[go: up one dir, main page]

WO2024123073A1 - Composition contenant l'idra-21 utilisé en tant que principe actif pour prévenir ou traiter une maladie musculaire - Google Patents

Composition contenant l'idra-21 utilisé en tant que principe actif pour prévenir ou traiter une maladie musculaire Download PDF

Info

Publication number
WO2024123073A1
WO2024123073A1 PCT/KR2023/019987 KR2023019987W WO2024123073A1 WO 2024123073 A1 WO2024123073 A1 WO 2024123073A1 KR 2023019987 W KR2023019987 W KR 2023019987W WO 2024123073 A1 WO2024123073 A1 WO 2024123073A1
Authority
WO
WIPO (PCT)
Prior art keywords
muscle
preventing
atrophy
active ingredient
idra
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.)
Ceased
Application number
PCT/KR2023/019987
Other languages
English (en)
Korean (ko)
Inventor
정승효
이경진
김수정
최하림
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.)
Ksb Tugen Inc
Original Assignee
Ksb Tugen Inc
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 Ksb Tugen Inc filed Critical Ksb Tugen Inc
Publication of WO2024123073A1 publication Critical patent/WO2024123073A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
    • 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
    • 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
    • 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
    • A23V2250/00—Food ingredients
    • A23V2250/30—Other Organic compounds

Definitions

  • Muscles are classified into skeletal muscle, smooth muscle, and cardiac muscle in terms of structure and function. Among these, skeletal muscle is located directly under the skin of the hands, feet, chest, and stomach, and strengthens bones and tendons throughout the body. There are about 600 voluntary muscles attached to bones. Skeletal muscle accounts for 40 to 50% of body weight and performs functions such as maintaining body temperature and generating energy. Additionally, skeletal muscles move or support bones through contraction, and at this time, muscle contraction occurs and is controlled by nerve signals.
  • Skeletal muscle atrophy is a condition in which the amount of skeletal muscle is reduced or completely lost, resulting in a decrease in the ability to support the human body or exercise. Skeletal muscle atrophy occurs due to denervation due to trauma, and causes conditions such as resting recumbency or joint immobilization. It is classified into skeletal muscle atrophy (pulmonary atrophy) that occurs due to immobility.
  • Skeletal muscle atrophy can occur for a variety of reasons. Even if it is not a special disease, it can occur due to aging or space flight, or it can occur in patients suffering from diseases such as cancerous cachexia, muscle loss, or muscular dystrophy.
  • Muscle atrophy can be viewed as a single disease, or as a symptom accompanying other diseases.
  • IDRA-21 is an AMPA receptor modulator and is well known as an ampakine substance, and the AMPA ( ⁇ -amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptor is a receptor-channel for glutamate. It is known to be involved in memory processes.
  • IRDA-21 is known to have activity in recovering cognitive impairment (The Journal of Pharmacology and Experimental Therapeutics. 272 (1): 300-9).
  • the present inventors completed the present invention by confirming that IDRA-21 is effective in muscular dystrophy.
  • the object is to provide a composition for preventing, alleviating, or treating muscle atrophy.
  • the object is to provide a composition for preventing, alleviating, or treating diseases related to muscular dystrophy.
  • a treatment for senile sarcopenia, atony, muscular atrophy, and muscle degeneration comprising the compound represented by Formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. It provides a pharmaceutical composition for the prevention or treatment of muscle diseases selected from the group consisting of muscle stiffness, amyotrophic axonal sclerosis, myasthenia gravis, myositis, muscle calcification, muscle ossification, muscle weakness-related diseases, and cachexia.
  • a treatment for senile sarcopenia, atony, muscular atrophy, etc. comprising the compound represented by Formula 1, a stereoisomer thereof, or a food-acceptable salt thereof as an active ingredient.
  • the compound represented by Formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof is administered to an individual in need in a pharmaceutically effective amount to treat senile sarcopenia, hypotonia (Prevents muscle diseases selected from the group consisting of atony, muscular atrophy, muscle degeneration, muscle rigidity, amyotrophic axonal sclerosis, myasthenia gravis, myositis, muscle calcification, muscle ossification, muscle weakness-related diseases, and cachexia, Provides a method of alleviation or treatment.
  • diseases related to senile sarcopenia atony, muscular atrophy, muscle degeneration, muscle rigidity, amyotrophic axonal sclerosis, myasthenia gravis, myositis, muscle calcification, muscle ossification, and muscle weakness. It provides use of the compound represented by Formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the prevention, alleviation or treatment of muscle disease selected from the group consisting of cachexia.
  • IRDA-21 When administered to a skeletal muscle atrophy model, IRDA-21 not only increases muscle mass and the size of myotube cells, but also has the effect of improving muscle performance, which can be used to prevent, improve, alleviate, or treat muscular atrophy or related diseases. useful.
  • Figures 1A to 1D are photographs or graphs showing the effects of dexamethasone treatment on the anterior tibial photograph, front leg strength, anterior tibial muscle lean muscle mass, and gastrocnemius (GS) lean muscle mass, respectively.
  • Figures 2a and 2b are graphs showing the effects of IDRA-21 treatment on the tibialis anterior (TA) and gastrocnemius (GS) photos and lean muscle mass of the gastrocnemius (GS), respectively.
  • Figure 3 is a graph showing changes in muscle strength according to IDRA-21 in the dexamethasone treatment model.
  • Figures 4a and 4b are graphs showing the effect of exercise load (Treadmill test), which is a muscle function, according to treatment with IDRA-21.
  • Figure 5 is a graph showing the effect of muscle performance test (Performance test) according to treatment with IDRA-21.
  • Figures 6A to 6C are photographs or graphs showing the effect of IDRA-21 on skeletal muscle mitochondrial function and skeletal muscle cell atrophy.
  • the compounds have one asymmetric carbon atom and exist as enantiomers.
  • the active enantiomer is known as (+)-IDRA-21, but is not limited thereto and includes both (+) and (-) enantiomers as well as racemates. It also includes all forms of stereoisomers that may exist.
  • IRDA-21 compound When referring to the IRDA-21 compound, it may refer to including all of its stereoisomers and pharmaceutically or foodologically acceptable salts thereof.
  • muscle atrophy refers to a condition in which the size of the muscle is reduced due to a decrease in the number of muscle fibers due to aging, long-term disuse, or various pathological degeneration. Muscular atrophy refers to all pathological conditions that occur due to various causes. . Muscular dystrophy does not only include cases diagnosed by a doctor where the degree of muscle atrophy requires treatment.
  • Muscular atrophy is a symptom and a specific disease in itself. Muscular atrophy can be caused by various causes, examples include senile sarcopenia, atony, muscle degeneration, muscle rigidity, and muscular dystrophy. It can be caused by, but is not limited to, muscle diseases selected from the group consisting of axonal sclerosis, myasthenia gravis, myositis, muscle calcification, muscle ossification, muscle weakness-related diseases and cachexia, aging, obesity, steroid administration, and spaceflight. does not
  • Muscular dystrophy also called muscular dystrophy or muscle disease
  • Muscular dystrophy is a progressive disease characterized by loss of walking ability due to gradual decrease in muscle strength, weakened respiratory muscle, and weakened heart function. It is a chronic disease that eventually leads to physical disability and dependence on others for all aspects of daily life. Muscle diseases can be divided into congenital muscle diseases and acquired muscle diseases. The cause is usually a chromosomal abnormality, and in some cases, it is caused by mutation regardless of family history. In addition, there are various causes, including inflammation, metabolic abnormalities, endocrine dysfunction, and toxicity.
  • muscular dystrophy includes Duchenne-type muscular dystrophy and Becker-type muscular dystrophy.
  • Administration of steroids includes long-term administration and includes long-term, regular or irregular administration for the treatment of diseases such as cancer, for example, for more than 1 week, more than 1 month, or more than 1 year. Among these, it may be administered more than once a day on more than 30%, 50%, or 70% of the days in the relevant period, either regularly or irregularly.
  • the muscle disease in the present invention involves muscle atrophy, and specifically, skeletal muscle atrophy.
  • the IRDA-21 compound When administered to an individual with a muscle disease accompanied by muscle atrophy, the IRDA-21 compound may, for example, increase muscle size in atrophied muscles, and in this case, muscle size increases by increasing the number of muscle fibers. It could be, or in another sense, it could be increasing muscle mass.
  • the IRDA-21 compound may increase the size, for example, diameter and/or area, of myotube cells in muscles experiencing muscle atrophy.
  • IRDA-21 is used to treat senile sarcopenia, atony, muscular atrophy, muscle degeneration, muscle rigidity, amyotrophic axonal sclerosis, myasthenia gravis, myositis, muscle calcification, muscle ossification, and muscle weakness. It is possible to prevent, alleviate, improve or treat muscle diseases selected from the group consisting of related diseases and cachexia. These muscle diseases may be independent of muscle atrophy, but usually, or preferably, cause muscle atrophy. It entails.
  • IRDA-21 compound can be used in the form of a pharmaceutically acceptable or foodologically acceptable salt, and the salt may include an acid addition salt formed by a pharmaceutically or foodologically acceptable free acid.
  • Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid, phosphorous acid, etc., aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanedio acids.
  • Non-toxic organic acids such as ate, aromatic acids, aliphatic and aromatic sulfonic acids, organic acids such as trifluoroacetic acid, acetate, benzoic acid, citric acid, lactic acid, maleic acid, gluconic acid, methanesulfonic acid, 4-toluenesulfonic acid, tartaric acid, fumaric acid, etc.
  • These pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, and nitrate.
  • IRDA-21 compound is administered in a “pharmacologically effective amount for prevention, mitigation, improvement or treatment.”
  • “Pharmaceutically effective amount” means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment or improvement, and the effective dose level is determined by the type and severity of the subject, age, gender, activity of the drug, It can be determined based on factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field. For example, effective amounts of 0.001 mg/kg to 1000 mg/kg, 0.01 mg/kg to 100 mg/kg or 0.1 to 20 mg/kg or 0.1 to 500 mg/kg are included.
  • the upper quantitative limit of the pharmaceutical composition of the present invention can be selected and implemented by a person skilled in the art within an appropriate range.
  • prevention means preventing the symptoms of the disease from occurring in advance by suppressing or blocking the symptoms of the disease by administering, ingesting, or applying it to an individual who is not suffering from the disease.
  • treatment includes complete cure of the symptoms of the disease as well as partial cure, improvement, and relief of the symptoms of the disease as a result of administration to an individual suffering from the disease.
  • the term “improvement” includes reduction or alleviation of symptoms of the target disease as a result of administration to an individual suffering from the disease.
  • the pharmaceutical composition or health functional food may contain an effective amount of the IDRA-21 compound alone or may contain one or more pharmaceutically or foodologically acceptable carriers, excipients, or diluents.
  • the pharmaceutically or foodologically acceptable carrier, excipient, or diluent refers to a substance that is physiologically acceptable and does not usually cause gastrointestinal upset, allergic reactions such as dizziness, or similar reactions when administered to humans.
  • the carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Examples include, but are not limited to, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers and preservatives may be additionally included.
  • IDRA-21 compound can be administered in various oral and parenteral dosage forms during clinical administration.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain one or more compounds and at least one excipient, such as starch, calcium carbonate, sucrose or lactose ( It is prepared by mixing lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups.
  • Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable esters such as ethyl oleate.
  • the pharmaceutical composition containing the IDRA-21 compound as an active ingredient can be administered parenterally, by subcutaneous injection, intravenous injection, intramuscular injection, or intrathoracic injection.
  • the compound in order to formulate a formulation for parenteral administration, is mixed with water along with a stabilizer or buffer to prepare a solution or suspension, which can be prepared in an ampoule or vial unit dosage form.
  • the composition may be sterilized and/or contain auxiliaries such as preservatives, stabilizers, wetting agents or emulsification accelerators, salts and/or buffers for adjusting osmotic pressure, and other therapeutically useful substances, and may be mixed, granulated, etc. using conventional methods. It can be formulated according to the coating or coating method.
  • Health food and health functional food compositions containing the above compounds according to the present invention can be added as is to food or used together with other foods or food ingredients, and can be used appropriately according to conventional methods.
  • the health functional food composition can be prepared according to the formulation of the pharmaceutical composition.
  • the health functional food composition can be used by appropriately modifying the pharmaceutical composition.
  • the mixing amount of the active substance can be appropriately determined depending on the purpose of use (prevention or improvement).
  • the amount of the composition in health foods and health functional foods can be 0.1 to 90 parts by weight of the total weight of the food.
  • the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
  • the health food and health functional food composition of the present invention has no particular restrictions on other ingredients other than containing the active substance of the present invention as an essential ingredient in the indicated ratio, and, like a typical beverage, various flavoring agents or natural carbohydrates are added as additional ingredients. It may contain.
  • natural carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)
  • synthetic flavoring agents sacharin, aspartame, etc.
  • the ratio of the natural carbohydrate may be generally about 1 to 20 parts by weight, preferably about 5 to 12 parts by weight, per 100 parts by weight of the health functional food composition of the present invention, but is not limited thereto.
  • health food and health functional food compositions containing the active ingredients of the present invention include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants, and thickening agents (cheese, chocolate, etc.) ), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.
  • the health food and health functional food composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks.
  • the ratio of these additives is not critical, but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the health food and health functional food composition containing the IDRA-21 compound, but is not limited thereto.
  • dexamethasone which is well known to reduce muscle mass
  • Dexamethasone is used to treat several diseases such as cancer, but it causes muscle atrophy by reducing the rate of protein synthesis and increasing the rate of protein degradation in skeletal muscle through the ubiquitin-proteasome system.
  • Two muscle ubiquitin ligases are related to Atrogin-1 and MuRF1.
  • Dexamethasone reduces MyoD (myogenic differentiation antigen) through Atrogin-1, and this mechanism leads to a decrease in muscle mass.
  • IP intraperitoneally
  • TA tibialis anterior
  • the thickness of the anterior tibial leg was photographed using DexaScan, and to measure muscle strength, strength adaptation training was performed at least 3 times before drug administration, and once every 3 days from the start of the test to the completion of the test. Muscle strength was evaluated for each repetition.
  • the mouse was placed in a muscle strength measuring device so that it could grab the grid with its front paws, and then its tail was slowly pulled with a constant force until it released the grid with its front paws. The maximum strength to grab the grid was measured five times, and the average value was obtained. was derived in Newton (N) units.
  • T1 the length from the upper limb to the medial dissection of the tibia in mice (tibia length: L) and the vertical distance from half the length of the tibia to the outer edge of the hindlimb muscle (muscle The thickness, T) was measured.
  • lean muscle mass lean body mass was measured targeting the tibialis anterior (TA) and gastrocnemius muscle (GS), and photographs were taken to minimize errors in test results due to stress. was limited to once a week.
  • the muscle mass improvement effect of IDRA-21 was confirmed compared to the muscle mass reduction effect caused by dexamethasone.
  • IDRA-21 dissolved in 0.5% Carboxymethylcellulose (CMC) and 0.1% Tween80 solvent was administered to the skeletal muscle atrophy model prepared in Example 1 at doses of 0.7, 2.1, and 6.3 mg/kg, and the control group was administered the solvent instead of IDRA-21. 100 ⁇ l was administered. It was administered orally once a day for a total of 21 days, starting 7 days before and 14 days after dexamethasone treatment. Afterwards, the lean muscle mass of the gastrocnemius muscle of the control group and the IDRA-21 treatment group was measured in the same manner as in Example 1.
  • CMC Carboxymethylcellulose
  • Tween80 solvent 100 ⁇ l was administered. It was administered orally once a day for a total of 21 days, starting 7 days before and 14 days after dexamethasone treatment. Afterwards, the lean muscle mass of the gastrocnemius muscle of the control group and the IDRA-21 treatment group was measured in the same manner as in Example 1.
  • the experimental animals in each group were adapted to the treadmill machine twice before measurement (1st time: incline 10° 5m/min for 10 minutes, 10m/min 10 minutes, 2nd time: incline 10° 5m/ min 5 minutes, 10m/min 15 minutes)
  • On the day of this experiment run at an initial speed of 10m/min and an incline of 10° for 20 minutes, then increase the speed by 2m/min every 2 minutes, and the end point is when you stay in a non-running state for 10 seconds.
  • the running distance and time were measured.
  • the muscle performance test was an agility test performed twice in total during the entire test period (on the 21st day from the start of the test).
  • the agility test was performed twice at each time point, and each test was performed blindly by a different performer.
  • Each evaluation item was scored as high (3 points), medium (2 points), and low (1 point), and the sum of the item scores for each individual was averaged and evaluated as a percentage as the final score.
  • Example 4 Effect of IDRA-21 on improving skeletal muscle atrophy
  • C2C12 mouse myogenic cells (ATCC, CRL-1772TM) were purchased and dispensed into 96 well cell culture plates and 6 well culture plates at 5 Growth media (GM) medium (Dulbecco's modified eagle's medium (DMEM) containing 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (P/S)-high glucose (% CO 2 , 95% O 2 incubation)
  • GM Growth media
  • DMEM Dulbecco's modified eagle's medium
  • FBS fetal bovine serum
  • P/S penicillin/streptomycin-high glucose
  • HS HS
  • DMEM-high glucose (4500 mg/L) containing 1% penicillin/streptomycin (P/S) were replaced and differentiated for 4 to 5 days with Dexamethasone 100 ⁇ M and IDRA-21.
  • Luminescence assay and light microscope observation were performed 2 days after treatment with 0.1, 1, and 10 ⁇ M, respectively.
  • ATP luminescence assay was performed on myotube cells prepared according to Example 4. Specifically, the C2C12 cells were seeded on a 96 flat clear black plate, washed once with 1PBS the next day, and then treated with 0.1, 1, and 10 ⁇ M of each drug prepared as differentiation medium. After drug treatment (2 days of differentiation), the medium on the plate was removed, 100 ⁇ L of ATP reagent was dispensed into each well, a dark environment was created with foil, and ATP luminescence was measured after 10 minutes (Room temperature (RT), veritas microplate luminometer; integration time 0.5sec). As a control, myotube cells not treated with IDRA-21 were used.
  • RT Room temperature
  • veritas microplate luminometer integration time 0.5sec
  • the ATP activity of myotube cells was found to be superior to that of the control group, and it was confirmed that the mitochondria were activated following IDRA-21 treatment, thereby increasing the production of ATP, and consequently suppressing skeletal muscle cell atrophy (Figure 6a ).
  • the diameter of myotube cells was confirmed to have recovered compared to the case treated with Dexamethasone.
  • the area of myotube cells was recovered to a superior level compared to the control group (FIGS. 6b and 6c).

Landscapes

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

Abstract

La présente invention concerne une composition pharmaceutique destinée à prévenir ou à traiter l'atrophie musculaire ou des maladies associées à celle-ci, contenant de l'IDRA-21 utilisé en tant que principe actif, et étant donné que la composition pharmaceutique peut inhiber efficacement l'atrophie musculaire, la composition pharmaceutique peut être avantageusement utilisée en tant que composition pour prévenir, traiter ou atténuer l'atrophie musculaire ou des maladies associées à celle-ci.
PCT/KR2023/019987 2022-12-07 2023-12-06 Composition contenant l'idra-21 utilisé en tant que principe actif pour prévenir ou traiter une maladie musculaire Ceased WO2024123073A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2022-0169937 2022-12-07
KR1020220169937A KR102873108B1 (ko) 2022-12-07 2022-12-07 Idra-21을 유효성분으로 포함하는 근육 질환의 예방 또는 치료용 조성물

Publications (1)

Publication Number Publication Date
WO2024123073A1 true WO2024123073A1 (fr) 2024-06-13

Family

ID=91379751

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2023/019987 Ceased WO2024123073A1 (fr) 2022-12-07 2023-12-06 Composition contenant l'idra-21 utilisé en tant que principe actif pour prévenir ou traiter une maladie musculaire

Country Status (2)

Country Link
KR (1) KR102873108B1 (fr)
WO (1) WO2024123073A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5488049A (en) * 1993-12-10 1996-01-30 Fidia - Georgetown Institute For The Neuro-Sciences Method of treating learning and memory disorders using benzothiadiazide derivatives as nootropic agents

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040063751A1 (en) * 2002-05-31 2004-04-01 Pharmacia Corporation Combination therapy for the treatment of amyotrophic lateral sclerosis (ALS) with cyclooxygenase-2 (COX-2) inhibitor(s) and a second drug
EP2422787A1 (fr) * 2010-08-17 2012-02-29 Neurotec Pharma, S.L. Diazoxyde pour une utilisation dans le traitement de la sclérose latérale amyotrophique

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5488049A (en) * 1993-12-10 1996-01-30 Fidia - Georgetown Institute For The Neuro-Sciences Method of treating learning and memory disorders using benzothiadiazide derivatives as nootropic agents

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BATTISTI UMBERTO M., JOZWIAK KRZYSZTOF, CANNAZZA GIUSEPPE, PUIA GIULIA, STOCCA GABRIELLA, BRAGHIROLI DANIELA, PARENTI CARLO, BRASI: "5-Arylbenzothiadiazine Type Compounds as Positive Allosteric Modulators of AMPA/Kainate Receptors", ACS MEDICINAL CHEMISTRY LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 3, no. 1, 12 January 2012 (2012-01-12), US , pages 25 - 29, XP093178540, ISSN: 1948-5875, DOI: 10.1021/ml200184w *
IMPAGNATIELLO F, IMPAGNATIELLO F, OBERTO A, LONGONE P, COSTA E, GUIDOTTI A: "7-Chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine S,S-dioxide: A partial modulator of AMPA receptor desensitization devoid of neurotoxicity", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 94, no. 13, 24 June 1997 (1997-06-24), pages 7053 - 7058, XP093178539, ISSN: 0027-8424, DOI: 10.1073/pnas.94.13.7053 *
KELVIN A. YAMADA; DOUGLAS F. COVEY; CHUNG Y. HSU; RONG HU; YUEFEI HU; YONG Y. HE: "The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury", ANNALS OF NEUROLOGY, JOHN WILEY AND SONS, BOSTON , US, vol. 43, no. 5, 8 October 2004 (2004-10-08), Boston , US , pages 664 - 669, XP071635397, ISSN: 0364-5134, DOI: 10.1002/ana.410430517 *
LOSI GABRIELE; PUIA GIULIA; BRAGHIROLI DANIELA; BARALDI MARIO: "IDRA-21, a positive AMPA receptor modulator, inhibits synaptic and extrasynaptic NMDA receptor mediated events in cultured cerebellar granule cells", NEUROPHARMACOLOGY, ELSEVIER, AMSTERDAM, NL, vol. 46, no. 8, 9 April 2004 (2004-04-09), AMSTERDAM, NL, pages 1105 - 1113, XP086201297, ISSN: 0028-3908, DOI: 10.1016/j.neuropharm.2004.02.011 *

Also Published As

Publication number Publication date
KR20240084979A (ko) 2024-06-14
KR102873108B1 (ko) 2025-10-17

Similar Documents

Publication Publication Date Title
DE60019814T2 (de) Pharmazeutische kombinationen enthaltend tegaserod und omeprazole und ihre verwendung zur behandlung gastrointestinaler krankheiten
KR101493016B1 (ko) 중약 조성물의 새로운 용도
CN108236608B (zh) 大麻二酚与氨己烯酸的药物组合物及其用途
WO2024123073A1 (fr) Composition contenant l'idra-21 utilisé en tant que principe actif pour prévenir ou traiter une maladie musculaire
US20210196675A1 (en) Use of ginkgo biloba terpene lactone in preparation of drugs for prevention and/or treatment of tremors and healthcare products
WO2010134769A2 (fr) Composition de prévention ou de traitement du syndrome du côlon irritable
WO2020067832A1 (fr) Composition, comprenant un dérivé de thiamine, pour la prévention ou le traitement de l'hypercortisolémie
WO2020231031A2 (fr) Composition comprenant du lactobacillus acidophilus pour prévenir, atténuer ou traiter l'arthromyalgie, les céphalées ou la sécheresse vaginale chez les femmes climatériques
WO2019117501A1 (fr) Composition et procédé de traitement, d'atténuation ou de prévention de crampes musculaires, contenant de l'alfoscérate de choline en tant que principe actif
WO2020184884A1 (fr) Composition destinée à prévenir ou à traiter l'obésité ou des troubles métaboliques d'origine lipidique
WO2020080673A1 (fr) Composition permettant de prévenir ou de traiter une maladie rétinienne contenant un extrait de centella asiatica
WO2022097764A1 (fr) Composition pharmaceutique comprenant de la prégabaline et de la tianeptine pour traiter une douleur neuropathique
WO2023182656A1 (fr) Composition pour la prévention, le traitement ou l'amélioration de maladies musculaires comprenant de la lévodropropizine en tant que principe actif
WO2020085612A1 (fr) Composition pharmaceutique pour le traitement de troubles dépressifs et de troubles de l'anxiété, contenant un mélange de créatinine et de taurine
WO2023132516A1 (fr) Composition pour la prévention, le traitement ou l'amélioration d'une maladie musculaire comprenant du sulpiride en tant que principe actif
CANGIANO et al. Penbutolol: a new beta blocker in the treatment of moderate essential hypertension
US5244900A (en) Method of use and compositions
US20250222042A1 (en) Composition for Preventing or Treating Bone and Muscle disease containing Eubacterium nodatum
WO2024049188A1 (fr) Composé à base de triazolo thiadiazine, et composition pour prévenir ou traiter la sarcopénie le contenant en tant que principe actif
WO2024049191A1 (fr) Composé à base de furylthiazole et composition pour prévenir ou traiter la sarcopénie le comprenant en tant que principe actif
US20240424043A1 (en) Composition for preventing or treating muscle disease comprising aralia elata extract
CN108066373A (zh) 一种防治2型糖尿病的药物及制备方法
KR20250021128A (ko) 세레브로리진을 유효성분으로 포함하는 근육질환의 예방 또는 치료용 조성물
KR20240051234A (ko) 심장질환용제 및 심장질환의 개선 방법
WO2020231029A2 (fr) Composition pour prévenir, atténuer ou traiter les bouffées de chaleur, les picotements des membres ou les palpitations chez les femmes ménopausées, contenant du lactobacillus acidophilus

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23901091

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 23901091

Country of ref document: EP

Kind code of ref document: A1