Composition for preventing or treating sarcopenia comprising fatty acid or derivative thereof

Abstract

The present invention relates to a pharmaceutical composition, a health functional food composition, or a health functional food for preventing, treating, or alleviating sarcopenia. According to the present invention, a pharmaceutical composition, a health functional food composition, or a health functional food, all comprising two types of compounds of the present invention as active ingredients for preventing, treating, or alleviating sarcopenia, can be more effective for sarcopenia.

Description

A composition for the prevention or treatment of sarcopenia comprising fatty acids or derivatives thereof

[0001] The present invention relates to a pharmaceutical composition, a health functional food composition, or a health functional food for the prevention, treatment, or improvement of sarcopenia.

[0002] The decline in muscle mass and strength is a major characteristic of human aging, and it is a factor that significantly impacts an individual's physical activity capacity, lifestyle, and appearance. The aging-related decrease in muscle mass and strength is a symptom of sarcopenia, a condition characterized by a decline in muscle mass and function as the number of muscle fibers decreases.

[0003] Patients with sarcopenia experience a decline in the ability to perform daily physical activities, such as walking speed or sitting down and standing up, due to a lack of muscle mass, and are easily exposed to the risk of falls as they frequently stumble. Furthermore, since muscles serve as an energy source within the body by storing glucose in the form of glycogen, a decrease in muscle mass can lead to symptoms such as easy fatigue or dizziness. In particular, with the increase in the elderly population, the number of patients with sarcopenia or those at risk of sarcopenia is rapidly increasing.

[0004] While exercise, protein, and calorie supplementation are known to be helpful for sarcopenia, they are not very beneficial for the elderly, who constitute the majority of patients, making the need for sarcopenia treatments urgent. However, drugs currently used for sarcopenia that demonstrate direct effects in improving muscle loss or increasing muscle mass are still at the clinical trial stage, and there are currently no drugs that have received final FDA approval.

[0005] Accordingly, various studies for the prevention or treatment of sarcopenia are actively underway, and Korean Registered Patent No. 10-1999916 discloses a composition for strengthening muscle power or preventing and treating sarcopenia using an extract of *Lysimachia japonica*. Furthermore, Korean Publication No. 10-2024-0054436 raises the need for the development of treatments for muscle function improvement and sarcopenia using natural substances that are safe for the elderly to consume and can be taken long-term, and discloses a β-lactoglobulin-derived peptide as a pharmaceutical composition for the prevention or treatment of sarcopenia. The development of compositions using various compounds and natural extracts demonstrates the potential for developing compositions for the prevention or treatment of sarcopenia.

[0006] Therefore, continuous research and development are necessary for the prevention, treatment, or improvement of sarcopenia.

[0007] Accordingly, the inventors have developed a composition for the prevention or treatment of sarcopenia using a compound with excellent efficacy. Furthermore, by mixing the compounds, they have completed a composition with even greater efficacy, a health functional food composition, and a health functional food.

[0008] To achieve the above objective, one aspect of the present invention provides a composition comprising at least one of the compounds represented by the following chemical formulas I to III as an active ingredient.

[0009] [Chemical Formula I]

[0010]

[0011] In the above chemical formula I,

[0012] R 1a is H or C1-C6 alkyl and

[0013] R 1b is a C3-C6 alkyl, and

[0014] [Chemical Formula II]

[0015]

[0016] In the above chemical formula II,

[0017] R 2a is a C1-C6 alkanedyl, and

[0018] R 2b and R 2c Each is independently a C3-C6 alkyl, and

[0019] [Chemical Formula III]

[0020]

[0021] In the above chemical formula III,

[0022] R 3a is a C1-C6 alcanthyl, and

[0023] R 3b , R 3c and R 3d Each is independently a C3-C6 alkyl.

[0024] Another aspect of the present invention provides a pharmaceutical composition for preventing or treating sarcopenia comprising at least one of the compounds represented by Formula I, Formula II, and Formula III as an active ingredient.

[0025] Another aspect of the present invention provides a food composition for preventing or improving sarcopenia comprising at least one of the compounds represented by Formula I, Formula II, and Formula III as an active ingredient.

[0026] Another aspect of the present invention provides a health functional food for the prevention or improvement of sarcopenia comprising at least one of the compounds represented by Formula I, Formula II, and Formula III as an active ingredient.

[0027] Another aspect of the present invention provides a composition for livestock feed for the prevention or improvement of sarcopenia comprising at least one of the compounds represented by Formula I, Formula II, and Formula III as an active ingredient.

[0028] Another aspect of the present invention provides a use of compounds represented by the formulas I, II, and III for the prevention or treatment of sarcopenia.

[0029] Another aspect of the present invention provides a method for preventing or treating sarcopenia using compounds represented by the formulas I, II, and III.

[0030] A composition containing the compound of the present invention has the effect of preventing, treating, or improving sarcopenia, and can be usefully utilized as a sarcopenia treatment or health supplement. In particular, it was confirmed that the effect of treating sarcopenia is excellent when the weight ratio of butanoate and hexanoate of the present invention is 1:2. Therefore, the composition of the present invention can prevent the loss of muscle mass, and thus can be used even more usefully as a sarcopenia treatment or health supplement.

[0031] Figure 1 is a diagram showing the 5-week experimental process of feeding a 20-month-old male mouse (C57BL / 6J).

[0032] Figure 2 is a graph and table comparing the grip strength values ​​measured before and after feeding of 20-month-old male mice at 4 weeks.

[0033] Figure 3 is a graph and table comparing the changes in running time of 20-month-old male mice before and after feeding at the 5th week.

[0034] Figure 4 is a graph showing the muscle mass relative to mouse weight after separating the muscle of a 20-month-old male mouse at the 5th week after feeding.

[0035] Figure 5 is a graph and table comparing the values ​​of the bite strength of 20-month-old male mice before feeding and at 4 weeks after feeding, according to the mixing ratios (1:1, 1:2, 2:1) of ethyl butanoate and ethyl hexanoate.

[0036] Figure 6 is a graph comparing grip strength values ​​measured at the 3rd and 5th week of administration after orally administering a drug mixed with tributyrin and trihexanoin in a weight ratio of 1:2 to 19-month-old mice at doses of 0 mg / kg, 100 mg / kg, 200 mg / kg, or 400 mg / kg six times a week.

[0037] Figure 7 is a graph comparing the change in running time of 19-month-old mice at the 6th week of administration, after orally administering a drug mixed with tributirin and trihexanoin in a weight ratio of 1:2 to 19-month-old mice at doses of 0 mg / kg, 100 mg / kg, 200 mg / kg, or 400 mg / kg six times a week.

[0038] Figure 8 is a graph comparing grip strength values ​​measured at the 5th week of administration in mice with muscle atrophy induced by orally administering a drug mixed with tributirin and trihexanoin in a weight ratio of 1:2 at doses of 0 mg / kg (mpk), 200 mg / kg (mpk), and 400 mg / kg (mpk) 6 times a week.

[0039] Figures 9a and 9b are graphs showing the body weight (Figure 9a) and food and water intake (Figure 9b) measured over 4 weeks by orally administering a drug containing tributirin and trihexanoin mixed in a weight ratio of 1:2 to 6-week-old ICR mice at doses of 0 mg / kg, 2000 mg / kg, and 4000 mg / kg seven times a week.

[0040] Figures 10a and 10b are graphs showing the weights of major organs (liver, heart, spleen, kidney, adrenal gland, thymus, uterus, ovary) measured at week 5 after orally administering a drug mixed with tributirin and trihexanoin in a weight ratio of 1:2 to 6-week-old ICR mice at doses of 0 mg / kg, 2000 mg / kg, and 4000 mg / kg seven times a week.

[0041] One aspect of the present invention provides a composition comprising at least one of compounds represented by the following chemical formulas I to III as an active ingredient.

[0042] [Chemical Formula I]

[0043]

[0044] In the above chemical formula I,

[0045] R 1a is H or C1-C6 alkyl and

[0046] R 1b is a C3-C6 alkyl, and

[0047] [Chemical Formula II]

[0048]

[0049] In the above chemical formula II,

[0050] R 2a is a C1-C6 alkanedyl, and

[0051] R 2b and R 2c Each is independently a C3-C6 alkyl, and

[0052] [Chemical Formula III]

[0053]

[0054] In the above chemical formula III,

[0055] R 3a is a C1-C6 alcanthyl, and

[0056] R 3b , R 3c and R 3dEach is independently a C3-C6 alkyl.

[0057] In some embodiments, R of chemical formula I 1a can be H or C1-C6 alkyl. Specifically, the above R 1a It may be H, methyl, ethyl, propyl, butyl, pentyl, or hexyl, but is not limited thereto.

[0058] In some embodiments, R of chemical formula I 1b may be propyl, butyl, pentyl, or hexyl. For example, the above R 1b may be n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, pentan-2-yl, pentan-3-yl, isopentyl, neopentyl, 2-methylbutyl, 2-methylbutane-2-yl, 3-methylbutane-2-yl, hexyl, hexane-2-yl, or hexane-3-yl. Preferably, R 1b It can be n-propyl or n-pentyl.

[0059] In some embodiments, R of Chemical Formula II 2a can be a C1-C6 alkanedyl. Specifically, the above R 2a It can be methane-1,1-diyl, ethane-1,1-diyl, ethane-1,2-diyl, propane-1,1-diyl, propane-1,2-diyl, propane-1,3-diyl, or propane-2,2-diyl.

[0060] In some embodiments, R of Chemical Formula II 2b and R 2c Each can independently be propyl, butyl, pentyl, or hexyl. For example, the above R 2b and R 2c Each may independently be propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, pentan-2-yl, isopentyl, neopentyl, hexyl, hexane-2-yl, or hexane-3-yl. For example, the above R 2b and R 2c They may be the same or different from each other.

[0061] In some embodiments, R of Chemical Formula III 3a may be a C1-C6 alkantrile. Specifically, the above R 3a It can be methane-1,1,1-triyl, ethane-1,1,1-triyl, ethane-1,1,2-triyl, ethane-1,2,1-triyl, propane-1,1,1-triyl, propane-1,1,2-triyl, propane-1,1,3-triyl, propane-1,2,1-triyl, propane-1,2,2-triyl, propane-1,2,3-triyl, propane-2,2,2-triyl.

[0062] In some embodiments, R of Chemical Formula III 3b , R 3c and R 3d Each can independently be propyl, butyl, pentyl, or hexyl. For example, the above R 3b , R 3c and R 3d Each may independently be propyl, isopropyl, butyl, sec-butyl, tert-butyl, pentyl, pentan-2-yl, isopentyl, neopentyl, hexyl, hexane-2-yl, or hexane-3-yl. For example, the above R 3b , R 3c and R 3d They may be the same or different from each other.

[0063] The composition of the present invention may include two or more different compounds represented by the above formulas I, II, and III.

[0064] The compound represented by the above formula I of the present invention may be a fatty acid or a fatty acid ester. The fatty acid or fatty acid ester may be butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, or an ester thereof. The above fatty acid esters are methyl butanoate, ethyl butanoate, propyl butanoate, butyl butanoate, pentyl butanoate, hexyl butanoate, methyl pentanoate, ethyl pentanoate, propyl pentanoate, butyl pentanoate, pentyl pentanoate, hexyl pentanoate, methyl hexanoate, ethyl hexanoate, propyl hexanoate, and butyl hexanoate. It may be hexanoate), pentyl hexanoate, hexyl hexanoate, methyl heptanoate, ethyl heptanoate, propyl heptanoate, butyl heptanoate, pentyl heptanoate, or hexyl heptanoate.

[0065] In one embodiment, the fatty acid may be butanoic acid or hexanoic acid (caproic acid). Additionally, the fatty acid ester may be methyl butanoate, ethyl butanoate, propyl butanoate, butyl butanoate, pentyl butanoate, hexyl butanoate, methyl hexanoate, ethyl hexanoate, propyl hexanoate, butyl hexanoate, pentyl hexanoate, or hexyl hexanoate. In one embodiment, the compound may be ethyl butanoate and / or ethyl hexanoate, but is not limited thereto.

[0066] The compound represented by the above chemical formula II of the present invention is propane-1,3-diyl dibutyrate ( ), 3-(butyryloxy)propyl hexanoate( ) or propane-1,3-diyl dihexanoate( It can be.

[0067] The compound represented by the above chemical formula III of the present invention is propane-1,2,3-triyl tributyrate ( ), 3-(butyrloxy)propane-1,2-diyl dihexanoate ( ), 2-(butyryloxy)propane-1,3-diyl dihexanoate ( ), 3-(hexanoyloxy)propane-1,2-diyl dibutyrate ( ), 2-(hexanoyloxy)propane-1,3-diyl dibutyrate ( ) or propane-1,2,3-triyl trihexanoate( ) can be.

[0068] When the composition of one embodiment includes a compound represented by the chemical formula I, it may include ethyl butanoate and ethyl hexanoate.

[0069] When the composition of one embodiment includes a compound represented by the above chemical formula II, propane-1,3-diyl dibutyrate ( ), 3-(butyryloxy)propyl hexanoate( ) and propane-1,3-diyl dihexanoate( It may include two different compounds selected from the group consisting of ).

[0070] Specifically, propane-1,3-diyl dibutyrate ( ) and propane-1,3-diyl dihexanoate( Two compounds composed of ) or 3-(butyryloxy)propyl hexanoate( It may include a compound selected alone.

[0071] When the composition of one embodiment includes a compound represented by the above chemical formula III, propane-1,2,3-triyl tributyrate ( ), 3-(butyrloxy)propane-1,2-diyl dihexanoate ( ), 2-(butyryloxy)propane-1,3-diyl dihexanoate ( ), 3-(hexanoyloxy)propane-1,2-diyl dibutyrate ( ), 2-(hexanoyloxy)propane-1,3-diyl dibutyrate ( ) and propane-1,2,3-triyl trihexanoate ( It may include two different compounds selected from the group consisting of ).

[0072] Specifically, propane-1,2,3-triyl tributyrate ( ) and propane-1,2,3-triyl trihexanoate ( Two types of compounds composed of ); or 3-(butyrloxy)propane-1,2-diyl dihexanoate( ), 2-(butyryloxy)propane-1,3-diyl dihexanoate ( ), 3-(hexanoyloxy)propane-1,2-diyl dibutyrate ( ) and 2-(hexanoyloxy)propane-1,3-diyl dibutyrate ( It may include a compound selected solely from the group consisting of ).

[0073] When the composition of one embodiment includes a compound represented by the above formula III, it may include propane-1,2,3-triyl tributyrate (tributyrin) and propane-1,2,3-triyl trihexanoate (trihexanoin).

[0074] The mixing weight ratio of two different compounds represented by the above formulas I, II, and III of the present invention may be 1:9 to 9:1, 2:8 to 8:2, 3:7 to 7:3, 4:6 to 6:4, or 5:5.

[0075] Specifically, the mixed weight ratio of ethyl butanoate and ethyl hexanoate represented by chemical formula I may be 1:9 to 9:1, 2:8 to 8:2, 3:7 to 7:3, 4:6 to 6:4, or 5:5. Preferably, the mixed weight ratio of the compounds may be 1:2.

[0076] Specifically, propane-1,3-diyl dibutyrate represented by chemical formula II ( ) and propane-1,3-diyl dihexanoate( The mixing weight ratio of ) may be 1:9 to 9:1, 2:8 to 8:2, 3:7 to 7:3, 4:6 to 6:4, or 5:5. Preferably, the mixing weight ratio of the compounds may be 1:2. In addition, It can be used alone.

[0077] Specifically, propane-1,2,3-triyl tributyrate represented by chemical formula III ( ) and propane-1,2,3-triyl trihexanoate ( The mixing weight ratio of ) may be 1:9 to 9:1, 2:8 to 8:2, 3:7 to 7:3, 4:6 to 6:4, or 5:5. Preferably, the mixing weight ratio of the compounds may be 1:2. In addition, 3-(butyrloxy)propane-1,2-diyl dihexanoate( ), 2-(butyryloxy)propane-1,3-diyl dihexanoate ( ), 3-(hexanoyloxy)propane-1,2-diyl dibutyrate ( ) or 2-(hexanoyloxy)propane-1,3-diyl dibutyrate ( ) can be used alone.

[0078] Specifically, the mixing weight ratio of propane-1,2,3-triyl tributyrate and propane-1,2,3-triyl trihexanoate represented by Chemical Formula III may be 1:9 to 9:1, 2:8 to 8:2, 3:7 to 7:3, 4:6 to 6:4, or 5:5. Preferably, the mixing weight ratio of the compounds may be 1:2.

[0079] More specifically, ethyl butanoate represented by chemical formula I, and propane-1,3-diyl dibutyrate represented by chemical formula II ( propane-1,2,3-triyl tributyrate represented by ) and chemical formula III ( Any one compound selected from the group consisting of ); and ethyl hexanoate represented by formula I, propane-1,3-diyl dihexanoate represented by formula II ( propane-1,2,3-triyl trihexanoate represented by ) and chemical formula III ( The mixing weight ratio of any one compound selected from the group consisting of ) may be 1:9 to 9:1, 2:8 to 8:2, 3:7 to 7:3, 4:6 to 6:4, or 5:5. Preferably, the mixing weight ratio of the compounds may be 1:2.

[0080] Another aspect of the present invention provides a pharmaceutical composition for the prevention or treatment of sarcopenia comprising at least one of compounds represented by Formula I, Formula II, and Formula III as an active ingredient.

[0081] The compounds represented by the above chemical formulas I, II, and III are the same as those described above.

[0082] As used herein, the term "sarcopenia" may refer to one or more of the symptoms exhibited by a population selected from the 'possible sarcopenia' group, in which one or more of muscle strength or physical activity ability is reduced compared to the normal group according to the Asian AWGS 2019 sarcopenia diagnostic algorithm, and the 'sarcopenia' group, in which muscle mass is reduced and muscle strength or physical activity ability is reduced. Additionally, according to the European EWGSOP2 sarcopenia diagnostic algorithm, it may refer to one or more of the symptoms exhibited by a population selected from the 'sarcopenia probable' group, in which only muscle strength is reduced, and the 'sarcopenia' group, in which muscle strength, muscle mass, or physical activity ability is reduced. That is, the pharmaceutical composition of the present invention may be achieved by improving one or more symptoms selected from the group consisting of muscle mass, muscle strength, and physical activity ability in subjects requiring prevention or treatment of sarcopenia.

[0083] As used in this specification, the term "prevention" is used to include, without limitation, any act that suppresses or delays the symptoms of muscle mass loss, muscle strength loss, and decline in physical activity capacity associated with sarcopenia.

[0084] As used in this specification, the term "treatment" is used to include, without limitation, all actions that improve or beneficially alter the aforementioned symptoms associated with sarcopenia.

[0085] The weight of the mixture of two different compounds represented by the above formulas I, II, and III of the present invention may be included at a concentration level ranging from 1 wt% to 100 wt% relative to the total weight of the pharmaceutical composition, that is, in an amount sufficient to achieve the desired effect. For example, the two different compounds represented by Formula I, Formula II, and Formula III of the present invention may each be 0.01 wt% to 100 wt%, 0.01 wt% to 90 wt%, 0.01 wt% to 80 wt%, 0.01 wt% to 70 wt%, 0.01 wt% to 60 wt%, 0.01 wt% to 50 wt%, 0.01 wt% to 30 wt%, 0.01 wt% to 20 wt%, 0.01 wt% to 10 wt%, 0.01 wt% to 5 wt%, 0.01 wt% to 0.5 wt%, or 0.01 wt% to 0.1 wt%, based on the total weight of the pharmaceutical composition. At this time, the mixing weight ratio of the two different compounds represented by Formula I, Formula II, and Formula III may be 1:9 to 9:1, 2:8 to 8:2, 3:7 to 7:3, 4:6 to 6:4, or 5:5. Preferably, the mixing weight ratio of the compounds may be 1:2. In one embodiment, the pharmaceutical composition may have a mixing weight ratio of 5:5, comprising 2.5 wt% of each of the two different compounds represented by Formula I relative to the total weight of the pharmaceutical composition.

[0086] In addition, specifically, the amount of the compound varies depending on the patient's weight, age, gender, health condition, diet, time of administration, method of administration, excretion rate, and severity of the disease. The pharmaceutical composition of the present invention may be administered once or several times a day, and the duration of administration may be from 1 day to 12 months, but may be administered without limitation until a preventive or therapeutic effect on sarcopenia appears.

[0087] A pharmaceutical composition comprising the compound of the present invention as an active ingredient may be formulated and used in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, and aerosols, external preparations, suppositories, or sterile injectable solutions according to conventional methods.

[0088] A pharmaceutical composition comprising the compound of the present invention as an active ingredient may further include a suitable carrier, excipient, or diluent according to conventional methods. Specifically, it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are commonly used when formulating. Solid dosage forms for oral administration include tablets, pills, powders, granules, and capsules, and these solid dosage forms may be prepared by mixing at least one excipient with the compound, for example, starch, calcium carbonate, sucrose, lactose, gelatin, etc. In addition, lubricants such as magnesium stearate and talc may be used in addition to simple excipients. Liquid dosage forms for oral administration include suspensions, liquid formulations, emulsions, and syrups, and may include various excipients, for example, wetting agents, sweeteners, flavoring agents, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. As non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used. As bases for suppositories, Witepsol, Macrogol, Tween 61, cocoa paste, laurin paste, glycerogelatin, etc. may be used.

[0089] A pharmaceutical composition comprising the compound of the present invention as an active ingredient may be administered to mammals such as rats, mice, livestock, and humans by various routes. All modes of administration may be administered, for example, by skin, oral, rectal, intravenous, intraperitoneal, intramuscular, subcutaneous, intradural, or intracerebroventricular injection, and preferably by either oral or intravenous route, but are not limited thereto.

[0090] The above administration may further contain one or more active ingredients exhibiting the same or similar functions. For administration, one or more pharmaceutically acceptable carriers may additionally be included. Pharmaceutically acceptable carriers may be used as a mixture of saline solution, sterile water, Ringer's solution, buffered saline solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added as needed. Furthermore, the compound according to the present invention is easy to formulate into various formulations, and can be formulated into infusion formulations such as aqueous solutions, suspensions, and emulsions, powders, tablets, capsules, pills, granules, or injectable solutions by additionally adding diluents, dispersants, surfactants, binders, and lubricants, for example.

[0091] Another aspect of the present invention provides a food composition for preventing or improving sarcopenia comprising at least one of compounds represented by Formula I, Formula II, and Formula III as an active ingredient.

[0092] The compounds represented by the above chemical formulas I, II, and III, sarcopenia, and prevention are the same as described above.

[0093] The food composition of the present invention may refer to a composition that can be used to manufacture a health functional food.

[0094] The health functional food of the present invention is a food prepared by adding the compound of the present invention to food materials such as beverages, teas, spices, chewing gum, and confectionery, or by encapsulating, powdering, or suspension, and is said to bring about specific health effects when consumed. Unlike general medicines, it has the advantage of being made from food and thus avoiding side effects that may occur with long-term use of medicines. The health functional food of the present invention obtained in this manner is very useful because it can be consumed on a daily basis, allowing for easy and convenient consumption to expect effects of preventing or improving sarcopenia.

[0095] The food of the present invention is not particularly limited in type as long as it can have the compound of the present invention added to it. Examples of food to which the compound of the present invention can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes.

[0096] Another aspect of the present invention provides a health functional food for the prevention or improvement of sarcopenia comprising at least one of compounds represented by Formula I, Formula II, and Formula III as an active ingredient.

[0097] The compounds represented by the above chemical formulas I, II, and III, sarcopenia, prevention, and health functional foods are the same as those described above.

[0098] The health functional food or food of the present invention may contain, as additional ingredients, various flavoring agents or natural carbohydrates, various nutritional agents, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.

[0099] The term "improvement" in the present invention is used without limitation to refer to any action that improves parameters associated with the treatment of sarcopenia, and may, for example, mean an action that at least reduces the severity of symptoms.

[0100] Accordingly, the food composition and health functional food of the present invention include two or more different compounds represented by chemical formulas I, II, and III.

[0101] Another aspect of the present invention provides a composition for livestock feed for the prevention or improvement of sarcopenia comprising at least one of compounds represented by Formula I, Formula II, and Formula III as an active ingredient.

[0102] The compounds represented by the above chemical formulas I, II, and III, sarcopenia, prevention, and health functional foods are the same as those described above.

[0103] The above feed composition may include a feed additive. The feed additive of the present invention corresponds to a supplementary feed under the Feed Management Act.

[0104] In the present invention, the term "feed" may refer to any natural or artificial prescribed food, single meal, etc., or the components of said single meal, for animals to eat, consume, and digest, or suitable for such purposes.

[0105] The types of the above feed are not particularly limited, and feeds commonly used in the relevant technical field may be used. Non-limiting examples of the above feed include plant-based feeds such as grains, root vegetables, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, meal or grain by-products; and animal-based feeds such as proteins, inorganic substances, oils and fats, minerals, single-cell proteins, zooplankton, or food waste. These may be used individually or in a mixture of two or more types.

[0106] In addition, the above feed additive may additionally contain a carrier that is permissible for monogastrics. In the present invention, the above feed additive may be used as is or with known carriers, stabilizers, etc., and, if necessary, various nutrients such as vitamins, amino acids, minerals, antioxidants, and other additives may be added. In terms of form, it may be in a suitable state such as powder, granules, pellets, or suspension. When supplying the feed additive of the present invention, it may be supplied to monogastrics alone or mixed with feed.

[0107] Another aspect of the present invention provides a use of a compound represented by Formula I, Formula II, and Formula III for the prevention or treatment of sarcopenia. Another aspect of the present invention provides a method for the prevention or treatment of sarcopenia using a compound represented by Formula I, Formula II, and Formula III.

[0108] The compounds represented by the above chemical formulas I, II, and III, sarcopenia, prevention, and treatment are the same as described above.

[0109] The present invention will be explained in more detail below through the following examples. However, these examples are intended to illustrate the invention and the scope of the invention is not limited to these examples.

[0110] Example 1. Confirmation of therapeutic effect on sarcopenia through fatty acid intake (1)

[0111] To confirm the therapeutic effect of sarcopenia through the intake of fatty acids butanoate and hexanoate, 20-month-old male mice (C57BL / 6J) were fed feed to which the respective compounds were added. The control group (CTL) was fed a free diet supplemented with ethyl octanoate at 5 wt% of the feed, the first experimental group was fed a free diet supplemented with ethyl butanoate at 5 wt% of the feed, and the second experimental group was fed a free diet supplemented with ethyl hexanoate at 5 wt% of the feed. Additionally, the third experimental group was fed a free diet supplemented with both ethyl butanoate and ethyl hexanoate at 2.5 wt% of the feed.

[0112] Specifically, since butanoate and hexanoate, which are fatty acids, are difficult to ingest due to their odor, they were supplied through feed in the form of ethyl butanoate and ethyl hexanoate, which are ethyl esters used as flavorings, so that they could be hydrolyzed by the esterase enzyme in the mouse body.

[0113] After feeding as described above, the grip strength of the mice was measured using a high-performance digital force gauge (SHIMPO) at 4 weeks from the start of feeding, and the running time was measured at 5 weeks. In addition, the weight of the muscles was measured by isolating them at 5 weeks (Fig. 1).

[0114] Example 1.1. Confirmation of therapeutic effect for sarcopenia through grip strength measurement

[0115] As shown in Figure 2, the results of measuring the grip strength after 4 weeks of feeding ethyl butanoate, ethyl hexanoate, or both of these compounds were compared with the results measured before feeding. At this time, the compound used as the control group (CTL) was ethyl octanoate.

[0116] As a result, it was confirmed that the grip strength of mice fed a diet containing either ethyl butanoate or ethyl hexanoate, respectively, was improved and increased compared to the control group. In addition, it was confirmed that the grip strength of mice fed a diet containing both ethyl butanoate and ethyl hexanoate was significantly higher than that of mice fed a diet containing either ethyl butanoate or ethyl hexanoate, respectively.

[0117] Example 1.2. Confirmation of sarcopenia treatment effect through running time measurement

[0118] As shown in Figure 3, the results of measuring running time after 5 weeks of feeding ethyl butanoate, ethyl hexanoate, or both of these compounds were compared with the results measured before feeding. At this time, the compound used as the control group (CTL) was ethyl octanoate.

[0119] As a result, no significant difference was observed in the change in running time of mice fed a diet containing ethyl butanoate compared to the control group. It was confirmed that the change in running time of mice fed a diet containing ethyl hexanoate improved compared to the control group. Furthermore, it was confirmed that the change in running time of mice fed a diet containing both ethyl butanoate and ethyl hexanoate was more improved than the change in running time of mice fed a diet containing either ethyl butanoate or ethyl hexanoate individually.

[0120] Example 1.3. Confirmation of therapeutic effect for sarcopenia through muscle weight measurement

[0121] As shown in Figure 4, after 5 weeks of feeding a diet containing ethyl butanoate, ethyl hexanoate, or both of these compounds, muscle tissue was isolated from mice and its weight was measured.

[0122] As a result, no difference in muscle mass was observed in mice fed a diet containing ethyl butanoate and ethyl hexanoate compared to the control group. However, it was observed that the muscle mass of mice fed a diet containing both ethyl butanoate and ethyl hexanoate increased compared to the control group.

[0123] Example 2. Confirmation of therapeutic effect on sarcopenia according to fatty acid mixture weight ratio

[0124] To confirm the therapeutic effect on sarcopenia according to the mixed weight of fatty acids, an experiment was conducted in the same manner as in Example 1. The first experimental group was fed a diet supplemented with ethyl butanoate and ethyl hexanoate in a 1:1 mixed weight ratio corresponding to 5 wt% of the feed. The second experimental group was fed a free diet supplemented with ethyl butanoate and ethyl hexanoate in a 1:2 mixed weight ratio corresponding to 5 wt% of the feed. Additionally, the third experimental group was fed a free diet supplemented with ethyl butanoate and ethyl hexanoate in a 2:1 mixed weight ratio corresponding to 5 wt% of the feed.

[0125] After supplying the feed as described above, the grip strength of the mouse was measured using a high-performance digital force gauge (SHIMPO) at a time when 4 weeks had passed since the start of feed supply.

[0126] As a result, as shown in Figure 5, it was confirmed that the effect was best when the weight ratio of the mixture of ethyl butanoate and ethyl hexanoate was 1:2.

[0127] Example 3. Confirmation of therapeutic effect on sarcopenia through fatty acid intake (2)

[0128] To confirm the therapeutic effect on sarcopenia, the fatty acids tributyrin and trihexanoin were mixed in a weight ratio of 1:2 and the drug prepared on the same day was orally administered to 19-month-old aged mice 6 times a week using a 1 mL syringe and a sieve (Table 1).

[0129] 0 mg / kg 100 mg / kg 200 mg / kg 400 mg / kg Number of mice 6 6 7 6 Dosage of tributyrin and trihexanoin 0 1 0 3 2 0 6 4 1 2 Trihexanoin mixing ratio 1:2 Corn oil 4 1 2 3 0 9 2 0 6 0 Method of administration Oral administration Total volume 5 mL / kg Solvent 0.5% CMC Administered 6 times a week

[0130] Example 3.1. Confirmation of therapeutic effect for sarcopenia through grip strength measurement

[0131] A drug prepared by mixing tributyrin and trihexanoin in a weight ratio of 1:2 was orally administered to 19-month-old aged mice six times a week, and limb grip strength was measured using a grip strength meter (BIOSEP) before drug administration and at weeks 3 and 5 of administration. The measured values ​​(N) were compared between groups based on the pre- and post-administration change in N / g values, which were corrected for body weight (g). Grip strength was analyzed using one-way ANOVA, and differences between groups were evaluated through post-hoc testing.

[0132] As a result, as shown in Figure 6, starting from the third week of administration, the grip strength of mice in the 200 mg / kg and 400 mg / kg administration groups increased in a dose-dependent manner compared to the 0 mg / kg administration group.

[0133] Example 3.2. Confirmation of sarcopenia treatment effect through running time measurement

[0134] A drug prepared by mixing tributyrin and trihexanoin in a weight ratio of 1:2 was administered to 19-month-old aged mice, and the running time measured at week 6 was compared with the results measured before administration. Running ability was measured once before and once after administration using a treadmill (DBL). Running time was analyzed using one-way ANOVA, and differences between groups were evaluated through post-hoc testing.

[0135] As a result, as shown in Figure 7, it was confirmed that the average running time was improved in a dose-dependent manner in the drug administration group compared to the 0 mg / kg administration group.

[0136] Example 4. Confirmation of the therapeutic effect on sarcopenia through grip strength measurement using muscle atrophy-induced mice

[0137] To confirm the therapeutic effect on sarcopenia, the fatty acids tributyrin and trihexanoin were mixed in a weight ratio of 1:2 and the drug prepared on the same day was orally administered to mice with muscle atrophy induced by a 60% high-fat diet using a 1 mL syringe and a syringe 6 times a week for 5 weeks to confirm the efficacy in improving muscle strength (Table 2).

[0138] 0 mg / kg 200 mg / kg 400 mg / kg Number of mice 7 7 6 Dosage of tributyrin and trihexanoin 0 2 0 6 4 1 2 Trityrin:trihexanoin mixing ratio 1:2 Corn oil 4 1 2 2 0 6 0 Method of administration Oral administration Total solution volume 5 mL / kg Solvent 0.5% CMC Administered 6 times a week

[0139] As in Example 3.1 above, grip strength of the limbs was measured before or after drug administration. As a result, as shown in Fig. 8, the 0 mpk (mg / kg) group showed a decrease in grip strength of approximately 28.8% compared to before administration, while the 200 mpk (mg / kg) and 400 mpk (mg / kg) drug administration groups showed decreases of approximately 21.2% and 15.8%, respectively. Thus, the therapeutic effect on sarcopenia was confirmed through the results of administering the drug to mice with induced muscle atrophy.

[0140] Example 5. Confirmation of repeated drug administration toxicity

[0141] A mixture of tributyrin and trihexanoin in a weight ratio of 1:2 was repeatedly administered to ICR mice 7 times a week for 4 weeks using a 1 mL syringe and diaphragm. To test for drug toxicity, the dosage was set at 2,000 mg / kg or 4,000 mg / kg, which is 10 times the corresponding dose, and administered repeatedly (Table 3).

[0142] 0 mg / kg 2000 mg / kg 4000 mg / kg Number of mice 8 8 8 Dosage of tributyrin and trihexanoin 0 20 00 40 00 Trityrin:trihexanoin mixing ratio 1:2 Method of administration: Oral Total solution volume 5 mL / kg Solvent 0.5% Gelatine administered 7 times a week

[0143] Body weight was measured twice a week, and feed and water intake were measured once a week. Clinical symptoms, such as changes in the mouse's appearance and behavior, were observed and recorded once a day. In addition, the major organs (liver, heart, spleen, kidney, adrenal gland, thymus, uterus, or ovary) of mice euthanized on day 29 of administration were separated and weighed individually.

[0144] Body weight and cumulative dietary intake were analyzed using Two-way Repeated ANOVA. To adjust for body weight differences between individuals, an analysis of covariance (ANCOVA) was performed with body weight as a covariate to evaluate the differences in organ weight between groups.

[0145] As a result, as shown in Figures 9a and 9b, it was confirmed that there were no significant differences between the groups in body weight and cumulative dietary intake during the repeated drug administration period.

[0146] In addition, as shown in Figures 10a and 10b and Table 4, the absolute weight of major organs was measured and analyzed with body weight set as a covariate, and it was confirmed that there was no significant difference between the groups.

[0147] OrganN (0 / 2000 / 4000)Group DF(Liver)Group F(F-value)Group p(p-value)Liver8 / 8 / 82, 214.0810.056Heart8 / 8 / 82, 210.6940.414Spleen8 / 8 / 82, 210.1480.705Thymus8 / 8 / 82, 211.7890.195Adrenal gland (L)8 / 8 / 82, 210.4230.523Adrenal gland (R)8 / 8 / 82, 211.3670.256Kidney (L)8 / 8 / 82, 210.4200.524Kidney (R)8 / 8 / 82, 211.7260.204Overy (L)8 / 8 / 82, 212.6470.119Overy (R)8 / 8 / 82, 213.4600.077Uterus8 / 8 / 82, 210.1220.731

[0148] p < 0.05 : *

Claims

1. A composition comprising at least one of the compounds represented by the following chemical formulas I to III as an active ingredient: [Chemical Formula I] In the above chemical formula I, R 1a is H or C1-C6 alkyl and R 1b is a C3-C6 alkyl, and [Chemical Formula II] In the above chemical formula II, R 2a is a C1-C6 alkanedyl, and R 2b and R 2c Each is independently a C3-C6 alkyl, and [Chemical Formula III] In the above chemical formula III, R 3a is a C1-C6 alcanthyl, and R 3b , R 3c and R 3d Each is independently a C3-C6 alkyl.

2. In Paragraph 1, A composition comprising two or more different compounds selected from the group consisting of compounds represented by the above chemical formulas I, II, and III.

3. In Paragraph 1, A composition comprising two or more different compounds represented by the above chemical formula I.

4. In Paragraph 3, Two or more different compounds represented by the above chemical formula I are R in the above chemical formula I 1b Ga C 3- C4 alkyl compounds and R 1b A composition comprising a compound in which is a C5-C6 alkyl.

5. In Paragraph 3, A composition comprising two or more different compounds represented by the above chemical formula I, wherein the compounds include ethyl butanoate and ethyl hexanoate.

6. In Paragraph 1, A composition comprising two or more different compounds represented by the above chemical formula II.

7. In Paragraph 1, The compound represented by the above chemical formula II is propane-1,3-diyl dibutyrate ( ) and propane-1,3-diyl dihexanoate( Two compounds composed of ) or 3-(butyryloxy)propyl hexanoate( A composition comprising a compound selected alone.

8. In Paragraph 1, A composition comprising two or more different compounds represented by the above chemical formula III.

9. In Paragraph 1, The compound represented by the above chemical formula III is propane-1,2,3-triyl tributyrate ( ) 및 propane-1,2,3-triyl trihexanoate( Two types of compounds composed of ); or 3-(butyrloxy)propane-1,2-diyl dihexanoate( ), 2-(butyryloxy)propane-1,3-diyl dihexanoate( ), 3-(hexanoyloxy)propane-1,2-diyl dibutyrate( ) 및 2-(hexanoyloxy)propane-1,3-diyl dibutyrate( A composition comprising a compound selected solely from the group consisting of ).

10. In Paragraph 8, A composition comprising two or more different compounds represented by the above chemical formula III, wherein the compounds include propane-1,2,3-triyl tributyrate and propane-1,2,3-triyl trihexanoate.

11. In Paragraph 1, A composition in which the mixing weight ratio of two different compounds in the above composition is 1:9 to 9:

1.

12. In Paragraph 1, Ethyl butanoate, a compound represented by the above chemical formula I, and propane-1,3-diyl dibutyrate, a compound represented by the chemical formula II ( propane-1,2,3-triyl tributyrate, a compound represented by ) and chemical formula III ( Any one compound selected from the group consisting of ); and Ethyl hexanoate, a compound represented by chemical formula I, and propane-1,3-diyl dihexanoate, a compound represented by chemical formula II ( propane-1,2,3-triyl trihexanoate, a compound represented by ) and chemical formula III ( A composition in which the mixing weight ratio of any one compound selected from the group consisting of ) is 1:9 to 9:

1.

13. A pharmaceutical composition for the prevention or treatment of sarcopenia comprising the composition of claim 1 as an active ingredient.

14. In Paragraph 13, A pharmaceutical composition for the prevention or treatment of sarcopenia, wherein the prevention or treatment of sarcopenia is achieved by improving one or more selected from the group consisting of muscle mass, muscle strength, and physical activity capacity in a subject requiring prevention or treatment of sarcopenia.

15. A food composition for the prevention or improvement of sarcopenia comprising the composition of claim 1 as an active ingredient.

16. A composition for livestock feed for the prevention or improvement of sarcopenia comprising the composition of claim 1 as an active ingredient.

17. Use of the composition of paragraph 1 for the prevention or treatment of sarcopenia.

18. A method for preventing or treating sarcopenia comprising the step of administering the composition of claim 1 to an individual.

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