KR20230138595A - Pharmaceutical composition for preventing or treating muscle disease containing Levodropropizine as an active ingredient - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for the prevention or treatment of muscle diseases containing levodropropizine as an active ingredient. Since the pharmaceutical composition can effectively inhibit muscle atrophy, it is used for the prevention, treatment or alleviation of muscle diseases such as muscular atrophy. One aspect of the present invention provides the pharmaceutical composition for preventing or treating muscle atrophy containing levodropropizine represented by chemical formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.

Description

Composition for preventing, treating or improving muscle disease containing levodropropizine as an active ingredient {Pharmaceutical composition for preventing or treating muscle disease containing Levodropropizine as an active ingredient}

The present invention relates to a pharmaceutical composition for preventing or treating muscle diseases containing levodropropizine as an active ingredient.

Muscles are classified into skeletal muscle, smooth muscle, and cardiac muscle in terms of structure and function. Among these, skeletal muscle is located directly under the skin of the hands, feet, chest, and stomach, and supports bones and tendons throughout the body. There are about 600 voluntary muscles attached to bones. Skeletal muscle accounts for 40 to 50% of body weight and performs functions such as maintaining body temperature and generating energy. Additionally, skeletal muscles move or support bones through contraction, and at this time, muscle contraction occurs and is controlled by nerve signals.

Skeletal muscle atrophy is a condition in which the amount of skeletal muscle is reduced or completely lost, resulting in a decrease in the ability to support the human body or exercise. Skeletal muscle atrophy occurs due to denervation due to trauma, and causes conditions such as resting recumbency or joint immobilization. It is classified into skeletal muscle atrophy (pulmonary atrophy) that occurs due to immobility.

Skeletal muscle atrophy is generally associated with reduced blood supply to the muscles, lack of exercise (immobilization), persistent weight loss, malnutrition or starvation, cancer, AIDS, congestive heart failure, and chronic obstructive pulmonary disease. It is known to be caused by a variety of causes, including pulmonary disease, renal failure, and severe burns.

Among them, dexamethasone is used to treat several diseases such as cancer, but it reduces the rate of protein synthesis in skeletal muscle and increases the rate of protein degradation through the ubiquitin-proteasome system, causing muscle atrophy. Two muscle ubiquitin ligases are related to Atrogin-1 and MuRF1. Dexamethasone reduces MyoD (myogenic differentiation antigen) through Atrogin-1, and this mechanism leads to a decrease in muscle mass.

A common method to treat skeletal muscle atrophy is prevention of muscle loss through exercise, but no fundamental treatment currently available on the market has been reported.

Accordingly, the present inventors completed the present invention by conducting research to develop a therapeutic agent that is excellent in preventing, treating, and improving muscle atrophy.

Republic of Korea Patent Publication No. 10-2022-0014187

One object of the present invention is to provide a pharmaceutical composition for preventing or treating muscle atrophy containing levodropropizine represented by Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient. :

Another object of the present invention is to provide a food composition for preventing or improving muscle atrophy containing levodropropizine represented by Formula 1 or a foodologically acceptable salt thereof as an active ingredient:

[Formula 1]

.

Another object of the present invention is to provide a health functional food composition for preventing or improving muscle atrophy containing levodropropizine represented by Formula 1 or a foodologically acceptable salt thereof as an active ingredient:

[Formula 1]

.

One aspect of the present invention provides a pharmaceutical composition for preventing or treating muscle atrophy containing levodropropizine or a pharmaceutically acceptable salt thereof represented by Formula 1 as an active ingredient:

[Formula 1]

.

The term “muscular atrophy” used in the present invention has the same meaning as “skeletal muscle atrophy” and refers to the loss of size and mass of muscle cells and muscle tissue. This type of muscle atrophy may be caused by a variety of reasons, such as being unable to move for a long time due to aging, serious illness, nerve damage, etc., or malnutrition.

The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical composition of the present invention are those commonly used in the manufacture of drugs, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, and gelatin. , calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, etc. It is not limited. In addition to the above ingredients, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (22nd ed., 2013).

The pharmaceutical composition of the present invention may contain various bases and/or additives necessary and appropriate for the formulation of the dosage form, and may include non-ionic surfactants, silicone polymers, extenders, fragrances, and preservatives within the range that do not reduce the effectiveness. , disinfectants, oxidation stabilizers, organic solvents, ionic or non-ionic thickeners, softeners, antioxidants, free radical destroyers, opacifiers, stabilizers, emollients, silicones, α-hydroxy acids, anti-foaming agents, humectants. , vitamins, insect repellent, fragrance, preservative, surfactant, anti-inflammatory agent, substance P antagonist, filler, polymer, propellant, alkalinizing or acidifying agent, or colorant.

The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. It can be. The dosage of the pharmaceutical composition of the present invention may be 0.001 to 1000 mg/kg for adults.

The pharmaceutical composition of the present invention can be administered orally or parenterally.

The pharmaceutical composition of the present invention can be administered in various dosage forms when administered orally. It may be administered in the form of solid preparations such as pills, powders, granules, tablets, or capsules, and may be administered in the form of various excipients such as wetting agents and sweeteners. , fragrances, preservatives, etc. may be further included. For example, when the composition of the present invention is formulated in the form of powder, granule, tablet or capsule, it may further include appropriate carriers, excipients and diluents commonly used in its preparation. The carriers, excipients and diluents include, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and/or mineral oil may be used, but are not limited to these. In addition, it may be prepared including diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants commonly used in formulation, and may further include lubricants such as magnesium stearate or talc in addition to the above excipients. .

The pharmaceutical composition of the present invention can be administered in various dosage forms when administered parenterally. Solid preparations include tablets, pills, powders, granules, capsules, etc., and liquid preparations include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water, liquid, and paraffin, various excipients such as humectants, sweeteners, fragrances, and preservatives may be included. Preparations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, and lyophilized preparations. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. Additionally, calcium or vitamin D3 can be added to improve the efficacy of the treatment.

Such compositions may be presented in unit-dose (single-dose) or multi-dose (several-dose) containers, such as sealed ampoules and vials, and may be immersed in a sterile liquid carrier, e.g., water for injection, immediately before use. It can be stored under freeze-drying conditions, which only requires the addition of . Ready-to-use preparations and suspensions can be prepared from sterile powders, granules and tablets.

According to one embodiment of the present invention, the muscle atrophy may be caused by any one selected from the group consisting of cancerous cachexia, muscle loss, aging, obesity, long-term administration of steroids, and space flight.

According to one embodiment of the present invention, the muscle aging-related diseases include senile sarcopenia, atony, muscular atrophy, muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia gravis, myositis, It may be any one disease selected from the group consisting of muscle calcification, muscle ossification, muscle weakness-related disease, and cachexia.

According to one embodiment of the present invention, the composition is used in the orbicularis oculi, masticatory muscles, tongue and neck muscles, thoracic girdle and arm muscles, arm and shoulder, intrinsic muscles of the hand, lower extremity and leg muscles, forelimb and foot muscles. It can be delivered to one or more target tissues selected from the group consisting of

According to one embodiment of the present invention, the steroid agent may be dexamethasone.

Levodropropizine, the active ingredient of the pharmaceutical composition of the present invention, can effectively prevent or treat muscle atrophy, a side effect caused by long-term administration of steroids, especially dexamethasone. That is, effective prevention or treatment of muscle atrophy is possible by administering the pharmaceutical composition of the present invention before and/or after administration of dexamethasone.

Another aspect of the present invention provides a food composition for preventing or improving muscle atrophy containing levodropropizine represented by Formula 1 or a foodologically acceptable salt thereof as an active ingredient:

[Formula 1]

.

When the composition of the present invention is manufactured as a food composition, the food may include drinks, meat, sausages, bread, biscuits, rice cakes, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, There are various soups, beverages, alcoholic beverages, vitamin complexes, dairy products and milk products, and it includes all health functional foods in the conventional sense.

In addition, it may contain ingredients commonly added during food production, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents. Examples of carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, oligosaccharides, etc.; and polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As a flavoring agent, natural flavoring agents (thaumatin, stevia extract (e.g., 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 manufactured as a drink, in addition to the levodropropizine of the present invention, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, Eucommia extract, jujube extract and/or licorice extract, etc. This may be additionally included.

In addition, the food composition of the present invention contains various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and It may contain salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.

These ingredients can be used independently or in combination, and the ratio of these additives can be selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the food composition of the present invention, but is not limited thereto.

According to one embodiment of the present invention, the muscle atrophy may be caused by long-term administration of dexamethasone.

Another aspect of the present invention provides a health functional food composition for preventing or improving muscle atrophy containing levodropropizine or a foodologically acceptable salt thereof represented by Chemical Formula 1 as an active ingredient:

[Formula 1]

.

The health functional food composition according to the present invention can be added as is to health functional food or used together with other foods or food ingredients, and can be used appropriately according to conventional methods. The mixing amount of the effective substance can be appropriately determined depending on the purpose of use (prevention or improvement). Generally, the amount of the composition in a health functional food may be 0.1 to 90 parts by weight of the total weight of the food. However, in the case of long-term intake for the purpose of maintaining health or regulating health, the amount may be below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.

The health functional food composition of the present invention has no particular restrictions on other ingredients other than containing levodropropizine, the active substance of the health functional food of the present invention, as an essential ingredient in the indicated ratio, and has various flavoring agents or natural ingredients like ordinary foods. It may contain additional ingredients such as carbohydrates. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The ratio of the natural carbohydrate may be generally about 1 to 20 parts by weight, preferably about 5 to 12 parts by weight, per 100 parts by weight of the health functional food composition of the present invention, but is not limited thereto.

In addition to the above, the health functional food composition containing the active substances of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and thickening agents (cheese, chocolate, etc.), and pects. It may contain acids and their salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc. In addition, the health functional food composition of the present invention may contain pulp for the production of natural fruit juice, fruit juice drinks, and vegetable drinks.

These ingredients can be used independently or in combination. The ratio of these ingredients is not that important, but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the health functional food composition containing the active substance of the present invention, but is not limited thereto.

According to one embodiment of the present invention, the muscle atrophy may be caused by long-term administration of dexamethasone.

According to a pharmaceutical composition for the prevention or treatment of muscle diseases containing levodropropizine as an active ingredient, it can effectively suppress muscle atrophy, so it can be usefully used for the prevention, treatment or improvement of muscle diseases such as muscle atrophy. You can.

Figure 1 is a photograph and graph showing the effects of dexamethasone treatment on the anterior tibial photograph (a), front leg strength (b), anterior tibial muscle length (c), and lean muscle mass (d).
Figure 2 shows a photograph of the tibialis anterior (TA) according to levodropropizine treatment (a), lean muscle mass of the tibialis anterior (b), muscle length of the tibialis anterior (T1) (c), and gastrocnemius muscle (GS). This is a photo and graph showing the effect of ) on lean muscle mass (d).
Figure 3 is a graph showing changes in muscle strength according to levodropropizine in the dexamethasone treatment model.
Figure 4 shows tibialis anterior muscle length (a), tibialis anterior lean muscle mass (b), total lean muscle mass (c), and total lean muscle mass (c) according to levodropropizine treatment on days 0, 7, 14, and 21. This is a graph showing the rate of change in lean muscle mass (d) of the gastrocnemius muscle.
Figure 5 is a photograph and graph showing the effect of levodropropizine on skeletal muscle mitochondrial function and skeletal muscle cell atrophy.

Hereinafter, the present invention will be described in more detail through one or more examples. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

Example 1. Preparation of dexamethasone-induced skeletal muscle atrophy model

To confirm the effect of skeletal muscle atrophy or muscle loss caused by dexamethasone, 10 mg/kg of dexamethasone was administered intraperitoneally (IP) for 14 days to create a skeletal muscle atrophy model, and then the muscle mass of the skeletal muscle atrophy model was measured. To confirm the reduction effect, leg thickness, grip strength, muscle length of the tibialis anterior (TA) muscle, and lean body mass were analyzed.

Specifically, the thickness of the anterior tibial leg was photographed using DexaScan, and to measure muscle strength, strength adaptation training was performed at least 3 times before drug administration, and once every 3 days from the start of the test to the completion of the test. Muscle strength was evaluated for each repetition. To evaluate muscle strength, the mouse was placed in a muscle strength measuring device so that it could grab the grid with its front paws, and then its tail was slowly pulled with a constant force until it released the grid with its front paws. The maximum strength to grab the grid was measured five times, and the average value was obtained. was derived in Newton (N) units. Additionally, to analyze the length of the tibialis anterior muscle (T1), the length from the upper limb to the medial dissection of the tibia in mice (tibia length: L) and the vertical distance from half the length of the tibia to the outer edge of the hindlimb muscle (muscle The thickness, T) was measured. Lastly, to measure lean muscle mass, lean body mass was measured targeting the tibialis anterior (TA) and gastrocnemius muscle (GS), and photographs were taken to minimize errors in test results due to stress. was limited to once a week.

As a result, the leg thickness of the dexamethasone-treated model was found to be reduced compared to normal mice (Figure 1(a)), and muscle strength, length of the tibialis anterior muscle, and lean muscle mass were all decreased (Figure 1(a)). In b) to (d)), the effect of dexamethasone on muscle mass reduction was confirmed, and it was confirmed that a skeletal muscle atrophy model was constructed.

Example 2. Confirmation of excellent muscle mass improvement effect of levodropropizine on dexamethasone-induced skeletal muscle atrophy model

The inhibitory effect of levodropropizine on muscle mass reduction compared to the muscle mass reduction effect caused by dexamethasone was confirmed.

Specifically, levodropropizine (恩, China) dissolved in 0.5% Carboxymethylcellulose (CMC) and 0.1% Tween80 solvent was administered to the skeletal muscle atrophy model prepared in Example 1 at a dose of 30 mg/kg, and the control group was administered levodropropizine (恩, China). Instead of pidgin, 100 μl of solvent was administered. It was administered orally once a day for a total of 21 days, starting 7 days before and 14 days after dexamethasone treatment. Thereafter, the change in thickness of the anterior tibia, lean muscle mass, muscle length, and lean muscle mass of the gastrocnemius muscle of the control and levodropropizine treated groups were measured in the same manner as in Example 1.

As a result, it was visually confirmed that the leg thickness of the levodropropizine-treated group was thicker than that of the control group (Figure 2(a)), and the lean muscle mass, muscle length, and gastrocnemius muscle of the anterior tibia of the levodropropizine-treated group were confirmed with the naked eye. Lean muscle mass was found to decrease gently compared to the control group (Figures 2(b) and (d)).

In addition, the rate of change in anterior tibial length, lean muscle mass, total lean muscle mass, and gastrocnemius muscle mass in the levodropropizine treatment group, as measured by photographs taken on days 0, 7, 14, and 21, was 21 It was shown to significantly increase on day 1 (Figure 4), confirming that levodropropizine inhibits skeletal muscle atrophy or reduction activity caused by dexamethasone.

Additionally, in the case of muscle strength, the strength of the control group decreased, while the strength of the levodropropizine-treated group showed a gradual increase over 14 days. In particular, after 5 days of dexamethasone administration, muscle strength was found to increase in the levodropropizine group compared to the control group, confirming that levodropropizine increases skeletal muscle while suppressing the effect of dexamethasone on muscle strength reduction (Figure 3).

Example 3. Confirmation of the excellent improvement effect of levodropropizine on muscle atrophy activity caused by TNF-α

When ATP, an intracellular energy, is activated, differentiation of myoblasts into myotubes occurs. Therefore, by analyzing mitochondrial activity when skeletal muscle cell atrophy is induced in differentiated myotube cells by the atrophic factor TNF-α, the effect of levodropropizine on improving skeletal muscle atrophy was confirmed.

Specifically, C2C12 mouse myogenic cells (ATCC, CRL-1772TM) were purchased ^and dispensed into 96 well cell culture plates and ⁶ well culture plates at 5 Growth media (GM) medium (Dulbecco's modified eagle's medium (DMEM) containing 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin (P/S)-high glucose (% CO ₂ , 95% O ₂ incubation) 4500 mg/L). In order to induce differentiation into myotube cells, it was confirmed that C2C12 mouse myoblasts were about 70 to 80% confluent, and then they were incubated with differentiation medium (Horse serum). DMEM-high glucose (4500mg/L) containing 2% HS and 1% penicillin/streptomycin (P/S) was replaced with DMEM-high glucose (4500mg/L)) and differentiated for 4 to 5 days. The formed myotube cells were injected with 10ng/ml of TNF-α and Luminescence assay and light microscope observation were performed 2 days after each treatment with 10 μM levodropropizine.

In order to confirm the effect of levodropropizine on improving muscle atrophy caused by TNF-α, ATP luminescence assay was performed on myotube cells prepared according to Example 3. Specifically, the C2C12 cells were seeded on a 96 flat clear black plate, washed once with 1×PBS the next day, and then treated with 10 μM of each drug prepared as differentiation medium. After drug treatment (2 days of differentiation), the medium on the plate was removed, 100 μL of ATP reagent was dispensed into each well, a dark environment was created with foil, and ATP luminescence was measured after 10 minutes (Room temperature (RT), veritas microplate luminometer; CellTiterGlo; integration time; 0.5sec). As a control, myotube cells that were not treated with levodropropizine were used.

After levodropropizine treatment, microscopic pictures of the myotube cells prepared according to Example 3 were analyzed to confirm the effect of improving muscle atrophy. Specifically , after C2C12 cell seeding, when confluency reached 70 to 80%, the cells were washed with 1×PBS and replaced with differentiation medium. After differentiation for 4 to 5 days, 10 ng/ml of each atrophic factor, TNF-α, and 10 μM of levodropropizine were prepared as GM at room temperature, then raised to 37°C and treated on myotubes. After 2 days, observation and photography were performed under a microscope (CCD, ×40, ×100), and the myotube diameter was measured using photos taken at 100x magnification (pixel).

As a result, the ATP activity of myotube cells was found to be superior to that of the control group, and it was confirmed that the mitochondria were activated following levodropropizine treatment, thereby increasing the production of ATP, and consequently suppressing skeletal muscle cell atrophy (Figure 5(a)). In addition, when treated with TNF-α, it was confirmed that muscle atrophy occurred due to a decrease in the diameter and area of myotube cells, whereas when treated with levodropropizine, the diameter of myotube cells was larger than when treated with TNF-α. Recovery was confirmed, and in particular, it was confirmed that the area of myotube cells was recovered to a level similar to that of the control group (Figures 5(b) and 5(c)).

Through these results, the excellent effect of improving muscle atrophy resulting from the use of levodropropizine was confirmed.

Preparation Example 1. Preparation of medicine

The active substance according to the present invention can be formulated in various forms depending on the purpose. The following illustrates several formulation methods containing the effective substance according to the present invention as an active ingredient, but the present invention is not limited thereto.

Production Example 1-1. Sanje

After mixing the ingredients according to Table 1, the powder was prepared by filling it in an airtight bubble.

division ingredient content One Active substance 2g 2 lactose 1g

Production Example 1-2. refine

After mixing the ingredients according to Table 2, tablets were manufactured by compressing them according to a conventional tablet manufacturing method.

division ingredient content One Active substance 100mg 2 corn starch 100mg 3 lactose 100mg 4 Magnesium Stearate 2mg

Production Example 1-3. capsule

After mixing the ingredients according to Table 3, capsules were prepared by filling them into gelatin capsules according to a typical capsule manufacturing method.

division ingredient content One Active substance 100mg 2 corn starch 100mg 3 lactose 100mg 4 Magnesium Stearate 2mg

Production Example 1-4. injection

The active substance according to the present invention was dissolved in an appropriate volume of sodium chloride BP for injection, the pH of the resulting solution was adjusted to pH 3.5 using dilute hydrochloric acid BP, and the volume was adjusted using sodium chloride BP for injection and thoroughly mixed. . The solution was filled into a 5 ml Type I ampoule made of transparent glass, encapsulated under an upper grid of air by dissolving the glass, and then sterilized by autoclaving at 120°C for more than 15 minutes to prepare an injection solution.

division ingredient content One Active substance 10㎍/㎖ 2 Dilute hydrochloric acid BP Until pH reaches 3.5 3 Sodium Chloride BP for Injection <1㎖

Production Example 1-5. nasal absorbent

According to the manufacturing method of a typical nasal absorbent, it is prepared to contain 3 mg of the active substance per 1 ㎖ of saline water (0.9% NaCl, w/v, solvent is purified water), filled into an opaque spray container, sterilized, and administered as a nasal absorbent. spray) was manufactured.

division ingredient content One Active substance 1.0 2 Sodium Acetate 0.3 3 Methylparaben 0.1 4 Propyl Paraben 0.02 5 sodium chloride Appropriate amount 6 HCL or NaOH pH adjustment appropriate amount

Production Example 1-6. liquid

According to a typical liquid preparation method, each ingredient according to Table 6 was dissolved in purified water, lemon flavor was added, and mixed. Purified water was added to the mixture to adjust the total volume to 100 ml, filled into a brown bottle, and sterilized to prepare a liquid.

division ingredient content One Active substance 100mg 2 Iseonghwadang 10g 3 Mannitol 5g 4 Purified water Appropriate amount

Production Example 2. Production of health food

The active substance according to the present invention can be manufactured into various types of health foods depending on the purpose. The following is an example of a manufacturing method of some health foods containing the active substance according to the present invention as an active ingredient, and the present invention is not limited thereto.

Production Example 3-1. dairy product

0.01 to 1 part by weight of the active substance of the present invention was added to milk, and various dairy products such as butter and ice cream were manufactured using the milk.

Production Example 3-2. Seonsik

Brown rice, barley, glutinous rice, and coix seed were gelatinized and dried using a known method, roasted, and then made into powder with a particle size of 60 mesh using a grinder. Black beans, black sesame seeds, and perilla seeds were steamed and dried using a known method, roasted, and then made into powder with a particle size of 60 mesh using a grinder. The effective substance of the present invention was concentrated under reduced pressure in a vacuum concentrator to prepare a dry powder. A linen meal was prepared by mixing the dried powders of the prepared grains, seeds, and active substances in the proportions according to Table 7.

division ingredient weight part One Brown rice 34 2 coix 19 3 barley 20 4 Perilla seeds 7 5 black beans 8 6 black sesame seeds 7 7 Active substance 2 8 wisdom 1.5 9 Rehmannia glutinosa 1.5 total 100

Manufacturing Example 3. Manufacturing of health functional food

The active substance according to the present invention can be manufactured into various types of health functional foods depending on the purpose. The following is an example of a manufacturing method of some health functional foods containing the effective substance according to the present invention as an active ingredient, and the present invention is not limited thereto.

Production Example 4-1. Health functional food 1

The composition ratio of the vitamin and mineral mixture in Table 8 is a mixture of ingredients relatively suitable for health functional foods as a preferred example, but the mixing ratio may be modified arbitrarily, and the above ingredients can be prepared according to a normal health functional food manufacturing method. After mixing, granules are prepared and can be used to manufacture a health functional food composition according to a conventional method.

division ingredient content One Active substance 100mg 2 vitamin mixture Appropriate amount 3 Vitamin A Acetate 70㎍ 4 Vitamin E 1.0mg 5 Vitamin B1 0.13mg 6 Vitamin B2 0.15mg 7 Vitamin B6 0.5mg 8 Vitamin B12 0.2㎍ 9 Vitamin C 10mg 10 biotin 10㎍ 11 Nicotinic acid amide 1.7mg 12 folic acid 50㎍ 13 Calcium Pantothenate 0.5mg 14 mineral mixture Appropriate amount 15 ferrous sulfate 1.75mg 16 zinc oxide 0.82㎎ 17 Magnesium Carbonate 25.3mg 18 Potassium Phosphate Monobasic 15mg 19 Calcium Phosphate Dibasic 55mg 20 Potassium citrate 90mg 21 calcium carbonate 100mg 22 Magnesium chloride 24.8mg

Production Example 4-1. Health functional food 2

The ingredients according to Table 9 were mixed according to a typical health drink manufacturing method, stirred and heated at 85° C. for about 1 hour, and the resulting solution was filtered and obtained in a sterilized container. Thereafter, it is sealed, sterilized and refrigerated for use in manufacturing the health drink composition of the present invention. The composition ratio according to Table 9 is a preferred embodiment of mixing ingredients that are relatively suitable for preferred drinks, but the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as demand class, demand country, and use purpose.

division ingredient content One Active substance 100mg 2 citric acid 100mg 3 oligosaccharide 100mg 4 plum concentrate 2mg 5 taurine 100mg 6 Purified water 500mg

So far, the present invention has been examined focusing on its embodiments. A person skilled in the art to which the present invention pertains will understand that the present invention may be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a restrictive perspective. The scope of the present invention is indicated in the claims rather than the foregoing description, and all differences within the equivalent scope should be construed as being included in the present invention.

Claims (9)

Pharmaceutical composition for preventing or treating muscle atrophy containing levodropropizine or a pharmaceutically acceptable salt thereof represented by Formula 1 as an active ingredient:
[Formula 1]
.
The pharmaceutical composition for preventing or treating muscle atrophy according to claim 1, wherein the muscular atrophy is caused by any one selected from the group consisting of cancerous cachexia, muscle loss, aging, obesity, long-term administration of steroids, and space flight. .
The method of claim 2, wherein the muscle aging-related diseases include senile sarcopenia, atony, muscular atrophy, muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia gravis, myositis, muscle calcification, A pharmaceutical composition for preventing or treating muscular atrophy, which is any one disease selected from the group consisting of muscle ossification, muscle weakness-related diseases, and cachexia.
The method of claim 1, wherein the composition is selected from the group consisting of the orbicularis oculi, masticatory muscles, tongue and neck muscles, thoracic girdle and arm muscles, arm and shoulder, intrinsic muscles of the hand, lower extremity and leg muscles, and forelimb and foot muscles. A pharmaceutical composition for preventing or treating muscle atrophy, wherein the composition is delivered to one or more selected target tissues.
The pharmaceutical composition for preventing or treating muscular atrophy according to claim 2, wherein the steroid agent is dexamethasone.
Food composition for preventing or improving muscle atrophy containing levodropropizine or a foodologically acceptable salt thereof represented by Formula 1 as an active ingredient:
[Formula 1]
.
The food composition for preventing or improving muscle atrophy according to claim 6, wherein the muscle atrophy is caused by long-term administration of dexamethasone.
Health functional food composition for preventing or improving muscle atrophy containing levodropropizine or a foodologically acceptable salt thereof represented by Chemical Formula 1 as an active ingredient:
[Formula 1]
.
The health functional food composition for preventing or improving muscle atrophy according to claim 8, wherein the muscle atrophy is caused by long-term administration of dexamethasone.