KR20220041265A - Composition for Preventing or Treating Muscular disease containing Valproic Acid - Google Patents

Abstract

Valproic acid according to the present invention inhibits skeletal muscle cell atrophy, suppresses reduction in grip strength and lean body mass, and prevents the loss of the anterior shin anterior tibial muscle and the calf muscle, thereby being able to be usefully used for the treatment of various muscle diseases.

Description

A composition for preventing or treating muscle disease containing valproic acid as an active ingredient {Composition for Preventing or Treating Muscular disease containing Valproic Acid}

The present invention relates to a composition for preventing or treating muscle disease containing valproic acid as an active ingredient.

Muscle is responsible for about 40% of the human body, and in order to maintain the functional ability of the human body and prevent metabolic diseases, it is essential to secure an appropriate muscle mass. It is largely divided into smooth muscle, cardiac muscle, and skeletal muscle, and skeletal muscle occupies a significant portion of the entire body and promotes skeletal movement.

Muscular disease progresses through a process in which independent living becomes impossible due to the weakening of skeletal muscles, which gradually impairs walking and mobility functions and makes activities of daily living (ADL) difficult. In addition, since it causes cardiopulmonary dysfunction and other complications, it is important to accurately understand and approach the characteristics of each muscle disease.

In sarcopenia, the motor nerve that induces skeletal muscle contraction degenerates, so that skeletal muscle contraction does not proceed, or normal skeletal muscle contraction does not proceed because the expression of a protein involved in muscle contraction in skeletal muscle is reduced or altered. In the long term, it is known that the motor nerve or skeletal muscle is transformed into a fibrous tissue. It is also known to be caused by various causes such as aging, hormonal abnormalities, malnutrition, lack of physical activity, and inflammation and degenerative diseases.

Muscular atrophy (muscular atrophy) is a disease in which the muscles of the extremities are atrophied, and the expression of MuRF-1 and Atrogin-1 is increased to break down the myosin heavy chain in the muscle, resulting in muscle atrophy in which the size of the muscle decreases. it is known

As a general method for preventing the aforementioned muscle disease, exercise, protein and calorie supplementation are known to be helpful, but it is not very helpful for most patients. In addition, drugs that have a direct effect on improving muscle loss and increasing muscle mass are still at the stage of clinical trials, and currently no drugs have finally received FDA approval. Accordingly, there is an urgent need to develop drugs for muscle diseases, particularly sarcopenia.

The present invention is to provide a pharmaceutical composition for preventing or treating muscle disease, and a food composition containing valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient.

An object of the present invention is to provide a food composition for muscle strengthening containing valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient.

One object of the present invention, to provide a pharmaceutical composition for the prevention and treatment of muscle diseases containing valproic acid (Valproic Acid) or a pharmaceutically acceptable salt of valproic acid as an active ingredient.

In addition, the present invention provides a food composition for preventing or improving muscle disease containing valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient.

In addition, the present invention provides a food composition for strengthening muscles containing valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient.

Valproic Acid or a salt thereof according to the present invention inhibits skeletal muscle cell atrophy, suppresses reduction in grip strength and lean body mass, as well as prevents the loss of the anterior tibialis anterior muscle and the calf muscle. It can be usefully used for treatment.

1 is a result of measuring the ATP activity of valproic acid in skeletal muscle cells and the inhibitory effect of muscle canal atrophy.
2 is a result of measuring and showing the inhibitory effect of muscle canal atrophy when valproic acid is treated in various concentrations in skeletal muscle cells.
3 is a graph showing changes in total body weight of a normal diet group, a Valproc acid group, an Exendin-4 group, and a fasting group.
4 is a graph showing the evaluation of the strength (Grip strength) ability of the normal diet group, the Valproc acid group, the Exendin-4 group and the fasting group.
5 shows the results of lean-fat and T1 (tibialis anterior) measurements for the normal diet group, Valproc acid group, Exendin-4 group, and the fasting group.
6 is a graph showing the change and weight of the gastrocnemius muscle in the normal diet group, the Valproc acid group, the Exendin-4 group and the fasting group.

While the present inventors were conducting various studies to develop natural substances for preventing and treating muscle diseases, valproic acid inhibits skeletal muscle cell atrophy, inhibits muscle strength and skeletal muscle atrophy, inhibits and restores tibialis anterior muscle loss, inhibits lean body mass loss and It was confirmed that the recovery effect was achieved, and the therapeutic agent for muscle disease of valproic acid was not known at all until now, and it is very significant in that it was developed for the first time by the present inventors.

The present invention relates to a pharmaceutical composition for the prevention or treatment of muscle disease containing valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient, and a muscle containing valproic acid as an active ingredient It relates to a food composition for preventing or improving disease.

The pharmaceutically acceptable salt may be an alkali metal salt or an alkaline earth metal salt, preferably a sodium salt, and most preferably sodium valproate.

The present invention relates to a composition for preventing or treating skeletal muscle atrophy or sarcopenia of valproic acid. ) and skeletal muscle atrophy using dual energy X-ray absorptiometry (DEXA), the inhibition and recovery of tibialis anterior muscle loss, inhibition and recovery of lean muscle mass, and the degree of recovery of gastrocnemius muscle were confirmed.

As the valproic acid compound according to the present invention, commercially available ones may be used, or those isolated from nature or prepared by chemical synthesis known in the art may be used.

Specifically, it can be seen that the composition containing the valproic acid or a pharmaceutically acceptable salt of valproic acid of the present invention as an active ingredient can be used for the prevention, improvement and treatment of muscle diseases. .

The muscle disease is sarcopenia, dystonia (atony), muscular dystrophy (muscular dystrophy), muscular atrophy (muscular atrophy), muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia gravis and cachexia (cachexia) from the group consisting of It may be one or more selected muscle diseases, preferably sarcopenia, and preferably sarcopenia induced by fasting.

Sarcopenia (sarcopenia) is a disease characterized by a decrease in the number or size of muscle fibers (myocytes) caused by various causes such as long bedtime, nutritional deficiency, reduced activity, and peripheral neuropathy. Skeletal sarcopenia can lead to muscle functional decline, weakness, and impaired activity, and furthermore, there is a risk of inducing metabolic diseases. The recent accelerated aging and increased inflammation due to increased stress, disruption of biological protein function, and hormonal changes are further amplifying the occurrence of sarcopenia.

The valproic acid was first manufactured in 1881 and started to be used for medicinal purposes in 1962, and is listed as the most essential and effective safe WHO essential medicine list in the medical system. It has the same chemical name as valproate, and although it is valproate or divalproex in the form of a drug, it is mainly known as valproic acid that acts on the human body. Although it is widely known as a migraine preventive agent for treating epilepsy and bipolar disorder, the size reduction (atrophy) and atrophy of skeletal muscle due to nutritional fasting has not been known at all so far, and the present inventors are While searching for substances for development, it was confirmed that valproic acid effectively controlled the inhibition of fasting-induced muscle atrophy and the recovery following a 75% restriction diet.

The valproic acid may be represented by the following formula (1).

[Formula 1]

Valproic acid of the present invention is broadly meant to include processed products formulated for administration to animals, such as valproic acid powder.

The valproic acid or salt thereof of the present invention inhibits the production of ATP in skeletal muscle cells and the reduction of the myotube diameter by TNF-α, the inhibition of weight loss in the in vivo fasting model, the inhibition of the reduction of grip strength, It can suppress fat loss and promote recovery according to 75% restriction diet, suppress anterior tibialis anterior muscle loss, and promote recovery according to 75% restriction diet, and suppress calf muscle loss.

Meanwhile, in the present specification, the term 'contained as an active ingredient' means including an amount sufficient to achieve the efficacy or activity of the active ingredient. For example, the valproic acid (Valproic Acid) is used at a concentration of 1 to 400 μM, preferably 10 to 300 μM. Since Valproic Acid or a salt thereof does not have side effects to the human body even when administered in excess, the upper quantitative limit of Valproic Acid or a salt thereof included in the composition of the present invention may be selected and implemented by those skilled in the art within an appropriate range. can

The pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant includes an excipient, a disintegrant, a sweetener, a binder, a coating agent, an expanding agent, a lubricant, A lubricant or flavoring agent may be used.

The pharmaceutical composition may be preferably formulated as a pharmaceutical composition by including one or more pharmaceutically acceptable carriers in addition to the active ingredients described above for administration.

Formulations of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectables. For example, for formulation in the form of a tablet or capsule, the active ingredient may be combined with an orally, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. In addition, if desired or required, suitable binders, lubricants, disintegrants and color-developers may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacanth or sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.

In the composition formulated as a liquid solution, acceptable pharmaceutical carriers are sterile and biocompatible, and include saline, sterile water, Ringer's solution, buffered saline, albumin injection, dextrose solution, maltodextrin solution, glycerol, ethanol and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostats may be added as needed. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to form an injectable formulation such as an aqueous solution, suspension, emulsion, etc., pills, capsules, granules or tablets.

Furthermore, by using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA by an appropriate method in the art, it can be preferably formulated according to each disease or component.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration.

A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration method, age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and response sensitivity of the patient, usually Thus, a skilled physician can easily determine and prescribe an effective dosage for the desired treatment or prevention. According to a preferred embodiment of the present invention, the daily dose of the pharmaceutical composition of the present invention is 0.001-10 g/kg.

The pharmaceutical composition of the present invention is prepared in unit dosage form by formulating using a pharmaceutically acceptable carrier and/or excipient according to a method that can be easily carried out by a person of ordinary skill in the art to which the present invention pertains. Alternatively, it may be prepared by being introduced into a multi-dose container. At this time, the formulation may be in the form of a solution, suspension, or emulsion in oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or stabilizer.

In addition, the present invention provides a food composition containing valproic acid as an active ingredient to prevent, treat or improve muscle diseases.

The food composition according to the present invention may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, sweets, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, gums, ice cream, vitamin complexes, health supplements , food additives, etc.

The food composition of the present invention may include a mixture containing valproic acid as an active ingredient, as well as ingredients commonly added during food production, for example, proteins, carbohydrates, fats, nutrients, seasoning and flavoring agents. Examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared as a drink or beverage, citric acid, high fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts in addition to the valproic acid of the present invention are additionally added. can be included

The present invention provides a health functional food comprising a food composition for the prevention, treatment or improvement of muscle disease comprising valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient. Health functional food is a food prepared by adding valproic acid or its salt to food materials such as beverages, teas, spices, gum, and confectionery, or by encapsulating, powdering, or suspension. It means that it brings a specific effect on health, but unlike general drugs, it has the advantage of not having side effects that may occur when taking the drug for a long time using food as a raw material. The health functional food of the present invention obtained in this way is very useful because it can be ingested on a daily basis. The amount of valproic acid or its salt added in such health functional food cannot be defined uniformly because it varies depending on the type of health functional food, but it can be added within the range that does not impair the original taste of the food. , It is usually in the range of 0.01 to 50% by weight, preferably 0.1 to 20% by weight, based on the target food. In addition, in the case of a health functional food in the form of pills, granules, tablets or capsules, it is usually added in an amount of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.

In addition, the present invention provides the use of valproic acid or a pharmaceutically acceptable salt of valproic acid for the manufacture of a medicament or food for the prevention, treatment or improvement of muscle-related diseases. As described above, valproic acid or a pharmaceutically acceptable salt of valproic acid may be used for muscle diseases.

In addition, the present invention provides a method for improving, preventing or treating a muscle disease, comprising administering to a mammal an effective amount of valproic acid or a pharmaceutically acceptable salt of valproic acid.

As used herein, the term "mammal" refers to a mammal that is the subject of treatment, observation or experimentation, preferably a human.

As used herein, the term "effective amount" refers to the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human as conceived by a researcher, veterinarian, physician or other clinician, which an amount that induces alleviation of the symptoms of a disease or disorder. It is apparent to those skilled in the art that the effective amount and frequency of administration for the active ingredient of the present invention will vary depending on the desired effect. Therefore, the optimal dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the content of active ingredients and other components contained in the composition, the type of formulation, and the age, weight, and general health of the patient It can be adjusted according to various factors including state, sex and diet, administration time, administration route and secretion rate of the composition, treatment period, and concurrently used drugs. In the prevention, treatment or improvement method of the present invention, for adults, when valproic acid is administered once to several times a day, it is preferably administered at a dose of 0.001 g/kg to 10 g/kg. .

In the treatment method of the present invention, the composition comprising valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient is oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal. , transdermal, topical, intraocular or intradermal routes.

The present invention relates to a food composition for strengthening muscles containing valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient. The composition includes a food composition or a health functional food. "Strengthening" refers to a phenomenon in which overall muscle strength is strengthened due to an increase in muscle strength and muscle density, an increase in skeletal muscle mass or an improvement in muscle function, and does not refer to an effect limited to a patient group of a specific disease.

The food composition according to the present invention may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, sweets, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, gums, ice cream, vitamin complexes, health supplements , food additives, etc.

The food composition of the present invention may include a mixture containing valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient, as well as ingredients commonly added during food production, for example For example, proteins, carbohydrates, fats, nutrients, seasonings and flavoring agents. Examples of the above-mentioned carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose, oligosaccharides and the like; and polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is prepared as a drink or beverage, citric acid, high fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts may be additionally included in addition to the valproic acid of the present invention. .

The present invention provides a health functional food comprising a food composition for the prevention, treatment or improvement of muscle disease comprising valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient. Health functional food refers to food prepared by adding active ingredients to food materials such as beverages, teas, spices, gum, and confectionery, or by encapsulating, powdering, or suspension, etc. However, unlike general drugs, it has the advantage of not having side effects that may occur when taking the drug for a long period of time by using food as a raw material. The health functional food of the present invention obtained in this way is very useful because it can be ingested on a daily basis. The amount of the active ingredient added in such a health functional food varies depending on the type of health functional food and cannot be uniformly defined, but may be added within a range that does not impair the original taste of the food, and is usually 0.01 to 50% by weight, preferably 0.1 to 20% by weight. In addition, in the case of a health functional food in the form of pills, granules, tablets or capsules, it is usually added in an amount of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.

In addition, the present invention provides a feed composition comprising valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient. The valproic acid or a pharmaceutically acceptable salt of valproic acid may be prepared in the same manner as in the case of the pharmaceutical composition or the food composition. Since the valproic acid of the present invention exhibits an overall muscle strength increase or strengthening effect due to an increase in skeletal muscle mass or an improvement in muscle function, it may be included in a feed composition as a growth promoter for animals or livestock. Specifically, the feed containing valproic acid according to the present invention as an active ingredient can be prepared in various types of feed known in the art, and preferably, a concentrated feed, roughage or special feed may be included.

The feed composition according to the present invention may include various feed additives.

In the present invention, the feed additive refers to a substance added to the feed for the purpose of various effects such as nutrient supplementation and weight loss prevention, enhancement of digestibility of fiber in feed, improvement of oil quality, prevention of reproductive disorders and improvement of fertility rate, and prevention of high temperature stress in summer. The feed additive of the present invention corresponds to an auxiliary feed under the Feed Management Act, and is a mineral preparation such as sodium bicarbonate (bicarbonate), bentonite, magnesium oxide, and composite minerals, and trace minerals such as zinc, copper, cobalt, and selenium. Preparations, kerotene, vitamin E, vitamins A, D, E, nicotinic acid, vitamins such as vitamin B complex, protective amino acids such as methionine and lyic acid, protective fatty acids such as fatty acid calcium salt, probiotics (lactic acid bacteria), yeast culture Water, live bacteria such as mold fermented products, yeast agents, and the like may be further included.

The feed composition according to the present invention is not particularly limited as long as it is an individual for the purpose of increasing or enhancing overall muscle strength and promoting growth due to an increase in skeletal muscle mass or improvement in muscle function, and any type of feed composition may be applied. The subject includes animals, such as non-primates (eg, cattle, pigs, horses, cats, dogs, rats, and mice) and primates (eg, monkeys, such as cynomolgous monkeys and mammals including chimpanzees). In another embodiment, the subject is a livestock animal (eg, horse, cow, pig, etc.) or pet animal (eg, dog or cat). Also fish, such as halibut, flounder, eel, freshwater eel, sea eel, eel.

The dosage of the feed composition according to the present invention will depend on a number of factors such as the species, size, weight and age of the animal. In principle, a typical dosage may range from 0.001 to 10 g per animal/day. However, the present invention is not limited thereto.

Hereinafter, preferred examples are presented to help the understanding of the present invention, but the following examples are merely illustrative of the present invention, and it will be apparent to those skilled in the art that various changes and modifications are possible within the scope and spirit of the present invention, It goes without saying that such variations and modifications fall within the scope of the appended claims.

Example 1

A commercially available (Sigma-Aldrich) valproic acid reagent having the structure of Formula 1 was purchased and used.

[Formula 1]

Test Example 1

C2C12 cells were aliquoted at 6×10 ⁵ cells/well in a 6 well plate and cultured for 24 hours. After 24 hours, it was replaced with a differentiation medium for cell differentiation, and the medium was changed every other day for 6 days. After 6 days, 10 μM valproic acid of Example 1 or 50 nM Exendin-4 + 10 ng/ml TNF-α was treated to react for 48 hours again. After 48 hours of reaction, the width of the cell root canal was checked with an optical microscope equipped with a digital camera.

1 is a result of measuring the ATP activity of valproic acid in skeletal muscle cells and the inhibitory effect of muscle canal atrophy.

As shown in FIG. 1 , when valproic acid was treated in skeletal muscle cells, it was confirmed that ATP activity and atrophy of myotubes were inhibited.

Test Example 2

C2C12 cells were aliquoted at 6×10 ⁵ cells/well in a 6 well plate and cultured for 24 hours. After 24 hours, it was replaced with a differentiation medium for cell differentiation, and the medium was changed every other day for 6 days. After 6 days, various concentrations (0, 0.01, 0.1, 1, 10, 30 μM) of Example 1 + 10 ng/ml TNF-α were treated and the reaction was performed again for 48 hours. After 48 hours of reaction, the width of the cell root canal was checked with an optical microscope equipped with a digital camera.

2 is a result of measuring and showing the inhibitory effect of muscle canal atrophy when valproic acid is treated in various concentrations in skeletal muscle cells.

As shown in FIG. 2 , it was confirmed that when the skeletal muscle cells were treated with 1 μM or more of valproic acid, the atrophy of the root canal was inhibited.

Test Example 3

1) Experimental animals

As the experimental animal, a C57BL/6 mouse 11-week-old model (male) was used. During breeding, the lighting time was set to 12 hours (07:00 to 19:00), and food and water were freely consumed.

2) Muscle loss model and sample

As shown in FIG. 3, after obtaining and acclimatizing the experimental animals, the experiment was performed by designing as shown in Table 1 below. For the feed, solid feed for experimental animals (Hana Bio, Seongnam, Gyeonggi-do, Korea) was provided, and the experimental animals were treated within a certain period of time (10:00-12:00 am). Changes in body weight were measured weekly. Individuals in the fasting group were housed in individual cages during the fasting period. Sample administration was administered once a week for a total of 20 times.

group process number of individuals normal diet (control) normal diet 9 Fasting 7~9 weeks 100% fast, 10~21 weeks 75% fast 9 Valproc acid group (experimental group) 100% fasting for 7~9 weeks, 75% fasting for 10~21 weeks + 10 μM of valproic acid administered once a week for a total of 20 times 9 Exendin-4 group (positive control group) 100% fasting for 7~9 weeks, 75% fasting for 10~21 weeks + 10 μM of valproic acid administered once a week for a total of 20 times 9

3) Weight change

Weight changes of the normal diet group, Valproc acid group, Exendin-4 group and fasting group were measured every week.

3 is a graph showing the total weight change of the normal diet group, the Valproc acid group, the Exendin-4 group and the fasting group. According to this, it can be seen that there is no significant change in body weight in the remaining groups except for the control group.

4) strength training

A grip strength test was performed to measure the grip strength. The maximum force presented when the forelimbs of the animal models of each group that pulled the tails horizontally in this state could no longer grip the rods of the device by holding the tails of the animal models of each group and allowing the rods of the device to be gripped with both forelimbs. was considered as the grip strength (g). Measurements were made once a week and 20 measurements were taken for each mouse. At this time, the force (grip strength) (g) for the weight of the animal model of each group was calculated and shown.

4 is a graph showing the evaluation of the grip strength ability of the normal diet group, the Valproc acid group, the Exendin-4 group and the fasting group. At the time, it was confirmed that the muscle strength was improved statistically significantly.

Thus, it was confirmed that the valproic acid of Example 1 according to the present invention is excellent in the efficacy of improving muscle strength.

5) Protective effect against muscle atrophy and recovery effect

The size of T1 (Tibialis anterior) was measured and compared from two-dimensional images taken by dual energy X-ray absorptiometry for the normal diet group, Valproc acid group, Exendin-4 group, and the fasting group.

Figure 5 shows the results of lean-fat and T1 (tibialis anterior) measurements for the normal diet group, Valproc acid group, Exendin-4 group, and the fasting group. Compared with the group, it was confirmed that the lean body mass increased statistically and the muscle atrophy inhibition/recovery effect on T1 was improved.

6) muscle tissue weight

In order to confirm the muscle loss, the weight of the tibialis anterior muscle (TA.M) and the gastrocnemius muscle (GA) was measured after autopsy and shown in FIG. 6 .

Figure 6 is the result of measuring the change and weight of the gastrocnemius muscle in the normal diet group, Valproc acid group, Exendin-4 group and the fasting group. According to this, the weight of the tibialis anterior muscle reduced due to fasting was It was increased by administration of proic acid, and the same result was confirmed in the calf muscle. The above result is expected by restoring the muscle mass lost by the valproic acid of Example 1 increasing protein synthesis in the muscle.

Claims (5)

A pharmaceutical composition for preventing and treating muscle diseases, comprising Valproic Acid or a pharmaceutically acceptable salt of Valproic acid as an active ingredient. The method of claim 1,
The valproic acid is a pharmaceutical composition for the prevention and treatment of muscle diseases, characterized in that represented by the following formula (1):
[Formula 1]

The method of claim 1,
The muscle disease is sarcopenia, dystonia (atony), muscular dystrophy (muscular dystrophy), muscular atrophy (muscular atrophy), muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia gravis and cachexia (cachexia) from the group consisting of A pharmaceutical composition for the prevention and treatment of muscle disease, characterized in that it is one or more selected muscle diseases. A food composition for preventing or improving muscle disease, comprising Valproic Acid or a pharmaceutically acceptable salt of Valproic acid as an active ingredient. A food composition for strengthening muscle strength containing valproic acid or a pharmaceutically acceptable salt of valproic acid as an active ingredient.

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