Composition for treating sarcopenia or osteoporosis by promoting myofiber formation or inhibiting osteoclast differentiation, comprising cyclo-L-phenylalanyl-L-proline dipeptide

Abstract

The present invention relates to a composition for preventing or treating sarcopenia or osteoporosis, comprising cyclo-L-phenylalanyl-L-proline dipeptide. The composition for preventing or treating sarcopenia or osteoporosis, comprising cyclo-L-phenylalanyl-L-proline dipeptide according to the present invention, can prevent or treat osteoporosis by reducing osteoclast differentiation associated with a decrease in bone density and promoting muscle fiber formation to increase muscle mass.

Description

[Technical field]

[0001] The present invention relates to a composition for treating osteoporosis caused by loss of muscle mass and loss of bone density, and more particularly to a composition for treating osteoporosis by promoting muscle fiber formation or inhibiting osteoclast differentiation, comprising cyclo-L-phenylalanyl-L-proline dipeptide. [Background technology]

[0002] As the body ages, body fat increases, solids and water decrease, and bone mass decreases, especially due to loss of calcium in bones, which leads to lower bone density, thinner cartilage tissue that is less elastic, which can lead to arthritis, and reduced voluntary muscle mass, which can lead to reduced mobility.

[0003] Among the structural changes in the body, the decline in physical ability and the decline in bone density in particular not only make daily activities in the elderly inconvenient, but also significantly increase the risk of fractures.

[0004] Hip fractures refer to fractures around the hip joint and occur primarily in people aged 70 years or older with severe osteoporosis. The primary cause is falls, and although there are various contributing factors, weakened muscles and reduced bone density are cited as major contributing factors.

[0005] As the population ages, interest in osteoporosis and geriatric sarcopenia has increased, but no meaningful solutions have yet been found. Specifically, hormones, bisphosphonates, RANKL antibodies, and PTH peptides are used as osteoporosis treatments, but they have limitations on the subjects and duration of use, and side effects have been reported. In addition, it has been reported that there is a clinical need for drugs that are easy to use because conventional drugs have low compliance when taken. In addition, biological drugs have been developed that target myostatin and activin receptors, which reduce muscle mass, but problems with relatively low efficacy and side effects have been reported.

[0006] A cyclic dipeptide (CDP) is a type of dipeptide formed by a peptide bond between two α-amino acids. Compared to a common dipeptide formed by one peptide bond, a cyclic dipeptide has two peptide bonds, forming a ring structure.

[0007] These small molecules are produced by physicochemical reactions or are obtained as by-products during microbial fermentation. There are many types of cyclic dipeptides depending on the amino acids that make up the dipeptides, but they share a common feature: the peptide bond provides stability to physical and chemical reactions, and the ring structure is hydrophobic, facilitating penetration into cells.

[0008] In order to understand the physiological effects of cFP on mammals, the inventors made extensive efforts to investigate the effects of oral administration of cFP on the musculoskeletal system of mice. As a result, they identified new uses of cyclo-L-phenylalanyl-L-proline dipeptide related to the prevention or treatment of sarcopenia and the prevention or treatment of osteoporosis, and thus completed the present invention. Summary of the Invention [Problem to be solved by the invention]

[0009] A composition for treating osteoporosis according to one embodiment of the present invention aims to prevent or treat osteoporosis by suppressing osteoclast differentiation associated with a decrease in bone mineral density.

[0010] A composition for treating osteoporosis according to another embodiment of the present invention aims to prevent or treat sarcopenia by promoting the formation of muscle fibers.

[0011] The object of the present invention is not limited to the above, and other objects not mentioned will be clearly understood by a person having ordinary skill in the art to which the present invention pertains from the following description. [Means for solving the problem]

[0012] In order to solve the above technical problems, a composition for preventing or treating sarcopenia or osteoporosis according to one aspect of the present invention comprises cyclo-L-phenylalanyl-L-proline dipeptide of the following chemical formula: [ka]

[0013] The composition herein may further comprise a pharma- ceutically acceptable carrier, excipient or diluent.

[0014] A composition for promoting myoblast differentiation and / or inhibiting osteoclast formation according to another embodiment of the present invention comprises cyclo-L-phenylalanyl-L-proline dipeptide.

[0015] A quasi-drug composition according to still another embodiment of the present invention contains cyclo-L-phenylalanyl-L-proline dipeptide.

[0016] A health functional food composition for muscle building and / or bone strengthening according to still another embodiment of the present invention comprises cyclo-L-phenylalanyl-L-proline dipeptide.

[0017] A feed additive composition for building muscle and / or strengthening bones in livestock according to still another embodiment of the present invention comprises cyclo-L-phenylalanyl-L-proline dipeptide.

[0018] According to yet another aspect of the present invention, there is provided a composition for promoting muscle fiber formation, comprising cyclo-L-phenylalanyl-L-proline dipeptide of the following chemical formula:

[0019] [ka]

[0020] According to yet another aspect of the present invention, there is provided a composition for inhibiting osteoclast differentiation, comprising cyclo-L-phenylalanyl-L-proline dipeptide of the following chemical formula: [ka]

[0021] In the present invention, the term "prevention" refers to any action that inhibits or delays the onset of sarcopenia or osteoporosis by administering a composition according to the present invention.

[0022] In the present invention, the term "treatment" refers to any action that suppresses, reduces or alleviates the symptoms of sarcopenia or osteoporosis by administering a composition according to the present invention.

[0023] The pharmaceutical composition of the present invention may be used as a single formulation, or may be prepared and used as a combined formulation by further containing a drug known to have a recognized therapeutic effect on sarcopenia or osteoporosis.

[0024] The pharmaceutical composition of the present invention may further comprise a pharma- ceutically acceptable carrier.

[0025] The term "pharmaceutical acceptable" means that it does not significantly irritate the organism and does not inhibit the biological activity and properties of the administered active substance.

[0026] The carrier may be a natural or non-natural carrier, and depending on the dosage form, various carriers such as diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants may be used to prepare the formulation. For example, solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations are prepared by mixing one or more compounds with at least one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate, talc, etc. are also used. Liquid preparations for oral administration include suspensions, oral liquids, emulsions, syrups, etc., and may include various excipients other than water and liquid paraffin, which are commonly used simple diluents, such as wetting agents, sweeteners, flavorings, preservatives, etc. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspensions that can be used include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. Suppository bases that can be used include witepsol, macrogol, Tween 61, cacao butter, laurin butter, glycerogelatin, etc.

[0027] The pharmaceutical composition may have any one of the dosage forms selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, oral liquids, emulsions, syrups, sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories.

[0028] The pharmaceutical compositions of the present invention may also contain a pharma- ceutically effective amount of cyclo-L-phenylalanyl-L-proline dipeptide.

[0029] In the present invention, the term "pharmacologically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to any medical treatment, and the effective dose level can be determined according to factors including the type and severity of the individual, age, sex, drug activity, sensitivity to the drug, administration time, administration route and excretion rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field.

[0030] The pharmaceutical compositions of the present invention can be administered as a sole therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents. Furthermore, they can be administered singly or multiple times.

[0031] Taking all of the above factors into consideration, it is important to administer an amount that does not cause side effects and provides the maximum effect at the minimum amount, and such a dosage can be easily determined by a person skilled in the art.

[0032] Preferably, the pharmaceutical composition according to the present invention contains cyclo-L-phenylalanyl-L-proline dipeptide at 0.001 to 1500 μg / mL, more preferably at 0.001 to 1000 μg / mL.

[0033] In another embodiment, the present invention provides a health functional food composition for preventing or improving sarcopenia or osteoporosis, comprising cyclo-L-phenylalanyl-L-proline dipeptide.

[0034] In the present invention, the term "amelioration" refers to any action of using the composition to improve or benefit the symptoms of an individual suspected of or suffering from sarcopenia or osteoporosis.

[0035] The food composition of the present invention may further comprise a food-acceptable carrier.

[0036] The food composition may have the function of helping to inhibit sarcopenia or osteoporosis.

[0037] The food composition of the present invention may be in the form of a pill, powder, granule, precipitate, tablet, capsule, or liquid, and there is no particular limitation on the type of food to which the cyclo-L-phenylalanyl-L-proline dipeptide of the present invention can be added, for example, various beverages, gum, tea, vitamin complexes, dietary supplements, etc.

[0038] The food composition may contain other ingredients that do not interfere with the inhibitory activity against sarcopenia or osteoporosis in addition to cyclo-L-phenylalanyl-L-proline dipeptide, and the type of the ingredients is not particularly limited. For example, various herbal extracts, food-acceptable food supplement additives, natural carbohydrates, etc., as in conventional foods, may be included as additional ingredients.

[0039] The term "food additive" used in the present invention means a component that can be added to food as a supplement, and can be appropriately selected and used by those skilled in the art as an additive when manufacturing health functional foods of various dosage forms. Examples of food additives include various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers, pectinic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated drinks, etc., but the types of food additives of the present invention are not limited to the above examples.

[0040] Examples of the natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, erythritol, etc. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (e.g., rebaudioside A), glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.

[0041] The food composition may be used for the production of a health functional food or may be included in a health functional food.

[0042] The term "health functional food" used in the present invention refers to food produced and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc., using raw materials or ingredients having useful functions for the human body. Here, functionality means that useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological effects can be obtained. The health functional food of the present invention can be produced by a method commonly used in the art, and during the production, raw materials and ingredients commonly added in the art can be added. In addition, unlike general medicines, since it uses food as a raw material, it has the advantage of being free of side effects that may occur when taking medicines for a long period of time, and is also highly portable.

[0043] When the composition according to the embodiment of the present invention is used in a health functional food, the composition can be added as it is or can be used together with other health functional foods or health functional food ingredients, and can be used appropriately according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment).

[0044] In general, the cyclo-L-phenylalanyl-L-proline dipeptide of the present invention can be added in an amount of 0.1 to 1% by weight, preferably 0.5 to 1% by weight, of the raw material composition during food production. However, when taking it for a long period of time for health and hygiene purposes or for health regulation purposes, the amount used may be less than the above range.

[0045] The type of the food is not particularly limited. Examples of the food to which the substance can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, drinking water, tea, energy drinks, alcoholic beverages, and vitamin complexes, and include all health functional foods in the usual sense.

[0046] The types of health functional foods that may contain the composition according to the embodiments of the present invention are not particularly limited, and specific examples include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, drinking water, tea, energy drinks, alcoholic beverages, and vitamin complexes, and may include all health functional foods in the usual sense, including foods used as feed for animals.

[0047] In addition, when the health functional food composition of the present invention is used in the form of a beverage, it may contain various sweeteners, flavorings, or natural carbohydrates as additional ingredients, as in ordinary beverages. The natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. The ratio of the natural carbohydrates is not limited thereto, but may be preferably about 0.01 to 0.04 g, more preferably 0.02 to 0.03 g, per 100 ml of the composition according to the embodiment of the present invention. The sweetener may be a natural sweetener such as thaumatin or stevia extract, or a synthetic sweetener such as saccharin or aspartame.

[0048] In addition to the above, the health functional food composition of the present invention may contain the various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated drinks, etc. In addition, it may contain fruit pulp for the production of natural fruit juice, fruit drinks and vegetable drinks.

[0049] In yet another aspect, the present invention provides a method for treating sarcopenia or osteoporosis, comprising administering an effective amount of cyclo-L-phenylalanyl-L-proline dipeptide to an individual at risk of developing sarcopenia or osteoporosis or suffering from sarcopenia or osteoporosis.

[0050] In the present invention, the individual refers to any animal, including humans, that is suffering from or may be suffering from sarcopenia or osteoporosis, and the individual can be effectively treated by administering the compound of the present invention or a pharma- ceutically acceptable salt thereof to an individual suspected of having sarcopenia or osteoporosis.

[0051] Specifically, the individual is an individual who needs treatment for sarcopenia or osteoporosis, and is not particularly limited as long as the individual is the one for which the treatment for sarcopenia or osteoporosis is intended, and the present invention can be applied to any individual. For example, the present invention can be applied to any individual, including non-human animals such as monkeys, dogs, cats, rabbits, guinea pigs, rats, mice, cows, sheep, pigs, goats, etc., humans, birds, and fish.

[0052] The term "administration" as used herein means introducing the compound of the present invention or a pharma- ceutically acceptable salt thereof into an individual by any suitable method, and the route of administration according to the embodiment of the present invention can be through various routes, such as oral or parenteral, as long as it can reach the target tissue.

[0053] An effective amount of a compound of the invention or a pharma- ceutically acceptable salt thereof means a pharma- ceutically effective amount.

[0054] In the present invention, the term "pharmacologically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to any medical treatment, and the effective dose level can be determined according to factors including the individual type and severity, age, sex, type of disease, drug activity, sensitivity to the drug, administration time, administration route and excretion rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field.

[0055] The compound of the present invention or its pharma- ceutically acceptable salt can be administered as a single therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents. It can be administered singly or multiple times. It is important to administer the amount that does not cause side effects and obtains maximum effect at the minimum amount by considering all the above factors, and this can be easily determined by those skilled in the art.

[0056] The preferred dosage will vary depending on the patient's condition and body weight, the severity of the disease, the drug form, the route and duration of administration, and the appropriate total daily dosage will be determined by the treating physician within the scope of sound medical judgment, but generally, an amount of 0.001 to 1000 mg / kg, preferably 0.05 to 200 mg / kg, more preferably 0.1 to 100 mg / kg, can be administered once or several times a day.

[0057] The route of administration may be any method commonly used in the art, including, without limitation, oral, rectal, or intravenous, intramuscular, subcutaneous, intrauterine, intrathecal, or intracerebrovascular injection. Effect of the Invention

[0058] A composition for treating osteoporosis according to an embodiment of the present invention can prevent or treat osteoporosis by suppressing osteoclast differentiation associated with a decrease in bone mineral density.

[0059] A composition for treating osteoporosis according to another embodiment of the present invention can prevent or treat sarcopenia by promoting the formation of muscle fibers.

[0060] The effects of the present invention are not limited to those described above, and other effects not mentioned will be clearly understood by those having ordinary skill in the art to which the present invention pertains from the following description. [Brief description of the drawings]

[0061] [Figure 1]FIG. 1 is a graph showing the results of promoting myofiber formation in myoblasts by cFP treatment ((A) Myotubes stained with LADD staining. Scale bar = 100 μm. (B) Myotube diameter and myotube nuclei number by vehicle and cFP treatment at different concentrations. ANOVA-Tukey test was performed). [Diagram 2] FIG. 1 is a graph showing the results of inhibition of osteoclast differentiation by cFP treatment (osteoclasts stained with TRAP staining (A) and the number of osteoclasts (B) after treatment with vehicle and cFP at different concentrations). [Diagram 3] FIG. 1 is a graph showing oral administration of cFP by gavage and the resulting increase in muscle mass in mice. [Figure 4] 1 is a graph showing the effect of cFP on the trabecular bone of mouse femur when the mouse was given free drinking. BEST MODE FOR CARRYING OUT THEINVENTION

[0062] The objectives and effects of the present invention, as well as the technical configuration for achieving them, will become clear by referring to the following detailed examples together with the accompanying drawings. When describing the present invention, detailed descriptions of known functions or configurations are omitted if they are deemed to unnecessarily obscure the gist of the present invention. In addition, the terms used below are defined in consideration of the functions in the present invention, and may vary depending on the intentions or practices of users or operators.

[0063] However, the present invention is not limited to the embodiments disclosed below, and may be realized in various different forms. The embodiments are provided merely to complete the disclosure of the present invention and to fully inform those skilled in the art of the present invention of the scope of the invention, and the present invention is defined only by the scope of the claims. Therefore, the definition should be based on the content of the entire specification.

[0064] Muscle growth is caused by the formation of myofibers through the binding of individual myoblasts. Therefore, the improvement of muscle growth can be estimated by the degree of myofiber formation in an environment in which myoblast binding is induced. To this end, myoblasts were isolated and cultured from the target muscle tissue, and the isolated myoblasts were used to observe whether myofibers were formed.

[0065] Next, the formation of muscle fibers can be evaluated by the number of myoblasts forming muscle fibers and the thickness of the formed muscle fibers. For this purpose, a high-magnification optical microscope was used to distinguish nuclei in muscle fibers by myofiber staining. The thickness of the muscle fibers was also measured.

[0066] Osteoclast differentiation is formed by cell-cell junctions as the differentiation of individual bone marrow-derived macrophages progresses. Therefore, we preferentially isolated and cultured only bone marrow-derived macrophages and used the isolated macrophages to differentiate into osteoclasts.

[0067] Next, a TRAP (tartrate-resistant acid phosphatase) staining method was used to determine the degree of differentiation of differentiated osteoclasts. When macrophages differentiate into osteoclasts, TRAP is produced, and by staining this, the degree of differentiation of osteoclasts can be quantified. In addition, to confirm the degree of maturation of osteoclasts, the number of cells that make up the osteoclasts was also counted. As mentioned above, the degree of differentiation of osteoclasts was analyzed using two indicators: the number of cells in the osteoclast nucleus and TRAP staining (tartrate-resistant acid phosphatase stain).

[0068] Next, according to the embodiment of the present invention, the increase in muscle weight and the increase in bone mass due to oral administration of cyclo-L-phenylalanyl-L-proline (cFP) were measured. The muscle weight was measured by isolating the mouse muscles according to the anatomical muscle classification and measuring the weight. In addition, the cancellous bone analysis of the mouse femur was performed using a high-resolution micro-CT (SMX-90CT system), and the analysis was started 1 mm below the growth plate of the femur, and the analysis was performed from the starting point to 1.5 mm below the bone. Each index means the following: bone volume / total volume (BV / TV, %), bone area / bone volume (BS / BV, 1 / mm), cancellous bone thickness (Tb.Th, mm), cancellous bone number per unit area (Tb.N, 1 / mm), cancellous bone porosity (Tb.Sp, mm).

[0069] The following describes the embodiments of the present invention in detail. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0070] Example 1: Differentiation of myoblasts by cFP treatment

[0071] B. Preparation of myoblasts Hindlimb muscle tissue was obtained after sacrificing 5-week-old male CrljOri:CD1(ICR) mice. The muscle tissue was minced with a scalpel for 5 min. The minced muscle solution was incubated at 37°C for 60 min and then centrifuged at 1500 rpm for 5 min. The obtained cells were plated on a cell culture dish without gelatin coating in Ham's F-10 medium containing 20% ​​heat-inactivated horse serum and 50 units / mL penicillin in the presence of basic FGF (2.5 ng / mL) for 1 h. After 1 h, the floating cells were transferred to a secondary cell culture dish without gelatin coating and cultured for 1 h. This process was repeated, and the cells were transferred to a gelatin-coated dish. The cultured cells were used as myoblasts.

[0072] B. Differentiation of myoblasts and LADD staining (muscle fiber formation experiment) Myoblasts obtained from muscle tissue were cultured in 48-well tissue culture plates pretreated with 10% Matrigel at 3 × 10 per well. 4 After culturing for about 24 hours, the growth medium was further cultured in DEM fusion medium containing 5% heat-inactivated horse serum and 50 units / mL penicillin / streptomycin. The medium was changed every two days. After culturing, the cells in 48 wells were washed with PBS (phosphate buffered saline) and fixed with 70% ethanol. After removing the ethanol, the formed myofibers were stained using LADD staining reagent containing toluidine blue and fuchsin. After incubation for 1 minute, the stained cells were washed with distilled water until the LADD staining solution could no longer be leached into the water. After washing, the cells were dried at room temperature for 10 minutes.

[0073] Figure 1 is a graph showing the results of promoting myoblast myofiber formation depending on the concentration of cFP treatment. Referring to Figure 1, it can be seen that the culture medium of myoblasts treated with cFP promoted myoblast fusion compared to myoblasts treated with vehicle ((A) myotubes stained with LADD staining. Scale bar = 100 μm.; (B) myotube diameter and myotube nuclei number after vehicle and cFP treatment at different concentrations. ANOVA-Tukey test was performed).

[0074] Example 2: Experiment on osteoclast formation by cFP treatment

[0075] B. μCT analysis Mouse femurs were analyzed with high-resolution μCT (SMX-90CT system; Shimadzu, Kyoto, Japan). μCT scan images were reconstructed with the VG Studio MAX 1.2.1 program (Volume Graphics, Heidelberg, Germany). Each 3D image was analyzed to measure bone volume, cortical bone volume, trabecular number, and trabecular separation using TRI / 3D-VIE (RATOC System Engineering, Kyoto, Japan). 3D images were obtained from a CT volume program (version 1.11, SkyScan).

[0076] B. Preparation of bone marrow-derived macrophages (BMM) Five-week-old male CrljOri:CD1(ICR) mice were sacrificed, and femurs and tibias were harvested from the mice. Bone marrow cells were obtained by flushing bone marrow from the femurs and tibias. Non-adherent bone marrow cells were cultured with α-MEM supplemented with M-CSF (30 ng / mL) for 3 days to generate bone marrow-derived macrophages (BMMs).

[0077] C. Osteoclast differentiation and tartrate-resistant acid phosphatase (TRAP) staining To generate osteoclasts, BMMs (4 × 10 4Cells (1000 cells / well) were cultured in 48-well plates for 4 days in α-MEM complete medium containing 10% (v / v) heat-inactivated fetal bovine serum (FBS) and 50 units / mL penicillin / streptomycin in the presence of M-CSF (30 ng / mL) and RANKL (100 ng / mL). The medium was replaced every 3 days. Multinucleated cells (MNCs) were observed on the 4th day. Cells were fixed in 10% formalin solution for 20 min and permeabilized with 0.1% Triton X-100 for 1 min. After washing twice with PBS, cells were stained using the Leukocyte Acid Phosphatase Assay Kit (Sigma-Aldrich) according to the manufacturer's manual. The degree of differentiation was evaluated by counting the number of differentiated osteoclasts per well, based on osteoclasts with 5 or more nuclei in the cells.

[0078] 2 is a graph showing the results of inhibition of osteoclast differentiation depending on the cFP treatment concentration. Referring to FIG. 2, it was confirmed that the differentiation of bone marrow-derived macrophages into osteoclasts was inhibited in a cFP concentration-dependent manner.

[0079] Example 3: Muscle and trabecular bone analysis after oral ingestion of cFP

[0080] B. Preparation of experimental mice Animal studies were performed in accordance with the guidelines for animal research. All experimental procedures were approved by the Animal Care Committee of Seoul National University Animal Hospital. Male C57BL / 6J mice, 4 or 6 weeks of age, were purchased from OrientBio (Seongnam, Korea) and kept in an SPF animal facility maintained at constant temperature (22°C) and humidity (55%) with a 12-h light / dark cycle. All animals were provided with a free feeding and drinking system. Oral gavage was provided every 24 h with cFP via a stainless steel feeding tube, and 100 μl of the solution was orally administered at each dose. Alternatively, cFP was mixed with drinking water and administered via the free drinking system. Mice were sacrificed in a carbon dioxide euthanasia chamber.

[0081] B. Muscle collection and weight measurement After euthanizing the mice using CO2 gas, the pectoralis major muscle, quadriceps muscle, and gastrocnemius muscle were separated according to the anatomical classification of the muscles. The weight of the separated muscles was measured using a microbalance.

[0082] C. Trabecular bone analysis of femur The femur was isolated from the euthanized mouse and the whole analysis data of the femur was obtained using a micro-CT machine. From the obtained data, the range was designated 1.5 mm toward the end of the mouse growth plate, starting from 1 mm toward the end, and the cancellous bone portion was reconstructed and analyzed to obtain the cancellous bone index.

[0083] FIG. 3 is a graph showing oral administration of cFP by gavage and the resulting increase in muscle mass in mice, and FIG. 4 is a graph showing the effect of cFP on the trabecular bone of mouse femur when the mice were given free drinking.

[0084] As shown in Figure 3, oral administration of cFP by gavage increased muscle mass in mice compared to the control group.Also, as shown in Figure 4, the trabecular bone indices BV / TV (bone volume / total bone volume), Tb.Th (trabecular thickness), and Tb.N (trabecular number) of the cFP-administered group were significantly higher, while the trabecular bone indices BS / BV (bone surface / trabecular bone volume), TB.Pf (trabecular bone pattern factor), and Tb.Sp (trabecular separation) of the purified water-administered group were lower.

[0085] In summary, it has been confirmed that cyclo-L-phenylalanyl-L-proline dipeptide can increase muscle mass and reduce osteoclast differentiation in the body by oral administration, in relation to muscle loss and osteoclast differentiation that lead to sarcopenia or osteoporosis.

[0086] In the present specification and drawings, preferred embodiments of the present invention are disclosed, and specific terms are used, but these are used in a general sense merely to easily explain the technical contents of the present invention and to aid in the understanding of the invention, and are not intended to limit the scope of the present invention. It is obvious to a person having ordinary knowledge in the technical field to which the present invention pertains that other modifications based on the technical idea of ​​the present invention can be implemented in addition to the embodiments disclosed in the present specification. [Industrial Applicability]

[0087] The present invention is applicable to the prevention or treatment of sarcopenia or osteoporosis.

Claims

1. A composition for preventing or treating sarcopenia or osteoporosis, comprising cyclo-L-phenylalanyl-L-proline dipeptide of the following formula: A composition that promotes muscle fiber formation and inhibits osteoclast differentiation. 【Chemistry 1】

2. The composition of claim 1 , wherein the composition further comprises a pharma- ceutically acceptable carrier, excipient or diluent.

3. A quasi-drug composition for preventing or improving sarcopenia or osteoporosis, comprising cyclo-L-phenylalanyl-L-proline dipeptide of the following chemical formula: A composition that promotes muscle fiber formation and inhibits osteoclast differentiation. 【Chemistry 2】

4. A health functional food composition for muscle and / or bone strengthening, comprising a cyclo-L-phenylalanyl-L-proline dipeptide of the following chemical formula: A composition that promotes muscle fiber formation and inhibits osteoclast differentiation. 【Chemistry 3】

5. A composition for use as a feed additive for muscle and / or bone strengthening in livestock, comprising cyclo-L-phenylalanyl-L-proline dipeptide of the following chemical formula: A composition that promotes muscle fiber formation and inhibits osteoclast differentiation. 【Chemistry 4】

6. 1. A method for treating sarcopenia or osteoporosis comprising administering to a non-human individual in need thereof an effective amount of a cyclo-L-phenylalanyl-L-proline dipeptide having the following formula: A therapeutic method for promoting muscle fiber formation and inhibiting osteoclast differentiation. 。 【Chemistry 5】

7. Use of cyclo-L-phenylalanyl-L-proline dipeptide having the following chemical formula for the manufacture of a medicine for treating sarcopenia or osteoporosis, which promotes the formation of muscle fibers and inhibits the differentiation of osteoclasts. 【Chemistry 6】

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