KR20200080892A - Composition comprising piperonal as active ingredients for muscle strengthening, development, differentiation, regeneration or inhibiting muscle atrophy - Google Patents

Abstract

The present invention relates to a composition for preventing or treating muscle diseases or improving muscle functions, including piperonal or a salt thereof as an active ingredient. Piperonal can increase expression of proteins related with muscle protein synthesis and an increase in muscle mass in muscle cells, can inhibit expression of enzymes participating in muscle protein decomposition from the level of mRNA, and thus can provide a muscle strengthening effect and can inhibit sarcopenia through muscle differentiation, muscle regeneration and an increase in muscle mass in the case of muscle diseases caused by muscle function degradation, muscle consumption or muscle degeneration. Therefore, piperonal can be used for preventing or treating muscle diseases, for muscle differentiation, muscle regeneration, muscle strengthening or muscle mass building, for accelerating muscle generation or for improving muscle functions.

Description

A composition having an effect of inhibiting muscle strengthening, muscle strengthening, muscle differentiation, muscle regeneration, and muscular dystrophy containing piperonal as an active ingredient {COMPOSITION COMPRISING PIPERONAL AS ACTIVE INGREDIENTS FOR MUSCLE STRENGTHENING, DEVELOPMENT, DIFFERENTIATION, REGENERATION OR INHIBITING MUSCLE ATRO

The present invention relates to a pharmaceutical composition for preventing or treating muscle disease comprising piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

In the Republic of Korea, the elderly population occupied 7.2% of the total population in 2000 and entered an aging society, and in 2050, it is expected to enter an aging society (more than 20%) (2013 Senior Statistics, Statistics Korea). The muscle mass of a person decreases with age (about 10-15% between 50 and 70 years of age, and decreases by 30% or more from 70 to 80 years of age), thereby weakening muscle strength and muscle function, which is called senile muscular dystrophy (sarcopenia). It is called. Senile muscular dystrophy is a major cause of limiting the independent life of the elderly by inducing activity disorders and gait disorders. In addition, myopathy decreases basal metabolic rate, increases insulin resistance, promotes type 2 diabetes, and increases the risk of developing hypertension and cardiovascular disease by 3-5 times. Currently, there are no drugs approved for the treatment of muscular dystrophy, and drug repositioning technology is being developed to apply myostatin inhibitors or other FDA-approved therapeutics for muscular dystrophy.

The muscles are largely divided into skeletal muscles, cardiac muscles, and visceral muscles. Of these, skeletal muscles are the largest amount of tissue in the human body, accounting for 40-45% of body weight. Skeletal muscles are attached to the bone through the tendon and act to create bone movement or strength. A single muscle is composed of numerous muscle fibers, and again, the muscle fibers are made of numerous myofibrillars composed of actin and myosin. When actin and myosin move in superimposition, the length of the muscle becomes shorter or longer, causing contraction and relaxation of the entire muscle. Increasing myofibrillar size means an increase in muscle fiber thickness, resulting in an increase in muscle.

The types of muscle fibers that make up the muscles are mainly classified into Type I, Type IIA, and Type IIB by metabolic processes and contraction rates that generate ATP. 'Type I muscle fiber' has a slow contraction rate and contains a large number of myoglobin and mitochondria, making it suitable for continuous and low-strength aerobic activity. Type I muscle fibers have a red color, so they are also called red muscles, and the soleus (soleus) typically belongs to them. On the other hand,'Type ⅡB muscle fiber' is very short due to its rapid contraction rate, but is used for high-intensity anaerobic exercise, and has a low myoglobin content and is white in color. 'Type IIA muscle fiber' has the intermediate characteristics of the two muscle fibers mentioned above. Not only does the composition of type I and II muscle fibers vary by part of the muscles with age, but all types of muscle fibers decrease.

Skeletal muscles have the characteristic of being regenerated and maintained according to the environment, but these characteristics are lost with age and consequently, as the aging progresses, the amount of muscle is reduced and muscle strength is also lost. Signaling systems that are involved in muscle growth and regeneration include signaling that is mediated by IGF-1 (insulin like growth factor 1)/AKT to regulate protein synthesis. 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 phosphorylation of ribosomal protein S6 kinase beta-1 (p70S6K1), increases mRNA translation, increases eukaryotic translation initiation factor 4 G (eIF4G) activity, and eukaryotic translation initiation factor 4E binding protein Phosphorylates 1(4E-BP1) protein. eIF4G and 4E-BP1 are involved in forming the eIF4F complex, that is, eIF4G binds to eIF4A and eIF4E to form the eIF4F complex, whereas when 4E-BP1 is phosphorylated, the binding ability with eIF4E is inhibited, thereby increasing the free eIF4E. . The latter combines with other translation initiation factors (eIF4G and eIF4A) to form an eIF4F complex, and the eIF4F complex thus formed stabilizes the ribosome structure, thereby promoting translation initiation, ultimately synthesizing proteins. (Bodine et al., Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.Nature cell biology, 3, 1014-1019, 2001).

In addition, AKT phosphorylation promotes muscle fiber growth by increasing eIF2B expression through GSK3 (glycogen synthase kinase 3) while inhibiting muscle loss by inhibiting 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 the 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 RING-finger protein-1 (MURF1) and Muscle Atrophy F-Box (MAFbx)/atrogin-1, which are muscle-specific ubiquitin-ligase, which Ubiquitin attaches to the lysine site of the target protein to promote protein breakdown, eventually leading to muscle loss (Gumucio et al., Atrogin-1, MuRF-1, and sarcopenia.Endocrine, 43, 12-21, 2013).

The present invention is to provide a pharmaceutical composition for preventing or treating muscle diseases, including piperonal or 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 problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the following materials.

The present invention provides a pharmaceutical composition for preventing or treating muscle disease comprising piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

The piperonal or a pharmaceutically acceptable salt thereof can increase the expression of p-4E-BP1 and p-p70S6K1 proteins.

The piperonal (Piperonal) or a pharmaceutically acceptable salt thereof may reduce the expression of MuRF1 (Muscle Ring-Finger Protein), MaFbx (Muscle atrophyF-box) or myostatin (Myostatin).

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

The muscle diseases include atony, muscular atrophy, muscular dystrophy, myasthenia gravis, cachexia, rigid spinesyndrome, amyotrophic lateral sclerosis. , Charcot-Marie-Tooth disease and 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, muscle regeneration or muscle strengthening, which includes piperonal 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, muscle regeneration or strengthening muscle, which includes piperonal 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, including piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a functional food composition for increasing muscle mass or promoting muscle production, including piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a functional food composition for improving muscle function comprising piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a cosmetic composition for improving muscle function comprising piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

The present invention relates to a composition for preventing or treating muscle disease, or for improving muscle function, comprising piperonal or a salt thereof as an active ingredient, wherein the piperonal synthesizes muscle protein in muscle cells and Muscle differentiation, muscle regeneration in muscle diseases caused by muscle function degradation, muscle wasting, or muscle degeneration because it can increase the expression of proteins related to increased muscle mass and inhibit the expression of enzymes involved in muscle protein degradation from the mRNA level. It can show muscle strengthening effect through increasing muscle mass, and can suppress muscle loss, for preventing or treating muscle disease, muscle differentiation, muscle regeneration and muscle strengthening or muscle mass increase or muscle production promotion or muscle Can be used to improve functionality.

1 and 2 show the results of analyzing changes in myotube length in mouse myoblasts. Values represent the mean±SEM of three experiments, and values indicated by different letters indicate statistical significance (P <0.05).
Figure 3 shows the results of confirming the changes in the mRNA expression level (FIG. 3A) and protein expression level (FIG. 3B) of proteolytic and synthesis-related molecules in mouse myoblasts treated with piperonal. Values represent mean±SEM of 3 experiments. (* = p <0.05, ** = p <0.01, [one-way ANOVA, Tukey's test])

The present inventors completed the present invention by confirming that it is effective in improving muscle loss and muscle loss by inhibiting the decomposition of muscle proteins and promoting synthesis in piperonal, a natural product with few side effects.

Hereinafter, terms of the present invention will be described.

In the present invention, "muscle" refers to the tendons, muscles, tendons, and "muscle function" refers to the ability to exert power by contraction of muscles, and the muscles can exert maximum contractility to overcome resistance. Includes muscle strength, the ability to exercise, muscle endurance, the ability to indicate how long or how many times a muscle can repeat contraction and relaxation at a given weight, and wits, the ability to exert strong power in a short period of time. This muscle function is proportional to muscle mass, and "improving muscle function" means improving muscle function better.

Piperonal is also called heliotropine, heliotropin, dioxymethyleneprotocatechuic aldehyde, piperonyl aldehyde, 3,4-benzodioxole-5-carboxaldehyde, 1,3-benzodioxole-5-carboxaldehyde, 3,4-methylene dihydroxybenzaldehyde, and the like. The piperonals are Capparis spinosa Linne (Caper), Cinnamomum camphora (Camphor), and Cucumis melo Linn (Melon). Galium verum var. asiaticum, Piper nigrum (Black Pepper, Pepper), Polianthes tuberosa (Tuberose, Manhyangok), Vaccinium corymbosum (American blueberry), Vanilla planifolia (Bourbon vanilla, Vanilla), Viola odorata (Apple leaf, fragrant violet) It is an alkaloid-based compound contained in plants such as. The structural formula of Piperonal is C ₈ H ₆ O ₃ , the molecular weight is 150.13 g/mol, and the structure is as shown in Chemical Formula 1.

[Formula 1]

Piperonal is listed in the Food and Drug Administration (FDA) and Korea Food and Drug Administration (KFDA) food additive databases as substances that can be used as flavoring agents.It is used in combinations of cherries and vanilla flavors, and is mainly used in ice cream and bakery products. It has been used. It has been reported that piperonal has a tumor suppressive effect in tumor animal models (Anto RJ, George J, Babu KV, Rajasekharan KN, Kuttan R., Antimutagenic and anticarcinogenic activity of natural and synthetic curcuminoids. Mutat Res. Sep 13;370(2):127-31, 1996), stimulating piperonal through the nasal cannula during patient magnetic resonance imaging (MRI) imaging for cancer diagnosis. As a result, it has been reported that it has an effect of lowering anxiety of patients (Redd WH, Manne SL, Peters B, Jacobsen PB, Schmidt H., Fragrance administration to reduce anxiety during MR imaging.J Magn Reson Imaging. Jul-Aug; 4(4):623-6, 1994). However, there are no known physiological mechanisms related to muscle strength and muscle.

Piperonal is known to be edible and relatively safe. When humans took 10 g of piperonal, toxicity was not observed (Von Oettingen, WF, Nat Inst Health Bull. No. 190, 342, 1949), and LD ₅₀ of piperonal was administered to rats. As a result of the measurement, 2,700 mg/kg body weight was reported (Jenner, PM, et al., Food Cosmet Toxicol. 2, 327, 1964). In addition, in an experiment in which a rat fed a piperonal supplement with 1% feed was fed for 28 weeks, no abnormalities were found in blood, major organ weight, and histology (Hagan, EC, et al., Fd Cosmet Toxicol) .5, 141,1967), toxicity was not observed in a study in which rats were ingested for 2 years by adding piperonal 0.1% and 0.5% to feed (FAO Nutr. Meet. Rep. Ser. No. 44A. WHO Fd. Add 68, 33, 73, 1968).

Hereinafter, the present invention will be described in detail.

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

The present invention provides a pharmaceutical composition for preventing or treating muscle disease, comprising piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for promoting muscle differentiation, muscle regeneration, or muscle strengthening, comprising piperonal 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, including piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

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

[Formula 1]

The method for obtaining the piperonal is not particularly limited, and may be used for separation from a plant containing the piperonal, chemically synthesized using a known manufacturing method, or commercially available one.

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

Specifically, representative molecules related to protein synthesis include p70S6K1, 4E-BP1, and eIF members, and these three molecules are regulated by higher mTORC activity. 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, these two molecules are involved in forming the eIF4F complex. In other words, eIF4G combines with eIF4A and eIF4E to form an eIF4F complex, whereas when 4E-BP1 is phosphorylated, the binding capacity with eIF4E is inhibited, thereby increasing the free eIF4E. The latter combines with other translation initiation factors (eIF4G and eIF4A) to form an eIF4F complex, and the eIF4F complex thus formed stabilizes the ribosome structure, thereby promoting translation initiation, ultimately increasing protein synthesis. MAFbx/Atrogin-1 (Muscle atrophy F-box) and MuRF1 (muscle RING finger 1) are muscle-specific ubiquitin-ligases, lysine targeting ubiquitin. ) As a representative protein that promotes proteolysis by attaching to the site and eventually induces muscle loss, the composition of the present invention reduces the expression of MuRF1 (Muscle Ring-Finger Protein) or MaFbx (Muscle atrophy F-box), It can inhibit muscle loss.

In the pharmaceutical composition of the present invention, the muscle disease includes a range of diseases caused by muscle function decline, muscle loss, muscle atrophy, muscle wasting, or muscle degeneration. Specifically, the muscle diseases include atony, muscle atrophy, muscular dystrophy, myasthenia gravis, cachexia, rigid spinesyndrome, amyotrophic lateral sclerosis (ALS), amyotrophic Lateral sclerosis, Charco-Marie-Tooth disease and sarcopenia are preferably at least one selected from the group consisting of, but are not limited to. In addition, the muscle wasting or degeneration occurs entirely due to factors, acquired factors, aging, and the like, and muscle wasting is characterized by gradual loss of muscle mass, weakness and degeneration of muscles, especially skeletal or veterinary muscles and cardiac muscles.

In addition, from the viewpoint of using the pharmaceutical composition of the present invention to promote muscle differentiation, muscle regeneration, or muscle strengthening, muscle cell differentiation is a muscle development program (muscle) that specifies components of muscle fibers such as contractile organs (myofibrils). developmental program). Useful therapeutic agents for differentiation are about 10% or more, more preferably 50% or more, and most preferably 100% or more of the amount of all muscle fiber components in diseased tissues, compared to equivalent tissues in similarly treated control animals. Can be increased.

In addition, from the viewpoint of using the pharmaceutical composition of the present invention to promote muscle differentiation, muscle regeneration or muscle strengthening, or to increase muscle mass, muscle growth is caused by an increase in fiber size and/or It can be caused by an increase in the number of fibers. 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 muscle fiber diameter. An increase in muscle fiber growth can be defined as an increase in diameter when defining the diameter as a shortening of the cross-section ellipsoid. Useful therapeutic agents are wet weight gain, protein content and/or in animals with at least 10% muscle degeneration compared to previously treated control animals (i.e., animals with degenerated muscle tissue not treated with muscle growth compounds). It is to increase the diameter by 10% or more, more preferably 50% or more, and most preferably 100% or more. Compounds that increase growth by increasing the number of muscle fibers are useful as therapeutic agents when it increases the number of muscle fibers in diseased tissues by at least 1%, more preferably at least 20%, and most preferably at least 50%. These percentage values were determined relative to the baseline level in untreated, disease-free comparative mammals or contralateral disease-free muscles when the compound is administered and acts locally.

In addition, from the viewpoint of using the pharmaceutical composition of the present invention to promote muscle differentiation, muscle regeneration or muscle strengthening, muscle regeneration refers to a process in which new muscle fibers are formed from muscle hair cells. 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 muscle cells refers to the induction of a muscle developmental program that characterizes the components of muscle fibers, such as contractile organs (myofibrils). A useful therapeutic agent for differentiation is about 10% or more, more preferably 50% or more, and most preferably 100% of the amount of all muscle fiber components in diseased tissues, compared to equivalent tissues in similarly treated control animals. Increase over.

In addition, from the viewpoint of using the pharmaceutical composition of the present invention for the purpose of increasing muscle mass or promoting muscle production, "increased muscle mass" is to improve muscle growth, among other body components, and to increase muscle mass through physical exercise and endurance enhancement. It is possible to increase and increase the muscle mass by administering a substance having a muscle increase effect to the body, and the type of muscle is not limited.

In the pharmaceutical composition of the present invention, the composition may include a volume of piperonal or a pharmaceutically acceptable salt thereof in a concentration of 0.1 μM to 1000 μM, but is not limited thereto. At this time, when the piperonal (Piperonal) is less than the concentration range, the protein synthesis and decomposition activity in muscle cells is lowered, there is a problem that it is difficult to exert a muscle disease prevention or treatment effect, and when it exceeds the concentration range, There may be toxic concerns, including cytotoxicity.

The piperonal 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 a salt. 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, bisulphite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate chloride, bromide, iodide 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, dinitro benzoate, hydroxybenzoate, meth Methoxybenzoate, phthalate, terephthalate, benzenesulfonate, toluenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycol Rate, malate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate or mandelate.

The acid addition salt according to the present invention is dissolved in a conventional method, for example, the piperonal in an excess aqueous acid solution, and the salt is water-miscible organic solvent such as methanol, ethanol, acetone or aceto. It can be prepared by precipitation using nitrile. It can also be prepared by heating the same amount of piperonal and acid or alcohol in water, followed by evaporation of the mixture to dryness or suction filtration of the precipitated salt.

In addition, bases can be used to make pharmaceutically acceptable metal salts. The alkali metal or alkaline earth metal salt is obtained, for example, by dissolving the compound in an excess of an alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the inexpensive compound salt, and evaporating and drying the filtrate. At this time, it is suitable to manufacture sodium, potassium or calcium salts as metal salts. Further, 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 piperonal 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, dissolving piperonal in a water-miscible organic solvent, for example acetone, methanol, ethanol, or acetonitrile, and adding an excess organic acid. Alternatively, it can be prepared by adding an acidic acid aqueous solution and then precipitating or crystallizing it. Subsequently, the solvent or excess acid in the mixture may be evaporated and then dried to obtain an added salt, or the precipitated salt may be filtered by suction filtration.

The pharmaceutical composition of the present invention may be various oral or parenteral formulations. When formulating the composition, one or more buffers (e.g. saline or PBS), antioxidants, bacteriostatic agents, chelating agents (e.g. EDTA or glutathione), fillers, extenders, binders, adjuvants (e.g., Aluminum hydroxide), suspensions, thickener wetting agents, disintegrating agents or surfactants, diluents or excipients.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include at least one excipient in one or more compounds, such as 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 hydroxy It is prepared by mixing propylmethyl-cellulose or gelatin. For example, tablets or dragees can be obtained by blending the active ingredient with a solid excipient and then grinding it and adding a suitable adjuvant to the granule mixture.

In addition, lubricants such as magnesium stearate, talc and the like are used in addition to simple excipients. Liquid preparations for oral administration include suspending agents, intravenous solutions, emulsions or syrups, etc. In addition to commonly used simple diluents such as water and liquid paraffin, various excipients, such as wetting agents, sweeteners, flavoring agents or preservatives, are included. Can. In addition, if necessary, cross-linked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may be added as a disintegrant, and may further include an anti-coagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent, and a preservative. .

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspension solvents, emulsions, lyophilized formulations or suppositories. As the non-aqueous solvent and suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, 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 for parenteral administration, external application to the skin; Injections that are injected intraperitoneally, rectal, intravenous, intramuscular, subcutaneous, intrauterine dura mater or cerebrovascular; Transdermal administration; Alternatively, nasal inhalants may be formulated according to methods known in the art.

The injections must be sterile and protected from contamination of microorganisms such as bacteria and fungi. For injections, examples of suitable carriers include, but are not limited to, solvents or dispersion media comprising water, ethanol, polyols (eg, glycerol, propylene glycol and liquid polyethylene glycol, etc.), mixtures thereof and/or vegetable oils. Can. More preferably, suitable carriers include Hanks' solution, Ringer's solution, phosphate buffered saline (PBS) with triethanol amine or isotonic solution 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 paraben, chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In addition, the injection may further include isotonic agents such as sugars or sodium chloride in most cases.

In the case of transdermal dosage forms, ointments, creams, lotions, gels, external solutions, pasta, linen agents, aerosols, and the like are included. In the above, transdermal administration means that the pharmaceutical composition is topically administered to the skin, so that an effective amount of the active ingredient contained in the pharmaceutical composition is delivered into the skin.

For inhalation dosages, the compounds used in accordance with the present invention may be pressurized packs or, using suitable propellants, such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoro ethane, 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 pressurized aerosols, the dosage unit can be determined by providing a valve that delivers a metered amount. For example, gelatin capsules and cartridges used in inhalers or insufflators can be formulated to contain a powder mixture of a compound and a suitable powder base such as lactose or starch. Formulations for parenteral administration are described in Remington's Pharmaceutical Science, 15th Edition, 1975.Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour, a prescription generally known to all pharmaceutical chemistries.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, "a pharmaceutically effective amount" means an amount sufficient to treat the disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type of patient's disease, severity, and activity of the drug , The sensitivity to the drug, the time of administration, the route of administration and rate of excretion, the duration of treatment, factors including the drugs used simultaneously, 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 in combination with other therapeutic agents, and may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. That is, the total effective amount of the pharmaceutical composition of the present invention can be administered to a patient in a single dose, and administered by a fractionated treatment protocol that is administered for a long time in multiple doses. Can. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect in a minimal 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 may vary depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease. As a daily dosage, when administered parenterally, it is preferably administered in an amount of 0.01 to 50 mg per kg of body weight per day, more preferably 0.1 to 30 mg per kg of body weight per day based on piperonal, and when administered orally May be administered in divided portions of 1 to several times to be administered in an amount of preferably 0.01 to 100 mg, more preferably 0.01 to 10 mg per 1 kg of body weight per day, based on the piperonal of the present invention. However, since the dosage may be increased or decreased depending on the route of administration, the severity of obesity, sex, weight, and age, the dosage is not limited to 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 may also be provided in the form of an external preparation containing piperonal as an active ingredient. When the pharmaceutical composition for preventing and treating muscle diseases of the present invention is used as an external preparation for skin, fat substances, organic solvents, solubilizers, thickeners and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents ), fragrance, surfactant, water, ionic emulsifier, nonionic emulsifier, filler, metal ion blocker, chelating agent, preservative, vitamin, blocker, wetting agent, essential oil, dye, pigment, hydrophilic active agent, lipophilic active agent Or it may contain an adjuvant commonly used in the field of skin science, 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 commonly used in the field of skin science.

When the pharmaceutical composition for preventing and treating muscle diseases of the present invention is provided as an external preparation for skin, the present invention is not limited thereto, and may be a formulation such as ointment, patch, gel, cream or spray.

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

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

In addition, the present invention provides a functional food composition for promoting muscle differentiation, muscle regeneration or muscle strengthening, which includes piperonal 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, including piperonal 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 piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

In the health functional food composition, specific contents of the piperonal are as described above.

In the health functional food composition for preventing or improving muscle diseases according to the present invention/promoting muscle differentiation, for muscle regeneration or for strengthening muscles/increasing muscle mass or promoting muscle production, the piperonal When 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 suitably used according to a conventional method. The mixing amount of the active ingredient can be appropriately determined according to each purpose of use, such as prevention, health, or treatment.

The formulation of the dietary supplement may be in the form of powders, granules, pills, tablets, capsules, as well as in the form of general foods or beverages.

The type of the food is not particularly limited, and examples of foods to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, and ice cream. There are products, various soups, beverages, teas, drinks, alcoholic beverages and vitamin complexes, and may include all foods in the ordinary sense.

In general, in the manufacture of food or beverage, the piperonal 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. However, in the case of long-term intake for the purpose of health and hygiene or for health control, the amount may be below the above range, and the present invention has no problem in terms of safety in terms of using fractions from natural products. It can also be used in the above amount.

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

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 salts thereof, alginic acid and salts thereof, organic acids, and protective colloids It may contain thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonic acid used in carbonated beverages. In addition, the health functional food composition for promoting muscle differentiation, muscle regeneration or muscle strengthening of the present invention may contain flesh for the preparation of natural fruit juices, fruit juice drinks and vegetable drinks. These ingredients can be used independently or in combination. The ratio of these additives is not limited, but is generally selected from 0.01 to 0.1 parts by weight compared to 100 parts by weight of the health functional food of the present invention.

Cosmetic composition for muscle function improvement

In addition, the present invention provides a cosmetic composition for improving muscle function comprising piperonal or a pharmaceutically acceptable salt thereof as an active ingredient. The cosmetic composition is not particularly limited, but may be used for external application to the skin or may be taken orally.

The composition for improving muscle function of the present invention may also be a cosmetic composition. The cosmetic composition of the present invention contains piperonal as an active ingredient and a basic cosmetic composition (face wash, cream, essence, cleansing foam and cleansing water-like face wash, pack, and bodioyl) along with dermatologically acceptable excipients. , Color cosmetics composition (foundation, lipstick, mascara, makeup base), hair product composition (shampoo, conditioner, hair conditioner, hair gel) and soap.

The excipients include, but are not limited to, for example, skin emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickening agents and solvents. In addition, fragrances, pigments, disinfectants, antioxidants, preservatives and moisturizers may be further included, and for the purpose of improving physical properties, may include thickeners, inorganic salts, synthetic polymer materials, and the like. For example, in the case of preparing the cleanser and the soap with the cosmetic composition of the present invention, it can be easily prepared by adding the piperonal to the conventional cleanser and the soap base. In the case of manufacturing a cream, it can be prepared by adding piperonal or a salt thereof to a cream base of a general oil-in-water type (O/W). Synthetic or natural materials such as proteins, minerals, vitamins, etc. for the purpose of improving physical properties may be additionally added to fragrances, chelating agents, pigments, antioxidants, preservatives, and the like.

The content of piperonal contained in the cosmetic composition of the present invention is not limited to this, but is preferably 0.001 to 10% by weight, and more preferably 0.01 to 5% by weight relative to the total weight of the total composition. If the content is less than 0.001% by weight, the desired anti-aging or anti-wrinkle effect cannot be expected, and if it is more than 10% by weight, there may be difficulties in safety or preparation of the formulation.

As described above, the composition comprising the piperonal of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient increases 4E-BP1 and p70S6K1 protein phosphorylation in myoblasts, MuRF1 and MaFbx/atrogin1 By inhibiting gene expression, muscle muscularization due to muscle function decline, muscle wasting, or muscle degeneration may exhibit muscle strengthening effects through muscle differentiation, muscle regeneration, and increase in muscle mass. It can be used for treatment, muscle differentiation, muscle regeneration and muscle mass increase or muscle function improvement.

Hereinafter, preferred embodiments are provided to help understanding of the present invention. However, the following examples are only provided to more easily understand the present invention, and the contents of the present invention are not limited by the following examples.

Example: The effect of inhibiting muscle enhancement and muscle loss of piperonal using mouse myoblasts

Example 1. Confirmation of myotube length change

1-1. Experiment method

1) Cell culture

Mouse myoblast cell line (C2C12 cell) was purchased from ATCC (Manassas, VA, USA) and used. The purchased cells were cultured in a 37°C, 5% CO ₂ incubator using 10% fetal bovine serum media (Gibco-BRL) and used in 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 potentiation effect, 100 μM of piperonal (Sigma) was treated for two days from the start of differentiation, and 100 μM of DMSO (dimethyl sulfoxide; Sigma) was treated as a control group. In order to confirm the efficacy of inhibiting muscle loss, dexamethasone (Sigma) 50 μM and piperonal (Sigma) 100 μM were treated for two days from the fourth day of differentiation.

2) Giemsa-wright staining

After washing the cells twice with PBS (Phosphate buffered saline), they were fixed with 100% methanol for 10 minutes. After the fixation was completed, the mixture was naturally dried at room temperature for 10 minutes and then stained for 30 minutes by dropping a giemsa-wright staining solution (Asan Pharmaceutical, Seoul) that specifically stains the myotube.

3) Measurement of myotube length

The dyed myotube was photographed at X40 magnification using a fluorescence microscope (IX 71, Olympus) and analyzed using image J software (USA). Six sections were randomly selected from each well and photographed under a microscope, and at least 100 myotube lengths from each well were analyzed (3 repeats/group).

1-2. Experiment result

1) Change in length of myotube

As a result of visually staining myotubes using a giemsa solution to confirm the muscle augmentation efficacy of piperonal targeting mouse myoblasts, the results showed that piperonal treatment was performed on myotubes ( myotube) was found to significantly increase the length of 41% (Fig. 1).

As a result of visually staining myotubes using a giemsa solution to confirm the efficacy of piperonal muscle loss inhibition in mouse myoblasts, the length of myotubes was visualized. Was confirmed to be significantly reduced, and piperonal treatment was found to significantly increase the myotube length decreased by 96% by dexamethasone (FIG. 2 ). Therefore, it can be seen that piperonal promotes muscle growth and suppresses muscle loss by increasing the length of myotubes in mouse myoblasts.

Example 2: Identification of mechanism of action

2-1. Experiment method

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

334 μl of Trizol solution per mouse myoblast 1*10 ⁷ cells was added and ground, followed by centrifugation at 4°C and 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 and isopropanol was 1:1. After shaking vigorously 10 times, it is left at room temperature for 15 minutes, centrifuged at 12,000 xg, 4°C for 10 minutes, and the supernatant is removed. After adding 1 mL of 70% ethanol to the remaining precipitate, 7,500 xg, 5 minutes at 4°C During centrifugation. 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 RNA samples extracted at wavelengths of 260 nm and 280 nm is measured using a UV/VIS spectrophotometer (Beckman coulter, DU730), and the integrity of the RNA samples is performed by agarose gel electrophoresis. (integrity) was confirmed.

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

Gene description Primers Sequences (5'→3') Annealing
temperature(℃) PCR
product (bp) MAFbx
(synonym: atrogin-1) F GTCCAGAGAGTCGGCAAGTC 63 141 R GTCGGTGATCGTGAGACCTT MuRF1
(synonym: TRAM63) F ACATCTACTGTCTCACGTGT 58 106 R TGTCCTTGGAAGATGCTTTG Myostatin F TCACGCTACCACGGAAACAA 60 166 R AGGAGTCTTGACGGGTCTGA IGF1 F GGGGACTTTCGTGACTGAGC 60 165 R GGTAGGTCCGGGTCGTTTAC Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) F GTGATGGCATGGACTGTGGT 55 163 R GGAGCCAAAAGGGTCATCAT

2) Western blotting

500 μL of 100 mM Tris-HCl, pH 7.4, 5 mM EDTA, 50 mM sodium pyrophosphate, 50 mM NaF in each well with media removed to perform Western blotting in cells , 100 mM orthovanadate, 1% Triton X-100, 1 mM phenylmethanesulfonyl fluoride, 2 μg/mL aprotinin, 1 μg/mL pepstatin A (pepstatin A), and 1 μg/mL A lysis buffer containing leupeptin was added and harvested, and 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 40 µg of the quantified protein was electrophoresed on an SDS polyacrylamide gel, it was transferred to a 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, gently shaken at 4°C for 12 hours, washed with TBS-T, and the membrane was again diluted with a secondary antibody diluted at a ratio of 1:2,000. Incubated together for 60 minutes and washed. In this case, S6K1, phopho-p70S6K1 (p-p70S6K1), 4E-BP1, phospho-4E-BP1 (p-4E-BP1) and GAPDH (Cell Signaling Technology, Beverly, MA, USA) were used as primary antibodies. . Finally, the protein was visualized on the X-ray film using an ECL Western blot detection kit (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) Expression changes of molecules related to protein synthesis and degradation

In this experiment, the expression changes of molecules related to protein synthesis and degradation by piperonal were examined in mouse myoblasts. In control cells (Dexa), the amount of p-p70S6K1 and p-4E-BP1 proteins related to protein synthesis was significantly reduced compared to normal cells (Basal), whereas the proteolytic genes MaFbx/atrogin1, MuRF1, and myostatin ( Myostatin) increased significantly and the muscle enhancer IGF1 expression decreased. Treatment with piperonal significantly increased the protein levels of p-p70S6K1 and p-4E-BP1 and the expression of IGF1, which was reduced by dexamethasone, while the expression of MuRF1 and MAFbx/atrogin1, myostatin was significant. Was reduced (Fig. 3). Therefore, it is believed that piperonal may have been involved in ultimately increasing the amount of muscle by increasing the p70S6K1 and 4E-BP1 protein phosphorylation and IGF1 genes in mouse myoblasts, and inhibiting MuRF1 and MAFbx/atrogin1 and myostatin gene expression.

Hereinafter, an example of manufacturing a pharmaceutical, food or cosmetic product containing the piperonal 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 specifically described. The pharmaceutical, food or cosmetic compositions of Preparation Examples 1 to 3 were prepared according to the following compositional components and composition ratios with the extract having excellent effect of preventing and treating muscle disease or improving muscle function, according to a conventional method.

[Production Example 1] Preparation of pharmaceutical composition

<1-1> Preparation of powder

Piperonal 20 mg

Lactose hydrate 100 mg

Talc 10 mg

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

<1-2> Preparation of tablets

Piperonal 10 mg

Corn starch 100 mg

Lactose hydrate 100 mg

Magnesium stearate 2mg

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

<1-3> Preparation of capsules

Piperonal 10 mg

Microcrystalline cellulose 3 mg

Lactose hydrate 14.8 mg

Magnesium stearate 0.2 mg

After mixing the above components, the capsules were prepared by filling the gelatin capsules according to a conventional method for preparing capsules.

<1-4> Preparation of Injection

Piperonal 10 mg

Mannitol 180 mg

2974 mg of sterile distilled water for injection

Sodium monohydrogen phosphate 26 mg

After mixing the above components, it was prepared with the above-mentioned ingredient content per ampoule (2 mL) according to the preparation method of a conventional injection.

<1-5> Preparation of liquid formulation

Piperonal 10 mg

Isomerized sugar 10 mg

Mannitol 5 mg

Purified water

Lemon flavor

Dissolve each of the above components by adding each component to purified water according to a conventional manufacturing method, add an appropriate amount of lemon flavor, adjust purified water to 100 mL, and sterilize to fill the brown bottle to prepare a liquid.

[Production Example 2] Preparation of healthy food

<2-1> Preparation of health supplements

Piperonal 10 mg

Vitamin mixture

Vitamin A Acetate 70 μg

Vitamin E 1.0 mg

Vitamin B ₁ 0.13 mg

Vitamin B ₂ 0.15 mg

Vitamin B ₆ 0.5 mg

Vitamin B ₁₂ 0.2 μg

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ folic acid

Calcium Pantothenate 0.5 mg

Mineral mixture Proper

Ferrous sulfate 1.75 mg

Zinc oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium phosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium citrate 30 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the vitamin and mineral mixture is a composition suitable for a relatively healthy food in a preferred embodiment, the composition ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for preparing a healthy food. , Granules can be prepared and used in the preparation of healthy food compositions according to conventional methods.

<2-2> Preparation of health drinks

Piperonal 10 mg

Vitamin C 15 g

Vitamin E (powder) 100 g

Iron lactate 19.75 g

Zinc oxide 3.5 g

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3 g

Purified water quantitation

After mixing the above components according to a conventional health drink manufacturing method, and stirring and heating at 85° C. for about 1 hour, the resulting solution is filtered, obtained in a sterilized 2 liter container, sealed and sterilized, then refrigerated and stored in the present invention. It is used for the preparation of healthy beverage compositions.

Although the above composition ratio is a mixture of components suitable for preference beverages in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, country of demand, and usage.

[Production 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 intended to be described in detail rather than to limit it.

<3-1> Nutrient Cosmetics (Milk Lotion)

Piperonal 2.0 wt%

Squalane 5.0 wt%

Wax 4.0 wt%

Polysorbate 60 1.5 wt%

Sorbitan sesquioleate 1.5 wt%

Liquid paraffin 0.5 wt%

Caprylic/Capric Triglyceride 5.0 wt%

Glycerin 3.0 wt%

Butylene glycol 3.0 wt%

Propylene glycol 3.0 wt%

Carboxyvinyl polymer 0.1 wt%

Triethanolamine 0.2 wt%

Preservatives, colorings, flavors

Purified water to 100% by weight

The above blending ratio is a composition in which a component suitable for nutrient makeup is mixed in a preferred embodiment, but the blending ratio may be arbitrarily modified, and may be prepared according to a manufacturing method in the general cosmetic field.

<3-2> Flexible Cosmetics (Skin Lotion)

Piperonal 2.0% by weight

Glycerin 3.0 wt%

Butylene glycol 2.0% by weight

Propylene glycol 2.0% by weight

Carboxyvinyl polymer 0.1% by weight

PEG 12 nonylphenyl ether 0.2% by weight

Polysorbate 80 0.4 wt%

Ethanol 10.0% by weight

Triethanolamine 0.1 wt%

Preservatives, colorings, flavors

Purified water to 100% by weight

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

<3-3> Nutrition Cream

Piperonal 2.0% by weight

Polysorbate 60 1.5 wt%

Solbitan sesquioleate 0.5% by weight

PEG60 cured castor oil 2.0 wt%

10% by weight of liquid paraffin

Squalane 5.0 wt%

Caprylic/Capric Triglyceride 5.0 wt%

Glycerin 5.0 wt%

Butylene glycol 3.0 wt%

Propylene glycol 3.0 wt%

Triethanolamine 0.2% by weight

Preservative dosage

Appropriate amount of pigment

Spices

Purified water to 100% by weight

The above blending ratio is a composition in which a component suitable for a nutrient cream is mixed in a preferred embodiment, but the blending ratio may be arbitrarily modified, and may be prepared according to a manufacturing method in the general cosmetic field.

<3-4> Massage Cream

Piperonal 1.0 wt%

Wax 10.0 wt%

Polysorbate 60 1.5 wt%

PEG 60 hardened castor oil 2.0% by weight

Solbitan sesquioleate 0.8% by weight

Liquid paraffin 40.0 wt%

Squalane 5.0 wt%

Caprylic/Capric Triglyceride 4.0 wt%

Glycerin 5.0 wt%

Butylene glycol 3.0 wt%

Propylene glycol 3.0 wt%

Triethanolamine 0.2% by weight

Preservatives, colorings, flavors

Purified water to 100% by weight

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

<3-5> Pack

Piperonal 1.0 wt%

Polyvinyl alcohol 13.0% by weight

Sodium carboxymethyl cellulose 0.2% by weight

Glycerin 5.0 wt%

Allantoin 0.1 wt%

Ethanol 6.0% by weight

PEG 12 nonylphenyl ether 0.3 wt%

Polysorbate 60 0.3 wt%

Preservatives, colorings, flavors

Purified water to 100% by weight

The above mixing ratio is a composition suitable for relatively suitable components in a pack, but the mixing ratio may be arbitrarily modified, and may be prepared according to a manufacturing method in the general cosmetic field.

<3-6> Gel

Piperonal 0.5% by weight

Sodium ethylenediamine acetate 0.05% by weight

Glycerin 5.0 wt%

Carboxyvinyl polymer 0.3% by weight

Ethanol 5.0 wt%

PEG 60 hardened castor oil 0.5% by weight

Triethanolamine 0.3 wt%

Preservatives, colorings, flavors

Purified water to 100% by weight

Although the above mixing ratio is a composition in which a component suitable for a gel is mixed in a preferred embodiment, the mixing ratio may be arbitrarily modified, and may be prepared according to a manufacturing method in the general cosmetic field.

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

The above description of the present invention is for illustration only, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified to 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.

<110> Industry-Academic Cooperation Foundation, Yonsei University <120> COMPOSITION COMPRISING PIPERONAL AS ACTIVE INGREDIENTS FOR MUSCLE STRENGTHENING, DEVELOPMENT, DIFFERENTIATION, REGENERATION OR INHIBITING MUSCLE ATROPHY <130> 1065034 <160> 10 <170> KoPatentIn 3.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MaFbx_F primer <400> 1 gtccagagag tcggcaagtc 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MaFbx_R primer <400> 2 gtcggtgatc gtgagacctt 20 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MuRF1_F primer <400> 3 acatctactg tctcacgtgt 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> MuRF1_R primer <400> 4 tgtccttgga agatgctttg 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Myostatin_F primer <400> 5 tcacgctacc acggaaacaa 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> Myostatin_R primer <400> 6 aggagtcttg acgggtctga 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> IGF_F primer <400> 7 ggggactttc gtgactgagc 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> IGF_R primer <400> 8 ggtaggtccg ggtcgtttac 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> GAPDH_F primer <400> 9 gtgatggcat ggactgtggt 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> GAPDH_R primer <400> 10 ggagccaaaa gggtcatcat 20

Claims (11)

A pharmaceutical composition for preventing or treating muscle disease comprising piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.
According to claim 1,
The piperonal (Piperonal) or a pharmaceutically acceptable salt thereof is a pharmaceutical composition for the prevention or treatment of muscle disease characterized in that it increases the expression of p-4E-BP1 and p-p70S6K1 proteins.
According to claim 1,
The piperonal (Piperonal) or a pharmaceutically acceptable salt thereof is MuRF1 (Muscle Ring-Finger Protein), MaFbx (Muscle atrophyF-box) or myostatin (Myostatin) to reduce the expression of muscle disease prevention Or a therapeutic pharmaceutical composition.
According to claim 1,
The muscle disease is a muscle disease prevention or treatment pharmaceutical composition characterized in that the muscle disease due to muscle function decline, muscle loss, muscle atrophy, muscle wasting or muscle degeneration.
The method according to any one of claims 1 to 4,
The muscle diseases include atony, muscular atrophy, muscular dystrophy, myasthenia gravis, cachexia, rigid spinesyndrome, amyotrophic lateral sclerosis. , Charco-Marie-Tooth disease (Charcot-Marie-Tooth disease) and muscle disease prevention or treatment pharmaceutical composition, characterized in that at least one selected from the group consisting of sarcopenia.
Piperonal (Piperonal) or a pharmaceutical composition for promoting muscle differentiation, muscle regeneration or muscle strengthening, comprising an pharmaceutically acceptable salt thereof as an active ingredient.
Health functional food composition for promoting muscle differentiation, muscle regeneration or strengthening muscle, which includes piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.
A pharmaceutical composition for increasing muscle mass or promoting muscle production, including piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.
Health functional food composition for increasing muscle mass or promoting muscle production, including piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.
Health functional food composition for improving muscle function, including piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.
A cosmetic composition for improving muscle function, comprising piperonal or a pharmaceutically acceptable salt thereof as an active ingredient.

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