KR20220160269A - Pharmaceutical composition for preventing or treating muscle disease containing Gallamine triethiodide as an active ingredient - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating muscle diseases containing Gallamine triethiodide or a pharmaceutically acceptable salt thereof as active component. The pharmaceutical composition can effectively control skeletal muscle atrophy or muscle loss, and thus can be used as an agent for preventing, treating, or relieving muscle diseases having various causes, for example, diseases such as skeletal muscle atrophy or sarcopenia.

Description

Pharmaceutical composition for preventing or treating muscle disease containing gallamine triethiodide as an active ingredient {Pharmaceutical composition for preventing or treating muscle disease containing Gallamine triethiodide as an active ingredient}

The present invention relates to a pharmaceutical composition for the prevention or treatment of muscle diseases comprising gallamine triethiodide as an active ingredient, and more particularly, to a pharmaceutical composition comprising gallamine triethiodide, a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient. By including, it relates to a pharmaceutical composition capable of preventing or treating muscle diseases such as skeletal muscle atrophy and sarcopenia caused by various causes by effectively controlling atrophy and reduction of muscles.

Skeletal muscle atrophy can be caused by a variety of causes, such as immobility, muscle disease, space travel, denervation, sepsis, administration of dexamethasone, reduced weight bearing, and reduced food intake. It is characterized by a decrease in mass and muscle fiber cross-sectional area. In addition, it is known to be caused by peripheral neuropathy pain, decline in muscle function that inevitably accompanies aging, and treatment such as plaster cast performed on patients with surgical damage.

The occurrence of the above-mentioned skeletal muscle atrophy can deteriorate the patient's quality of life due to problems such as weakness, induction of activity disorder, and extension of functional recovery period. It is one of the immediate problems that must be resolved in order to pursue a healthy and humane life and move toward a welfare state.

Muscles regulate muscle production with a balance between anabolic and catabolism. At this time, in muscle cells, various biosignal transmission processes are regulated in this regard. 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) or an increase in the number of muscle fibers (hyperplasia), resulting in excessive muscle production.

On the other hand, progressive weakness and loss of function of muscles threatens the quality of life and lowers the survival rate of cancer patients in particular. More than 30% of cancer patients die due to weight loss due to muscle loss, and this loss of muscle function is due to myo-proteins degeneration, muscle fiber cross-sectional area, and muscle strength. ), decreased nuclear number of myofibers, and reduced insulin responsiveness.

Besides cancer, muscle loss can also be caused by the aging process and various chronic diseases. As aging progresses, some of the newly generated skeletal muscle is replaced with fibrous tissue, resulting in sarcopenia in which the body's skeletal muscle mass and strength are reduced, and hypertension, impaired glucose tolerance and diabetes, obesity, dyslipidemia, It is known that muscle loss appears even in chronic diseases, such as atherosclerosis and cardiovascular disease, whose incidence increases with age (Pharmacol Res. 2015, 99, 86).

A general method for preventing the above-mentioned skeletal muscle atrophy is to prevent muscle loss through exercise, but there is no fundamental treatment currently on the market, and the development of countermeasures, preventive agents, therapeutic agents, and improvement agents that can prevent this can be mentioned. There is a need for research on this.

The pharmaceutical composition according to the present invention can be usefully used for the prevention, treatment, and improvement of skeletal muscle atrophy and muscle diseases, and furthermore, identification of the active ingredient material is thought to be of great help in the future development of medicine and pharmacology.

Republic of Korea Patent No. 10-0447929

An object of the present invention is to provide a pharmaceutical composition for preventing or treating muscle diseases, comprising gallamine triethiodide represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:

[Formula 1]

Another object of the present invention is to provide a health food composition for the prevention or improvement of muscle diseases comprising the gallamine triethiodide or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a health functional food composition for preventing or improving muscle diseases, comprising the gallamine triethiodide or a pharmaceutically acceptable salt thereof as an active ingredient.

The technical problem to be achieved by the present invention is not limited to the above-mentioned technical problem, and other technical problems not mentioned can be clearly understood by those skilled in the art from the description below. There will be.

In order to solve the above problems,

The present invention provides a pharmaceutical composition for preventing or treating muscle diseases, comprising gallamine triethiodide represented by the following formula (1) or a pharmaceutically acceptable salt thereof as an active ingredient:

[Formula 1]

In addition, the present invention provides a health food composition for the prevention or improvement of muscle diseases comprising the gallamine triethiodide or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a health functional food composition for preventing or improving muscle diseases, comprising the gallamine triethiodide or a pharmaceutically acceptable salt thereof as an active ingredient.

The pharmaceutical composition for the prevention or treatment of muscle diseases comprising Gallamine triethiodide or a pharmaceutically acceptable salt thereof of the present invention as an active ingredient can effectively control skeletal muscle atrophy or muscle loss, which can cause various causes. It can be used as an agent for preventing, treating or improving diseases such as muscle diseases caused by, for example, skeletal muscle atrophy and sarcopenia.

The effects of the present invention are not limited to the above effects, and should be understood to include all effects that can be inferred from the configuration of the invention described in the detailed description or claims of the present invention.

Figure 1 is a result of comparing photos (a), muscle strength (b), length (c) of the tibialis anterior muscle, and lean muscle mass (d) of the tibialis anterior muscle of a dexamethasone-treated model (Dexamethasone) and a normal model (Normal). .
Figure 2 is a result of comparing the weight (a), muscle strength (b), length (c and d) of the anterior tibialis anterior muscle of the group treated with the dexamethasone treatment model (Dexamethasone) and the gallamine triethiodide of the present invention to be.
Figure 3 shows lean muscle mass (a), calf muscle (GS) muscle mass (b), and tibialis anterior bone (TA) of the group treated with dexamethasone and gallamine triethiodide of the present invention This is the result of comparing the muscle mass (c) of
4 is a result of measuring the protective effect of gallamine triethiodide against TNF-α-induced skeletal muscle cell atrophy using luminescence analysis and an optical microscope.

Hereinafter, the present invention will be described in more detail. However, the present invention can be implemented in many different forms, and the present invention is not limited by the embodiments described herein, and the present invention is only defined by the claims to be described later.

In addition, terms used in the present invention are only used to describe specific embodiments, and are not intended to limit the present invention. In the entire specification of the present invention, 'include' a certain element means that other elements may be further included without excluding other elements unless otherwise stated. In addition, the 'include' also means that the component is used alone.

pharmaceutical composition

One aspect of the present invention provides a pharmaceutical composition for preventing or treating muscle diseases, comprising gallamine triethiodide represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient:

[Formula 1]

Gallamine triethiodide is known as a non-depolarising muscle relaxant.

Gallamine is known to be the first synthetic neuromuscular blocking drug used clinically and exhibits anticholinesterase effects. By inhibiting cholinesterase, it prevents the degradation of acetylcholine and As an indirect cholinergic agonist by inhibiting choline (acetylcholine), it acts on autonomic ganglia, parasympathetic postganglionic fibers, and skeletal muscle endplates. Furthermore, gallamine triethiodide is widely used for the treatment of rheumatic diseases accompanying musculoskeletal disorders, neuralgia after neurogenic hyperkinesia, pain caused by spinal cord injury, and muscle spasms.

Specifically, the gallamine triethiodi binds to muscarinic acetylcholine receptors in the post-synaptic membrane of the motor end plate, in particular, to cholinergic receptor sites and Nicotine presynaptic acetylcholine receptors that bind and competitively block the transmission of acetylcholine, blocking muscle neurotransmission, preventing activation of muscle contraction processes, and inhibiting the release of acetylcholine (acetylcholine receptors).

Since the mechanism of gallamine triethiodide as a muscle disease prevention and muscle relaxant is known, it can be expected that the present invention will be effective in treating and blocking the cause of muscle diseases including skeletal muscle atrophy or sarcopenia, but directly researching this The results are non-existent.

Therefore, the present inventors effectively control the skeletal muscle atrophy and muscle loss of gallamine triethiodide through animal models and cell experiments to prevent, treat, and improve muscle diseases caused by various causes, especially skeletal muscle atrophy. confirmed and completed the present invention.

In one embodiment of the present invention, the muscular disease is atony, muscular atrophy, muscular dystrophy, muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia, cachexia, skeletal muscle It may be at least one selected from the group consisting of muscle atrophy and senile sarcopenia, for example, skeletal muscle atrophy or senile sarcopenia.

In one embodiment of the present invention, the gallamine triethiodide can promote mitochondrial functional activity, facial muscles, neck muscles, back muscles, arm muscles, shoulder muscles, chest muscles, abdominal muscles, gluteal muscles, back muscles, It may be characterized in that it is delivered to one or more target tissues selected from the group consisting of leg muscles, foot muscles, hand muscles, and intrinsic muscles of the hand, for example, leg muscles.

The pharmaceutical composition of the present invention may further contain a known therapeutic agent for muscle diseases in addition to gallamine triethiodide or a pharmaceutically acceptable salt thereof as an active ingredient, and may be used in combination with other known therapies for the treatment of these diseases. have.

In the present invention, the term "prevention" refers to any activity that inhibits or delays the occurrence, spread, and recurrence between households by administration of the pharmaceutical composition according to the present invention, and "treatment" refers to gallamine triethiodide of the present invention. Or a pharmaceutically acceptable salt thereof, or any action that improves or beneficially changes the symptoms of muscle disease by administering a composition containing the same. Those of ordinary skill in the art to which the present invention pertains will be able to determine the degree of improvement, enhancement and treatment by knowing the exact criteria of the disease for which the composition of the present application is effective by referring to the data presented by the Korean Medical Association, etc. will be.

In the present invention, the term "therapeutically effective amount" used in combination with an active ingredient means an effective amount to prevent or treat a target disease, and the therapeutically effective amount of the composition of the present invention depends on several factors, such as the method of administration. , target site, condition of the patient, etc. may vary. Therefore, when used in the human body, the dosage should be determined in an appropriate amount considering both safety and efficiency. It is also possible to estimate the amount to be used in humans from the effective amount determined through animal experiments. These considerations in determining an effective amount can be found, for example, in Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; and E.W. Martined., Remington's Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" means an amount that is sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment and does not cause side effects, and the effective dose level is the patient's Factors including health status, type of muscle disease, cause of muscle disease, severity, activity of drug, sensitivity to drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, drugs used in combination or concurrently, and It may be determined according to other factors well known in the medical field.

The pharmaceutical composition of 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 times. Considering all of the above factors, it is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.

The pharmaceutical composition of the present invention may further include a carrier, diluent, excipient, or a combination of two or more thereof commonly used in biological preparations, for example, a pharmaceutically acceptable carrier.

As used herein, the term "pharmaceutically acceptable" means exhibiting non-toxic properties to cells or humans exposed to the composition. The pharmaceutically acceptable carrier is not particularly limited as long as it is suitable for in vivo delivery of the composition, for example, Merck Index, 13th ed., Merck & Co. Inc. , saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components may be mixed and used. Customary additives may be added.

In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate formulations for injection, such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets. Furthermore, it can be preferably formulated according to each disease or component by using an appropriate method in the art or by using a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990).

In one embodiment of the present invention, the pharmaceutical composition is one or more selected from the group consisting of oral dosage forms, external preparations, suppositories, sterile injectable solutions and sprays, for example, capsules, solutions, injections, soft capsules, and granules. , Or it may be a tablet formulation, more preferably an oral or injection formulation.

As used herein, the term "administration" means providing a predetermined substance to an individual or patient by any suitable method, and parenteral administration (eg, intravenous, subcutaneous, intraperitoneal) according to the desired method or applied topically as an injectable formulation) or administered orally.

The active substance of the present invention can be administered in various oral and parenteral formulations during clinical administration, and when formulated, diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants are used. It is manufactured by

Solid preparations for oral administration include tablets, patients, powders, granules, capsules, troches, etc., and these solid preparations contain one or more active substances of the present invention and at least one excipient such as starch, calcium carbonate, It is prepared by mixing sucrose, lactose or gelatin. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, or syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. can

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspension solutions, emulsions, freeze-dried formulations, suppositories, and the like. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerol, gelatin, and the like may be used.

In addition, the effective dosage of the active substance of the present invention for the human body may vary depending on the patient's age, weight, sex, dosage form, health condition and disease degree, and is generally about 0.001-100 mg/kg/day, Preferably it is 0.01-35 mg/kg/day. Based on an adult patient weighing 70 kg, it is generally 0.07-7000 mg/day, preferably 0.7-2500 mg/day, and once or twice a day at regular intervals according to the judgment of a doctor or pharmacist. It may be divided into several doses.

The pharmaceutical composition of the present invention may be administered by any device capable of transporting an active substance to a target cell. Preferred administration methods and formulations include intravenous injections, subcutaneous injections, intradermal injections, intramuscular injections, drip injections, and the like. Injections include aqueous solvents such as physiological saline and ring gel solutions, non-aqueous solvents such as vegetable oils, higher fatty acid esters (eg, oleic acid ethyl, etc.), alcohols (eg, ethanol, benzyl alcohol, propylene glycol, glycerin, etc.). Stabilizers (e.g., ascorbic acid, sodium hydrogensulfite, sodium pyrosulfite, BHA, tocopherol, EDTA, etc.) to prevent deterioration, emulsifiers, buffers to control pH, A pharmaceutical carrier such as a preservative (eg, phenylmercuric nitrate, thimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol, etc.) may be included.

As used herein, the term "subject" refers to monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats, rabbits, including humans who have or may develop the above muscle disease. or all animals including guinea pigs, and the above diseases can be effectively prevented or treated by administering the pharmaceutical composition of the present invention to a subject. The pharmaceutical composition of the present invention may be administered in parallel with existing therapeutic agents.

The pharmaceutical composition of the present invention may further include pharmaceutically acceptable additives, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate. , Lactose, Mannitol, Taffy, Gum Arabic, Pregelatinized Starch, Corn Starch, Powdered Cellulose, Hydroxypropyl Cellulose, Opadry, Sodium Starch Glycolate, Carnauba Lead, Synthetic Aluminum Silicate, Stearic Acid, Magnesium Stearate, Aluminum Stearate, Calcium stearate, white sugar, dextrose, sorbitol and talc may be used. The pharmaceutically acceptable additive according to the present invention is preferably included in an amount of 0.1 part by weight to 90 parts by weight based on the composition, but is not limited thereto.

pharmaceutically acceptable salts

The active substance of the present invention can be used in the form of a pharmaceutically acceptable salt, and an acid addition salt formed by a pharmaceutically acceptable free acid is useful as the salt. The term “pharmaceutically acceptable salt” refers to a concentration that has an effective effect that is relatively non-toxic and harmless to patients. It means inorganic addition salt. For these salts, inorganic and organic acids can be used as free acids, hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, perchloric acid, and phosphoric acid can be used as inorganic acids, and citric acid, acetic acid, lactic acid, maleic acid, and fumarin as organic acids. Acids, gluconic acid, methanesulfonic acid, glycolic acid, succinic acid, tartaric acid, galacturonic acid, embonic acid, glutamic acid, aspartic acid, oxalic acid, (D) or (L) malic acid, maleic acid, methanesulfonic acid, ethanesul For example, phonic acid, 4-toluenesulfonic acid, salicylic acid, citric acid, benzoic acid or malonic acid may be used. In addition, these salts include alkali metal salts (sodium salt, potassium salt, etc.) and alkaline earth metal salts (calcium salt, magnesium salt, etc.) and the like. For example, acid addition salts include acetate, aspartate, benzate, besylate, bicarbonate/carbonate, bisulfate/sulfate, borate, camsylate, citrate, edisylate, esylate, formate, fumarate, Gluceptate, gluconate, glucuronate, hexafluorophosphate, hybenzate, hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide, isethionate, lactate, malate, malic Eight, malonate, mesylate, methyl sulfate, naphthylate, 2-naphsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate, saccharide Lates, stearates, succinates, tartrates, tosylates, trifluoroacetates, aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, Potassium, sodium, tromethamine, zinc salts and the like may be included, of which hydrochloride or trifluoroacetate is preferred.

The acid addition salt according to the present invention is obtained by dissolving an active material in an organic solvent such as methanol, ethanol, acetone, methylene chloride, acetonitrile, etc. by a conventional method, for example, filtering and drying the precipitate produced by adding an organic or inorganic acid. It can be prepared by distillation of a solvent and excess acid under reduced pressure, followed by drying or crystallization in an organic solvent.

In addition, a pharmaceutically acceptable metal salt may be prepared using a base. An alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt, and evaporating and drying the filtrate. At this time, it is pharmaceutically suitable to prepare a sodium, potassium or calcium salt as the metal salt. Also, the corresponding silver salt is obtained by reacting an alkali metal or alkaline earth metal salt with a suitable silver salt (eg, silver nitrate).

Furthermore, the present invention includes not only active substances and pharmaceutically acceptable salts thereof, but also possible solvates, hydrates, isomers, optical isomers and the like that can be prepared therefrom.

Health food and health functional food composition

One aspect of the present invention provides a health food and health functional food composition for preventing or improving muscle diseases comprising Gallamine triethiodide represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient do:

[Formula 1]

There is no particular restriction on the type of food. Examples of foods to which the active substance of the present invention can be added are dairy products including drinks, meat, sausages, bread, biscuits, rice cakes, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, chewing gum, ice cream, There are various soups, beverages, alcoholic beverages and vitamin complexes, dairy products and milk-processed products, etc., and includes both health foods and health functional foods in a conventional sense.

Health food and health functional food compositions containing active substances according to the present invention may be added to food as it is or used together with other foods or food ingredients, and may be appropriately used according to conventional methods. The mixing amount of the active substance may be appropriately determined according to its purpose of use (for prevention or improvement). In general, the amount of the composition in health food and health functional food may be added in an amount of 0.1 to 90 parts by weight based on the total weight of food. However, in the case of long-term intake for the purpose of health maintenance or health control, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount greater than the above range.

The health food and health functional food composition of the present invention is not particularly limited in other ingredients except for containing the active substance of the present invention as an essential ingredient in the indicated ratio, and various flavoring agents or natural carbohydrates are added as additional ingredients like conventional beverages. may contain Examples of the aforementioned 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 dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (eg rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can advantageously be used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 of the health functional food composition of the present invention.

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

These components may be used independently or in combination. The ratio of these additives is not so critical, but is generally selected in the range of 0.1 to about 20 parts by weight per 100 parts by weight of the health food and health functional food composition containing the active substance of the present invention.

A pharmaceutical composition, health food composition, and health functional food composition for preventing, treating, or improving muscle diseases, comprising Gallamine triethiodide or a pharmaceutically acceptable salt thereof as an active ingredient of the present invention, is a composition for skeletal muscle atrophy or As it can effectively control muscle loss, it can be used as an agent for preventing, treating, or improving muscle diseases caused by various causes, such as skeletal muscle atrophy and sarcopenia.

The present invention will be described in more detail through the following examples. However, the following examples are only for specifying the content of the present invention, and the present invention is not limited thereto.

Example

Preparation Example 1. Preparation of Gallamine triehiodide

Gallamine triehiodide represented by Formula 1 below was used by purchasing a commercially available (Med Chem Express, USA) reagent:

[Formula 1]

Preparation Example 2. Preparation of dexamethasone treatment model

A dexamethasone treatment model was prepared by inducing skeletal muscle atrophy or muscle loss by administering dexamethasone to mice for 14 days, and the effect of the dexamethasone treatment on skeletal muscle atrophy is shown in FIG. 1 .

Referring to FIG. 1, it can be confirmed that muscle function indicators, grip strength, length of the Tibialis Anteriors (TA), and lean body mass (Lean Body Mass), which are muscle function indicators, are reduced in mice treated with dexamethasone. there was.

Experimental Example 1. Comparison of preventive or therapeutic effects of skeletal muscle atrophy or sarcopenia according to administration of gallamine triethiodide

In the preparation process of the dexamethasone treatment model of Preparation Example 2, at the same time as the administration of dexamethasone, gallamine triethiodide was orally administered at a concentration of 30 mg/kg to increase skeletal muscle atrophy or muscle reduction efficacy in terms of muscle strength Test (Grip Strength), Tibialis Anteriors (TA) Length (Diameter), Lean Body Mass, Gastrocnemius Muscle (GS) and Tibialis Anteriors (TA) Muscle Mass (Lean Mass) ) was confirmed, and the results are shown in FIGS. 2 and 3.

Referring to FIG. 2, Gallamine triethiodide was administered in body weight, grip strength test in terms of muscle function, and muscle diameter of Tibialis Anteriors (TA). It was confirmed that the group was effective.

Referring to FIG. 3, looking at the results represented by Lean Body Mass, Lean Mass of Gastrocnemius Muscle (GS) and Lean Mass of Tibialis Anteriors (TA), the group treated with only dexamethasone It was confirmed that the group administered with gallamine triethiodide excelled in suppressing skeletal muscle atrophy or reduction.

Experimental Example 2. Confirmation of protective effect against skeletal muscle cell atrophy induced by atrophic factor TNF-α in differentiated myotubes

The differentiation of myoblasts (myoblasts) into myotubes proceeds only when the activation of ATP, which is intracellular energy, is preceded. The protective effect of gallamine triethiodide against skeletal muscle cell atrophy was demonstrated by increasing mitochondrial activity using luminescence assay and optical microscope.

Dispense 5 x 10 ³ cells/well and 2 x 10 ⁵ cells/well of C2C12 mice myoblasts on a 96 well cell culture plate and a 6 well culture plate, respectively, confirm 80% to 90% confluency, and then treat the differentiation medium for 5 days. Myotubes formed after differentiation were treated with TNF-α and gallamine triethiodide, and 2 days later, luminescence assay and optical microscopy were performed.

4 shows the results of Luminescence assay measurement of ATP generated by mitochondrial activity following treatment with Gallamine triethiodide and the photographic effect of cell atrophy defense caused by TNF-α in fully differentiated Myotubes. .

Referring to FIG. 4, the functional activity of mitochondria is judged by the length and area of the myotube and the activity of generating ATP, and the myotube atrophy defense effect is judged. Myotube atrophy is inhibited at 10 μM of Gallamine triethiodide was able to confirm that

Manufacturing example of drug

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

<Pharmaceutical Preparation Example 1> Preparation of powder

active substance 2g

lactose 1 g

After mixing the above ingredients, the powder was prepared by filling in an airtight bag.

<Pharmaceutical Preparation Example 2> Preparation of tablets

active substance 100 mg

corn starch 100 mg

Lactose 100 mg

magnesium stearate 2 mg

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

<Pharmaceutical Preparation Example 3> Preparation of capsules

active substance 100 mg

corn starch 100 mg

Lactose 100 mg

magnesium stearate 2 mg

After mixing the above ingredients, capsules were prepared by filling gelatin capsules according to a conventional capsule preparation method.

<Pharmaceutical Preparation Example 4> Preparation of Injections

active substance 10 μg/mL

dilute hydrochloric acid BP until pH 3.5

Sodium Chloride BP for Injection up to 1 ml

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 with dilute hydrochloric acid BP, the volume was adjusted with sodium chloride BP for injection, and mixed thoroughly. . The solution was filled into a 5 ml type I ampoule made of transparent glass, sealed under an upper grid of air by dissolving the glass, and sterilized by autoclaving at 120 DEG C for 15 minutes or more to prepare an injection solution.

<Pharmaceutical Preparation Example 5> Preparation of Nasal Spray

active substance 1.0g

sodium acetate 0.3g

Methylparaben 0.1 g

Propylparaben 0.02g

sodium chloride Appropriate amount

HCl or NaOH pH Adjustment Appropriate amount

Purified water Appropriate amount

According to the conventional method for preparing nasal absorbents, saline (0.9% NaCl, w/v, solvent is purified water) is prepared to contain 3 mg of active substance per 1 mL, filled in an opaque spray container and sterilized to prepare nasal absorbents. manufactured.

<Pharmaceutical Preparation Example 6> Preparation of liquid formulation

active substance 100 mg

Lee Seonghwadang 10g

mannitol 5g

Purified water Appropriate amount

According to the conventional method for preparing liquids, each component is dissolved in purified water, lemon flavor is added, the above components are mixed, and purified water is added to adjust the total volume to 100 mL, and then filled in a brown bottle and sterilized to prepare a liquid formulation. did

Production example of health food

The active substance according to the present invention can be manufactured into various types of health food depending on the purpose. The following exemplifies methods for producing some health foods containing the active substances according to the present invention as active ingredients, but the present invention is not limited thereto.

<Health food manufacturing example 1> Manufacturing of dairy products

0.01-1 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 prepared using the milk.

<Health food production example 2> Production of wire food

Brown rice, barley, glutinous rice, and adlay were alphanized by a known method, dried, roasted, and then prepared into a powder having a particle size of 60 mesh using a grinder. Black beans, black sesame seeds, and perilla seeds were also steamed and dried by a known method, roasted, and then prepared into powder with a particle size of 60 mesh using a grinder. The active substance of the present invention was concentrated under reduced pressure in a vacuum concentrator to obtain a dry powder. It was prepared by blending the dry powder of grains, seeds and active substances prepared above in the following ratio.

Cereals (brown rice 34 parts by weight, adlay 19 parts by weight, barley 20 parts by weight),

Seeds (7 parts by weight of perilla seeds, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds),

Active substance (2 parts by weight),

reishi (1.5 parts by weight), and

Rehmannia glutinosa (1.5 parts by weight).

Production example of health functional food

The active substance according to the present invention can be manufactured into various types of health functional food depending on the purpose. The following exemplifies a method for producing some health functional foods containing the active substance according to the present invention as an active ingredient, but the present invention is not limited thereto.

<Health functional food manufacturing example 1> Manufacturing of health functional food

active substance 100 mg

vitamin mixture Appropriate amount

Vitamin A Acetate 70 µg

vitamin E 1.0mg

vitamin B1 0.13mg

vitamin B2 0.15mg

vitamin B6 0.5mg

vitamin B12 0.2 µg

vitamin C 10 mg

biotin 10 µg

nicotinic acid amide 1.7mg

folic acid 50 µg

Calcium Pantothenate 0.5mg

mineral mixture Appropriate amount

ferrous sulfate 1.75mg

zinc oxide 0.82mg

magnesium carbonate 25.3mg

Potassium Phosphate Monobasic 15mg

Dibasic calcium phosphate 55mg

potassium citrate 90mg

calcium carbonate 100 mg

magnesium chloride 24.8 mg

Although the composition ratio of the above vitamin and mineral mixture was prepared by mixing ingredients suitable for relatively health functional foods in a preferred embodiment, the mixing ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health functional food manufacturing method. Then, granules can be prepared and used in the preparation of health functional food compositions according to conventional methods.

<Health functional food manufacturing example 2> Manufacturing of health functional beverages

active substance 100 mg

citric acid 100 mg

oligosaccharide 100 mg

plum concentrate 2 mg

taurine 100 mg

Add purified water to 500 mL

After mixing the above components according to the usual health drink manufacturing method, stirring and heating at 85 ° C. for about 1 hour, the resulting solution is filtered and obtained in a sterilized container, sealed and sterilized, and then refrigerated according to the present invention. It is used in the manufacture of health beverage compositions. Although the composition ratio is a mixture of ingredients suitable for a relatively favorite beverage in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as the class of demand, the country of demand, and the purpose of use.

So far, the present invention has been looked at with respect to its preferred embodiments. Those skilled in the art to which the present invention pertains will be able to understand that the present invention can 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 limiting point of view. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the equivalent scope will be construed as being included in the present invention.

Claims (14)

A pharmaceutical composition for the prevention or treatment of muscle diseases comprising Gallamine triethiodide represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient:
[Formula 1]

According to claim 1,
The muscle diseases include atony, muscular atrophy, muscular dystrophy, muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia, cachexia, skeletal muscle atrophy and geriatric muscle. A pharmaceutical composition, characterized in that at least one selected from the group consisting of sarcopenia.
According to claim 1,
The gallamine triethiodide is a pharmaceutical composition, characterized in that to promote mitochondrial functional activity.
According to claim 1,
One or more targets selected from the group consisting of facial muscles, neck muscles, back muscles, arm muscles, shoulder muscles, chest muscles, abdominal muscles, gluteal muscles, back muscles, leg muscles, foot muscles, hand muscles, and intrinsic muscles of the hand. A pharmaceutical composition characterized in that it is delivered to a tissue.
According to claim 1,
A pharmaceutical composition further comprising a pharmaceutically acceptable carrier.
According to claim 1,
A pharmaceutical composition having a dosage form of any one of capsules, solutions, injections, soft capsules, granules, or tablets.
A health food composition for preventing or improving muscle diseases, comprising Gallamine triethiodide represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

According to claim 7,
The muscle diseases include atony, muscular atrophy, muscular dystrophy, muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia, cachexia, skeletal muscle atrophy and geriatric muscle. A health food composition, characterized in that at least one selected from the group consisting of sarcopenia.
According to claim 7,
The gallamine triethiodide is a health food composition characterized in that it promotes mitochondrial functional activity.
According to claim 7,
The health food is a health food composition, characterized in that selected from various drinks, meat, sausages, bread, candy, snacks, noodles, ice cream, dairy products, soups, ionic beverages, beverages, alcoholic beverages, gum, tea and vitamin complexes.
A health functional food composition for preventing or improving muscle diseases, comprising Gallamine triethiodide represented by Formula 1 below or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

According to claim 11,
The muscle diseases include atony, muscular atrophy, muscular dystrophy, muscle degeneration, muscle stiffness, amyotrophic axonal sclerosis, myasthenia, cachexia, skeletal muscle atrophy and geriatric muscle. Health functional food composition, characterized in that at least one selected from the group consisting of sarcopenia.
According to claim 11,
The gallamine triethiodide is a health functional food composition characterized in that it promotes mitochondrial functional activity.
According to claim 11,
The health functional food is a health functional food composition, characterized in that the food in the form of tablets, capsules, pills or liquids.

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