KR102483300B1 - Composition for improving muscle atrophy comprising ginsenoside Rf, ginsenoside composition comprising gincenoside Rf, or mixture thereof as an effective component - Google Patents

Abstract

The ginsenoside Rf of the present invention, the ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them promotes the expression of Myosin Heavy Chain, a muscle differentiation marker, regulates energy homeostasis in the body, and develops and grows skeletal muscle. It promotes AMPK phosphorylation, which plays an important role in regulation, and can increase exercise capacity, increase muscle strength, increase muscle mass, and alleviate muscle atrophy by increasing swimming duration in forced swimming tests in animal experiments. It can be used as a food composition for improving muscle function, a cosmetic composition for improving muscle function, a food composition for improving or preventing sarcopenia, or a pharmaceutical composition for treating or preventing sarcopenia.

Description

Composition for improving muscle atrophy comprising ginsenoside Rf, ginsenoside composition comprising ginsenoside Rf, or a mixture of any one or more of these as an active ingredient , or mixture thereof as an effective component}

The present invention relates to ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a food composition for improving muscle function, such as increasing exercise capacity, increasing muscle strength or increasing muscle mass, comprising a mixture of any one or more of these as an active ingredient, It relates to a cosmetic composition for improving muscle function, a food composition for improving or preventing sarcopenia, or a pharmaceutical composition for treating or preventing sarcopenia.

Skeletal muscle is the largest organ in the human body, accounting for 40-50% of the total body weight, and plays an important role in various metabolic functions in the body, including energy homeostasis and heat generation. A person's muscle decreases by more than 1% every year from the age of 40, and at the age of 80, 50% of the maximum muscle mass decreases, and muscle loss in old age is recognized as the most important factor in deteriorating overall physical function. As aging progresses, it is recognized that the body shape changes, such as muscle and fat content and skeletal distortion.

If insulin secretion is abnormal, energy cannot be properly supplied to the cells, which can cause muscle development disorders, and sarcopenia increases in diabetic patients than in the general population. In addition, muscle loss causes arthritis, back pain, and chronic pain to further increase, and symptoms of urinary incontinence caused by abdominal obesity can be aggravated, and injuries caused by fractures can increase depression in old age and lead to death. Sarcopenia is a major cause of deteriorating quality of life in association with various diseases.

Sarcopenia is known to be closely related to geriatric chronic diseases such as osteoporosis, insulin resistance, and arthritis, and the decrease in physical activity due to aging can be suppressed through the prevention or improvement of sarcopenia. The global progressive ataxia and muscle weakness treatment market recorded approximately USD 14 billion in 2011 and is expected to grow at a compound annual growth rate of 9.4% thereafter to reach approximately USD 23.5 billion in 2017.

In patients with sarcopenia, the number of myoblasts is reduced due to disorders in the recruitment, activity or proliferation of satellite cells, which are stem cells of myoblasts, and the proliferation and differentiation of myoblasts are reduced, thereby reducing the number of myoblasts in patients with sarcopenia. At the histological level, the size and number of muscle fibers decrease, resulting in reduced muscle function.

As studies on the epidemiology of sarcopenia have been actively conducted in the US and Europe for the past 10 years, interest in the clinical importance of sarcopenia has recently exploded. In early studies, the main results were that sarcopenia caused a decrease in quality of life due to general weakness, activity disorder, and loss of muscle strength. this has been reported In addition, since chronic diseases such as diabetes, metabolic syndrome, obesity, chronic renal failure, and chronic liver failure are induced in patients with sarcopenia, and ultimately increase mortality, sarcopenia is attracting attention as a disease that should be appropriately treated. .

Recently, in the United States, it has been reported that the possibility of physical disability in patients with sarcopenia increases by about 1.5 to about 3.5 times, resulting in an annual social cost of 18.5 billion USD. In Korea, according to the National Health and Nutrition Examination Survey, the prevalence of sarcopenia is 42.0% of men and 42.7% of women over the age of 60, which is a very common disease.

Currently, it is known that exercise, protein and calorie supplementation are helpful for sarcopenia, but it is not very helpful for the elderly, who account for the majority of sarcopenia patients, and therefore, sarcopenia treatment is urgently needed. However, drugs currently used for sarcopenia that show a direct effect on improving muscle loss and increasing muscle mass are still at the level of clinical trials, and there is currently no FDA-approved drug. Therefore, there are efforts to develop some selective androgen receptor modulators, activin receptor antagonists, fast skeletal muscle troponin inhibitors, etc.

Therefore, a food composition for improving muscle function, such as increasing exercise capacity, increasing muscle strength or increasing muscle mass, a cosmetic composition for improving muscle function, and improving or preventing sarcopenia using natural substances that are safe to consume and can be taken for a long period of time for patients with sarcopenia or the elderly. There is a need for a food composition or a pharmaceutical composition for treating or preventing sarcopenia.

On the other hand, it has been reported that ginsenoside Rg1 or Rb1 among the active ingredients of ginseng is related to muscle differentiation, but ginsenoside Rf, which is not contained in Korean ginseng and is characteristically present in Korean ginseng, has been reported to be related to muscle differentiation, muscle strength enhancement, or athletic ability improvement. It is not known whether this is related.

Korean Registered Patent No. 2011957 Republic of Korea Patent No. 1999916

Ginsenoside Rg1 from Panax ginseng enhances myoblast differentiation and myotube growth, 2017, Journal of Ginseng Research Ginsenoside Rb1 and Rb2 upregulate Akt/mTOR signalingemediated muscular hypertrophy and myoblast differentiation, 2019, Journal of Ginseng Research

An object of the present invention is to provide a food composition for improving muscle function comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

In addition, another object of the present invention is to provide a cosmetic composition for improving muscle function comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

In addition, another object of the present invention is to provide a food composition for improving or preventing sarcopenia comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient. It is to do.

Another object of the present invention is to provide a pharmaceutical composition for the treatment or prevention of sarcopenia comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient. It is to do.

The present invention for achieving the above object provides a food composition for improving muscle function containing ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

In addition, the present invention provides a cosmetic composition for improving muscle function comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

In addition, the present invention provides a food composition for improving or preventing sarcopenia comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for the treatment or prevention of sarcopenia comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

The ginsenoside Rf of the present invention, the ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them promotes the expression of Myosin Heavy Chain, a muscle differentiation marker, regulates energy homeostasis in the body, and develops and grows skeletal muscle. It promotes AMPK phosphorylation, which plays an important role in regulation, and can increase exercise capacity, increase muscle strength, increase muscle mass, and alleviate muscle atrophy by increasing swimming duration in forced swimming tests in animal experiments.

Figure 1 is a photograph confirming the expression of MHC (Myosin Heavy Chain) through Western blot when ginsenosides Rf, Rb2 and Rg1 were treated with 10, 20 and 40 μM, respectively.
FIG. 2 is a graph comparing the relative expression levels of the Western blot band size showing the expression of MHC (Myosin Heavy Chain) of FIG. 1 with respect to actin.
Figure 3 is a photograph confirming the phosphorylation of AMPK (5'-adenosine monophosphate-activated protein kinase) through Western blot when ginsenosides Rf, Rb2 and Rg1 were treated with 10, 20 and 40 μM, respectively.
Figure 4 shows the relative expression level of the western blot band size of the phosphorylated p-AMPK (phosphorylated 5'-adenosine monophosphate-activated protein kinase) of Figure 3 with respect to non-phosphorylated AMPK (phosphorylated 5'-adenosine monophosphate-activated protein kinase) is a graph that compares
Figure 5 confirms MHC, PGC-1α, phosphorylated p-AMPK, and phosphorylated p38 through Western blot when ginsenoside Rf 10 μM and ginsenosides Rh1 and Rg2 were treated in combination with 0.2, 1, and 5 μM, respectively. It is a picture.
FIG. 6 is a graph comparing relative expression levels of MHC, PGC-1α, phosphorylated p-AMPK, and phosphorylated p38 with respect to actin of FIG. 5 .
Figure 7 confirms MHC, PGC-1α, phosphorylated p-AMPK, and phosphorylated p38 through Western blot when ginsenoside Rf 10 μM and ginsenosides Rk3 and Rh4 were treated with 0.2, 1, and 5 μM, respectively. It is a picture.
FIG. 8 is a graph comparing relative expression levels of MHC, PGC-1α, phosphorylated p-AMPK, and phosphorylated p38 with respect to actin of FIG. 7 .
9 is when ginsenosides Rf, Rb2, and Rg1 were mixed with ginsenosides Rf, Rb2, and Rg1 at 10 and 20 μM, respectively, in Hwagisam (AG, 100 μg/mL), the expression of MHC (Myosin Heavy Chain) was confirmed by Western blotting, and for actin It is a graph showing the relative expression level.

The present invention relates to a food composition for improving muscle function comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

In addition, the present invention relates to a cosmetic composition for improving muscle function comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

In addition, the present invention relates to a food composition for improving or preventing sarcopenia comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

In addition, the present invention relates to a pharmaceutical composition for the treatment or prevention of sarcopenia comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

The composition may further include ginsenoside Rh1, a ginsenoside composition comprising ginsenoside Rh1, or a mixture of any one or more of them.

The composition contains 1 to 100 parts by weight of ginsenoside Rh1 component, 2 parts by weight or more, 5 parts by weight or more, 10 parts by weight or more, 20 parts by weight or more, 30 parts by weight or more, 40 parts by weight or more, based on 100 parts by weight of ginsenoside Rf component. It may be more than 90 parts by weight, 80 parts by weight or less, 70 parts by weight or less, or 60 parts by weight or less.

The ginsenoside composition containing the ginsenoside Rf may be a ginsenoside Rf concentrate obtained by treating a plant of the genus Panax or its extract through at least one process selected from heating, enzymatic treatment, and fermentation.

The ginsenoside composition containing ginsenoside Rh1 may be a ginsenoside Rf concentrate obtained by treating a Panax genus plant or its extract through at least one process selected from heating, enzymatic treatment, and fermentation.

In addition, the Panax genus plant extract may be an extract using water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.

The water does not need to be particularly limited if it is suitable for food production, but for example, ground water, purified water, distilled water, deionized water, etc. may be used.

The alcohol having 1 to 4 carbon atoms is not particularly limited, but may be, for example, methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol, or normal-butanol, and preferably ethanol.

The mixed solvent does not need to be particularly limited, but for example, in the case of a mixed solvent of water and ethanol, 5 to 95% by weight aqueous ethanol solution, 10 to 90% by weight aqueous ethanol solution, 20 to 80% by weight aqueous ethanol solution, 30 to 70% by weight Aqueous solutions of ethanol may be used.

The preparation of the water extract is not particularly limited, but may be prepared by extracting a plant of the genus Panax with water at 10 to 100° C. for 2 to 60 hours.

The preparation of the alcohol extract or the extract of a mixed solvent of water and alcohol is not particularly limited, but, for example, it is prepared by extracting a plant of the genus Panax with a 30 to 70% by weight aqueous ethanol solution at 20 to 60 ° C. for 2 to 48 hours. do.

The Panax genus plants include Panax ginseng, Panax quinquefolia, Panax notoginseng, Panax japonica, Panax trifolia, Panax pseudoginseng, and Panax vietnamensis. ) and any one or more selected from these cultured roots.

The Panax genus plant may be any one or more selected from roots, seeds, fruits, and leaves of the plants.

The ginsenoside composition containing the ginsenoside Rf or the ginsenoside composition containing the ginsenoside Rh1 is an extract of the Panax genus plant, a fraction fractionated therefrom, a concentrate obtained by further concentrating these extracts or fractions, It also includes purified or separated purified products, and is used in the sense of including dry products obtained by drying the extracts, fractions, concentrates, or purified products, or pulverized powders thereof. For the preparation of the purified product, a variety of additionally carried out, such as passing through an ultrafiltration membrane having a molecular weight cut-off value, or separation by various chromatography (made for separation according to size, charge, hydrophobicity or affinity). A purification method may be added.

The above composition, i.e. 1) a ginsenoside composition comprising ginsenoside Rf, or 2) a mixture of ginsenoside compositions comprising ginsenoside Rf and ginsenoside Rf, or 3) ginsenoside Rf, ginsenoside A ginsenoside composition containing side Rf, or a mixture of any one or more thereof; and a ginsenoside Rh1, a ginsenoside composition containing ginsenoside Rh1, or a mixture of any one or more thereof; a mixture of ginsenoside 30% by weight or more, 35% by weight or more, 40% by weight or more, 45% by weight or more, 50% by weight or more, 60% by weight or 70% by weight or more, and may also contain 80% by weight or less, 90% by weight or less, 95% by weight or less, 99% by weight or less, or 100% by weight or less of ginsenoside Rf, Side Rf weight divided by ginsenoside Rg1 weight is 1 or more, 1.1 or more, 1.2 or more, 1.3 or more, 1.4 or more, 1.5 or more, 2 or more, 3 or more, 4 or more, 5 or more, 10 or more, 20 or more, 30 It may be 40 or more, 50 or more, 100 or more, or 500 or more, and may be 10000 or less, 5000 or less, or 1000 or less.

The above composition, i.e. 1) a ginsenoside composition comprising ginsenoside Rf, or 2) a mixture of ginsenoside compositions comprising ginsenoside Rf and ginsenoside Rf, or 3) ginsenoside Rf, ginsenoside A ginsenoside composition containing side Rf, or a mixture of any one or more thereof; and a mixture of ginsenoside Rh1, a ginsenoside composition containing ginsenoside Rh1, or a mixture of any one or more thereof; 20% by weight or more, 22% by weight or more, 25% by weight or more, 30% by weight or more, 35% by weight or more, 40% by weight or more, 45% by weight or more, 50% by weight or more of the total weight of all ginsenosides or more, 60% or more, or 70% or more by weight, and may contain 80% or less, 90% or less, 95% or less, 99% or less, or 100% or less by weight of ginsenoside Rf. The total weight of the panaxatriol ginsenoside may be the total weight of ginsenosides Rg1, Rg2, Re, Rh1 and Rf.

The above composition, i.e. 1) a ginsenoside composition comprising ginsenoside Rf, or 2) a mixture of ginsenoside compositions comprising ginsenoside Rf and ginsenoside Rf, or 3) ginsenoside Rf, ginsenoside A ginsenoside composition containing side Rf, or a mixture of any one or more thereof; and a ginsenoside Rh1, a ginsenoside composition containing ginsenoside Rh1, or a mixture of any one or more thereof; a mixture of ginsenoside 10% by weight or more, 12% by weight or more, 15% by weight or more, 20% by weight or more, 25% by weight or more, 30% by weight or more, 35% by weight or more, 40% by weight or more, 45% by weight or more % or more, 50 wt% or more, 60 wt% or more, or 70 wt% or more, and 80 wt% or less, 90 wt% or less, 95 wt% or less, 99 wt% or less, or 100% by weight or less, wherein the total weight of ginsenosides is the total weight of panaxatriol ginsenosides combined with ginsenosides Rg1, Rg2, Re, Rh1 and Rf and ginsenosides Rb1, Rb2, Rg3, Rh2 , Rc and Rd may be the sum of the total weight of panaxadiol ginsenoside.

The term 'contained as an active ingredient' means 1) ginsenoside Rf, 2) ginsenoside composition containing ginsenoside Rf, or 3) any one or more mixtures thereof, or 4) ginsenoside Rf, ginsenoside A ginsenoside composition comprising side Rf, or a mixture of any one or more thereof; and ginsenoside Rh1, a ginsenoside composition comprising ginsenoside Rh1, or a mixture of any one or more thereof; This means that it contains an amount sufficient to

In the improvement of muscle function, 'muscle' comprehensively refers to tendons, muscles, and tendons, and 'muscle function' refers to the ability to exert force by contraction of muscles, and to overcome resistance, muscle strength to exert contraction forces; muscular endurance, which is the ability of a muscle to contract and relax for a given weight for how long or how many times; and instantaneous power, which is the ability to exert strong force within a short period of time. For example, muscle function improvement may be any one selected from among exercise capacity increase, muscle strength increase, and muscle mass increase.

The sarcopenia refers to a disease in which the volume and strength of muscles gradually decline due to decreased muscle function, muscle wasting or muscle degeneration, and includes muscular atrophy, myasthenia gravis, muscular dystrophy, muscle stiffness, hypotonia, muscle weakness, muscular dystrophy, and muscular atrophy. It may be any one selected from lateral sclerosis and myasthenia gravis.

The present invention relates to a food composition for improving muscle function or improving or preventing sarcopenia, comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

The food composition may further include ginsenoside Rh1, a ginsenoside composition containing ginsenoside Rh1, or a mixture of any one or more of them.

The 'food composition' refers to ginsenoside Rf as an active ingredient, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them, as well as standards and specifications of food commonly used in food production ('food composition'). It includes food ingredients and food additives that can be used as foods described in the Codex') and food additives described in the Codex.

It does not need to be particularly limited, but includes, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavoring agents. The carbohydrates include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sugar, lactose and the like; oligosaccharides or polysaccharides such as dextrin, starch syrup, cyclodextrin and the like; Sugar alcohols such as xylitol, sorbitol, erythritol and the like can be used. As the flavoring agent, natural flavoring agents (thaumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) may be used.

The ginsenoside Rf, the ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient when preparing a food composition ginsenoside Rf, ginsenoside containing ginsenoside Rf The composition, or a mixture of any one or more of them, does not need to be particularly limited as long as the content exhibits the effect of improving muscle function or sarcopenia, but is, for example, 0.1 to 99% by weight, 0.5 to 95% by weight, 1 to 90% by weight, 2 to 80% by weight, 3 to 70% by weight, 4 to 60% by weight, may be included in 5 to 50% by weight.

In the food composition, the active ingredient, ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them varies depending on the condition, weight, presence or absence of disease, and duration, but usually can be appropriately selected by the technician of For example, it may be 1 to 5,000 mg, preferably 5 to 2,000 mg, more preferably 10 to 1,000 mg, still more preferably 20 to 800 mg, and most preferably 50 to 500 mg based on the daily dose. There is, and the number of administrations need not be particularly limited, but can be adjusted by a person skilled in the art within the range of three times a day to once a week. In the case of long-term intake for the purpose of health and hygiene or health control, it may be less than the above range.

The food composition does not need to be particularly limited, but may be, for example, a powder, granule, tablet, capsule, pill, extract, jelly formulation, tea bag formulation or beverage formulation.

In addition, in order to impart functionality to improve muscle function or sarcopenia by ultraviolet rays to general foods, the ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of these may be added. Foods that can be used do not need to be particularly limited, but for example, confectionery, bread or rice cakes, processed cocoa products or chocolates, meat or eggs exemplified in the standards and specifications of food under Article 7 of the Food Sanitation Act ('Food Code') Processed products, processed fish products, tofu or jelly, noodles, teas, coffee, beverages, special purpose foods, pastes, seasonings, dressings, kimchi, salted fish, pickled foods, stewed foods, alcoholic beverages, raisins, and other foods can In addition, it can be added to dairy products, processed meat products, packaged meat, and egg products exemplified in the processing standards and ingredient specifications of livestock products ('Livestock Codex') according to Article 4 of the Livestock Products Sanitation Control Act.

On the other hand, the ginsenoside Rf, the ginsenoside composition containing ginsenoside Rf, or a food composition containing a mixture of any one or more of these as an active ingredient can be used alone as a "health functional food that helps improve muscle function". It can be used as "functional health food that helps increase muscle strength", "functional health food that helps improve exercise capacity" or "functional food that helps improve sarcopenia".

The 'health functional food' refers to food manufactured (including processing) according to legal standards using raw materials or ingredients having functional properties useful for the human body (Article 3, Subparagraph 1 of the Health Functional Food Act). The term 'health functional food' may differ in terminology or scope from country to country, but 'Dietary Supplement' in the US, 'Food Supplement' in Europe, 'Health Functional Food' or 'Health Functional Food' in Japan. It may correspond to 'Food for Special Health Use (FoSHU)' or 'Health Food' in China.

The food composition or health functional food may additionally contain food additives, and the suitability as a food additive is determined according to the standards and standards for the item in accordance with the general rules and general test methods of the 'Food Additive Code' unless otherwise specified. follow

In addition, the health functional food can be used in combination with the ginsenoside Rf, the ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them, together with functional food ingredients related to improvement of muscle function or sarcopenia. there is.

The present invention relates to a cosmetic composition for improving muscle function comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

The cosmetic composition may further include ginsenoside Rh1, a ginsenoside composition containing ginsenoside Rh1, or a mixture of any one or more of them.

When used as the cosmetic composition for improving muscle function, additionally a fatty substance, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a foaming agent, a fragrance, a surfactant, and water. , ionic emulsifiers, nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blockers, wetting agents, essential oils, dyes, pigments, hydrophilic actives, lipophilic actives or lipid vesicles, etc. It may contain adjuvants commonly used in the field of dermatology, such as any other ingredients used as In addition, the components may be introduced in an amount generally used in the field of skin science.

The cosmetic composition is not particularly limited, but may be in formulations such as ointments, patches, gels, creams, or sprays.

The present invention relates to a pharmaceutical composition for treating or preventing sarcopenia comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient.

The pharmaceutical composition may further include ginsenoside Rh1, a ginsenoside composition containing ginsenoside Rh1, or a mixture of any one or more of them.

In addition, the present invention provides a method for treating sarcopenia by administering the composition to humans or non-human animals.

In addition, the present invention provides a novel use of ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more thereof for the preparation of a drug for the treatment of sarcopenia.

The 'pharmaceutical composition' or 'medicament' refers to ginsenoside Rf as an active ingredient, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them, as well as suitable suitable substances commonly used in the manufacture of pharmaceutical compositions, etc. It may further include carriers, excipients and diluents.

The 'carrier' is a compound that facilitates the addition of the compound into cells or tissues. The 'diluent' is a compound diluted in water that not only stabilizes the biologically active form of the subject compound, but also dissolves the compound.

The carrier, excipient, and diluent are not particularly limited, but, for example, lactose, glucose, sugar, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

The amount of the pharmaceutical composition or drug used may vary depending on the age, sex, and weight of the patient or animal to be treated, and above all, the condition of the subject to be treated, the specific category or type of disease to be treated, the route of administration, and the treatment used will depend on the properties.

The pharmaceutical composition or medicament is appropriately selected according to the absorption rate and excretion rate of the active ingredient in the body, the age and weight, sex and condition of the patient or animal to be treated, the severity of the disease to be treated, etc.

It is generally preferred to administer 0.1 to 1,000 mg/kg, preferably 1 to 500 mg/kg, more preferably 5 to 250 mg/kg, and most preferably 10 to 100 mg/kg per day. The unit dosage formulation thus formulated can be administered several times at regular time intervals as needed.

The pharmaceutical composition or medicament may be administered individually as a prophylactic or therapeutic agent, or in combination with other therapeutic agents, or may be administered sequentially or simultaneously with conventional therapeutic agents.

The pharmaceutical composition or medicine may be formulated into oral dosage forms such as powders, granules, tablets, capsules, troches, suspensions, emulsions, syrups, aerosols and the like according to conventional methods. When formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, troches, etc., and these solid preparations contain at least one excipient such as starch, calcium carbonate, sugar or lactose, and gelatin in the compound. It can be prepared by mixing etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. .

The method for treating sarcopenia is directed to a human or a non-human animal, particularly a mammal, wherein 1) ginsenoside Rf, 2) a ginsenoside composition containing ginsenoside Rf, or 3) a mixture of any one or more of these , or 4) ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more thereof; and ginsenoside Rh1, a ginsenoside composition containing ginsenoside Rh1, or any of these Any one or more mixtures; by oral administration of a mixture of, for example, the ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more thereof to a subject to be treated with sarcopenia. to be administered orally.

Whether or not the subject to be treated with sarcopenia may be the case of increased skin moisture loss, decreased skin moisture content, increased skin roughness, or decreased skin elasticity.

The dosage, administration method and number of administrations for the treatment may refer to the dosage, administration method and number of administrations of the pharmaceutical composition or medicine.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments. However, these examples are intended to explain the present invention in more detail, and it will be apparent to those skilled in the art that the scope of the present invention is not limited thereto.

Experimental Example 1: Confirmation of muscle differentiation effect of ginsenoside Rf

The expression of myosin heavy chain (MHC), a biomarker for muscle differentiation, was confirmed by Western blotting when treated with ginsenoside Rf, a specific component of Korean ginseng, at different concentrations.

C2C12 muscle cells were purchased from the American Type Culture Collection (ATCC) and used. C2C12 muscle cells were cultured using DMEM medium containing 10% FBS and 1% antibiotics in an incubator at 37°C and 5% CO2 conditions. Muscle differentiation is induced when the medium is replaced with 2% horse serum DMEM medium, and ginsenosides Rf, Rg1 and Rb2 are treated 2 days after treatment with differentiation inducing conditions (DM, 2% horse serum DMEM medium) to muscle cells (C2C12), respectively. did

Western blotting was used to confirm changes in protein expression. Samples were prepared using cell lysis buffer (cell signaling) to which protease inhibitors and phosphatase inhibitors were added to the cell pellets prepared by the above-mentioned method. After quantifying the protein by the BCA method, the same amount of protein is mixed with the SDS sample buffer, heated at 95℃ for 10 minutes to denature the protein, and used for the experiment. Samples were electrophoresed on a gradient SDS-polyacrylamide gel. After transferring the protein of the gel to a nitrocellulose (NC) membrane, it is blocked with 5% skim milk solution at room temperature for 1 hour. Thereafter, the primary antibody was incubated overnight at 4 ° C., and the appropriate secondary antibody attached to HRP was attached, and the expression of each protein was confirmed by a chemiluminescent method using an ECL solution, as shown in FIG. 1.

The muscle differentiation effect of ginsenoside Rg1 is described in "Ginsenoside Rg1 from Panax ginseng enhances myoblast differentiation and myotube growth, 2017, Journal of Ginseng Research", and the muscle differentiation effect of ginsenoside Rb2 is described in "Ginsenoside Rg1 from Panax ginseng enhances myoblast differentiation and myotube growth, 2017, Journal of Ginseng Research", so these ginsenosides were used as positive controls.

It was confirmed that MHC protein expression was increased in ginsenoside Rf compared to ginsenosides Rg1 and Rh2, which have known myogenic efficacy (see FIGS. 1 and 2). In particular, at a concentration of 20 μM, ginsenoside Rf increased myogenic efficacy by 4.1 times compared to ginsenoside Rg1, and at a concentration of 40 μM, ginsenoside Rf increased myogenic efficacy by 5.3 times compared to ginsenoside Rb2.

Experimental Example 2: Confirmation of the energy metabolism increasing effect of ginsenoside Rf

Muscle differentiation also occurs due to an increase in energy metabolism. AMPK (5'-adenosine monophosphate-activated protein kinase) is a major enzyme regulating energy homeostasis in the body and is known to play an important role in skeletal muscle development and growth control. Changes in phosphorylation of AMPK, a signal protein related to energy metabolism, by treatment with ginsenosides Rf, Rb2 and Rg1 were confirmed using the Western blot method of Experimental Example 1, and the results are shown in FIGS. 3 and 4.

Phosphorylation of AMPK, a well-known marker related to energy metabolism, was all increased by treatment with ginsenosides Rf, Rb2 and Rg1.

In particular, ginsenoside Rf significantly increased phosphorylation of AMPK compared to ginsenosides Rb2 and Rg1 at both concentrations of 20 μM and 40 μM. Therefore, it can be seen that ginsenoside Rf influenced the induction of muscle differentiation through AMPK phosphorylation.

Experimental Example 3: Confirmation of synergistic effect with ginsenoside Rf and other ginsenosides

Ginsenoside Rf is a ginsenoside specifically present in Korean ginseng (Panax ginseng) and red ginseng prepared therefrom. Ginsenoside Rf works together with other ginsenosides to increase muscle differentiation and energy metabolism. It was confirmed that the effect was shown.

Among the ginsenosides administered in combination with ginsenoside Rf, a total of 7 ginsenosides, Rh1, Rg2, Rk3, Rh4, Rk1, (S)-Rg3 and Rg5, which are known to have increased content in red ginseng extracts compared to white ginseng. Sides were targeted.

C2C12 muscle cells prepared in the same manner as in Experimental Example 1 were treated with 5, 10, and 20 μM of ginsenoside Rf, respectively, 2 days after treatment with differentiation inducing conditions (DM, 2% horse serum DMEM medium), and ginsenoside Rh1 with 10 μM Rf. , Rg2, Rk3, Rh4, Rk1, (S)-Rg3 and Rg5 were treated with 0.2, 1 and 5 µM of 7 ginsenosides respectively.

In the same way as in Experimental Example 1, a Western blot method was used to confirm protein expression changes (see FIGS. 5 and 7), and the relative protein expression levels were calculated using Image J program and shown in FIGS. 6 and 8 ( Ginsenosides Rk1, (S)-Rg3 and Rg5 results not shown).

Ginsenoside Rh1, Rg2, Rk3, Rh4, Rk1, (S)-Rg3, and Rg5, ginsenosides administered in combination with ginsenoside Rf. Among the total of seven ginsenosides, only the combined treatment with Rh1 was compared to the treatment with Rf alone. The expression of myosin heavy chain (MHC), a muscle differentiation biomarker, was increased, and in particular, a synergistic effect was shown when 10 to 50 parts by weight of Rh1 was treated with respect to 100 parts by weight of Rf (see FIGS. 5 and 6).

Phosphorylated p-AMPK, PGC-1α, and phosphorylated p-p38, which are related to energy metabolism, were examined after western blotting, and the relative protein expression levels were confirmed. As a result, synergistic effects were not clearly confirmed in phosphorylated p-AMPK, a top regulator, but PGC-1α was not clearly identified. Ginsenosides Rh1, Rg2, Rk3, Rh4, Rk1, (S)-Rg3 and Rg5 administered in combination with ginsenoside Rf for -1α and phosphorylated p-p38 In combination with Rh1 among a total of 7 ginsenosides In only one case, a significant synergistic effect was shown compared to the case of Rf alone treatment. In particular, in the case of phosphorylated p-p38, which is the most important index, treatment with 2 to 50 parts by weight of Rh1 relative to 100 parts by weight of Rf showed a significant synergistic effect. In particular, when Rh1 was 2 to 10 parts by weight, a higher synergistic effect was shown (see FIGS. 5 and 6).

Experimental Example 4: Confirmation of muscle differentiation efficacy of ginsenoside composition containing ginsenoside Rf

Dried ginseng from Wisconsin was used for Hwagi ginseng. Hot water extraction was performed three times for 2 hours each using a reflux cooling extractor at 80 ° C with 50 times distilled water for 1 g of Korean ginseng. The supernatant was filtered using a Whatman No2 filter paper, concentrated under reduced pressure, diluted again in distilled water, and lyophilized to prepare a hot water extract of Hwagisam.

The Hwagi ginseng hot water extract did not contain ginsenoside Rf, but contained 0.32 mg/g of ginsenoside Rg1 and 0.33 mg/g of ginsenoside Rb2.

A ginsenoside composition containing ginsenoside Rf by mixing 10 μM and 20 μM of ginsenoside Rf with the hot-water extract of ginseng ginseng (100 μg/mL), ginsenoside in the hot-water extract of ginseng ginseng (100 μg/mL) A ginsenoside composition containing ginsenoside Rg1 by mixing 10 μM and 20 μM of Rg1, respectively, and ginsenoside Rb2 by mixing 10 μM and 20 μM of ginsenoside Rb2 with the hot water extract (100 μg/mL) of Hwagisam, respectively Each of the ginsenoside compositions containing was prepared.

The expression of myosin heavy chain (MHC), a muscle differentiation biomarker, was confirmed using the same Western blotting method as in Experimental Example 1, and the results are shown in FIG. 9 .

In the ginsenoside composition containing ginsenoside Rg1 in which 10 μM and 20 μM of ginsenoside Rg1 were mixed, and ginsenoside composition containing ginsenoside Rb2 in which 10 μM and 20 μM of ginsenoside Rb2 were mixed, respectively, Although an increase in MHC expression could not be confirmed, in the ginsenoside composition containing ginsenoside Rf by mixing 10 μM and 20 μM of ginsenoside Rf, respectively, with Hwagi ginseng hot water extract (100 μg/mL), MHC expression was 1.77, respectively. It was confirmed that the increase was 1.6 times and 1.6 times.

Examples of formulations of foods, cosmetics, or pharmaceutical compositions containing the ginsenoside Rf or the ginsenoside composition containing the ginsenoside Rf of the present invention are described below, but the present invention is not intended to limit them, but only specifically is to explain

Formulation Example 1. Preparation of powder

Ginsenoside Rf 500 mg

Lactose 100 mg

Talc 10 mg

A powder is prepared by mixing the above ingredients and filling them in an airtight bag.

Formulation Example 2. Preparation of tablets

Ginsenoside Rf 300 mg

Corn Starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

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

Formulation Example 3. Preparation of capsule formulation

Ginsenoside Rf 200 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium stearate 0.2 mg

Capsules are prepared by mixing the above ingredients and filling them into gelatin capsules according to a conventional capsule preparation method.

Formulation Example 4. Preparation of Injections

Ginsenoside Rf 600 mg

Mannitol 180 mg

Sterile Distilled Water for Injection 2974 mg

Na ₂ HPO _4, 12H ₂ O 26 mg

It is prepared with the above component content per 1 ampoule according to the conventional method for preparing injections.

Formulation Example 5. Preparation of liquid formulation

Ginsenoside Rf 4 g

Isomerized sugar 10 g

5 g mannitol

Appropriate amount of purified water

According to the conventional liquid formulation manufacturing method, each component is dissolved in purified water, lemon flavor is added in an appropriate amount, the above components are mixed, and then purified water is added to adjust the total amount to 100g, and then filled into a brown bottle to be sterilized. to prepare a liquid.

Formulation Example 6. Preparation of granules

Ginsenoside composition containing 1% by weight of ginsenoside Rf 1,000 mg

Appropriate amount of vitamin mixture

Vitamin A Acetate 70 μg

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

Vitamin B12 0.2 μg

Vitamin C 10 mg

10 μg of biotin

Nicotinamide 1.7 mg

Folic acid 50 μg

Calcium Pantothenate 0.5 mg

Appropriate amount of mineral mixture

Ferrous sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium Carbonate 25.3 mg

Potassium Phosphate Monobasic 15 mg

Dibasic Calcium Phosphate 55 mg

Potassium citrate 90 mg

Calcium Carbonate 100 mg

Magnesium Chloride 24.8 mg

Although the composition ratio of the above vitamin and mineral mixture was prepared by mixing ingredients suitable for granules in a preferred embodiment, the mixing ratio may be arbitrarily modified, and after mixing the above ingredients according to a conventional granule manufacturing method, It can be prepared and used for preparing a health functional food composition according to a conventional method.

Formulation Example 7. Manufacturing of functional beverages

Ginsenoside composition containing 1% by weight of ginsenoside Rf 1,000 mg

Citric Acid 1,000 mg

100 g of oligosaccharides

2 g plum concentrate

1 g of taurine

Add purified water to total 900 mL

After mixing the above ingredients according to the normal health drink manufacturing method, stirring and heating at 85 ° C. for about 1 hour, the resulting solution is filtered and collected in a sterilized 2 L container, sealed and sterilized, and then refrigerated. It is used for preparing the functional beverage composition of the present invention.

Although the composition ratio is a mixture of ingredients suitable for a relatively favorite beverage in a preferred embodiment, the mixing ratio may be arbitrarily modified according to regional and ethnic preferences such as the class of demand, the country of demand, and the purpose of use.

Claims (20)

A food composition for improving or preventing sarcopenia, comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient. The food composition for improving or preventing sarcopenia according to claim 1, further comprising ginsenoside Rh1, a ginsenoside composition containing ginsenoside Rh1, or a mixture of any one or more of them. The food composition for improving or preventing sarcopenia according to claim 2, wherein the composition contains 1 to 100 parts by weight of ginsenoside Rh1 component based on 100 parts by weight of ginsenoside Rf component. The method of claim 1, wherein the ginsenoside composition containing ginsenoside Rf is a ginsenoside Rf concentrate obtained by treating a plant of the genus Panax or its extract through at least one process selected from heating, enzymatic treatment, and fermentation. A food composition for improving or preventing sarcopenia. The method of claim 2, wherein the ginsenoside composition containing ginsenoside Rh1 is a ginsenoside Rf concentrate obtained by treating a plant of the genus Panax or its extract through at least one process selected from heating, enzyme treatment, and fermentation. A food composition for improving or preventing sarcopenia. The method according to claim 4 or 5, wherein the Panax genus plants are selected from Panax ginseng, Panax quinquefolia, Panax notoginseng, Panax japonica, Panax trifolia, and Himalayan ginseng. (Panax pseudoginseng), Vietnam ginseng (Panax vietnamensis), and a food composition for improving or preventing sarcopenia, characterized in that at least one selected from cultured roots thereof. The food composition for improving or preventing sarcopenia according to claim 6, wherein the Panax genus plant is any one or more selected from roots, seeds, fruits and leaves of the plant. The method according to any one of claims 1 to 5, wherein the composition contains 30% by weight or more of ginsenoside Rf based on the total weight of ginsenosides consisting of the sum of ginsenosides Rf, Rh1, Rg1 and Rb2, and A food composition for improving or preventing sarcopenia, characterized in that the value obtained by dividing the weight of senoside Rf by the weight of ginsenoside Rg1 is 1 or more. The method according to any one of claims 1 to 5, wherein the composition contains 20% by weight or more of ginsenoside Rf based on the total weight of panaxatriol ginsenoside, and the total weight of panaxatriol ginsenoside is A food composition for improving or preventing sarcopenia, characterized in that it is the weight of the sum of ginsenosides Rg1, Rg2, Re, Rh1 and Rf. The method according to any one of claims 1 to 5, wherein the composition contains 10% by weight or more of ginsenoside Rf based on the total weight of ginsenosides, and the total weight of ginsenosides includes ginsenosides Rg1, Rg2, Re , Sarcopenia characterized in that the total weight of panaxatriol ginsenoside combined with Rh1 and Rf and the total weight of panaxadiol ginsenoside combined with ginsenosides Rb1, Rb2, Rg3, Rh2, Rc and Rd Food composition for improvement or prevention of. The food composition for improving or preventing sarcopenia according to claim 1, wherein the composition has any one activity selected from increasing muscle strength and increasing muscle mass. delete delete delete delete delete The method of any one of claims 1 to 5, wherein the sarcopenia is any one selected from muscular dystrophy, myasthenia gravis, muscular dystrophy, myasthenia gravis, hypotonia, muscle weakness, muscular dystrophy, amyotrophic lateral sclerosis and myasthenia gravis. Food composition for improvement or prevention of sarcopenia, characterized in that. A pharmaceutical composition for the treatment or prevention of sarcopenia comprising ginsenoside Rf, a ginsenoside composition containing ginsenoside Rf, or a mixture of any one or more of them as an active ingredient. The pharmaceutical composition for the treatment or prevention of sarcopenia according to claim 18, further comprising ginsenoside Rh1, a ginsenoside composition containing ginsenoside Rh1, or a mixture of any one or more of them. The muscle according to claim 18 or 19, wherein the sarcopenia is any one selected from muscular dystrophy, myasthenia gravis, muscular dystrophy, myasthenia gravis, hypotonia, muscle weakness, muscular dystrophy, amyotrophic lateral sclerosis and myasthenia gravis. A pharmaceutical composition for the treatment or prevention of sarcopenia.

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