WO2022231063A1

WO2022231063A1 - Composition for preventing or treating muscle-aging-associated diseases or hereditary muscular diseases, containing andrographolide succinate as active ingredient

Info

Publication number: WO2022231063A1
Application number: PCT/KR2021/008370
Authority: WO
Inventors: 김보경; 정승효; 이경진; 김수정
Original assignee: 주식회사 케이에스비튜젠
Priority date: 2021-04-26
Filing date: 2021-07-01
Publication date: 2022-11-03

Abstract

The present invention relates to a composition for preventing or treating muscle aging-associated diseases including sarcopenia or hereditary muscular diseases including Duchenne muscular dystrophy (DMD), containing andrographolide succinate as an active ingredient. Andrographolide succinate, which is the compound of the present invention, and a complex preparation containing same are contained as active ingredients so that differentiation from myoblasts into myotubes is promoted or induced, and the onset of muscle-aging-associated diseases, including muscle aging-related sarcopenia and skeletal muscle atrophy, or DMD is delayed, or a reduction in at least one symptom or the severity or frequency of the diseases is effectively regulated, and thus diseases that could be caused by Duchenne muscular dystrophy can be alleviated, prevented or treated.

Description

Composition for the prevention or treatment of muscle aging-related diseases or hereditary muscle diseases containing andrographolide succinate as an active ingredient

The present invention relates to skeletal muscle atrophy, sarcopenia, muscle-derived head and neck disease, muscle aging-derived vision disease or Duchenne Muscular Dystrophy (DMD) containing sacopenia containing androglapholide succinate as an active ingredient. ) relates to a composition for preventing or treating hereditary muscle disease, including.

The present invention effectively controls skeletal muscle atrophy and sarcopenia using androglapholide succinate as an active ingredient in various animal models and cell test methods to prevent and treat muscle diseases, particularly skeletal muscle atrophy, caused by various causes. and pharmaceutical compositions and uses thereof as ameliorating agents.

In addition, the present invention prevents Duchenne muscular dystrophy by effectively controlling the onset delay, at least one symptom, or reduction in severity or frequency of DMD using androglapholide succinate as an active ingredient in an animal model of Duchenne muscular dystrophy. , to a pharmaceutical composition and its use as a therapeutic and ameliorating agent.

Skeletal muscle atrophy can be caused by various causes, such as immobility, muscle disease, space travel, denervation, sepsis, dexamethasone administration, weight loss, decreased dietary intake, and muscle mass and muscle fiber crossing. It is characterized in that the area is reduced.

It is also known to be caused by treatment such as peripheral neuropathic pain, a decrease in muscle function that inevitably accompanies aging, and a treatment such as a plaster cast performed on a surgically injured patient. The occurrence of such muscle atrophy can lead to a decrease in the quality of life of the patient due to problems such as weakness, induction of activity impairment, and prolongation of the functional recovery period. In particular, aging, which is rapidly increasing worldwide, and overcoming of degenerative diseases are one of the immediate problems that must be solved in order to pursue a healthy and humane life and move forward to a welfare state.

In muscle, anabolic and catabolism are balanced to regulate muscle production, and in this case, various biological signal transduction processes are regulated within muscle cells. When a signal transduction reaction that induces synthesis rather than degradation of muscle protein is activated, the synthesis of muscle protein is increased, leading to an increase in muscle size (hypertrophy, hypertrophy) or an increase in the number of muscle fibers (hyperplasia), resulting in excessive muscle production.

Progressive muscle weakness and loss of function threaten the quality of life and decrease the survival rate of cancer patients. More than 30% of cancer patients die due to weight loss due to muscle loss, and this loss of muscle function is due to degeneration of myo-proteins, muscle fiber cross-sectional area, and muscle strength. ), the number of muscle fibers (nuclear number of myofibers), and insulin responsiveness are commonly accompanied.

In addition to cancer, muscle loss can also be caused by aging and various chronic diseases. As aging progresses, sarcopenia occurs, in which a portion of newly generated skeletal muscle is replaced with fibrous tissue, and the amount and strength of skeletal muscle of the human body is reduced. In addition, muscle loss occurs in chronic diseases that increase with age, such as hypertension, impaired glucose tolerance, diabetes, obesity, dyslipidemia, atherosclerosis, and cardiovascular disease (Pharmacol Res. 2015, 99, 86). ).

A general method for preventing muscle atrophy is prevention of muscle loss through exercise, but there is no fundamental treatment currently on the market. At a time when a clear treatment for such patients with muscular atrophy has not been developed, it is necessary to study the development of countermeasures and prevention/treatment/improvement agents that can prevent muscular atrophy. Therefore, the pharmaceutical composition according to the present invention is considered to be useful for the prevention, treatment and improvement of these muscular atrophy diseases. Furthermore, it is thought that the identification of the active ingredient will be of great help to the development of pharmaceutical science in the future.

Muscular dystrophy is a disease related to muscle degeneration that includes gait disturbance as a whole, and is different from muscle loss (senile sarcopenia) caused by aging. All muscular dystrophy is characterized as progressive. Muscular dystrophy includes Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, Facioscapulohumeral Dyscular Dystrophy, Llimb-Girdle dystrophy, and Llimb-Girdle dystrophy (Llimb-Girdle). myotonic dystrophy (including congenital forms of type 1 myotonic dystrophy).

Muscular dystrophy generally occurs in some or all of the muscles of each part of the body, but the pattern of occurrence differs depending on the type of muscular dystrophy. In addition, the typical symptoms of muscular dystrophy are decreased muscle motor function, decreased use of one or more muscles, drooling due to decreased masticatory movement, difficulty speaking and eating, drooping eyelids, and frequent falls. In adults, weakness in the strength of a muscle or several muscles, muscle loss and resulting walking problems, muscle hypertrophy, muscle pseudohypertrophy, fat infiltration of muscle, replacement of muscle by non-contractile tissue (e.g., myofibrosis), muscle necrosis and/or cognitive or behavioral impairment/intellectual impairment.

Duchenne muscular dystrophy is a rare disease in which the skeletal and cardiac muscles are gradually weakened and lost due to progressive muscle dysplasia. more known. Usually, the DMD gene exists between chromosomes Xp21.2 and Xp21.1 with a size of 2.4 Mb, has 79 exons, and the mRNA size is about 14 kb. It is known that dystrophin protein, the cause of the disease, is produced mainly in skeletal muscle and cardiac muscle cells, and is also produced in small amounts by nerve cells in certain parts of the brain.

Due to the progressive degeneration of skeletal muscle due to an abnormality in dystrophin protein, the muscle itself is replaced by connective tissue or fat, and pseudohypertrophy of the muscle is progressing. Such Duchenne muscular dystrophy mainly presents symptoms such as muscle weakness, difficulty walking and breathing, and intellectual disability. Most of the patients die before the age of 30 due to abdominal muscle atrophy and respiratory problems due to spinal and thoracic deformities.

Currently, there is no specific treatment method for DMD, and there are therapeutic options through gene therapy and various administration of steroids. only % Therefore, although some signs and symptoms of DMD patients can be delayed, there is currently no satisfactory treatment method.

Andrographolide is a major component of Andrographis paniculata along with andrographiside, Andropanoside, Andrographin, Panicolin, etc. have.

Andrographolide is a Labdane (= natural bicyclic diterpene) diterpenoid isolated from the stem and leaves of Andrographis paniculata. Labdane is a natural bicyclic diterpene. It forms the structural core of various natural medicines collectively known as Labdanes or Labdane diterpenes, and this ingredient has been found to have a great hepatoprotective function. It has been confirmed through research and is used as an anti-inflammatory and anticancer agent.

Androglapholide Succinate is one of the main ingredients of Andrographis paniculata along with Andrographolide. There are no studies on skeletal muscle atrophy and sarcopenia.

In addition, Androglapholide Succinate is one of the main ingredients of Andrographis Paniculata along with Andrographolide. Although it is widely used to treat infections, there is no study on hereditary muscle disease.

Accordingly, the present inventors effectively control skeletal muscle atrophy and sarcopenia of androglapholide succinate through various animal models and cell test methods to prevent, treat and improve muscle diseases, particularly skeletal muscle atrophy, caused by various causes. was confirmed.

The present inventors also provide methods and compositions for treating muscular dystrophy, including Duchenne muscular dystrophy or Becker muscular dystrophy, as a therapeutic agent comprising, among other things, Androglapholide Succinate and a pharmaceutically addable salt. In some embodiments, the present invention provides oral and intraperitoneal administration of Androglapholide Succinate using an animal model suffering from or susceptible to DMD to reduce or delay the onset of at least one symptom or frequency of DMD. A method of treating DMD is provided.

The inventor of the present invention observes and compares the size (mass) of muscles, strength and movement (performance) of muscles in dexamethasone-treated or aging animal models as a method for evaluating the effectiveness of skeletal muscle atrophy recovery drugs, so that the drug effectively reduces skeletal muscle atrophy The present invention was completed by confirming that the

Accordingly, an object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of muscle aging-related diseases comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

Another object to be solved by the present invention is to provide a food composition for improving or preventing sarcopenia comprising androglapholide succinate or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object to be solved by the present invention is to provide a food composition for promoting muscle differentiation, regenerating muscles or strengthening muscles, comprising androglapholide succinate or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object to be solved by the present invention is to provide a food composition for improving exercise ability comprising androglapholide succinate or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object to be solved by the present invention is to provide a method for treating sarcopenia by administering the composition to a human or an animal other than a human.

Another object to be solved by the present invention is to provide a novel use of Androglapholide Succinate or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of sarcopenia, or an animal medicament.

[Formula 1]

In addition, the inventor of the present invention is a method for evaluating the effectiveness of Duchenne muscular dystrophy delay and recovery drugs in the 4-week-old C57BL/10ScSn-Dmdmdx/J Duchenne muscular dystrophy mouse model of muscle size (Mass), muscle strength (Strength) and movement By observing and comparing (Performance), the present invention was completed by confirming that the drug effectively regulates muscle pseudohypertrophy and muscle weakness inhibition.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating hereditary muscle disease, comprising the compound represented by Formula 1, a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

Another object to be solved by the present invention is to provide a food composition for improving or preventing hereditary muscle disease comprising androglapholide succinate or a pharmaceutically acceptable salt thereof as an active ingredient.

In order to achieve the object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating muscle aging-related diseases, comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient do.

[Formula 1]

In addition, the present invention provides a food composition for preventing or improving muscle aging-related diseases comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[Formula 1]

The composition may increase muscle mass or prevent muscle loss.

The sarcopenia may be due to aging.

In one embodiment of the present invention, the muscle aging-related disease is senile sarcopenia, atony, muscular atrophy, muscle degeneration, myositis, amyotrophic axonal sclerosis, myasthenia gravis, myositis, muscle It may be selected from the group consisting of calcification, muscle ossification, muscle-derived head and neck disease, muscle aging-derived vision disease, muscle weakness-related disease, and cachexia.

In one embodiment of the present invention, the composition may promote mitochondrial functional activity.

In one embodiment of the present invention, the composition may be administered by one or more methods selected from the group consisting of intravenous, intradermal, inhalation, transdermal (topical), intraorbital, subcutaneous, intramuscular, oral and transmucosal administration. .

In one embodiment of the present invention, the composition is composed of orbicularis muscle, masticatory muscle, tongue and neck muscle, rib cage and arm muscle, arm and shoulder, hand intrinsic muscle, lower extremity and leg muscle, forelimb and foot muscle can be delivered to one or more target tissues selected from the group.

In one embodiment of the present invention, the disease may be induced by steroids or atrophic factors.

In addition, in order to achieve the object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating hereditary muscle disease comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient do.

In addition, the present invention provides a food composition for preventing or improving hereditary muscle disease comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[Formula 1]

The composition may be to increase muscle mass, or to prevent muscle hypertrophy and muscle loss.

The sarcopenia may be due to a gene deletion.

In one embodiment of the present invention, the hereditary muscle disease is Duchenne muscular dystrophy, Becker muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, facial scapula brachial dystrophy ( It may be selected from the group consisting of Facioscapulohumeral Muscular Dystrophy), Llimb-Girdle Muscular Dystrophy, Type 1 Myotonic Dystrophy, and Type 2 Muscular Dystrophy.

In one embodiment of the present invention, the composition comprises orbicularis muscle, masticatory muscle, head and neck muscles including tongue and neck muscles, thoracic thoracic and arm muscles, arms and shoulders, intrinsic muscles of hands, lower extremities and leg muscles, forelimbs and It may be delivered to one or more target tissues selected from the group consisting of foot muscles.

The present invention relates to a composition for treating diseases related to muscle aging, and the like, wherein the compound of the present invention, a pharmaceutically acceptable salt thereof, or a hydrate thereof has an effect of effectively preventing, improving and treating skeletal muscle atrophy or sarcopenia. Therefore, the present invention containing the compound can be usefully applied to related pharmaceutical and health functional food fields.

In addition, the present invention relates to a composition for treating hereditary muscle disease, and the like, wherein the compound of the present invention, a pharmaceutically acceptable salt or hydrate thereof, effectively prevents, improves and treats hereditary muscle disease including Duchenne muscular dystrophy. . Therefore, the present invention containing the compound can be usefully applied to related pharmaceutical and health functional food fields.

1 is a result showing the effect on skeletal muscle atrophy by dexamethasone treatment.

Figure 2 shows the effect of andrographolide (Androglapholide) 30mg / kg oral administration and androglapholide succinate (Androglapholide Succinate) 30mg / kg intraperitoneal administration on body weight and muscle function, grip strength is the result

3 shows the inhibitory effect on skeletal muscle atrophy according to the administration method at the same concentration of 30 mg/kg of androglapholide and androglapholide succinate, lean body mass, anterior shin tibia This is the result of checking the lean mass of (Tibialis Anteriors, TA) and the lean mass of the gastrocnemius muscle (GS).

4 shows the inhibitory effect on skeletal muscle atrophy according to the administration method at the same concentration of 30 mg/kg of androglapholide and androglapholide succinate, Muscle Diameter of Tibialis Anteriors, TA. It is a result represented by T1.

5 shows the effects of androglapholide and androglapholide succinate on skeletal muscle atrophy according to the same 30mg/kg concentration and same intraperitoneal administration (IP) method. ) and the results representing the Treadmill test.

Figure 6 shows the effect of androglapholide and androglapholide succinate on skeletal muscle atrophy according to the same 30mg/kg concentration same intraperitoneal administration (I.P.) method Lean Body Mass , Lean mass of the anterior tibialis anteriors (Tibialis Anteriors, TA) and the Lean Mass of the gastrocnemius muscle (GS).

7 shows the effect of androglapholide and Androglapholide Succinate on skeletal muscle atrophy according to the same concentration (30mg/kg) and the same intraperitoneal administration (IP); Tibialis Anteriors , TA) is the result shown by Muscle Diameter T1.

8 is an oral administration of 30mg/kg concentration of Androglapholide Succinate and 60mg/kg I.P. These are results showing the efficacy of skeletal muscle atrophy or muscle reduction according to 14-day administration in terms of lean mass and length (Diameter) of the anterior tibialis anteriors (TA), and functional aspects of muscles with a grip strength test.

9 is a result showing the effect of andrographolide (Androglapholide) and andrographolide succinate (Androglapholide Succinate) on skeletal muscle mitochondrial function and skeletal muscle cell atrophy.

Figure 10 is a 4-week-old C57BL / 10ScSn-Dmdmdx / J Duchenne type mouse model andrographolide succinate (Androglapholide Succinate) 30mg / kg intraperitoneal administration for 28 days gastrocnemius muscle (Gastrocnemius Muscle, GS) muscle itself is combined It is a result showing the effect of replacement with tissue or fat and on pseudohypertrophy of muscle.

11 is a 4-week-old C57BL/10ScSn-Dmdmdx/J Duchenne-type mouse model intraperitoneal administration at 30mg/kg concentration of androglapholide succinate for 28 days, cost-effectiveness of total lean body mass (Lean Body Mass) Pseudohypertrophy) is a result showing the effect.

Figure 12 is a 4-week-old C57BL / 10ScSn-Dmdmdx / J Duchenne type mouse model andrographolide succinate (Androglapholide Succinate) 30mg / kg intraperitoneal administration for 28 days Lean Mass of the anterior tibialis anteriors (Tibialis Anteriors, TA) and results showing the effect on Muscle Diameter T1.

Figure 13 is a 4-week-old C57BL / 10ScSn-Dmdmdx / J Duchenne type mouse model andrographolide succinate (Androglapholide Succinate) 30mg / kg intraperitoneal administration for 28 days is muscle function Grip Strength and Treadmill ) is the result showing the effect on the test.

Hereinafter, the present invention will be described in detail.

Provided is a pharmaceutical composition for preventing or treating muscle aging-related diseases, comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[Formula 1]

In the present invention, "muscle aging-related disease" may mean a disease that causes muscle weakness or loss. The muscle weakness or loss is not limited to the aging of the individual, and may be caused by hypoxia, chemicals and drugs, physical factors, infectious factors, immune or inflammatory reactions, infectious factors, nutritional imbalance, space travel, and steroids or alcohol It is a concept that includes those induced by drugs, such as.

In addition, it provides a pharmaceutical composition for preventing or treating hereditary muscle disease comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[Formula 1]

In the present invention, "hereditary muscle disease" refers to a group of genetic disorders caused by genetic factors as a group of very diverse diseases that invade the nervous system and skeletal muscle tissue. It is caused by abnormalities in 600 different genes that affect motor neurons, peripheral motor neurons, neuromuscular junctions, or muscles themselves. It corresponds to a disease different from atrophy (senile sarcopenia).

In the present invention, "pharmaceutically acceptable salt" means a salt formed with any inorganic or organic acid or base that does not cause serious irritation to the administered organism and does not impair the biological activity and physical properties of the compound. As the salt, a salt commonly used in the art may be used, such as an acid addition salt formed with a pharmaceutically acceptable free acid. Specifically, the pharmaceutically acceptable salts include, but are not limited to, salts derived from the following pharmacologically or physiologically acceptable inorganic acids and organic acids and bases.

Examples of suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid , benzoic acid, malonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, and the like. Such pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, ioda. Id, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate , sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methylbenzoate Toxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycol late, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate or mandelate. Salts derived from suitable bases may include alkali metals such as sodium, or potassium, alkaline earth metals such as magnesium.

In addition, the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate). In addition, androglapholide succinate of the present invention includes all salts, hydrates and solvates that can be prepared by conventional methods as well as pharmaceutically acceptable salts.

In the present invention, “hydrate” refers to a compound represented by Formula 1 or a pharmaceutically acceptable salt thereof to which water is bound by a non-covalent intermolecular force, and may include a stoichiometric or non-stoichiometric amount of water. . Specifically, the hydrate may contain water in a ratio of about 0.25 mole to about 10 moles based on 1 mole of the active ingredient, and more specifically, about 0.5 mole, about 1 mole, about 1.5 mole, about 2 mole, about 2.5 moles, about 3 moles, about 5 moles, and the like.

As used herein, the term “prevention” refers to any action that suppresses symptoms or delays the onset of symptoms by administration of the pharmaceutical composition according to the present invention.

As used herein, the term “treatment” refers to any action in which symptoms are improved or beneficially changed by administration of the pharmaceutical composition according to the present invention.

The pharmaceutical composition according to the present invention includes the compound represented by Formula 1, a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient, and may include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier is commonly used in the formulation, and includes, but is not limited to, saline, sterile water, Ringer's solution, buffered saline, cyclodextrin, dextrose solution, maltodextrin solution, glycerol, ethanol, liposome, and the like. It does not, and may further include other conventional additives such as antioxidants and buffers, if necessary.

In addition, diluents, dispersants, surfactants, binders, lubricants, etc. may be additionally added to injectable formulations such as aqueous solutions, suspensions and emulsions, powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc. It can be formulated in the form of mold formulations, external preparations, or suppositories. Regarding suitable pharmaceutically acceptable carriers and formulations, formulations can be preferably made according to each component using the method disclosed in Remington's literature. The pharmaceutical composition of the present invention is not particularly limited in dosage form, but it can be formulated as an injection or oral ingestion, and when an injection is used, it can be formulated in a form in which the durability of the active ingredient is improved.

The pharmaceutical composition of the present invention may be administered orally or administered parenterally (eg, intravenously or subcutaneously) according to a desired method, and the dosage may vary depending on the patient's condition and body weight, degree of disease, drug form, Depending on the route and time of administration, it may be appropriately selected by those skilled in the art.

In one embodiment, the composition according to the present invention may be prepared as an aqueous solution for parenteral administration, preferably a buffered solution such as Hank's solution, Ringer's solution or physically buffered saline. Can be used. Aqueous injection suspensions may contain substrates capable of increasing the viscosity of the suspension, such as sodium carboxymethylcellulose, sorbitol or dextran.

The composition of the present invention may be administered systemically or locally, and may be formulated into a formulation suitable for such administration by a known technique. For example, for oral administration, it may be administered by mixing with an inert diluent or an edible carrier, sealed in a hard or soft gelatin capsule, or compressed into a tablet. For oral administration, the active compound may be mixed with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers and the like.

Various formulations for injection, parenteral administration, etc. can be prepared according to techniques known in the art or commonly used techniques. Androglapholide and Androglapholide Succinate were dissolved in saline or buffer and stored in a freeze-dried state, and then stored in an effective amount of Androglapholide and Androglapholide Succinate. succinate) can be administered by oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, enteral, topical, sublingual or rectal routes. Included. Oral or parenteral administration is preferred. As used herein, the term "parenteral" includes subcutaneous, intradermal, intravenous, intramuscular, intraarticular, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques, and is intended for rectal administration. It may also be administered in the form of a suppository.

Meanwhile, subjects to which the pharmaceutical composition of the present invention can be administered may include all animals.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type, severity, and drug activity of the patient. , sensitivity to the drug, administration time, administration route and excretion rate, duration of treatment, factors including concurrent drugs, and other factors well known in the medical field. The composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple. In consideration of all of the above factors, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by those skilled in the art.

Specifically, the effective amount of the composition according to the present invention may vary depending on the age, sex, and weight of the patient, and may be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, and the like.

In the present invention, the muscle aging-related disease is senile sarcopenia, atony, muscular atrophy, muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia gravis, myositis, muscle calcification, muscle ossification, It may be at least one disease selected from the group consisting of muscle-derived head and neck disease, muscle aging-derived vision disease, muscle weakness-related disease, and cachexia.

In the present invention, the muscle weakness-related disease refers to any disease that can occur due to muscle weakness, and is a disease in which the differentiation ability of myoblasts is reduced or weakened due to a decrease in myocytes in the body or a decrease in satellite cell activity. It means a disease that can be prevented, improved, or treated through

In the present invention, the composition may promote mitochondrial functional activity.

In the present invention, the composition may be administered by one or more methods selected from the group consisting of intravenous, intradermal, inhalation, transdermal (topical), intraorbital, subcutaneous, intramuscular, oral and transmucosal administration.

In the present invention, the composition is one selected from the group consisting of orbicularis muscle, masticatory muscle, tongue and neck muscle, rib cage and arm muscle, arm and shoulder, hand intrinsic muscle, lower extremity and leg muscle, forelimb and foot muscle It can be delivered to more than one target tissue.

In the present invention, the disease may be induced by steroids or atrophic factors.

In the present invention, steroid is a generic term for compounds having a generic steroid nucleus structure in which one cyclopentyl ring is attached to three cyclohexyl rings, and may preferably refer to a cortisol steroid.

In the present invention, cell atrophy may appear in the form of cell adaptation due to cell damage. These cell damage factors can be caused by hypoxia, chemicals and drugs, physical factors, infectious factors, immune or inflammatory responses, infectious factors, and nutritional imbalance. , IL-6, TNF-α, NF-κB, Dexamethasone, and the like.

In the present invention, the hereditary muscle disease is Duchenne muscular dystrophy, Becker muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy), It may be selected from the group consisting of Llimb-Girdle Muscular Dystrophy, Type 1 Myotonic Dystrophy, and Type 2 Muscular Dystrophy.

In another aspect, the present invention provides a food composition for preventing or improving muscle aging-related diseases, comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[Formula 1]

[Formula 1]

The food composition is a concept including health functional food.

As used herein, the term “improvement” refers to any action that at least reduces a parameter related to the condition to be treated, for example, the severity of symptoms.

In the food composition of the present invention, the compound represented by Formula 1, a pharmaceutically acceptable salt thereof, or a hydrate thereof may be added to food as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. have. The mixing amount of the compound represented by Formula 1, a pharmaceutically acceptable salt thereof, or a hydrate thereof may be appropriately determined depending on the purpose of its use (for prevention or improvement). In general, in the production of food or beverage, the composition of the present invention is added in an amount of 15% by weight or less, preferably 10% by weight or less, based on the raw material. However, in the case of long-term ingestion for health and hygiene or health control, the amount may be less than or equal to the above range.

The health functional food composition of the present invention is not particularly limited in other ingredients other than containing the above ingredients as an essential ingredient in the indicated ratio, and may contain various flavoring agents or natural carbohydrates as additional ingredients like a conventional beverage. . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of the natural carbohydrate can be appropriately determined by the selection of those skilled in the art.

In addition to the above, the health functional food composition of the present invention includes 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 salts thereof, Alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like may be contained. These components may be used independently or in combination. The proportion of these additives may also be appropriately selected by those skilled in the art.

Without conflict, the description of the pharmaceutical composition may be applied to the description of the food composition.

Hereinafter, the present invention will be described in more detail through examples. However, the following examples are intended to illustrate the present invention, and the scope of the present invention is not limited thereto.

<실시예 1> <Example 1>

Commercially available (Androglapholide) and androglapholide succinate (Androglapholide Succinate) reagents having the structure of Formula 1 (Xianjiatianbio, China) were purchased and used.

<시험예 1><Test Example 1>

Differentiation of myoblasts (myoblasts) into myotubes is preceded by the activation of ATP, which is an intracellular energy, and the increase in ATP activity can accelerate the rate of differentiation by increasing the activity of mitochondria in myoblasts. Andrographolide (Androglapholide) and andrographolide succinate (Androglapholide Succinate) by increasing the activity of mitochondria induces ATP activity and promotes differentiation of myoblasts was confirmed through Luminescence assay. In addition, the protective effect against skeletal muscle cell atrophy induced by the atrophic factor TNF-α in myotubes that have been differentiated was also demonstrated using luminescence assay and light microscopy. Dexamethasone treatment of Androglapholide and Androglapholide Succinate and the effects of aging model on skeletal muscle atrophy by weight, grip strength, and skeletal muscle atrophy by dexamethasone (dual energy X) -ray absorptiometry (DEXA) was used to determine the inhibition and recovery of tibialis anterior muscle loss, inhibition and recovery of lean muscle mass, and recovery of gastrocnemius muscle.

<시험예 1-1> 덱사메타손 처리 마우스 골격근 위축에 미치는 영향을 확인<Test Example 1-1> Dexamethasone treatment to determine the effect on skeletal muscle atrophy in mice

In the dexamethasone-induced sarcopenia model, skeletal muscle atrophy or muscle reduction was induced by intraperitoneal administration of 100 μl of dexamethasone at a concentration of 10 mg/kg to 8-week-old male ICR mice for 12 days.

As shown in FIG. 1 , the grip strength, which is an indicator of muscle function, was measured by dexamethasone using a mouse experimental grip strength meter (Jeongdo BNP Grip strength meter, Korea). The measurement method is the measurement value when the experimenter holds the tail while gently holding the body of the mouse and then pulls the tail at a constant speed and the mouse releases both front paws was recorded. The highest tension out of a total of 5 measurements was considered as the grip strength (g). The anterior tibialis anterior muscle and lean body mass were measured using dual energy X-ray absorptiometry (DEXAmetry). As a result, it was confirmed that all of the indicators shown in Figure 1 were reduced by dexamethasone.

<시험예 1-2> 덱사메타손 처리 골격근 위축 마우스 모델을 이용하여 안드로그라폴라이드(Androglapholide)와 안드로그라폴라이드 석시네이트(Androglapholide Succinate)의 동일 농도에서 투여방식에 따른 골격근 위축 또는 근육감소증의 예방 또는 치료 효과 비교<Test Example 1-2> Prevention of skeletal muscle atrophy or sarcopenia according to the administration method at the same concentration of androglapholide and androglapholide succinate using a dexamethasone-treated skeletal muscle atrophy mouse model or Comparison of treatment effects

In the dexamethasone-induced sarcopenia model in mice, dexamethasone was administered for 12 days and oral administration of androglapholide 30mg/kg concentration was simultaneously performed, and androglapholide succinate 30mg/kg I.P. Efficacy of skeletal muscle atrophy or muscle reduction was evaluated by Body Weight, Grip Strength and Lean Body Mass in terms of muscle function, Lean Mass of Tibialis Anteriors (TA), Gastrocnemius Muscle, GS) Lean Mass and the length (Diameter) of the Tibialis Anteriors (TA) were confirmed.

As a result, as shown in Figure 2, in the grip strength test (Grip Strength) and muscle loss measurement index in terms of muscle function, body weight, 30mg/kg concentration I.P. Andrographolide succinate (Androglapholide Succinate) of the administration method was confirmed to have a superior effect than andrographolide (Androglapholide).

In addition, as shown in FIG. 3, in the lean mass of lean body mass and the anterior tibialis anteriors (TA), 30 mg/kg concentration I.P. It was confirmed that the administration method of Androglapholide Succinate and the oral administration method of 30mg/kg had a similar effect, but in Lean Mass of Gastrocnemius Muscle (GS). Andrographolide succinate (Androglapholide Succinate) was confirmed to have a superior effect.

Furthermore, as shown in Figure 4, in the length (Diameter) of the anterior shin tibialis anteriors (Tibialis Anteriors, TA), 30mg / kg concentration I.P. It was confirmed that the administration method of Androglapholide Succinate and the oral administration method of 30mg/kg androglapholide had similar effects.

<시험예 1-3> 덱사메타손 처리 골격근 위축 마우스 모델을 이용하여 안드로그라폴라이드(Androglapholide)와 안드로그라폴라이드 석시네이트(Androglapholide Succinate)의 동일 농도와 동일 투여방식에 따른 골격근 위축 또는 근육감소증의 예방 또는 치료 효과 비교<Test Example 1-3> Prevention of skeletal muscle atrophy or sarcopenia according to the same concentration and administration method of androglapholide and androglapholide succinate using a dexamethasone-treated skeletal muscle atrophy mouse model or compare treatment effects

In the dexamethasone-induced sarcopenia model in mice, dexamethasone was administered for 12 days, and at the same time, Androglapholide and Androglapholide Succinate were administered at a concentration of 30mg/kg I.P. By administration, the efficacy of skeletal muscle atrophy or muscle reduction was measured by body weight, lean body mass, lean mass of Tibialis Anteriors (TA), lean mass of gastrocnemius muscle (GS) and Diameter of the anterior shinbone (Tibialis Anteriors, TA) was checked, and grip strength and treadmill tests were performed in terms of muscle function. Treadmill test run the mouse on a treadmill at 14 m/min at a 5˚ inclination, increasing the speed by 2 m/min every 1 min until it reached 20 m/min, and the end of the measurement was the depletion of the mouse stamina, resulting in mechanical stab stimulation and Refusal to run despite electric shock stimulation was set as the end point of the measurement.

As a result, as shown in FIG. 5, the same concentration (30 mg/kg) and the same administration method (I.P.) of androglapholide and androglapholide succinate, body weight , It was confirmed that androglapholide succinate had a superior effect than androglapholide in the grip strength test and the treadmill test in terms of muscle function.

In addition, as shown in FIG. 6, andrographolide succinate (Lean Body Mass), Lean Mass of Tibialis Anteriors (TA), and Lean Mass of Gastrocnemius Muscle (GS) Androglapholide Succinate) was confirmed to have a superior effect than androglapholide (Androglapholide).

Furthermore, as shown in FIG. 7 , it was confirmed that androglapholide Succinate has a superior effect than androglapholide even in the length (Diameter) of the Tibialis Anteriors (TA). did.

<시험예 1-4> 노화(Aged) 마우스 모델을 이용하여 안드로그라폴라이드 석시네이트(Androglapholide Succinate)의 골격근 위축 또는 근육감소증의 예방 또는 치료 효과 결과<Test Example 1-4> Results of the prevention or treatment effect of androglapholide succinate on skeletal muscle atrophy or sarcopenia using an aged mouse model

Oral administration of 30mg/kg concentration of Androglapholide Succinate and 60mg/kg I.P. The efficacy of skeletal muscle atrophy or muscle reduction by administration, the grip strength test in terms of muscle function, and the lean mass and length (Diameter) of the tibialis anteriors (TA) were confirmed.

As a result, as shown in FIG. 8 , the grip strength of the functional aspect of the muscle was determined by Androglapholide Succinate 60 mg/kg I.P. It was confirmed that the administration showed a superior effect, and the lean mass and length (Diameter) of the anterior tibialis anteriors (TA) also confirmed that the skeleton of aged mice excellently suppressed atrophy or reduction.

<시험예 1-5> 근원세포의 분화 촉진과 분화된 근원세포 Myotube에 세포위축인자(Atrophic factor) TNF-α 로 유발되는 골격근 세포 위축(skeletal muscle cell atrophy)에 대한 방어효과<Test Example 1-5> Promoting differentiation of myoblasts and protective effect against skeletal muscle cell atrophy induced by the atrophic factor TNF-α in the differentiated myoblast Myotube

To promote the differentiation of myoblasts, the C2C12 mice myoblast cell line was dispensed at a concentration of 5x10 ³ cells/well in a 96-well cell culture plate, 70-80% confluence was confirmed, and then the culture medium and differentiation medium were changed. The differentiation medium was treated with Androglapholide and Androglapholide Succinate, and ATP activity was measured during differentiation for 5 days by Luminescence assay. To measure the protective effect against skeletal muscle cell atrophy, C2C12 mice myoblasts were dispensed at 5x10 ³ cells/well and 2x10 ⁵ cells/well, respectively, in a 6-well cell culture plate and a 6-well culture plate, 80-90% confluency was confirmed, and then the differentiation medium was cultured. TNF-α and TNF-α in Myotube formed after 5 days of differentiation After 2 days of treatment with androglapholide and androglapholide succinate, suction the medium, and after dispensing 100 μL of 2.0 CellTiter (promega) reagent into weel, measure luminescence after 10-12 minutes of reaction time Measured with the instrument, TNF-α and After 2 days of treatment with androglapholide and androglapholide succinate, 5 pictures were taken at random with an optical microscope (magnification: 40×, 100×).

As a result, as shown in FIG. 9, the protective effect against atrophy of skeletal muscle cells and the promotion of differentiation of skeletal muscle cells were produced by mitochondrial activity according to the treatment with androglapholide and androglapholide succinate. It was confirmed that ATP had a concentration-dependent protective effect against TNF-α-induced cell atrophy in the results of luminescence assay and fully differentiated Myotube.

In addition, as shown in FIG. 9, myoblasts are differentiated into myotube cells, and when treated with androglapholide and androglapholide succinate, the differentiation from myoblasts to myotube cells is promoted. was confirmed (Luminescence increased). In addition, it was confirmed that myotube atrophy was inhibited from 1 μM or more for Androglapholide and Androglapholide Succinate to 10 μM or more (Mitochondrial functional activity due to tube length and area and ATP generation activity) judged).

<시험예 2><Test Example 2>

The effect of Androglapholide Succinate on skeletal muscle function by C57BL/10 ScSn-Dmdmdx/J Duchenne type mouse model (THE JACKSON LABORATORY, USA) Grip Strength, Treadmill test was confirmed, and skeletal muscle atrophy was delayed and recovered by measuring the degree of pseudohypertrophy of total lean body mass, tibialis anterior muscle (TA), and quadriceps longus muscle (GS) using dual energy X-ray absorptiometry (DEXA). Or the degree of muscle reduction was confirmed.

<시험예 2-1> 안드로그라폴라이드 석시네이트(Androglapholide Succinate)의 처리에 따른 마우스 장딴지근(GS)의 가성비대화(Pseudohypertrophy)에 미치는 영향을 확인<Test Example 2-1> Confirm the effect on pseudohypertrophy of the mouse calf muscle (GS) according to the treatment of androglapholide succinate (Androglapholide Succinate)

In a 4-week-old C57BL/10ScSn-Dmdmdx/J Duchenne muscular dystrophy mouse model, androglapholide succinate was intraperitoneally administered (I.P.) at a concentration of 30mg/kg for 28 days, followed by dexamemetry (Dual energy X-ray). Using absorptiometry, DEXAmetry), a region of interest (ROI) was designated for the calf muscle (GS) and fat accumulation was measured to determine the effect of the calf muscle (GS) on pseudohypertrophy of the muscle that is converted to fat.

As a result, as shown in FIG. 1 , it was confirmed that the lean mass of the calf muscles (GS) increased and the fat decreased by the Androglapholide Succinate treatment.

<시험예 2-2> 안드로그라폴라이드 석시네이트(Androglapholide Succinate)의 처리에 따른 마우스의 제지방의 가성비대화(Pseudohypertrophy)에 미치는 영향을 확인<Test Example 2-2> Confirmation of the effect on pseudohypertrophy of lean muscle in mice according to the treatment of androglapholide succinate

In the Duchenne muscular dystrophy mouse model, androglapholide succinate was administered intraperitoneally (I.P.) at a concentration of 30 mg/kg for 28 days, and dexamemetry (Dual energy X-ray absorptiometry, DEXAmetry) By measuring the fat distribution, the effect on pseudohypertrophy of total lean body mass was confirmed.

As a result, as shown in FIG. 2 , it was confirmed that the total lean body fat of the mouse was increased and the fat decreased by the androglapholide succinate treatment.

<시험예 2-3> 안드로그라폴라이드 석시네이트(Androglapholide Succinate)의 처리에 따른 듀센형 근이영양증 마우스모델의 앞정강이 전경골(TA)근 위축의 지연 및 예방 또는 치료 효과 확인<Test Example 2-3> Confirmation of the effect of delay and prevention or treatment of anterior tibialis anterior (TA) muscular atrophy in a mouse model of Duchenne muscular dystrophy following the treatment of androglapholide succinate

In a mouse model of Duchenne muscular dystrophy, androglapholide succinate was administered intraperitoneally (I.P.) at a concentration of 30 mg/kg for 28 days using dexamemetry (Dual energy X-ray absorptiometry, DEXAmetry) for the anterior tibialis anterior tibia. The Lean Mass and length (Diameter) of the anterior tibialis anterior bone (TA) of the mouse were confirmed by designating the region of interest (ROI) as (TA).

As a result, as shown in FIG. 3, it was confirmed that the length (Diameter) and Lean Mass of the anterior tibialis anterior bone (TA) were significantly inhibited from being reduced by the administration of Androglapholide Succinate. .

<시험예 2-4> 안드로그라폴라이드 석시네이트(Androglapholide Succinate)의 처리에 따른 듀센형 근이영양증 마우스모델의 근기능 유지 효과 확인<Test Example 2-4> Confirmation of the muscle function maintenance effect of Duchenne muscular dystrophy mouse model according to the treatment of androglapholide succinate

In a mouse model of Duchenne muscular dystrophy, androglapholide succinate was administered intraperitoneally (I.P.) at a concentration of 30mg/kg for 28 days to perform a grip strength test in terms of muscle function. It was measured using Jeongdo BNP Grip strength meter, Korea). The measurement method is the measurement value when the experimenter holds the tail while gently holding the body of the mouse and then pulls the tail at a constant speed and the mouse releases both front paws was recorded. The highest tension out of a total of 5 measurements was considered as the grip strength (g), and the Treadmill test was performed by running the mouse on a treadmill at 14 m/min with a 5˚ inclination, and the speed every minute until reaching 20 m/min. was increased by 2 m/min, and the end of the measurement was confirmed by statistical processing by setting the running rejection as the end point of the measurement despite the mechanical stabbing stimulation and the electric shock stimulation due to the exhaustion of the mouse's physical strength.

As a result, as shown in FIG. 4 , it was confirmed that the treatment of androglapholide succinate had a superior effect in grip strength and treadmill, which are measures of muscle function. .

제조예 1. 약학 조성물의 제조Preparation Example 1. Preparation of a pharmaceutical composition

Preparation Example 1-1. Preparation of powders

Citral 20 mg

Lactose hydrate 100 mg

Talc 10 mg

The above ingredients were mixed and filled in an airtight bag to prepare a powder.

Preparation 1-2. manufacture of tablets

LY2090314 10 mg

Corn Starch 100 mg

Lactose hydrate 100 mg

Magnesium stearate 2 mg

After mixing the above ingredients, tablets were prepared by tableting according to a conventional method for manufacturing tablets.

Preparation Example 1-3. Preparation of capsules

LY2090314 10 mg

Microcrystalline Cellulose 3 mg

Lactose hydrate 14.8 mg

Magnesium stearate 0.2 mg

After mixing the above ingredients, the capsules were prepared by filling in gelatin capsules according to the usual method for preparing capsules.

Preparation Example 1-4. manufacture of injections

LY2090314 10 mg

mannitol 180 mg

Sterile distilled water for injection 2974 mg

Sodium monohydrogen phosphate 26 mg

After mixing the above ingredients, the content of the above components per 1 ampoule (2 mL) was prepared according to a conventional method for preparing injections.

Preparation Example 1-5. Preparation of liquids

LY2090314 10 mg

isomerized sugar 10 mg

mannitol 5 mg

Purified water appropriate amount

Lemon flavored amount

The above components are dissolved by adding each component to purified water according to a conventional manufacturing method, and after adding an appropriate amount of lemon flavor, purified water is added to adjust the total volume to 100 mL, sterilized, and filled in a brown bottle to prepare a solution.

제조예 2. 건강식품의 제조Preparation Example 2. Preparation of health food

Preparation Example 2-1. Manufacturing of health supplements

LY2090314 10 mg

appropriate amount of vitamin mixture

70 μg of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

Biotin 10 μg

Nicotinamide 1.7 mg

50 μg of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture appropriate amount

Ferrous sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium citrate 30 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

The composition ratio of the vitamin and mineral mixture is a composition that is relatively suitable for health food in a preferred embodiment, but the mixing ratio may be arbitrarily modified. , to prepare granules, and can be used in the manufacture of health food compositions according to a conventional method.

Preparation Example 2-2. Manufacturing of health drinks

LY2090314 10 mg

15 g vitamin C

100 g vitamin E (powder)

19.75 g of iron lactate

3.5 g zinc oxide

3.5 g of nicotinic acid amide

0.2 g vitamin A

0.25 g of vitamin B1

0.3 g of vitamin B2

Purified water quantitative

After mixing the above ingredients according to a conventional health drink manufacturing method, after stirring and heating at 85 for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2l container, sealed and sterilized, and then refrigerated. It is used in the manufacture of health beverage compositions.

Although the composition ratio is prepared by mixing ingredients suitable for relatively favorite beverages in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and national preferences such as demanding class, demanding country, and use.

Claims

A pharmaceutical composition for the prevention or treatment of muscle aging-related diseases comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[Formula 1]
The method of claim 1, wherein the muscle aging-related disease is senile sarcopenia, atony, muscular atrophy, muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia gravis, myositis, muscle calcification, A pharmaceutical composition that is one or more diseases selected from the group consisting of muscle ossification, muscle weakness-related diseases, and cachexia.
The pharmaceutical composition according to claim 1, wherein the composition promotes mitochondrial functional activity.
According to claim 1, wherein the composition is administered by one or more methods selected from the group consisting of intravenous, intradermal, inhalation, transdermal (topical), intraorbital, subcutaneous, intramuscular, oral and transmucosal administration. enemy composition.
The composition of claim 1, wherein the composition is selected from the group consisting of orbicularis muscle, masticatory muscle, tongue and neck muscle, rib cage and arm muscle, arm and shoulder, intrinsic muscle of hand, lower extremity and leg muscle, forelimb and foot muscle. A pharmaceutical composition that is delivered to one or more selected target tissues.
The pharmaceutical composition according to claim 1, wherein the disease is induced by steroids or atrophic factors.
A food composition for preventing or improving muscle aging-related diseases, comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[Formula 1]
The method of claim 7, wherein the muscle aging-related disease is senile sarcopenia, atony, muscular atrophy, muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia gravis, myositis, muscle calcification, A food composition that is one or more diseases selected from the group consisting of muscle ossification and cachexia.
The food composition according to claim 7, wherein the composition promotes mitochondrial functional activity.
8. The method of claim 7, wherein the composition is selected from the group consisting of orbicularis muscle, masticatory muscle, tongue and neck muscle, rib cage and arm muscle, arm and shoulder, intrinsic muscle of hand, lower extremity and leg muscle, forelimb and foot muscle. A food composition that is delivered to one or more selected target tissues.
The food composition of claim 7, wherein the disease is induced by steroids or cell atrophic factors (Atrophic factor).
A pharmaceutical composition for preventing or treating a hereditary muscle disease comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[Formula 1]
The method according to claim 12, wherein the hereditary muscle disease is Duchenne muscular dystrophy, Becker muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, Facioscapulohumeral muscular dystrophy. Dystrophy), zone-type muscular dystrophy (Llimb-Girdle Muscular Dystrophy), type 1 muscle tonic dystrophy (Myotonic Dystrophy) and type 2 muscle tone dystrophy will be selected from the group consisting of, a pharmaceutical composition.
The method of claim 12, wherein the composition is administered by one or more methods selected from the group consisting of intravenous, intradermal, inhalation, transdermal (topical), intraorbital, subcutaneous, intramuscular, oral and transmucosal administration. enemy composition.
13. The method of claim 12, wherein the composition is selected from the group consisting of orbicularis muscle, masticatory muscle, tongue and neck muscle, rib cage and arm muscle, arm and shoulder, intrinsic muscle of hand, lower extremity and leg muscle, forelimb and foot muscle. A pharmaceutical composition that is delivered to one or more selected target tissues.
A food composition for preventing or improving hereditary muscle disease comprising a compound represented by the following formula (1), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[Formula 1]
The food composition of claim 16, wherein the hereditary muscle disease is Duchenne muscular dystrophy.
17. The method of claim 16, wherein the composition is selected from the group consisting of orbicularis muscle, masticatory muscle, tongue and neck muscle, rib cage and arm muscle, arm and shoulder, intrinsic muscle of hand, lower extremity and leg muscle, forelimb and foot muscle. A food composition that is delivered to one or more selected target tissues.