WO2021167123A1 - Composition comprising straight chain alkane having 14 to 17 carbon atoms as active ingredient, for muscle strengthening, muscle enhancement, muscle differentiation, muscle regeneration, or sarcopenia suppression - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating muscle disorders, comprising a straight chain alkane having 14 to 17 carbon atoms, such as tetradecane and heptadecane, or a pharmaceutically acceptable salt thereof as an active ingredient.

Description

A composition having a muscle strengthening, muscle strengthening, muscle differentiation, muscle regeneration or sarcopenia inhibitory effect containing a straight chain alkane having 14 to 17 carbon atoms as an active ingredient

The present invention relates to a pharmaceutical composition for preventing or treating muscle disease, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In 2000, the elderly population accounted for 7.2% of the total population, entering an aging society, and in 2050, it is expected to enter a super-aging society (more than 20%). A person's muscle mass decreases with age (10 to 15% at the age of 50 to 70, and by more than 30% at the age of 70 to 80), and as a result, muscle strength and muscle function are also weakened, which is referred to as sarcopenia. it is said Geriatric sarcopenia is a major cause of limiting the independent life of the elderly by causing activity and gait disturbances. In addition, sarcopenia lowers the basal metabolic rate, increases insulin resistance, promotes the development of type 2 diabetes, and increases the risk of hypertension and cardiovascular disease by 3-5 times. Currently, there are no drugs approved for the treatment of sarcopenia, and drug repositioning technology is being developed that applies myostatin inhibitors or other treatment agents for other diseases approved by the FDA to sarcopenia.

Muscles are largely divided into skeletal muscle, cardiac muscle, and visceral muscle. Of these, skeletal muscle is the tissue present in the largest amount in the human body, and accounts for 40-45% of the body weight. Skeletal muscle attaches to bones through tendons and plays a role in generating bone movement or force. One muscle is composed of numerous muscle fibers, which in turn are made of numerous myofibres composed of actin and myosin. When actin and myosin overlap each other, the length of the muscle shortens or lengthens, causing overall muscle contraction and relaxation. An increase in the size of the myofibrils means an increase in the thickness of the muscle fibers, resulting in an increase in the muscle.

The types of muscle fibers constituting the muscle are mainly classified into Type I, Type IIA, and Type IIB according to the metabolic process that generates ATP and the rate of contraction. 'Type I muscle fiber' has a slow contraction rate and contains a large number of myoglobin and mitochondria, so it is suitable for continuous and low-intensity aerobic activity. Type I muscle fibers are red in color, so they are also called red muscles, and the soleus is representative. On the other hand, 'Type IIB muscle fibers' have a fast contraction rate and are used for very short but high-intensity anaerobic exercise. 'Type IIA muscle fibers' have intermediate characteristics between the aforementioned two muscle fibers. As people age, the composition of type I and II muscle fibers for each muscle region changes, and all types of muscle fibers decrease.

Skeletal muscle has the characteristics of being regenerated and maintained depending on the environment, but these characteristics are lost with age, and as a result, as aging progresses, muscle mass is reduced and muscle strength is also lost. As a signal transduction system involved in muscle growth and regeneration, there is a signal transduction that regulates protein synthesis mediated by IGF-1 (insulin like growth factor 1)/AKT. When the IGF-1 receptor (IGF-1R) present in the muscle cell membrane is activated, AKT phosphorylation is increased through IRS1 and PI3K phosphorylation, and the latter activates mTORC phosphorylation. Activation of mTORC increases the phosphorylation of ribosomal protein S6 kinase beta-1 (p70S6K1) to increase mRNA translation and at the same time increases the activity of eukaryotic translation initiation factor 4 G (eIF4G), and eukaryotic translation initiation factor 4E binding protein 1(4E-BP1) phosphorylates the protein. eIF4G and 4E-BP1 are involved in the formation of the eIF4F complex, that is, eIF4G binds to eIF4A and eIF4E to form the eIF4F complex, whereas phosphorylation of 4E-BP1 inhibits the binding ability to eIF4E, increasing free eIF4E. . The latter binds with other translation initiation factors (eIF4G and eIF4A) to form the eIF4F complex, which stabilizes the ribosome structure, thereby promoting translation initiation and ultimately protein synthesis. will increase

In addition, AKT phosphorylation promotes muscle fiber growth by increasing eIF2B expression through GSK3 (glycogen synthase kinase 3), while suppressing muscle loss by suppressing the expression of FOXO (forkhead box O), a transcription factor related to proteolysis. Muscle loss is regulated by signaling mediated by receptors of the TGF-β family, including myostatin, transforming growth factor beta (TGF-β), and activin. When a ligand binds to the TGF-β type II receptor, it phosphorylates the type I receptor, and the latter phosphorylates the smad 2/3 complex, eventually activating FOXO. The latter increases the gene expression of muscle-specific ubiquitin-ligase, muscle RING-finger protein-1 (MURF1) and Muscle Atrophy F-Box (MAFbx)/atrogin-1, which By attaching ubiquitin to the lysine site of the target protein, it promotes protein degradation and eventually induces muscle reduction.

The present invention relates to a straight chain alkane having 14 to 17 carbon atoms. Or to provide a pharmaceutical composition for the prevention or treatment of muscle disease, including a pharmaceutically acceptable salt thereof as an active ingredient.

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

The present invention provides a pharmaceutical composition for preventing or treating muscle diseases, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

The linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof may increase the expression of p-4E-BP1 and p-p70S6K1 proteins.

The linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof may reduce the expression of MuRF1 (Muscle Ring-Finger Protein), MaFbx (Muscle atrophyF-box) or myostatin.

The muscle disease may be a muscle disease due to decreased muscle function, muscle loss, muscle atrophy, muscle wasting or muscle degeneration.

The muscle disease is dystonia, muscular atrophy, muscular dystrophy, myasthenia gravis, cachexia, rigid spinesyndrome, amyotrophic lateral sclerosis (Lou Gehrig's disease, amyotrophic lateral sclerosis). , Charcot-Marie-Tooth disease (Charcot-Marie-Tooth disease) and sarcopenia (sarcopenia) may be any one or more selected from the group consisting of.

In addition, the present invention provides a pharmaceutical composition for promoting muscle differentiation, regenerating muscles or strengthening muscles, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a health functional food composition for promoting muscle differentiation, regenerating muscles or strengthening muscles, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for increasing muscle mass or promoting muscle production, comprising a straight chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a health functional food composition for increasing muscle mass or promoting muscle generation, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a health functional food composition for improving muscle function comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a cosmetic composition for improving muscle function comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

The linear alkane having 14 to 17 carbon atoms may be tetradecane or heptadecane.

In addition, the present invention provides a method for preventing or treating a muscle disease comprising administering or taking a composition comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient to an individual.

In addition, the present invention provides a method for promoting muscle differentiation, regenerating or strengthening muscles, comprising administering or taking a composition comprising a straight chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient to an individual. to provide.

In addition, the present invention provides the use of a composition comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient for preventing or treating muscle disease.

The present invention also provides the use of a composition comprising a straight-chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient to promote muscle differentiation, regenerate muscle, or strengthen muscle.

The present invention relates to a composition for preventing or treating muscle disease or improving muscle function, comprising, as an active ingredient, a linear alkane having 14 to 17 carbon atoms or a salt thereof, such as tetradecane, heptadecane, etc. The same straight-chain alkanes having 14 to 17 carbon atoms can increase the expression of proteins related to muscle protein synthesis and increase muscle mass in muscle cells, and can inhibit the expression of enzymes involved in muscle protein degradation from the mRNA level, thereby reducing muscle function and reducing muscle mass. In muscle diseases caused by wasting or muscle degeneration, it can exhibit a muscle strengthening effect through muscle differentiation, muscle regeneration, and increase in muscle mass, and can inhibit muscle loss, for the prevention or treatment of muscle diseases, muscle differentiation, muscle regeneration and It can be used to strengthen muscle or increase muscle mass or promote muscle production or improve muscle function.

1 and 2 are results of analyzing the length change of myotube in mouse myoblasts. Values represent the mean±SEM of three experiments, and values indicated by different letters represent statistical significance (P <0.05).

3 is a result of analyzing changes in myotube cell thickness, length, and fusion index in mouse myoblasts. Values represent the mean±SEM of three experiments, and values indicated by different letters represent statistical significance (P <0.05).

Figure 4 shows the results of confirming the change in the mRNA expression level (Figure 4a) and protein expression level (Figure 4b) of proteolysis and synthesis-related molecules in tetradecane-treated mouse myoblasts. Values represent the mean±SEM of three experiments, and values indicated by different letters represent statistical significance (P <0.05).

Figure 5 shows the results of confirming the change in the mRNA expression level (Figure 5a) and protein expression level (Figure 5b) of proteolysis and synthesis-related molecules in heptadecan-treated mouse myoblasts. Values represent the mean±SEM of three experiments. (* = p < 0.05, ** = p < 0.01, [one-way ANOVA, Tukey's test])

The present inventors have completed the present invention by confirming that natural products with few side effects are effective in improving muscle strength and loss by inhibiting the decomposition of muscle proteins and promoting their synthesis.

Hereinafter, the terms of the present invention will be described.

In the present invention, "muscle" refers to tendons, muscles, and tendons comprehensively, and "muscular function" means the ability to exert force by contraction of the muscle, and the muscle can exert maximum contractile force to overcome resistance. These include muscle strength, which is the ability to be able to, muscular endurance, which is the ability to repeat contraction and relaxation for how long or how many times a muscle can repeat contractions and relaxations with a given weight, and instantaneous power, which is the ability to exert strong force in a short period of time. This muscle function is proportional to the muscle mass, and "improving muscle function" means improving the muscle function for the better.

The Cas No. of tetradecane is 629-59-4, the molecular formula is C ₁₄ H ₃₀ , and the molecular weight is 198.394 g/mol, and the structure is as shown in Formula 1 below. The IUPAC name of tetradecane is tetradecane and N-TETRADECANE; Tridecane, methyl-; and so on. Tetradecane is a colorless liquid, with a melting point of 4-6 ℃ and a boiling point of 253-257 ℃.

[Formula 1]

Tetradecane includes Laurus nobilis (Bay laurel, bay leaf), Anethum graveolens (Dill, dill root), Pimenta dioica (Jamaica pepper, allspice) Citrus×limon (Lemon, lemon) Satureja hortensis (Summer savory, summer savory), etc. It is mainly contained in plants of

Tetradecane is registered as a flavoring agent in the Korea Food and Drug Administration (KFDA) food additive database and is used as a supplement.

The physiological activity of tetradecane reported so far is antibacterial, and Origanum vulgare L.spp. Seven gram-positive and gram-negative bacteria ( Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae ) and three fungi ( Candida albicans, Saccharomya and Aspergillus niger ) was verified through the results showing antibacterial properties.

On the other hand, as a result of oral administration to rats in the toxicity test of tetradecane, the LD ₅₀ value is known to be 15,000 mg/kg.

Cas No. of heptadecane is 629-78-7, the structural formula is C ₁₇ H ₃₆ , and the molecular weight is 240.475 g/mol, and the structure is as shown in Chemical Formula 2 below. The IUPAC name of heptadecane is Heptadecane and N-Heptadecane; Heptadekan; Also known as Hexadecane. Heptadecane is a colorless liquid with a melting point of 21.1 to 22.9 °C and a boiling point of 301.9 °C.

[Formula 2]

Heptadecane is derived from Hamamelis (Witch hazel leaf), Dialium guineense wild. It is mainly contained in plants such as fruit, Aloe vera (Aloe vera sap, aloe vera sap), Cocos nucifera (Coconut tree, coconut) seed oil, and Carica papaya (Papaya) seed oil.

Heptadecane is registered as a flavoring agent in the Korea Food and Drug Administration (KFDA) food additive database and is used as a supplement.

The physiological activity of heptadecane reported to date is anti-inflammatory, and in rats that received 20 mg/kg and 40 mg/kg of heptadecane, respectively, the amount of COX-2 and iNOS protein decreased in a concentration-dependent manner of heptadecane, and NF The anti-inflammatory effect was demonstrated through the inactivation of -kB.

Meanwhile, as a result of intravenous administration to mice in a toxicity test of heptadecane, the LDLo value is known to be 9,821 mg/kg.

Hereinafter, the present invention will be described in detail.

Pharmaceutical composition for preventing or treating muscle disease/promoting muscle differentiation, regenerating or strengthening muscles/increasing muscle mass or promoting muscle generation

The present invention provides a pharmaceutical composition for preventing or treating muscle disease, comprising a straight-chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for promoting muscle differentiation, regenerating muscles or strengthening muscles comprising a straight chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for increasing muscle mass or promoting muscle production, comprising a straight-chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

The linear alkane having 14 to 17 carbon atoms may be tetradecane or heptadecane.

In the pharmaceutical composition of the present invention, the tetradecane (Tetradecane) is preferably a compound having the structure of the following [Formula 1], but is not limited thereto, and those skilled in the art as having the same or similar activity as tetradecane (Tetradecane) All isomers, hydrates or derivatives within the range that can be understood by

[Formula 1]

In addition, in the pharmaceutical composition of the present invention, the heptadecane is preferably a compound having the structure of the following [Formula 2], but is not limited thereto, and has the same or similar activity as that of heptadecane. Any isomer, hydrate or derivative within the range that can be understood by those skilled in the art is applicable:

[Formula 2]

The method for obtaining the straight-chain alkane, such as Tetradecane or Heptadecane, is not particularly limited, and is isolated from a plant containing the straight-chain alkane, chemically synthesized using a known method, or commercially available. that can be used

In the pharmaceutical composition of the present invention, the straight-chain alkane or a pharmaceutically acceptable salt thereof can increase the expression of p-4E-BP1 and p-p70S6K1 proteins, MuRF1 (Muscle Ring-Finger Protein), MaFbx ( Mus scle atrophy F-box) or myostatin may decrease the expression.

Specifically, representative molecules related to protein synthesis include p70S6K1, 4E-BP1, and eIF members, and the activity of these three molecules is regulated by the upper mTORC. Activation of mTORc phosphorylates p70S6K1, and activated p70S6K1 phosphorylates 40S ribosomal protein S6 to increase mRNA translation. In addition, activation of mTORC increases the activity of eIF4G and phosphorylates 4E-BP1 at the same time, and these two molecules are involved in the formation of the eIF4F complex. That is, eIF4G binds to eIF4A and eIF4E to form an eIF4F complex, while phosphorylation of 4E-BP1 inhibits its binding ability to eIF4E, increasing free eIF4E. The latter binds with other translation initiation factors (eIF4G and eIF4A) to form the eIF4F complex, which stabilizes the ribosome structure and promotes translation initiation, ultimately increasing protein synthesis. MAFbx/Atrogin-1 (Muscle atrophy F-box) and MuRF1 (muscle RING finger 1) are muscle-specific ubiquitin-ligases, and ubiquitin is converted to lysine of the target protein. ) as a representative protein that promotes protein degradation by attaching to the site and eventually induces muscle reduction, the composition of the present invention reduces the expression of MuRF1 (Muscle Ring-Finger Protein) or MaFbx (Muscle atrophy F-box), May inhibit muscle loss.

In the pharmaceutical composition of the present invention, the muscle disease includes a range of diseases caused by decreased muscle function, muscle loss, muscle atrophy, muscle wasting or muscle degeneration. Specifically, the muscle disease is atony, muscular atrophy, muscular dystrophy, myasthenia gravis, cachexia, rigid spinesyndrome, amyotrophic lateral sclerosis (Lou Gehrig's disease, amyotrophic). lateral sclerosis), Charcot-Marie-Tooth disease (Charcot-Marie-Tooth disease) and sarcopenia is preferably at least one selected from the group consisting of, but is not limited thereto. In addition, the muscle wasting or degeneration occurs due to genetic factors, acquired factors, aging, etc., and muscle wasting is characterized by a gradual loss of muscle mass, weakness and degeneration of muscles, particularly skeletal or voluntary muscles and cardiac muscles.

In addition, from the viewpoint of using the pharmaceutical composition of the present invention for muscle differentiation promotion, muscle regeneration, or muscle strengthening, the differentiation of muscle cells is a muscle generation program that specifies components of muscle fibers such as contractile organs (myofibril). developmental program). Useful therapeutic agents for differentiation include at least about 10%, more preferably at least 50%, and most preferably at least 100% of the amount of all myofibrils in diseased tissue as compared to equivalent tissue in a similarly treated control animal. can increase

In addition, from the viewpoint of using the pharmaceutical composition of the present invention for muscle differentiation promotion, muscle regeneration or muscle strengthening, or for increasing muscle mass, muscle growth is achieved by an increase in fiber size and/or This can be caused by an increase in fiber count. The growth of the muscle can be measured by A) an increase in wet weight, B) an increase in protein content, C) an increase in the number of muscle fibers, and D) an increase in the muscle fiber diameter. An increase in muscle fiber growth can be defined as an increase in diameter when the diameter is defined as the shortening of a cross-sectional ellipsoid. A useful therapeutic agent is an animal that has degenerated muscle by at least 10% relative to a previously similarly treated control animal (i.e., an animal with degenerated muscle tissue not treated with a muscle growth compound), the wet gain, protein content and/or increasing the diameter by at least 10%, more preferably at least 50%, and most preferably at least 100%. Compounds that increase growth by increasing the number of muscle fibers are useful as therapeutics when they increase the number of muscle fibers in diseased tissue by at least 1%, more preferably at least 20%, and most preferably at least 50%. These percentage values are determined relative to basal levels in untreated and unaffected comparative mammals or in contralateral unaffected muscle when the compound is administered and acted locally.

In addition, from the viewpoint of using the pharmaceutical composition of the present invention for promoting muscle differentiation, regenerating muscles or strengthening muscles, muscle regeneration refers to a process in which new muscle fibers are formed from myoblasts. Useful therapeutic agents for regeneration increase the number of new fibers by at least about 1%, more preferably at least 20%, and most preferably at least 50%, as described above.

Differentiation of myocytes refers to the induction of a muscle developmental program that specifies components of muscle fibers such as the contractile organ (myofibril). Useful therapeutics for differentiation include at least about 10%, more preferably at least 50%, and most preferably 100% of the amount of all muscle fiber components in the diseased tissue as compared to equivalent tissue in a similarly treated control animal. increase more than

In addition, from the viewpoint of using the pharmaceutical composition of the present invention for increasing muscle mass or promoting muscle generation, "increasing muscle mass" refers to enhancing the growth of muscles, especially among body components, and improving muscle mass through physical exercise and endurance improvement. It is possible to increase the muscle mass by administering a substance having a muscle-increasing effect into the body, and the type of muscle is not limited.

In the pharmaceutical composition of the present invention, the composition may contain a straight-chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof, such as tetradecane, heptadecane, etc., in a concentration of 0.1 μM to 1000 μM, but limited thereto. doesn't happen At this time, when the linear alkane is less than the concentration range, protein synthesis and decomposition activity in muscle cells is lowered, so there is a problem in that it is difficult to prevent or treat muscle diseases, and when it exceeds the concentration range, including cytotoxicity There may be toxicity concerns.

The straight-chain alkane having 14 to 17 carbon atoms of the present invention may be used in the form of a pharmaceutically acceptable salt, and as the salt, an acid addition salt formed by a pharmaceutically acceptable free acid is useful. Acid addition salts include inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid and aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes. It is obtained from non-toxic organic acids such as dioates, aromatic acids, aliphatic and aromatic sulfonic acids. Such pharmaceutically non-toxic salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, ioda. Id, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate , sebacate, fumarate, maleate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, Toxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycol late, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate or mandelate.

The acid addition salt according to the present invention is prepared by a conventional method, for example, by dissolving the straight-chain alkane such as tetradecane or heptadecane in an excess of an aqueous acid solution, and dissolving the salt in a water-miscible organic solvent such as methanol, ethanol, It can be prepared by precipitation using acetone or acetonitrile. It can also be prepared by heating an equal amount of a straight-chain alkane such as tetradecane or heptadecane and an acid or alcohol in water, followed by evaporating the mixture to dryness, or by suction filtration of the precipitated salt.

In addition, a pharmaceutically acceptable metal salt may be prepared using a base. The 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. In this case, 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). In addition, the straight-chain alkane such as tetradecane and heptadecane of the present invention includes all salts, hydrates and solvates that can be prepared by conventional methods as well as pharmaceutically acceptable salts.

The addition salt according to the present invention can be prepared by a conventional method, for example, by dissolving a straight-chain alkane such as tetradecane and heptadecane in a water-miscible organic solvent, for example, acetone, methanol, ethanol, or acetonitrile, and an excess of It can be prepared by adding an organic acid or adding an aqueous acid solution of an inorganic acid, followed by precipitation or crystallization. Subsequently, after evaporating the solvent or excess acid from this mixture, it can be dried to obtain an addition salt, or it can be prepared by suction filtration of the precipitated salt.

The pharmaceutical composition of the present invention may be in various oral or parenteral formulations. When formulating the composition, one or more buffers (eg, saline or PBS), antioxidants, bacteriostatic agents, chelating agents (eg, EDTA or glutathione), fillers, bulking agents, binders, adjuvants (eg, aluminum hydroxide), suspending agents, thickening agents, wetting agents, disintegrating agents or surfactants, diluents or excipients.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations include at least one excipient in one or more compounds, for example, starch (corn starch, wheat starch, rice starch, potato starch, etc.), calcium carbonate, sucrose, lactose, dextrose, sorbitol, mannitol, xylitol, erythritol maltitol, cellulose, methyl cellulose, sodium carboxymethylcellulose and hydroxypropyl It is prepared by mixing methyl-cellulose or gelatin. For example, tablets or dragees can be obtained by blending the active ingredient with a solid excipient, grinding it, adding suitable adjuvants, and processing it into a granule mixture.

In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral administration include suspensions, internal solutions, emulsions, or syrups. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances or preservatives are used. may be included. In addition, in some cases, cross-linked polyvinylpyrrolidone, agar, alginic acid or sodium alginate may be added as a disintegrant, and an anti-aggregant, lubricant, wetting agent, flavoring agent, emulsifier and preservative may be additionally included. have.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspension solutions, emulsions, lyophilized formulations or suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerol, gelatin, etc. may be used.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and when administered parenterally, for external use; intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebrovascular injection; transdermal administration; Alternatively, it may be formulated according to a method known in the art in the form of a nasal inhalant.

In the case of the injection, it must be sterile and protected from contamination by microorganisms such as bacteria and fungi. For injection, examples of suitable carriers include, but are not limited to, water, ethanol, polyols (eg, glycerol, propylene glycol and liquid polyethylene glycol, etc.), mixtures thereof, and/or a solvent or dispersion medium containing vegetable oil. can More preferably, suitable carriers include Hanks' solution, Ringer's solution, phosphate buffered saline (PBS) containing triethanolamine or isotonic solutions such as sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose. etc. can be used. In order to protect the injection from microbial contamination, it may further include various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In addition, in most cases, the injection may further contain an isotonic agent such as sugar or sodium chloride.

In the case of transdermal administration, forms such as ointment, cream, lotion, gel, external solution, pasta, liniment, and air are included. In the above, transdermal administration means that an effective amount of the active ingredient contained in the pharmaceutical composition is delivered into the skin by topically administering the pharmaceutical composition to the skin.

In the case of administration by inhalation, the compounds for use according to the invention may be administered in pressurized packs or using a suitable propellant, for example, dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. It can be conveniently delivered in the form of an aerosol spray from a nebulizer. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount. For example, gelatin capsules and cartridges for use in inhalers or insufflators may be formulated to contain a powder mixture of the compound and a suitable powder base such as lactose or starch. Formulations for parenteral administration are described in formulary commonly known in all pharmaceutical chemistry.

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

The dosage of the pharmaceutical composition of the present invention varies depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate and severity of disease. The daily dose is preferably 0.01 to 50 mg, more preferably 0.1 to 30 mg per 1 kg of body weight per day based on a straight-chain alkane having 14 to 17 carbon atoms, such as tetradecane, heptadecane, etc. when administered parenterally. and when administered orally, preferably 0.01 to 100 mg, more preferably 0.01 to 10 mg per 1 kg of body weight per day based on a linear alkane having 14 to 17 carbon atoms, such as tetradecane or heptadecane of the present invention. It can be administered in divided doses from 1 to several times to be administered in an amount of However, since it may increase or decrease depending on the route of administration, the severity of obesity, sex, weight, age, etc., the dosage is not intended to limit the scope of the present invention in any way.

The pharmaceutical composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

The pharmaceutical composition of the present invention can also be provided in the form of an external preparation containing a straight-chain alkane having 14 to 17 carbon atoms, such as tetradecane and heptadecane, as an active ingredient. When the pharmaceutical composition for the prevention and treatment of muscle diseases of the present invention is used as an external preparation for skin, additionally, a fatty substance, an organic solvent, a solubilizer, a thickening agent and a gelling agent, an emollient, an antioxidant, a suspending agent, a stabilizer, and a foaming agent (foaming agent) ), fragrance, surfactant, water, ionic emulsifier, nonionic emulsifier, filler, sequestering agent, chelating agent, preservative, vitamin, blocker, wetting agent, essential oil, dye, pigment, hydrophilic active agent, lipophilic active agent Or it may contain adjuvants commonly used in the field of dermatology, such as any other ingredients commonly used in external preparations for skin, such as lipid vesicles. In addition, the ingredients may be introduced in an amount generally used in the field of dermatology.

When the pharmaceutical composition for preventing and treating muscle disease of the present invention is provided as an external preparation for skin, it may be in the form of an ointment, patch, gel, cream or spray, but is not limited thereto.

Health functional food composition for preventing or improving muscle disease/promoting muscle differentiation, regenerating muscle or strengthening muscle/increasing muscle mass or promoting muscle generation

In addition, the present invention provides a health functional food composition for preventing or improving muscle disease comprising a straight chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a health functional food composition for promoting muscle differentiation, regenerating muscles or strengthening muscles, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a health functional food composition for increasing muscle mass or promoting muscle production, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a health functional food composition for improving muscle function comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.

The linear alkane having 14 to 17 carbon atoms may be tetradecane or heptadecane.

In the health functional food composition, specific details of the linear alkane having 14 to 17 carbon atoms, such as tetradecane or heptadecane, are the same as described above.

In the health functional food composition for preventing or improving muscle disease/promoting muscle differentiation, regenerating or strengthening muscle/increasing muscle mass or promoting muscle generation, the tetradecane, heptadecane, etc. When a straight-chain alkane having 14 to 17 carbon atoms is used as an additive in a health functional food, it can be added as it is or used with other foods or food ingredients, and can be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined according to each purpose of use, such as prevention, health or treatment.

The formulation of health functional food may be in the form of powder, granules, pills, tablets, and capsules, as well as in the form of general food or beverages.

There is no particular limitation on the type of food, and examples of food to which the substance can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, and dairy products including ice cream. , various soups, beverages, teas, drinks, alcoholic beverages, vitamin complexes, and the like, and may include all foods in a conventional sense.

In general, in the production of food or beverage, the linear alkane having 14 to 17 carbon atoms, such as tetradecane and heptadecane, may be added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on 100 parts by weight of the raw material. have. However, in the case of long-term intake for health and hygiene or health control, the amount may be less than or equal to the above range, and in the present invention, there is no problem in terms of safety in terms of using a fraction from a natural product. It can also be used in larger amounts.

Beverages among health functional foods according to the present invention may contain various flavoring agents or natural carbohydrates as additional ingredients, like conventional beverages. The above-mentioned natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetener, natural sweeteners such as taumatine and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate may be about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the beverage according to the present invention.

In addition to the above, the health functional food composition for promoting muscle differentiation, muscle regeneration, or muscle strengthening according to the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloids It may contain thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages. In addition, the health functional food composition for promoting muscle differentiation, regenerating muscles or strengthening muscles of the present invention may contain fruit for the production of natural fruit juice, fruit juice beverage, and vegetable beverage. These components may be used independently or in combination. The ratio of these additives is not limited, but is generally selected in the range of 0.01 to 0.1 parts by weight relative to 100 parts by weight of the health functional food of the present invention.

Cosmetic composition for improving muscle function

In addition, the present invention provides a cosmetic composition for improving muscle function comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient. The straight chain alkane may be tetradecane or heptadecane. The cosmetic composition is not particularly limited, but may be used for external use on the skin or may be orally ingested.

The composition for improving muscle function of the present invention may also be a cosmetic composition. The cosmetic composition of the present invention contains a linear alkane having 14 to 17 carbon atoms, such as tetradecane and heptadecane, as an active ingredient, and a basic cosmetic composition (lotion, cream, essence, cleansing foam, and cleansing water) together with dermatologically acceptable excipients. It can be prepared in the form of face wash, pack, body oil), color cosmetic composition (foundation, lipstick, mascara, makeup base), hair product composition (shampoo, conditioner, hair conditioner, hair gel) and soap.

The excipient is not limited thereto, but may include, for example, an emollient, a skin penetration enhancer, a colorant, a fragrance, an emulsifier, a thickening agent, and a solvent. In addition, it may further include a fragrance, a colorant, a disinfectant, an antioxidant, a preservative and a moisturizing agent, and may include a thickener, an inorganic salt, a synthetic polymer material, etc. for the purpose of improving physical properties. For example, in the case of manufacturing a face wash and soap with the cosmetic composition of the present invention, it can be easily prepared by adding a straight-chain alkane having 14 to 17 carbon atoms, such as tetradecane and heptadecane, to a conventional face wash and soap base. When preparing a cream, it can be prepared by adding a straight-chain alkane having 14 to 17 carbon atoms or a salt thereof, such as tetradecane, heptadecane, etc., to a general oil-in-water type (O/W) cream base. Here, synthetic or natural materials such as proteins, minerals, vitamins, etc. for the purpose of improving physical properties such as fragrances, chelating agents, pigments, antioxidants, and preservatives may be additionally added.

The content of a straight-chain alkane having 14 to 17 carbon atoms, such as tetradecane or heptadecane, contained in the cosmetic composition of the present invention is not limited thereto, but is preferably 0.001 to 10% by weight, and 0.01 to 5% by weight based on the total weight of the composition. It is more preferable that If the content is less than 0.001% by weight, the desired anti-aging or anti-wrinkle effect cannot be expected, and if it exceeds 10% by weight, there may be difficulties in safety or formulation.

As described above, the composition of the present invention, i.e., a composition comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof, such as tetradecane, heptadecane, etc., as an active ingredient, is a 4E-BP1 and p70S6K1 protein in myoblasts. By increasing phosphorylation and suppressing the expression of MuRF1 and MaFbx/atrogin1 genes, it is possible to exhibit a muscle strengthening effect through muscle differentiation, muscle regeneration, and increase in muscle mass in muscle diseases caused by decreased muscle function, muscle wasting or muscle degeneration. As it can be inhibited, it can be used for preventing or treating muscle diseases, for muscle differentiation, for muscle regeneration and for increasing muscle mass, or for improving muscle function.

Hereinafter, preferred examples are presented to help the understanding of the present invention. However, the following examples are only provided for easier understanding of the present invention, and the contents of the present invention are not limited by the following examples.

<Example: Analysis of the efficacy of muscle enhancement and muscle loss inhibition using mouse myoblasts>

Example 1. Confirmation of change in myotube length

1. Check myotube length change

1-1. Experimental method

1) Cell culture

① When tetradecane is treated

Mouse myoblast cell line (C2C12 cell) was purchased from ATCC (Manassas, VA, USA) and used. The purchased cells were cultured in an incubator at _{37° C. and 5% CO 2} using 10% fetal bovine serum media (Gibco-BRL) and used for the experiment. When the cells were 80% confluent, they were differentiated into myotubes using 2% horse serum media (Gibco-BRL). In order to confirm the muscle strengthening effect, 100 μM of tetradecane (CAS Number 629-59-4, Sigma) was treated for two days from the day the differentiation started, and control cells were treated with 100 μM of DMSO (dimethyl sulfoxide; Sigma). . To check the muscle loss inhibitory effect, 50 μM of dexamethasone (dexa; Sigma) and 100 μM of tetradecane (CAS Number 629-59-4, Sigma) were co-treated for two days from the fourth day of differentiation.

② When heptadecane is treated

Mouse myoblast cell line (C2C12 cell) was purchased from ATCC (Manassas, VA, USA) and used. The purchased cells were cultured in an incubator at _{37° C. and 5% CO 2} using 10% fetal bovine serum media (Gibco-BRL) and used for the experiment. When the cells were 80% confluent, they were differentiated into myotubes using 2% horse serum media (Gibco-BRL). 100 μM of heptadecane (CAS Number 629-78-7, Sigma) was treated for two days from the day the differentiation started. Control cells were treated with 100 μM of DMSO (dimethyl sulfoxide; Sigma).

2) Giemsa-wright staining

Cells were washed twice with PBS (Phosphate buffered saline) and then fixed with 100% methanol for 10 minutes. After fixation was completed, it was dried naturally at room temperature for 10 minutes, and then a giemsa-wright staining solution specifically staining myotubes was dropped and stained for 30 minutes.

3) Measurement of myotube thickness, length and fusion index

① When tetradecane is treated

The stained myotubes were photographed at X40 magnification using a fluorescence microscope (IX 71, Olympus), and then analyzed using image J software (image J software, USA). Six parts were randomly selected from each well and photographed under a microscope, and the length of at least 100 myotubes from each well was analyzed (repeat 3 times/Group).

② When heptadecane is treated

Stained myotubes were photographed at x40 and x100 magnifications using a fluorescence microscope (IX 71, Olympus), and then analyzed using image J software (image J software, USA). Six parts were randomly selected from each well and photographed under a microscope, and the thickness and length of at least 100 myotubes and at least 400 nuclei were analyzed from each well (repeat 3 times/Group).

1-2. Experiment result

1) Confirmation of muscle strengthening effect of tetradecane (check change in myotube cell length)

To confirm the muscle enhancing effect of tetradecane in mouse myoblasts, myotubes were specifically stained with Giemsa solution and visualized. As a result, tetradecane treatment was performed on myotubes. It was found to significantly increase the length of the 43% (Fig. 1).

Then, as a result of visualizing myotubes using giemsa solution to confirm the muscle loss inhibitory efficacy of tetradecane in mouse myoblasts, myotubes were treated with dexamethasone. It was confirmed that the length of was significantly reduced, and tetradecane treatment was confirmed to significantly increase the length of myotubes reduced by dexamethasone by 40% (FIG. 2). Therefore, it can be seen that tetradecane promotes muscle growth and inhibits muscle loss by increasing the length of myotubes in mouse myoblasts.

2) Confirmation of changes in myotube cell thickness, length and fusion index by heptadecane

In order to check the myotube thickness, length, and fusion index change by heptadecan in mouse myoblasts, myotube cells were specifically stained using Giemsa solution and then x40, Visualized by microscopy at x100 magnification. It was visually confirmed that heptadecane treatment increased myotube cell thickness, length and fusion index compared to normal cells (Basal) (FIG. 3A). As a result of quantification using Image J software, heptadecan also significantly increased the thickness (Myotube diameter), length, and fusion index by 30%, 37%, and 37%, respectively, compared to normal cells (Basal) (Fig. 3B). . Therefore, it can be seen that heptadecan promotes muscle growth by increasing the thickness, length and fusion index of myotube cells in mouse myoblasts.

Example 2: Identification of the mechanism of action

2-1. Experimental method

1) RNA isolation and RT (real-time) PCR (quantitative reverse-transcription polymerase chain reacion) using the Trizol method

334 μl of a Trizol solution per 1*10 ⁷ mouse myoblast cells was added and ground, followed by centrifugation at 4° C., 12,000 × g for 10 minutes. After transferring the supernatant to a new tube, 67 μl of chloroform was added and vortexed. Again, the supernatant was transferred to a new tube, and isopropanol was added so that the ratio of the supernatant to isopropanol was 1:1. Shake vigorously 10 times, leave at room temperature for 15 minutes, centrifuge at 12,000 × g, 4°C for 10 minutes, remove the supernatant, and add 1 mL of 70% ethanol to the remaining precipitate, then 7,500 × g, Centrifugation was carried out at 4° C. for 5 minutes. After removing the ethanol, the tube containing the RNA precipitate was dried at room temperature for 15 minutes, and the RNA pellet was dissolved using nuclease free water. The concentration of the RNA sample extracted at 260 nm and 280 nm wavelength was measured using a UV/VIS spectrophotometer (Beckman coulter, DU730), and the integrity of the RNA sample was performed by agarose gel electrophoresis. (integrity) was confirmed.

Synthesis of cDNA by performing reverse transcription using oligo dT primer and superscript reverse transcriptase (GIBCO BRL, Gaithersburg, MD, USA) targeting RNA samples extracted from mouse myoblasts did. Using the cDNA obtained through reverse transcription as a template, and using the 5' and 3' flanking sequences of the gene cDNA to be amplified as a primer, iQ SYBR green supermix (Bio-Rad ) and CFX Connect™ Real-Time PCR Detection System (Bio-Rad) were used to perform quantitative PCR, and the primer sequences used are shown in Table 1.

[Table 1]

2) Western blotting

To perform Western blotting on cells, 500 µL of 100 mM Tris-HCl, pH 7.4, 5 mM EDTA, 50 mM sodium pyrophosphate, 50 mM NaF, in each well from which the media was removed , 100 mM orthovanadate, 1% Triton X-100, 1 mM phenylmethanesulfonyl fluoride, 2 μg/mL aprotinin, 1 μg/mL pepstatin A (pepstatin A), and a lysis buffer containing 1 μg/mL leupeptin was added and harvested. After centrifugation at 1,300 × g, 4 ° C for 20 minutes, the middle layer was taken and brad Proteins were quantified according to the Bradford method (Bio-Rad). After electrophoresis of 40 μg of the quantified protein on SDS polyacrylamide gel, it was transferred to nitrocellulose membranes (Amersham, Buckinghamshire, UK). The membrane was washed three times for 10 minutes using tris-buffered saline and tween 20 solution (TBS-T), and then washed with 10% skim milk. Blocked for 60 minutes. The membrane was put in a primary antibody diluted at a ratio of 1:1,000, shaken gently at 4°C, incubated for 12 hours, washed using TBS-T, and the membrane was again diluted with a secondary antibody diluted at a ratio of 1:2,000 They were incubated together for 60 minutes and washed. At this time, the primary antibodies were S6K1, phopho-p70S6K1 (p-p70S6K1), 4E-BP1, phospho-4E-BP1 (p-4E-BP1) and GAPDH (Cell Signaling Technology, Beverly, MA, USA) were used. . Finally, the protein was visualized on an X-ray film using an ECL Western blot detection kit (RPN2106, Amersham, Arlington Heights, IL, USA). The band visualized on the X-ray film was scanned and quantified using Quantity One analysis software (Bio-Rad).

2-2. Experiment result

1) Confirmation of expression changes of molecules related to protein synthesis and degradation by tetradecane

In this experiment, expression changes of molecules related to protein synthesis and degradation by tetradecane were confirmed in mouse myoblasts. In the case of dexamethasone-treated control cells (Dexa), compared to normal cells (Basal) not treated with dexamethasone, the amounts of p-p70S6K1 and p-4E-BP1 proteins related to protein synthesis were significantly reduced, whereas proteolysis The expression of the genes MaFbx/atrogin1, MuRF1, and myostatin was significantly increased, and the expression of the muscle enhancer gene IGF1 was decreased. Treatment with tetradecane significantly increased the protein amounts of p-p70S6K1 and p-4E-BP1 and the expression of IGF1, which were decreased by dexamethasone, while the expression of MuRF1 and MAFbx/atrogin1 and Myostatin was significantly decreased. (Fig. 4). Therefore, it is thought that tetradecane was ultimately involved in increasing the amount of muscle by increasing p70S6K1 and 4E-BP1 protein phosphorylation and IGF1 gene in mouse myoblasts, and suppressing MuRF1 and MAFbx/atrogin1 and myostatin gene expression. do.

2) Confirmation of expression changes of molecules related to protein synthesis and degradation by heptadecane

Expression changes of molecules related to protein synthesis and degradation by heptadecane were confirmed in mouse myoblasts. Heptadecane treatment significantly increased the amounts of p-p70S6K1 and p-4E-BP1 proteins related to protein synthesis compared to normal cells (Basal), while the expression of proteolytic genes MaFbx/atrogin1, MuRF1, and Myostatin was significantly decreased, and the expression of IGF1, a muscle enhancing gene, was increased (FIG. 5). Therefore, heptadecane is thought to be involved in ultimately increasing muscle mass by increasing 4E-BP1 and p70S6K1 protein phosphorylation and IGF1 gene expression in mouse myoblasts, and suppressing MuRF1, MAFbx/atrogin1, and Myostatin gene expression.

Hereinafter, an example of the preparation of a pharmaceutical, food or cosmetic containing tetradecane or heptadecane as an active ingredient according to the present invention will be described, but the present invention is not intended to be limited thereto, but only to be described in detail. The pharmaceutical, food or cosmetic compositions of Preparation Examples 1 to 3 were prepared according to a conventional method according to the following composition ingredients and composition ratios with an extract excellent in the prevention and treatment of muscle disease or improvement of muscle function.

[Preparation Example 1] Preparation of pharmaceutical composition

<1-1> Preparation of powder

Tetradecane or Heptadecane 20 mg

Lactose hydrate 100 mg

Talc 10 mg

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

<1-2> Preparation of tablets

Tetradecane or heptadecane 10 mg

Corn Starch 100 mg

Lactose hydrate 100 mg

Magnesium stearate 2 mg

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

<1-3> Preparation of capsules

Tetradecane or heptadecane 10 mg

Microcrystalline Cellulose 3 mg

Lactose hydrate 14.8 mg

Magnesium stearate 0.2 mg

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

<1-4> Preparation of injection

Tetradecane or heptadecane 10 mg

mannitol 180 mg

Sterile distilled water for injection 2974 mg

Sodium monohydrogen phosphate 26 mg

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

<1-5> Preparation of liquid preparation

Tetradecane or heptadecane 10 mg

isomerized sugar 10 mg

mannitol 5 mg

Purified water appropriate amount

Lemon flavored amount

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

[Production Example 2] Preparation of health food

<2-1> Manufacturing of health supplements

Tetradecane or heptadecane 10 mg

appropriate amount of vitamin mixture

70 μg of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B ₁ 0.13 mg

Vitamin B ₂ 0.15 mg

Vitamin B ₆ 0.5 mg

0.2 μg of vitamin B ₁₂

Vitamin C 10 mg

Biotin 10 μg

Nicotinamide 1.7 mg

50 μg folic acid

Calcium pantothenate 0.5 mg

Mineral mixture appropriate amount

Ferrous sulfate 1.75 mg

Zinc oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium citrate 30 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

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

<2-2> Manufacture of health drinks

Tetradecane or heptadecane 10 mg

15 g vitamin C

100 g vitamin E (powder)

19.75 g of iron lactate

3.5 g zinc oxide

3.5 g of nicotinic acid amide

0.2 g vitamin A

0.25 g of vitamin B1

0.3 g of vitamin B2

Purified water quantitative

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

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

[Preparation Example 3] Preparation of cosmetic composition

Hereinafter, an example of the preparation of a cosmetic composition containing the extract of the present invention will be described, but the present invention is not intended to limit the present invention, but to describe it in detail.

<3-1> Nutrient lotion (milk lotion)

2.0% by weight of tetradecane or heptadecane

5.0 wt% squalane

beeswax 4.0 wt%

1.5 wt% polysorbate 60

1.5 wt% of sorbitan sesquioleate

Liquid paraffin 0.5 wt%

5.0 wt% caprylic/capric triglycerides

Glycerin 3.0 wt%

Butylene glycol 3.0 wt%

Propylene glycol 3.0 wt%

0.1 wt% of carboxyvinyl polymer

0.2% by weight of triethanolamine

Preservatives, colors and fragrances

Purified water to 100% by weight

Although the above compounding ratio is a composition that is relatively suitable for nutrient lotion in a preferred embodiment, the mixing ratio may be arbitrarily modified, and it may be prepared according to a manufacturing method in the field of cosmetics.

<3-2> Softening lotion (skin lotion)

2.0 wt% of tetradecane or heptadecane

Glycerin 3.0 wt%

Butylene glycol 2.0 wt %

propylene glycol 2.0 wt %

Carboxyvinyl Polymer 0.1 wt %

PEG 12 nonylphenyl ether 0.2 wt %

Polysorbate 80 0.4 wt %

Ethanol 10.0 wt%

Triethanolamine 0.1 wt %

Preservatives, colors and fragrances

Purified water to 100% by weight

Although the above compounding ratio is a composition that is relatively suitable for softening lotion in a preferred embodiment, the mixing ratio may be arbitrarily modified, and it can be prepared according to a manufacturing method in the general cosmetic field.

<3-3> Nourishing Cream

tetradecane or heptadecane 2.0 wt %

Polysorbate 60 1.5 wt %

Sorbitan sesquioleate 0.5 wt %

PEG60 hydrogenated castor oil 2.0 wt%

Liquid paraffin 10 wt %

5.0 wt% squalane

5.0 wt % caprylic/capric triglycerides

glycerin 5.0% by weight

Butylene glycol 3.0 wt %

Propylene glycol 3.0 wt %

Triethanolamine 0.2 wt %

Appropriate amount of preservative

appropriate amount of color

spice

Purified water to 100% by weight

The above compounding ratio is a composition that is relatively suitable for nourishing creams in a preferred embodiment, but the mixing ratio may be arbitrarily modified, and it can be prepared according to a manufacturing method in the general cosmetic field.

<3-4> Massage cream

1.0% by weight of tetradecane or heptadecane

Beeswax 10.0 wt%

Polysorbate 60 1.5 wt %

PEG 60 hydrogenated castor oil 2.0 wt %

Sorbitan sesquioleate 0.8 wt %

Liquid paraffin 40.0 wt %

5.0 wt% squalane

4.0 wt % caprylic/capric triglycerides

glycerin 5.0% by weight

Butylene glycol 3.0 wt %

Propylene glycol 3.0 wt %

Triethanolamine 0.2 wt %

Preservatives, colors and fragrances

Purified water to 100% by weight

Although the above mixing ratio is a composition that is relatively suitable for massage cream in a preferred embodiment, the mixing ratio may be arbitrarily modified, and it may be prepared according to a conventional manufacturing method in the cosmetic field.

<3-5> pack

1.0% by weight of tetradecane or heptadecane

Polyvinyl alcohol 13.0 wt %

Sodium carboxymethyl cellulose 0.2 wt %

glycerin 5.0% by weight

Allantoin 0.1 wt%

ethanol 6.0 wt%

PEG 12 nonylphenyl ether 0.3 wt %

Polysorbate 60 0.3 wt %

Preservatives, colors and fragrances

Purified water to 100% by weight

Although the above compounding ratio is a composition that is relatively suitable for the pack in a preferred embodiment, the mixing ratio may be arbitrarily modified, and it can be prepared according to a manufacturing method in the field of cosmetics.

<3-6> Gel

0.5% by weight of tetradecane or heptadecane

Sodium ethylenediamine acetate 0.05 wt %

glycerin 5.0% by weight

Carboxyvinyl Polymer 0.3 wt %

ethanol 5.0 wt%

PEG 60 hydrogenated castor oil 0.5 wt %

Triethanolamine 0.3 wt %

Preservatives, colors and fragrances

Purified water to 100% by weight

Although the above mixing ratio is a composition that is relatively suitable for gel composition in a preferred embodiment, the mixing ratio may be arbitrarily modified, and it can be prepared according to a manufacturing method in a conventional cosmetic field.

The blending ratio is a composition that is relatively suitable for a cosmetic composition in a preferred embodiment, but it can be applied to cosmetics for various uses, including other color cosmetics, and is a drug that can be applied thinly to the human body according to its efficacy, that is, It can be used for manufacturing as an ointment, and the mixing ratio can be arbitrarily modified according to regional and ethnic preferences such as the demanding class, demanding country, and use.

The description of the present invention described above is for illustration, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive.

Claims (16)

1. A pharmaceutical composition for preventing or treating muscle disease, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.
2. According to claim 1,

   The linear alkane is a pharmaceutical composition for preventing or treating muscle disease, characterized in that tetradecane or heptadecane.
3. According to claim 1,

   The linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof is a pharmaceutical composition for preventing or treating muscle disease, characterized in that it increases the expression of p-4E-BP1 and p-p70S6K1 proteins.
4. According to claim 1,

   The straight-chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof is a muscle disease characterized in that it reduces the expression of MuRF1 (Muscle Ring-Finger Protein), MaFbx (Muscle atrophyF-box) or myostatin. A pharmaceutical composition for prophylaxis or treatment.
5. According to claim 1,

   The muscle disease is a muscle disease prevention or treatment pharmaceutical composition, characterized in that the muscle disease due to reduced muscle function, muscle reduction, muscle atrophy, muscle wasting or muscle degeneration.
6. 6. The method according to any one of claims 1 to 5,

   The muscle disease is dystonia, muscular atrophy, muscular dystrophy, myasthenia gravis, cachexia, rigid spinesyndrome, amyotrophic lateral sclerosis (Lou Gehrig's disease, amyotrophic lateral sclerosis). , Charcot-Marie-Tooth disease (Charcot-Marie-Tooth disease) and muscle atrophy (sarcopenia), characterized in that any one or more selected from the group consisting of a pharmaceutical composition for preventing or treating muscle disease.
7. A pharmaceutical composition for promoting muscle differentiation, regenerating muscles or strengthening muscles, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.
8. A health functional food composition for promoting muscle differentiation, regenerating or strengthening muscles, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.
9. A pharmaceutical composition for increasing muscle mass or promoting muscle production, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.
10. A health functional food composition for increasing muscle mass or promoting muscle generation, comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.
11. A health functional food composition for improving muscle function comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.
12. A cosmetic composition for improving muscle function comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.
13. A method for preventing or treating muscle disease, comprising administering or taking a composition comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient to an individual.
14. A method for promoting muscle differentiation, regenerating or strengthening muscles, comprising administering or taking a composition comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient to an individual.
15. Use of a composition for preventing or treating a muscle disease comprising a linear alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient.
16. A composition comprising a straight-chain alkane having 14 to 17 carbon atoms or a pharmaceutically acceptable salt thereof as an active ingredient is used for promoting muscle differentiation, regenerating muscles or strengthening muscles.

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