
  • muscle atrophy can be caused by a variety of factors, including the absence of mechanical stimulation, starvation, and cancer.
  • Muscle atrophy can be defined as the loss of muscle tissue resulting from disuse, disease of the muscle itself, or damage to the nerves that control it. In general, disuse can lead to a significant loss of muscle strength, which can gradually progress to muscle atrophy. Furthermore, individuals living in environments without gravity can also experience muscle weakness due to decreased calcium and muscle strength.
  • Muscle atrophy due to disease of the muscle itself includes myasthenia gravis, muscular dystrophy (progressive muscular dystrophy, myotonic dystrophy, Duchenne, Becker, limb-girdle, facioscapulohumeral), and inflammation that occurs in the muscle itself, and muscle atrophy due to damage to the nerves that control the muscle includes spinal muscular amyotrophy (Berardnig-Hoffmann type, Kugelberg-Welander disease), amyotrophic lateral sclerosis (ALS): Lou Gehrig's disease, and spinobular muscular atrophy (Kennedy's disease).
  • spinal muscular amyotrophy Boardnig-Hoffmann type, Kugelberg-Welander disease
  • ALS amyotrophic lateral sclerosis
  • Skennedy's disease spinobular muscular atrophy
  • Sarcopenia refers to a condition in which skeletal muscle mass and function are reduced. Sarcopenia can be caused by a variety of factors, including aging, hormonal imbalances, nutritional deficiencies, lack of physical activity, inflammation, and degenerative diseases. Aging and sex hormone deficiencies are known to be the primary causes. Advances in medical technology and the development of various treatments have led to increased life expectancy worldwide, leading to a growing aging population. Consequently, the demand for sarcopenia treatment is expected to continue to grow.
  • the inventors of the present invention isolated useful metabolites from probiotic strains and confirmed that the isolated compounds have effects of increasing muscle mass and inhibiting muscle atrophy, thereby completing the present invention.
  • the purpose of the present invention is to provide a pharmaceutical composition for preventing or treating muscle disease, which comprises a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Another object of the present invention is to provide a food composition for preventing or improving muscle disease, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • Another object of the present invention is to provide a pharmaceutical composition for promoting muscle differentiation, muscle regeneration or muscle strengthening, comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Another object of the present invention is to provide a food composition for promoting muscle differentiation, muscle regeneration or muscle strengthening, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • Another object of the present invention is to provide a pharmaceutical composition for increasing muscle mass or promoting muscle production, comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Another object of the present invention is to provide a food composition for increasing muscle mass or promoting muscle production, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • Another object of the present invention is to provide a pharmaceutical composition for improving muscle function, which comprises a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • Another object of the present invention is to provide a food composition for improving muscle function, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • Another object of the present invention is to provide a method for treating muscle disease, comprising the step of administering to a subject a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof.
  • the present invention provides a pharmaceutical composition for preventing or treating muscle disease, which comprises a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a food composition for preventing or improving muscle disease, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition for promoting muscle differentiation, muscle regeneration or muscle strengthening, comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a food composition for promoting muscle differentiation, muscle regeneration or muscle strengthening, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition for increasing muscle mass or promoting muscle production, comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a food composition for increasing muscle mass or promoting muscle production, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition for improving muscle function, comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a food composition for improving muscle function, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • the present invention provides a method for treating muscle disease, comprising the step of administering to a subject a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof.
  • the probiotic metabolite of the present invention was confirmed to protect muscle cells and promote muscle fiber differentiation. Furthermore, in an animal model of dexamethasone-induced muscle atrophy or sarcopenia, it was confirmed to increase muscle mass and muscle function, suppress the expression of factors associated with muscle breakdown, and increase the expression of factors associated with muscle synthesis and regeneration.
  • the probiotic metabolite contributes to the alleviation of muscle atrophy by modulating dexamethasone-induced sugar, amino acid, and fatty acid metabolism, and thus can be usefully utilized in related industries.
  • Figure 1 is a diagram illustrating the method for producing a sarcopenia animal model of the present invention, the drug administration schedule, and the experimental group.
  • Figure 2 is a diagram confirming the MGO-AGEs crushing ability of the probiotic metabolite of the present invention.
  • Figure 3 is a diagram confirming the cytotoxicity and cytoprotective effects of the probiotic metabolite of the present invention (A: cytotoxicity confirmed, B: muscle cell protection confirmed).
  • Figure 4 is a diagram confirming the increase in myotube formation of the probiotic metabolite of the present invention and the positive control group using Jenner-Giemsa staining.
  • Figure 5 is a diagram confirming the protective effect of probiotic metabolites on myotube formation in dexamethasone-induced myotube formation inhibition.
  • Figure 6 is a Western blot analysis of the expression of muscle synthesis factors in a cell model in which dexamethasone-induced muscle atrophy was induced.
  • Figure 7 is a diagram quantifying the weight loss following administration of probiotic metabolites in an animal model of dexamethasone-induced muscle atrophy or sarcopenia (A: confirmation of weight change, B: quantification of weight change, C: quantification of food intake).
  • Figure 8 is a diagram quantifying muscle weight according to administration of probiotic metabolites in an animal model of dexamethasone-induced muscle atrophy or sarcopenia.
  • Figure 9 is a diagram showing an increase in quadriceps femoris tissue density confirmed by H&E staining following administration of probiotic metabolites in an animal model of dexamethasone-induced muscular atrophy or sarcopenia (A: staining result, B: quantification of staining result).
  • Figure 10 is a diagram showing the accumulation of collagen in the quadriceps femoris muscle following administration of probiotic metabolites to an animal model of dexamethasone-induced muscle disease, as confirmed by Sirius red staining.
  • Figure 11 is a diagram showing an increase in gastrocnemius muscle tissue density confirmed by H&E staining following administration of probiotic metabolites in an animal model of dexamethasone-induced muscular atrophy or sarcopenia (A: staining result, B: quantification of staining result).
  • Figure 12 is a diagram showing the accumulation of collagen in the gastrocnemius muscle following administration of probiotic metabolites to an animal model of dexamethasone-induced muscle disease, as confirmed by Sirius red staining.
  • Figure 13 is a diagram showing the quantification of intestinal length according to the administration of probiotic metabolites in an animal model of dexamethasone-induced muscular atrophy or sarcopenia (A: intestinal length quantification, B: intestinal length/body weight quantification).
  • Figure 14 is a diagram quantifying the results of a treadmill test according to the administration of probiotic metabolites in an animal model of dexamethasone-induced muscle atrophy or sarcopenia (A and C: results at week 1, B and D: results at week 2).
  • Figure 15 shows the quantification of grip strength according to the administration of probiotic metabolites in an animal model of dexamethasone-induced muscle atrophy or sarcopenia (A: 1st week results, B: 2nd week results).
  • Figure 16 is a diagram showing the results of analyzing the calf thickness according to the administration of probiotic metabolites in an animal model of dexamethasone-induced muscle atrophy or sarcopenia using Micro-CT (A: micro-CT results, B: calf area quantification, C: fibula and tibial distance quantification).
  • A micro-CT results
  • B calf area quantification
  • C fibula and tibial distance quantification
  • Figure 17 is a Western blot analysis of the expression of muscle decomposition or muscle synthesis factors in the gastrocnemius muscle tissue following administration of probiotic metabolites in an animal model of dexamethasone-induced muscle atrophy or sarcopenia.
  • Figure 18 is a Western blot analysis of the expression of muscle breakdown or muscle synthesis factors in quadriceps femoris tissue following administration of probiotic metabolites in a dexamethasone-induced muscle atrophy or sarcopenia animal model.
  • Figure 19 is a Western blot analysis of the expression of muscle decomposition or muscle synthesis factors in the extensor digitorum longus muscle tissue following administration of probiotic metabolites in an animal model of dexamethasone-induced muscle atrophy or sarcopenia.
  • Figure 20 is a diagram showing the results of multivariate statistical analysis of the metabolic differences between groups in blood and gastrocnemius muscle tissue according to the administration of probiotic metabolites in a dexamethasone-induced muscle atrophy or sarcopenia animal model.
  • Figure 21 is a diagram analyzing the pattern of metabolite content and altered metabolic pathways between groups in blood and gastrocnemius muscle tissue according to the administration of probiotic metabolites in an animal model of dexamethasone-induced muscular dystrophy or sarcopenia (A. Comparison of metabolite content between groups, B. Altered major metabolic pathways).
  • Figure 22 is a diagram confirming the MGO-AGEs decomposition ability according to the form and amino acid composition of probiotic metabolites.
  • Figure 23 is a diagram showing the expression of muscle decomposition factors according to the form and amino acid composition of probiotic metabolites using Western blot (A: Western blot results, B: protein expression quantification).
  • the present invention provides a pharmaceutical composition for preventing or treating muscle disease, comprising a compound represented by the following chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the compound of the above chemical formula 1 of the present invention may be named gamma-glutamylmethionine (GM) and may be a compound with CAS number 17663-87-5.
  • GM gamma-glutamylmethionine
  • prevention means any act of suppressing symptoms or delaying progression of a specific disease by administering the composition of the present invention.
  • treatment means any act of improving or beneficially altering the symptoms of a specific disease by administering the composition of the present invention.
  • pharmaceutically acceptable salts means those salts which, within the scope of sound medical judgment, are suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic reaction, and the like, and which are proportional to a reasonable advantage/disadvantage ratio.
  • S. M. Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, which is incorporated herein by reference.
  • Pharmaceutically acceptable salts of the compounds of the present invention include those derived from suitable inorganic and organic acids and bases.
  • Examples of pharmaceutically acceptable, non-toxic acid addition salts are salts of amino groups formed with inorganic acids such as hydrochloric, hydrobromic, phosphoric, sulfuric, and perchloric acids, or with organic acids such as acetic, oxalic, maleic, tartaric, citric, succinic, or malonic acids, or formed using other methods used in the art, such as ion exchange.
  • inorganic acids such as hydrochloric, hydrobromic, phosphoric, sulfuric, and perchloric acids
  • organic acids such as acetic, oxalic, maleic, tartaric, citric, succinic, or malonic acids, or formed using other methods used in the art, such as ion exchange.
  • salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate,
  • Salts derived from suitable bases include alkali metal, alkaline earth metal, ammonium, and N + ( C1-4 alkyl) 4 salts.
  • Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like.
  • pharmaceutically acceptable salts include, when appropriate, non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates.
  • the pharmaceutical composition of the present invention may further include an adjuvant in addition to the active ingredient.
  • an adjuvant known in the art may be used without limitation. However, for example, Freund's complete adjuvant or incomplete adjuvant may be further included to enhance its effectiveness.
  • the pharmaceutical composition according to the present invention can be prepared in a form in which the active ingredient is mixed with a pharmaceutically acceptable carrier.
  • the pharmaceutically acceptable carrier includes carriers, excipients, and diluents commonly used in the pharmaceutical field.
  • Pharmaceutically acceptable carriers that can be used in the pharmaceutical composition of the present invention include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • the pharmaceutical composition of the present invention can be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions, each according to a conventional method.
  • Solid preparations for oral administration include tablets, pills, powders, granules, and capsules, and such solid preparations can be prepared by mixing the active ingredient with at least one excipient, such as starch, calcium carbonate, sucrose, lactose, and gelatin.
  • excipients such as starch, calcium carbonate, sucrose, lactose, and gelatin.
  • lubricants such as magnesium stearate and talc can also be used.
  • Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups, and in addition to commonly used diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives can be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories.
  • Non-aqueous solvents and suspensions can include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • Suppository bases include witepsol, Tween 61, cocoa butter, laurin, and glycerogelatin.
  • composition according to the present invention can be administered to a subject via various routes. All modes of administration are contemplated, including oral, intravenous, intramuscular, subcutaneous, and intraperitoneal injection.
  • the dosage of the pharmaceutical composition according to the present invention is selected in consideration of the age, weight, sex, physical condition, etc. of the subject. It is obvious that the concentration of the active ingredient included in the pharmaceutical composition can be selected in various ways depending on the subject, and it is preferably included in the pharmaceutical composition at a concentration of 0.01 to 5,000 ⁇ g/ml. If the concentration is less than 0.01 ⁇ g/ml, pharmaceutical activity may not be observed, and if it exceeds 5,000 ⁇ g/ml, it may be toxic to the human body.
  • the compound may increase muscle mass, and the increase in muscle mass may be an increase in muscle canal diameter or muscle thickness.
  • the compound may increase muscle function.
  • the compound may inhibit the expression of a muscle degradation factor
  • the muscle degradation factor may be a glucocorticoid receptor (GR), muscle atrophy F-box (MAFbx/Atrogin-1), or muscle-specific RING finger protein 1 (MuRF1).
  • the compound may increase the expression of a muscle growth factor
  • the muscle growth factor may be myoblast determination protein 1 (MyoD), myogenin, or myosin heavy chain (MyH).
  • the compound may increase intestine length.
  • the compound may regulate a metabolite related to muscle synthesis.
  • regulating the muscle synthesis-related metabolites may be by increasing the amount of a factor selected from the group consisting of glycine, tyrosine, sucrose, pyruvic acid, glyoxylic acid, 3-deoxytetronic acid, octadecanedioic acid, thymine, 1,2-propanediol, and ethylene glycol in plasma, and by increasing the amount of 12-S-HETE or LPE 18:3 in muscle.
  • a factor selected from the group consisting of glycine, tyrosine, sucrose, pyruvic acid, glyoxylic acid, 3-deoxytetronic acid, octadecanedioic acid, thymine, 1,2-propanediol, and ethylene glycol in plasma
  • regulating the muscle synthesis-related metabolites may be by reducing the amount of a factor selected from the group consisting of threonine, lactose, mannitol, sorbitol, fumaric acid, 2-hydroxybutric acid, 15,16-DiHODE, dodecanedioic acid, uric acid, and indol-3-propanoic acid in plasma, and may be by reducing the amount of gluconic acid in muscle.
  • a factor selected from the group consisting of threonine, lactose, mannitol, sorbitol, fumaric acid, 2-hydroxybutric acid, 15,16-DiHODE, dodecanedioic acid, uric acid, and indol-3-propanoic acid in plasma
  • the muscle disease may be a disease selected from the group consisting of muscular atrophy, myopathy, muscular degeneration, myasthenia, muscular injury, dystrophinopathy, myopathy, muscular dystrophy, cachexia, and sarcopenia, and is preferably muscular atrophy or sarcopenia, but is not limited thereto.
  • the present invention provides a food composition for preventing or improving muscle disease, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • improvement means any action that at least reduces a parameter associated with the condition being treated, for example, the severity of a symptom.
  • the food composition of the present invention may contain, in addition to containing the effective ingredient of the present invention, various flavoring agents or natural carbohydrates as additional ingredients, like conventional food compositions.
  • natural carbohydrates examples include monosaccharides such as glucose, fructose, etc.; disaccharides such as maltose, sucrose, etc.; and polysaccharides such as dextrin, cyclodextrin, etc., and common sugars, and sugar alcohols such as xylitol, sorbitol, erythritol, etc.
  • natural flavoring agent thaumatin
  • stevia extract e.g., rebaudioside A, glycyrrhizin, etc.
  • synthetic flavoring agent sacharin, aspartame, etc.
  • the food composition of the present invention can be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods.
  • Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gum, candy, ice cream, alcoholic beverages, vitamin complexes, and health supplements.
  • the food composition may contain, in addition to the extract as an active ingredient, various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.
  • the food composition of the present invention may contain fruit pulp for producing natural fruit juice, fruit juice drinks, and vegetable drinks.
  • the functional food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. for the purpose of preventing or treating muscle diseases.
  • the term "health functional food composition" in the present invention refers to a food manufactured and processed using raw materials or ingredients having functionality useful to the human body according to Act No. 6727 on Health Functional Foods, and means to be consumed for the purpose of obtaining a useful effect for health purposes such as regulating nutrients for the structure and function of the human body or physiological effects.
  • the health functional food of the present invention may include conventional food additives, and whether it is suitable as a food additive is determined by the specifications and standards for the relevant item according to the general provisions and general test methods of the Food Additives Codex approved by the Ministry of Food and Drug Safety, unless otherwise specified.
  • Items listed in the "Food Additives Codex” include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Examples thereof include natural additives such as persimmon pigment, licorice extract, crystalline cellulose, high-molecular weight pigment, and guar gum; mixed preparations such as sodium L-glutamate preparations, noodle additive alkaline agents, preservative preparations, and tar color preparations.
  • a health functional food in tablet form can be prepared by mixing the active ingredient of the present invention with excipients, binders, disintegrants, and other additives, granulating the mixture using a conventional method, and then adding a lubricant, etc.
  • the health functional food in tablet form can contain a maturing agent, etc., if necessary.
  • hard capsules can be prepared by filling a mixture of the active ingredient of the present invention with additives such as excipients into a conventional hard capsule
  • soft capsules can be prepared by filling a mixture of the active ingredient of the present invention with additives such as excipients into a capsule base such as gelatin.
  • the above soft capsules may contain plasticizers such as glycerin or sorbitol, coloring agents, preservatives, etc., as needed.
  • the ring-shaped health functional food can be prepared by molding a mixture of the active ingredient of the present invention with an excipient, a binder, a disintegrant, etc., using a conventionally known method, and, if necessary, can be coated with white sugar or another coating agent, or the surface can be coated with a material such as starch or talc.
  • the granular health functional food can be manufactured into a granular form by mixing a mixture of the active ingredient of the present invention with an excipient, a binder, a disintegrant, etc., using a conventionally known method, and, if necessary, can contain a flavoring agent, a flavoring agent, etc.
  • the present invention provides a pharmaceutical composition for promoting muscle differentiation, muscle regeneration or muscle strengthening, comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a food composition for promoting muscle differentiation, muscle regeneration or muscle strengthening, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition for increasing muscle mass or promoting muscle production, comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a food composition for increasing muscle mass or promoting muscle production, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition for improving muscle function, comprising a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention provides a food composition for improving muscle function, which comprises a compound represented by the above chemical formula 1 or a food-wise acceptable salt thereof as an active ingredient.
  • the present invention provides a method for treating muscle disease, comprising the step of administering to a subject a compound represented by the above chemical formula 1 or a pharmaceutically acceptable salt thereof.
  • the treatment method of the present invention comprises administering to a subject a therapeutically effective amount of the compound of the above chemical formula 1 or a pharmaceutically acceptable salt thereof. It is preferred that the specific therapeutically effective amount for a specific subject be applied differently depending on various factors including the type and degree of the response to be achieved, the specific composition including whether other agents are used in some cases, the age, body weight, general health condition, sex and diet of the subject, the time of administration, the route of administration and the secretion rate of the composition, the treatment period, drugs used together or simultaneously with the specific composition, and similar factors well known in the medical field.
  • the daily dosage is 0.0001 to 100 mg/kg, preferably 0.01 to 100 mg/kg, based on the amount of the pharmaceutical composition of the present invention, and can be administered 1 to 6 times a day.
  • the dosage or administration of each active ingredient should be such that the content of each active ingredient is not excessively high and side effects are not caused. Therefore, it is preferred that the effective amount of a composition suitable for the purpose of the present invention be determined in consideration of the above-mentioned matters.
  • the above object is applicable to any mammal, which includes not only humans and primates, but also livestock such as cows, pigs, sheep, horses, dogs and cats.
  • the compound of chemical formula 1 of the present invention can be administered to mammals such as rats, mice, livestock, and humans via various routes. All modes of administration are conceivable, and for example, it can be administered orally, rectally, or by intravenous, intramuscular, subcutaneous, intrauterine, or intracerebroventricular injection.
  • the compound of chemical formula 1 which is a metabolite derived from the probiotic strain of the present invention, was identified through strain metabolite profiling. Thereafter, in order to utilize the compound of chemical formula 1 in an experiment to improve muscle disease, the compound of chemical formula 1 ( ⁇ -Glutamyl-methionine, ⁇ -GM), which is a probiotic metabolite (ProM), was purchased from Peptron through a request for synthesis.
  • ⁇ -Glutamyl-methionine ⁇ -GM
  • ProM probiotic metabolite
  • Example 1 Preparation for confirmation of improvement in dexamethasone-induced muscle disease by probiotic metabolites.
  • MGO-AGEs methylglyoxal-derived advanced glycation endproducts
  • TBSA 2,4,6-trinitrobenzene sulfonic acid
  • MGO-AGEs prepared by reacting methylglyoxal (MGO) with bovine serum albumin (BSA) at 37°C for 7 days, were mixed with the compound of formula 1 (10, 100, or 200 ⁇ M) at a concentration of 1 mg/mL, homogenized, and reacted for 24 hours. Then, 0.1% TNBSA and 4% NaHCO 3 were added, and reacted for 2 hours. The reaction was then terminated by adding 10% SDS and 1 N HCl, and the AGE degradation products were quantified by measuring the absorbance at 340 nm using a microplate reader (Molecular Devices, San Jose, CA, USA).
  • C2C12 cells (ATCC, USA), a mouse myoblast cell line, were cultured in Dulbecco's Modified Eagle Medium (DMEM, Welgene, Korea) supplemented with 10% fetal bovine serum (Welgene) and 1% penicillin/streptomycin at 5% CO2 and 37°C.
  • DMEM Dulbecco's Modified Eagle Medium
  • Welgene fetal bovine serum
  • penicillin/streptomycin 5% CO2 and 37°C.
  • To induce myotube differentiation of myoblasts cells were seeded at a cell density of 2.5 ⁇ 105 in 6-well plates and cultured for 2 days. When the cells reached 90% confluence, the medium was replaced with differentiation DMEM containing 2% horse serum, and the cells were treated with the compound of formula 1 or 1 and 5 ⁇ M curcumin (CU), as a positive control, during the differentiation process for 6 days.
  • C2C12 myotubes were treated with 50 ⁇ M DEX for
  • C2C12 cells were seeded in 96-well plates at a concentration of 1 ⁇ 10 4 cells and cultured under 5% CO 2 and 37°C conditions. When the cells were more than 80% confluent, the cells were treated with the compound of formula 1 at a concentration of 0.01, 0.1, 1, 5, 10, or 20 ⁇ M and cultured in serum-free medium for an additional 24 hours. After that, 100 ⁇ l of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution (0.5 mg/ml, Sigma-Aldrich) was added and reacted for 2 hours. The resulting formazan product was dissolved in DMSO and the absorbance was measured at 540 nm using a microplate reader (BioTek, Winooski, VT, USA).
  • MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
  • the length, width, and area of the root canals were measured by staining differentiated C2C12 cells with Jenner-Giemsa. After Jenner-Giemsa staining, the root canals were washed twice with cold PBS and fixed with 4% paraformaldehyde. The root canal images were then observed using an optical microscope (Olympus, Tokyo, Japan).
  • mice Eight-week-old C57BL/6N mice were purchased from Orient Bio (Republic of Korea) and acclimated for 1 week before use in the experiment. Mice were housed at 23 ⁇ 1°C with a 12-h light/dark cycle and were provided unlimited access to water and a standard laboratory diet. All animal experiments were performed in accordance with the ethical guidelines established by the Laboratory Animal Research Center, College of Pharmacy, Gachon University, Seongnam, Republic of Korea, and the experimental protocol was approved by the Institutional Animal Care and Use Committee of Gachon University (GU1-2023-IA0032-00).
  • mice were divided into the following groups: a vehicle group (CON group) administered with a solvent; a DEX group (NC group) administered with dexamethasone at a concentration of 20 mg/kg; a positive control group (OXY, PC group) treated with 50 mg/kg of oxymetholone and 20 mg/kg of dexamethasone; a group treated with 5 mg/kg of the compound of formula 1 and 20 mg/kg of dexamethasone (ProM 5); and a group treated with 20 mg/kg of the compound of formula 1 and 20 mg/kg of dexamethasone (ProM 20).
  • CON group CON group
  • NC group DEX group
  • OXY, PC group positive control group treated with 50 mg/kg of oxymetholone and 20 mg/kg of dexamethasone
  • ProM 5 a group treated with 5 mg/kg of the compound of formula 1 and 20 mg/kg of dexamethasone
  • ProM 20 a group treated with 20 mg/kg of the compound of formula 1 and 20
  • the compound of formula 1 and oxymetholone were administered orally daily for 14 days, and dexamethasone was injected subcutaneously daily at a concentration of 20 mg/kg to induce muscle atrophy.
  • the specific drug administration schedule and classification of the experimental groups are shown in Fig. 1.
  • mice were humanely sacrificed, and the gastrocnemius (GCM), quadriceps femoris (QD), extensor digitorum longus (EDL), plantaris (PLA), and soleus (SOL) muscles were isolated and weighed. Muscle tissues were then frozen in liquid nitrogen and stored and fixed at -80°C.
  • GCM gastrocnemius
  • QD quadriceps femoris
  • EDL extensor digitorum longus
  • PDA plantaris
  • SOL soleus Muscle tissues were then frozen in liquid nitrogen and stored and fixed at -80°C.
  • treadmill and grip strength tests were performed. Specifically, the treadmill test was performed on days 7 and 14 after sample administration using an 8-lane treadmill with a motivation grid (JD-A-22, Republic of Korea). The treadmill test involved placing mice on a flat treadmill at a speed of 10 m/min for 3 min, increasing the speed to 2 m/min every 2 min. The running time (seconds) and speed (meters per minute) until exhaustion (maximal exercise) were recorded and compared between each group.
  • Grip strength of mice was measured using a grip dynamometer (BIO-G53, BIOSEB, USA). The grip strength test involved allowing mice to grasp a wire mesh with their forelimbs, and the grip strength value obtained when force was applied momentarily to the tail was recorded. Grip strength was measured twice, on days 7 and 14 after inducing muscle atrophy and after sample administration. Each group of mice was tested three times. The recorded grip strength values were finally quantified by dividing the value by body weight (g/g).
  • the thighs obtained from sacrificed mice were fixed in 10% neutral buffered formalin and photographed using a Micro-CT scanner (SkyScan1276, Bruker, Belgium) to measure the width and radius of the thigh.
  • the analysis conditions are as shown in Table 1 below.
  • the width and radius of the thigh were measured at the midpoint, with the total length being from the thigh head to the beginning of the fibula bone based on the tibia bone.
  • the width measurement refers to the measurement of the muscle width in the cut plane
  • the radius measurement refers to the length of the line segment of the midline of the fibula bone from the position corresponding to the shank.
  • MicroCT scan conditions Resolution 2 K Source Voltage 40 kV Source Current 200 ⁇ A Image Pixels 18 ⁇ m Exposure Times 650 ms Rotation Step 2 ° Rotation in Degree 180 ° Average Frames 2 Filter 1 mm Al Scan Duration 3 m : 28 s
  • Quadriceps femoris (QD) and gastrocnemius (GCM) muscles obtained from sacrificed mice were fixed in 10% neutral buffered formalin, embedded in paraffin, and sectioned at 2.5 ⁇ m.
  • the cross-sectional area of each muscle tissue was measured using hematoxylin and eosin staining (H&E staining; Sigma-Aldrich, USA).
  • the degree of collagen fibrosis was analyzed using Picro-Sirius Red (Sigma-Aldrich, USA) staining. Both staining processes included deparaffinization, rehydration, dehydration, dexylene, and mounting using DPX mounting agent (Sigma-Aldrich, USA).
  • QD tissue (30 mg) or C2C12 myotubes were homogenized in RIPA buffer containing a protease/phosphatase inhibitor cocktail. The homogenate was centrifuged at 12,000 rpm for 1 h at 4°C, and protein (30 ⁇ g) was separated by SDS-PAGE to measure expression. The separated proteins were then transferred to nitrocellulose membranes and incubated with primary antibodies against muscle atrophy F-box (MAFbx/Atrogin-1), Muscle-specific RING finger protein 1 (MuRF1), Myoblast Determination protein 1 (MyoD), Myogenin, Myosin heavy chain (MyH), and GAPDH, which are proteins associated with muscle atrophy, at 4°C for 18 h.
  • MAFbx/Atrogin-1 Muscle-specific RING finger protein 1
  • MyoD Myoblast Determination protein 1
  • MyH Myosin heavy chain
  • GAPDH GAPDH
  • the membranes were then washed with TBST, and HRP-conjugated secondary antibodies were added and incubated at room temperature for 1 h. After the reaction was completed, the membrane was visualized and analyzed using a ChemiDoc XRS+ imaging system (Bio-Rad, USA).
  • Metabolomic analysis was performed on serum and GCM tissue obtained from sacrificed mice.
  • 80 ⁇ L of serum was homogenized with 1 mL of 100% methanol and incubated at -20°C for 2 hours to precipitate proteins.
  • the homogenate was centrifuged at 10,000 g for 10 minutes at 4°C, and the supernatant was dried using a speed vacuum.
  • the dried extract was re-dissolved in 0.3 mL of 50% methanol and used for instrumental analysis.
  • the homogenate was centrifuged at 10,000 g for 5 minutes at 4°C, and the supernatant was transferred to a 2-mL tube, where 0.5 mL of water was added and mixed. After centrifugation of the mixture using the same method, 1 mL of the polar layer (upper part) and 0.2 mL of the non-polar layer (lower part) were obtained from the separated mixture and dried using a speed vacuum. The dried extracts of the polar and non-polar layers of the muscle were redissolved using 0.2 mL of 50% and 100% methanol, respectively, and then filtered through a 0.22 ⁇ m syringe before being used for instrumental analysis.
  • LC-MS analysis was performed on the nonpolar layer extracts of serum and muscle. 0.1 mL of the solution was placed in a container and analyzed using UHPLC-Orbitrap-MS/MS. A Phenomenes KINETEX C18 column was used as the stationary phase, and water (A) with 0.1% formic acid and acetonitrile (B) with 0.1% formic acid were used as the mobile phase to separate the substances. In addition, GC-MS analysis was performed on the polar layer extracts of serum and muscle. After redrying the re-dissolved solution, derivatization (oximation, silylation) was performed. An Rtx-5MS column was used as the stationary phase, and the substances were separated through helium and temperature control.
  • Methylglyoxal-derived advanced glycation end products are compounds produced through metabolic reactions with various biomolecules, and have recently been reported to have negative effects on skeletal muscle, reducing exercise capacity and promoting muscle atrophy. Accordingly, the crushing ability of MGO-AGE of chemical formula 1 of the present invention was confirmed. As a result, as shown in Fig. 2, it was confirmed that when the compound of chemical formula 1 was treated, the degree of MGO-AGE crushing increased in a concentration-dependent manner, and thus the ratio of free amines increased.
  • Proteins of the MyoD and Myogenin pathways are known as proteins for muscle differentiation, and MyH is known as a marker of muscle differentiation. Therefore, the expression of muscle differentiation proteins according to treatment with the compound of chemical formula 1 of the present invention was quantified. As a result, as shown in Fig. 6, the expression of MyoD, Myogenin, and MyH related to muscle synthesis and differentiation was confirmed. Compared to the group treated with DEX, when the compound of chemical formula 1 was treated, the expression of MyoD and Myogenin was confirmed to increase in a concentration-dependent manner. In addition, it was confirmed that MyH tended to increase with treatment with chemical formula 1.
  • the compound of chemical formula 1 increased the muscle mass of the gastrocnemius (GCM), quadriceps femoris (QD), extensor digitorum longus (EDL), and plantaris (PLA) in DEX-induced muscular dystrophy, while no significant difference was observed in the soleus (SOL) (Fig. 8), confirming that the compound of chemical formula 1 of the present invention has various effects on muscle protection depending on the type of muscle. Therefore, it was confirmed that the probiotic metabolite of the present invention increases the muscle mass of muscles with high exercise volume even when a muscular dystrophy-inducing substance such as DEX is administered.
  • GCM gastrocnemius
  • QD quadriceps femoris
  • EDL extensor digitorum longus
  • PPA plantaris
  • the quadriceps femoris (QD) and gastrocnemius (GCM) tissues were stained with H&E staining, and as a result, in the NC group treated with DEX, the density of muscle fibers in the tissues decreased compared to the CON group, but in the group treated with the compound of chemical formula 1 of the present invention, the density of the decreased muscle fibers increased in a concentration-dependent manner (Figs. 9 to 11).
  • intestinal tissues were obtained from each group of sacrificed mice, and intestinal length was measured to confirm whether intestinal muscle damage was induced by DEX.
  • the intestinal length was reduced compared to the CON group, but in the group treated with the compound of chemical formula 1 of the present invention, the reduced intestinal length was confirmed to have significantly increased (Fig. 13).
  • mice administered DEX muscle function was decreased, and it was confirmed that the running time, speed, and grip strength decreased in the second week of the experiment.
  • mice administered the compound of chemical formula 1 of the present invention it was confirmed that the running time, speed, and grip strength significantly increased, confirming that the probiotic metabolite of the present invention can increase muscle function even in a state of muscle wasting.
  • GCM gastrocnemius
  • the expression of muscle degradation proteins, Atrogin-1 and MuRF-1 was significantly increased in the NC group administered DEX compared to the CON group.
  • the compound of chemical formula 1 of the present invention was administered, the increased expression of Atrogin-1 and MuRF-1 was confirmed to decrease.
  • the expression of muscle synthesis factors, MyoD and Myogenin was decreased by the administration of DEX.
  • the compound of chemical formula 1 was treated, the decreased expression of MyoD and Myogenin was confirmed to increase significantly (Fig. 17).
  • the expression of muscle degradation proteins Atrogin-1 and MuRF-1 was significantly increased in the NC group administered DEX compared to the CON group, but it was confirmed that the increased expression of Atrogin-1 and MuRF-1 was significantly reduced when the compound of chemical formula 1 of the present invention was administered.
  • the expression of muscle synthesis factors MyoD and Myogenin was decreased by the administration of DEX, but a tendency to increase was confirmed when the compound of chemical formula 1 was treated (Fig. 18).
  • the expression of muscle degradation proteins, Atrogin-1 and MuRF-1 was significantly increased in the NC group administered DEX compared to the CON group, but it was confirmed that the increased expression of Atrogin-1 and MuRF-1 was significantly reduced when the compound of chemical formula 1 of the present invention was administered.
  • the expression of muscle synthesis factors, MyoD and Myogenin was decreased by the administration of DEX, but it was confirmed that the decreased expression of MyoD and Myogenin was increased when the compound of chemical formula 1 was treated (Fig. 19).
  • Methylglyoxal-derived advanced glycation end products are compounds produced through metabolic reactions with various biomolecules, and have recently been reported to have negative effects on skeletal muscle, reducing exercise capacity and promoting muscle atrophy. Accordingly, in the present invention, the MGO-AGEs decomposition ability was confirmed according to the structure and amino acid composition of the probiotic metabolite. As a result, as described in Fig. 22, among the GM (Glutamyl-methionine) of the present invention, it was confirmed that ⁇ -GM had a significantly increased free amine ratio compared to alpha or beta GM.
  • DEX treatment was found to increase the activity of the glucocorticoid receptor (GR) and to increase the expression of Atrogin-1 and MuRF1, a type of E3 ligase that is a biomarker of muscle atrophy.
  • GR glucocorticoid receptor
  • Atrogin-1 and MuRF1 a type of E3 ligase that is a biomarker of muscle atrophy.
  • curcumin it was confirmed to suppress GR activity and regulate the expression of Atrogin-1 and MuRF.
  • the probiotic metabolite of the present invention was confirmed to protect muscle cells and promote muscle fiber differentiation. Furthermore, in an animal model of dexamethasone-induced muscle atrophy or sarcopenia, it was confirmed to increase muscle mass and muscle function, suppress the expression of factors related to muscle breakdown, and increase the expression of factors related to muscle synthesis and regeneration. It was confirmed that the probiotic metabolite contributed to the alleviation of muscle atrophy by regulating the metabolism of sugars, amino acids, and fatty acids altered by dexamethasone.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Neurology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Mycology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Il a été confirmé que les métabolites probiotiques selon la présente invention protègent les cellules musculaires et favorisent la différenciation des fibres musculaires. De plus, il a été confirmé dans un modèle animal d'atrophie musculaire ou de sarcopénie induite par la dexaméthasone que les métabolites probiotiques ont augmenté la masse musculaire et la fonction musculaire, ont inhibé l'expression de facteurs associés à la dégradation musculaire, et ont augmenté l'expression de facteurs associés à la synthèse et à la régénération musculaires. Il a été confirmé que les métabolites probiotiques contribuent à atténuer l'atrophie musculaire par régulation du métabolisme du sucre, des acides aminés et des acides gras, modifié par la dexaméthasone.
PCT/KR2025/007032 2024-05-24 2025-05-23 Composition pour la prévention ou le traitement de maladies musculaires comprenant un métabolite probiotique en tant que principe actif Pending WO2025244466A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2024-0067660 2024-05-24
KR20240067660 2024-05-24

Publications (1)

Publication Number Publication Date
WO2025244466A1 true WO2025244466A1 (fr) 2025-11-27

Family

ID=97795550

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2025/007032 Pending WO2025244466A1 (fr) 2024-05-24 2025-05-23 Composition pour la prévention ou le traitement de maladies musculaires comprenant un métabolite probiotique en tant que principe actif

Country Status (2)

Country Link
KR (1) KR20250169118A (fr)
WO (1) WO2025244466A1 (fr)

Also Published As

Publication number Publication date
KR20250169118A (ko) 2025-12-02

Similar Documents

Publication Publication Date Title
WO2017039365A1 (fr) Méthode d'inhibition de l'absorption et/ou de promotion de l'excrétion de lipides à l'aide de d-psicose
WO2018194309A1 (fr) Composition pharmaceutique contenant de l'indirubine en tant que substance active
WO2012008788A2 (fr) Composition contenant de la sérine en tant que principe actif pour la prévention et le traitement de stéatoses hépatiques, et utilisation de celle-ci
WO2020040432A1 (fr) Composition pharmaceutique pour prévenir ou traiter des maladies musculaires, contenant un extrait de baie de ginseng en tant que principe actif
WO2015108394A1 (fr) Composition cosmétique contenant un composé dérivé de l'hydroxypyranone pour stimuler la différenciation des adipocytes
WO2021033994A1 (fr) Composition comprenant un extrait de salvia miltiorrhiza ou de paeonia lactiflora utilisé comme principe actif pour la prévention ou le traitement d'un trouble du métabolisme des lipides
WO2020218720A1 (fr) Composition pour la prévention ou le traitement de troubles musculaires ou l'amélioration de la fonction musculaire, contenant un extrait de leonurus japonicus ou de la léonurine
WO2015034247A1 (fr) Composition contenant un composé de monoacétyldiacylglycérol comme principe actif pour prévenir ou traiter la dermatite atopique
WO2025244466A1 (fr) Composition pour la prévention ou le traitement de maladies musculaires comprenant un métabolite probiotique en tant que principe actif
WO2019083132A1 (fr) Composition à effet anti-âge comprenant de la cytochalasine d ou la protéine sag, et méthode de criblage de substances à effet anti-âge
WO2021261660A1 (fr) Procédé de préparation d'extrait de farine d'huile de sésame et composition alimentaire le comprenant en tant que principe actif pour la prévention ou le soulagement de la colite
WO2014126285A1 (fr) Composition pour la prévention ou le traitement de la fibrose rénale, comprenant du diméthylfumarate en tant que principe actif
WO2019078381A1 (fr) Composition pharmaceutique, composition alimentaire et additif alimentaire pour prévenir, soulager ou traiter la perte, la faiblesse et l'atrophie musculaires, contenant, à titre de principe actif, une bactérie enterococcus faecalis, le liquide de culture ou des cellules mortes de celle-ci
WO2025244469A1 (fr) Composition pour la prévention ou le traitement de maladies musculaires comprenant un métabolite probiotique en tant que principe actif
WO2017082479A1 (fr) Composition pharmaceutique destinée à la prévention ou au traitement de l'obésité comprenant un extrait embryonnaire de fève germée
WO2022270760A1 (fr) Méthode de traitement de la stéatohépatite non alcoolique par la co-administration d'un dérivé de la curcumine et d'un inhibiteur du récepteur de tgf-β
WO2022231309A1 (fr) Composition alimentaire et composition pharmaceutique pour prévenir ou soulager la sarcopénie, contenant du collagène de faible poids moléculaire en tant que principe actif
WO2013085351A1 (fr) Composition pharmaceutique comprenant une diaminodiphénylsulfone ou ses sels pharmaceutiquement acceptables et permettant de prévenir ou de traiter des maladies associées à l'atrophie musculaire
WO2019031655A1 (fr) Composition comprenant du thymol comme principe actif pour prévenir ou traiter les rides de la peau ou la dermatite atopique
WO2018208107A1 (fr) Composition pour atténuer, prévenir ou traiter un trouble du sommeil ou composition pour supprimer la résistance à un agoniste du site de liaison aux benzodiazépines du récepteur gaba-a, ou pour atténuer un effet secondaire d'un agoniste du site de liaison aux benzodiazépines du récepteur gaba-a, chaque composition comprenant du phloroglucinol en tant que principe actif
WO2023229104A1 (fr) Composition de complexe probiotique ayant des fonctions immunomodulatrices et d'homéostasie immunitaire
WO2018038313A1 (fr) Nouveau composé d'acide diynoique, et composition pharmaceutique pour prévenir ou traiter des maladies osseuses le comprenant
WO2021002642A1 (fr) Composition pour prévenir ou traiter la polyarthrite rhumatoïde, comprenant du venin de serpent
WO2022060024A1 (fr) Composition contenant un extrait d'agrume en tant que principe actif pour améliorer la santé osseuse
WO2010055974A1 (fr) Composition pour la prévention et le traitement du diabète et des troubles liés à un syndrome métabolique contenant de l’obovatol et des dérivés correspondants comme ingrédients actifs