WO2022244915A1 - Composition comprising euscaphic acid, and use thereof for relieving fatigue - Google Patents

Abstract

The present invention relates to a composition comprising a euscaphic acid, and the use thereof for relieving fatigue and, more specifically, to a food composition, a health functional food composition, and/or a pharmaceutical composition for relieving fatigue by means of euscaphic acid which exhibits a physical fatigue-relieving effect through anti-inflammatory and antioxidant activities. Further, the present invention provides a fatigue relieving method using a euscaphic acid, and the use of a euscaphic acid when preparing a food product or a drug for relieving fatigue.

Description

Compositions comprising Euscapic Acid and their use for fatigue recovery

The present invention relates to a composition containing Euscaphic acid and its use for fatigue recovery, and more particularly, to fatigue recovery using Euscapic acid, which has an effect on physical fatigue recovery through anti-inflammatory and antioxidant activities A food composition, a health functional food composition, and/or a pharmaceutical composition are provided. In addition, the present invention provides a fatigue recovery method using euscapic acid and the use of euscapic acid in the preparation of food or medicine for fatigue recovery.

Fatigue is largely divided into mental and physical fatigue, and among them, physical fatigue is a state in which the force required for muscle contraction activity is not sufficiently exerted or maintained, and the physical or mental ability is not recovered by rest due to overwork or energy depletion. Decreased state, defined as reduced work efficiency or motor performance. Drowsiness, fatigue, exhaustion, drowsiness, poor concentration, headache, muscle pain and the like are known as typical symptoms of fatigue.

The causes of general physical fatigue are known, such as deficiency or unavailability of energy sources stored in the body, accumulation of fatigue substances such as active oxygen due to metabolism, and loss of homeostasis in the body. In particular, it has been found that the generation of active oxygen is further increased by excessive physical activity, excessive mental/physical stress, and the like.

On the other hand, fatigue is not caused by one factor, but is often caused by a combination of various factors. For example, fatigue can be caused by physical diseases such as cancer, tuberculosis, diabetes, liver disease, hyperthyroidism, heart failure, and anemia, and mental problems such as severe stress, depression, anxiety, sleep disorders, and maladjustment to social life. You may feel fatigued, and excessive physical activity can also make you feel fatigued.

In order to recover from physical fatigue, supply of sufficient energy sources, rest, suppression and removal of fatigue substances in the body, etc. are required, but in fact, sufficient nutrition and rest are not achieved in busy modern society. Therefore, it is necessary to develop a material capable of restoring or suppressing fatigue.

On the other hand, in relation to anti-fatigue, Korean Patent Publication No. 10-2012-0033443 discloses an anti-fatigue composition using a rhubarb extract and a manufacturing method thereof, and Korean Patent Publication No. 10-2016-0122110 discloses a fermented placenta composition. An anti-fatigue composition using is disclosed, but nothing is known about the anti-fatigue efficacy of euscapic acid.

Under this background, the present inventors have confirmed that Euscapic Acid has anti-inflammatory or antioxidant activity and exhibits excellent fatigue recovery effect by regulating various indicators related to anti-fatigue activity in blood, muscle and liver through this activity, completed the present invention.

Accordingly, an object of the present invention is to provide a composition for recovering from fatigue using yuscapic acid.

Another object of the present invention is to provide a method for recovering from fatigue using eucalyptus acid.

Another object of the present invention is to provide use of euscapic acid in the preparation of food or medicine for fatigue recovery.

In order to solve the above problems, the present invention provides a food composition for fatigue recovery comprising Euscaphic acid or a food chemically acceptable salt thereof.

In addition, the present invention provides a health functional food composition for fatigue recovery comprising yuscapic acid or a food-acceptable salt thereof.

The present invention also provides a pharmaceutical composition for relieving fatigue comprising euscapic acid or a pharmaceutically acceptable salt thereof.

In another aspect, the present invention provides a method for recovering from fatigue comprising administering an effective amount of yuscapic acid, or a pharmaceutically acceptable salt or pharmaceutically acceptable salt thereof, to a subject in need thereof.

Further, the present invention provides the use of euscapic acid, or a food-acceptable salt or pharmaceutically-acceptable salt thereof, in the preparation of a food or medicine for fatigue recovery.

According to a preferred embodiment of the present invention, the fatigue may include physical fatigue or chronic fatigue.

According to another preferred embodiment of the present invention, the physical fatigue may include muscle fatigue.

According to another preferred embodiment of the present invention, the fatigue recovery effect may be induced by an anti-inflammatory or antioxidant effect.

According to another preferred embodiment of the present invention, the composition may exhibit any one or more of the effects of a) to h):

a) at least one effect selected from the group consisting of reducing lactate dehydrogenase (LDH) activity in blood, reducing blood urea nitrogen (BUN), reducing aspartate aminotransferase (AST) activity, and reducing alanine aminotransferse (ALT) activity;

b) intramuscular glycogen increasing effect;

c) any one or more effects selected from the group consisting of reducing blood glucose level, reducing lactate level, reducing cortisol level, and reducing CK (creatine kinase) level;

d) any one or more effects selected from the group consisting of increasing the level of free fatty acid in the blood and increasing the level of SOD (Superoxide dismutase);

e) reducing the level of Malondialdehyde (MDA) in the blood;

f) any one or more effects selected from the group consisting of increased SOD (Superoxide dismutase) activity and increased catalase activity in the liver;

g) any one or more effects selected from the group consisting of increased intramuscular SOD (Superoxide dismutase) activity and increased citrate synthase activity; and

h) at least one effect selected from the group consisting of reducing the level of TNF-α in the blood, reducing the level of IL-6, reducing the level of IL-1β and reducing the level of IL-4.

The fatigue recovery composition using euscapic acid according to the present invention exhibits an excellent anti-fatigue effect through anti-inflammatory or antioxidant activity, more specifically, through any one or more of the following a) to h), thereby reducing accumulated in the body It is effective in recovering from fatigue: a) Any one selected from the group consisting of reducing LDH (Lactate dehydrogenase) activity in blood, BUN (Blood urea nitrogen) reduction, AST (aspartate aminotransferase) activity reduction, and ALT (alanine aminotransferse) activity reduction more than one effect; b) intramuscular glycogen increasing effect; c) any one or more effects selected from the group consisting of reducing blood glucose level, reducing lactate level, reducing cortisol level, and reducing CK (creatine kinase) level; d) any one or more effects selected from the group consisting of increasing the level of free fatty acid in the blood and increasing the level of SOD (Superoxide dismutase); e) reducing the level of Malondialdehyde (MDA) in the blood; f) any one or more effects selected from the group consisting of increased SOD (Superoxide dismutase) activity and increased catalase activity in the liver; g) any one or more effects selected from the group consisting of increased intramuscular SOD (Superoxide dismutase) activity and increased citrate synthase activity; and h) any one or more effects selected from the group consisting of reducing the level of TNF-α in the blood, reducing the level of IL-6, reducing the level of IL-1β and reducing the level of IL-4.

1 is a graph showing the levels of the inflammatory markers TNF-α and IL-6 according to treatment with euscapic acid in a muscle cell line (C2C12) induced by oxidative stress.

Figure 2 is a graph showing the levels of antioxidant markers SOD, catalase and MDA according to euscapic acid treatment in the muscle cell line (C2C12) induced by oxidative stress.

Figure 3 is a graph showing the change in immobility time according to the administration of yuscapic acid in a forced swimming test (FST) measured weekly for 4 weeks.

Figure 4 is a graph showing the levels of LDH, BUN, AST and ALT, which are indicators related to fatigue improvement in blood according to the administration of euscapic acid in a forced swimming load test.

5 is a graph showing the intramuscular glycogen content according to the administration of euscapic acid in a forced swimming load test.

6 is a graph showing the levels of glucose, lactic acid, cortisol, and CK, which are biochemical indicators related to fatigue improvement in the blood according to the administration of euscapic acid in a forced swimming load test.

7 is a graph showing the levels of free fatty acids and SOD, which are biochemical indicators related to fatigue improvement in blood according to the administration of euscapic acid in a forced swimming load test.

8 shows the concentration of MDA in blood according to the administration of euscapic acid in the forced swimming load experiment.

9 is a graph showing the activities of the antioxidant enzymes SOD and catalase in the liver according to the administration of euscapic acid in a forced swimming load experiment.

10 is a graph showing the activities of intramuscular SOD and citrate synthase according to the administration of euscapic acid in a forced swimming load test.

11 is a graph showing the levels of inflammation-related indicators TNF-α, IL-6, IL-1β, and IL-4 in blood following administration of euscapic acid in a forced swimming load experiment.

As described above, in order to recover from physical fatigue, supply of sufficient energy sources, rest, suppression and removal of fatigue substances in the body, etc. are required. However, there is a continuous demand for the development of materials that can effectively restore or suppress fatigue.

The present inventors completed the present invention by confirming that Euscapic Acid has anti-inflammatory or antioxidant activity, and exhibits excellent fatigue recovery effect by regulating various indicators related to anti-fatigue activity in blood, muscle and liver through this activity. did

Accordingly, a first aspect of the present invention is a food composition for fatigue recovery comprising euscapic acid or a food-acceptable salt thereof and/or a health function for fatigue recovery comprising euscapic acid or a food-acceptable salt thereof. It relates to food compositions.

In the food composition of the present invention, Euscaphic acid included as an active ingredient is a pentacyclic triterpenoid compound having the structure of the following [Formula 1], calf DNA polymerase α ( It is known as a DNA polymerase inhibitor that inhibits pol α) and rat DNA polymerase β (pol β) (Murakami C, et al. Novel anti-inflammatory compounds from Rubus sieboldii, triterpenoids, are inhibitors of mammalian DNA polymerases. Biochim Biophys Acta. 2002 Apr 29;1596(2):193-200.), known to induce apoptosis (Dai W, et al. Euscaphic acid inhibits proliferation and promotes apoptosis of nasopharyngeal carcinoma cells by silencing the PI3K/AKT/mTOR signaling pathway. Am J Transl Res. 2019 Apr 15;11(4):2090-2098.).

[Formula 1]

In the food composition of the present invention, the yuscapic acid may be artificially synthesized or commercially available. In addition, it can be used after being purified from a substance containing euscapic acid or from a natural source.

By use of the term "purified" it is intended to mean that the euscapic acid is in a concentrated form compared to the form obtainable from nature. Purified components can be concentrated from their natural sources or obtained through chemical synthesis.

In the present invention, the term "fatigue" is a phenomenon in which physical and mental abilities are reduced, and can be classified into pathological fatigue, physiological fatigue, and psychological fatigue. First, pathological fatigue refers to the occurrence of diseases such as liver function deterioration, diabetes, and gastrointestinal diseases due to a sense of fatigue. Second, the feeling of fatigue as fatigue substances accumulate in the blood is called physiological fatigue. Physiological fatigue is caused by a lack of phosphocreatinine in muscles, accumulation of protons in muscles (acidemia), lack of glucagon in muscles, a decrease in blood glucose concentration, and an increase in the ratio of certain amino acids in plasma, which affects peripheral and central fatigue. will give Third, psychological fatigue refers to fatigue caused by emotional conflict, anxiety, or boredom, and refers to a state in which the strength or sensitivity of cells, muscles, or organs is temporarily reduced after continuous activity or stimulation.

In the food composition of the present invention, the fatigue includes physical fatigue or chronic fatigue. Specifically, physical fatigue includes, but is not limited to, muscle fatigue due to excessive physical activity. Muscle fatigue can manifest as symptoms of fatigue, decreased endurance, reduced speed, or lethargy.

Chronic fatigue is fatigue caused by physical diseases such as cancer, tuberculosis, diabetes, liver disease, hyperthyroidism, heart failure, and anemia, fatigue caused by mental problems such as severe stress, depression, anxiety, sleep disorders, and maladjustment to social life, or excessive physical fatigue. Fatigue caused by activity lasting for more than 6 months or recurring symptoms.

Key indicators of the degree of fatigue include cytokines, MDA and SOD. Cytokines bind to specific receptors present in the cell membrane of target cells and activate signal transduction pathways, ultimately changing enzyme activity or gene expression. Increased cytokines due to exercise can cause an inflammatory response in muscle tissue.

MDA (Malondialdehyde) is an oxide used as an indicator of tissue damage, and is an indicator for evaluating oxidative stress, a major substance that causes intramuscular fatigue in muscle tissue. When MDA increases due to exercise-related stress, muscle tissue is damaged.

In addition, there is SOD (Superoxide dismutase) as an antioxidant enzyme related to oxidative stress. SOD is an antioxidant enzyme that catalyzes the reaction of converting superoxide into oxygen and hydrogen peroxide (H ₂ O ₂ ), and serves to remove free radicals from the blood. An increase in SOD in the blood reduces muscle fatigue .

Therefore, in a specific embodiment of the present invention, anti-inflammatory and antioxidant effects according to Euscapic acid treatment were confirmed in muscle cell lines in which oxidative stress was induced. As a result, as shown in FIGS. 1 and 2, the levels of TNF-α and IL-6, which were increased by oxidative stress, were significantly decreased by treatment with euscapic acid (FIG. 1), and The levels of SOD and catalase were significantly increased by treatment with euscapic acid (FIG. 2), and the level of MDA increased by oxidative stress was significantly decreased by treatment with euscapic acid (FIG. 2), resulting in anti-inflammatory and antioxidant It was confirmed that the effect of improving intramuscular fatigue can be induced through activity.

LDH (Lactate dehydrogenase) is an enzyme that produces ATP by anaerobic glycolysis during muscle activity and catalyzes the reaction between pyruvic acid and lactic acid. It is mainly present in red blood cells and muscle cells. When cell membrane permeability increases due to direct cell membrane destruction and tissue necrosis caused by severe physical exercise and lipid peroxidation caused by stress, LDH in the cytoplasm is released into the blood, and the blood LDH concentration is used as an index of muscle damage.

Serum aspartate amino-transferase (AST) and alaninetransferase (ALT) are also called serum glutamic oxalate transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT). In particular, ALT is said to act so that protein can be used as energy by accelerating the reaction of converting amino acids from glutamate into pyruvic acid during long-term intense exercise. AST and ALT are present in almost all organs, in particular, AST is present in a large amount in the heart, liver, and skeletal muscle, and ALT is present in a large amount in the liver. Although they are present in small amounts in serum, they are known to cause an increase in AST values after excessive exercise and to be hardly affected by diet.

Glycogen is stored in the liver (2-10%) and skeletal muscle (1-2%), and the glycogen stored in the liver is mainly used in the brain and kidneys. When liver glycogen is depleted during high-intensity endurance exercise, muscle glycogen becomes an energy source. Therefore, an increase in glycogen, an energy source, means a decrease in fatigue.

Therefore, in another specific embodiment of the present invention, the anti-fatigue effect was confirmed by measuring the immobility time change and various anti-fatigue related indicators according to the Euspicic acid treatment through a mouse forced swimming load test. As shown in FIG. 3 , it was confirmed that the immobility time of the group administered with euscapic acid was reduced compared to the control group not administered with euscapic acid. In addition, as shown in FIGS. 4 and 5, compared to the control group not administered with Euscapic Acid, the group administered with Yuscapic Acid significantly reduced the levels of LDH, BUN, AST and ALT in the blood (FIG. 4 ), muscle glycogen levels were also increased (FIG. 5), confirming that the anti-fatigue effect was induced.

When the blood glucose concentration decreases and the sugar production process is inhibited due to lack of oxygen, fatigue is felt due to the increase in lactic acid production.

In addition, when oxygen supply to muscles cannot keep up with the speed of glycolysis during intense exercise, pyruvic acid is produced as lactic acid by lactate dehydrogenase. When the human body is acidified due to the accumulation of lactic acid, the intracellular pH drops, which reduces the activity of enzymes, suppressing mitochondrial oxidation and muscle relaxation and contraction activities. Therefore, in the case of sudden intense exercise, muscle pain may be caused as the intracellular pH is lowered.

Cortisol is a stress hormone secreted by the adrenal cortex of the kidney in response to acute stress, and serves to supply the body with the necessary energy to fight stress. The secreted cortisol releases more blood to each organ of the body so that the body can fight against external stimuli such as stress, resulting in increased pulse and respiration. However, excessive stress or chronic stress increases the blood level of cortisol and increases appetite, causing fat accumulation, and also increases blood pressure, increasing the risk of high blood pressure, and may cause damage to muscle tissue. have. Anxiety and nervousness may follow, and symptoms such as chronic fatigue, chronic headaches, and insomnia may appear along with weight gain.

CK (Creatine kinase) is an enzyme that is present in many muscles and is released into the blood when muscle cells are damaged to create an energy source. CK plays a role in synthesizing creatinine phosphate necessary for ATP resynthesis (the process of synthesizing ATP from ADP and phosphocreatinine) during anoxia in muscle cells during exercise.

Therefore, in another specific embodiment of the present invention, changes in the levels of glucose, lactic acid, cortisol, and CK, which are biochemical indicators related to blood fatigue improvement according to Euscapic acid treatment, were confirmed through a forced swimming load test in mice. As a result, as confirmed in FIG. 6, compared to the control group not administered with euscapic acid, the group administered with euscapic acid had reduced blood glucose levels and significantly reduced lactic acid, cortisol, and CK levels. appeared to be The levels of glucose, lactic acid, and CK in the blood, which were increased due to exercise load, decreased with administration of Euscapic Acid, confirming that Euscapic Acid is effective in recovering from muscle fatigue. In addition, the level of cortisol in the blood, which was rapidly increased by physical stress such as forced swimming, was significantly decreased according to the administration of euscapic acid, which confirmed that euscapic acid was effective for chronic fatigue recovery.

Free fatty acid (FFA) in the blood is known to be the most important energy source that is released from fat cells into the blood during exercise and circulates. Thus, free fatty acids are used as an energy source through the sugar production process, which reduces fatigue.

Therefore, in another specific embodiment of the present invention, changes in the levels of FFA and SOD, which are biochemical indicators related to fatigue improvement in the blood, according to Euscapic Acid treatment were confirmed through a forced swimming load test in mice. As a result, as shown in FIG. 7 , the FFA level in the blood and the SOD level were significantly increased in the group administered with euscapic acid compared to the control group not administered with euscapic acid. The levels of FFA and SOD in the blood, which were reduced by exercise load, increased with the administration of euscapic acid, confirming that euscapic acid is effective in recovering from muscle fatigue.

As described above, MDA increases due to exercise-related stress and damages muscle tissue.

Therefore, in another specific embodiment of the present invention, the change in the level of MDA in blood according to the treatment with euscapic acid was confirmed through a mouse forced swimming load test. As a result, as confirmed in FIG. 8 , the MDA level in blood was significantly reduced in the group administered with euscapic acid compared to the control group not administered with euscapic acid. The level of MDA in blood, which was increased due to exercise load, decreased with administration of Euscapic Acid, confirming that Yuscapic Acid was effective in recovering from muscle fatigue.

CAT (Catalase) is an enzyme that converts hydrogen peroxide converted by SOD into water and oxygen, and helps improve fatigue by suppressing the accumulation of hydrogen peroxide generated during exercise.

Therefore, in another specific embodiment of the present invention, SOD and CAT activities in the liver according to Euspicic acid treatment were confirmed through a mouse forced swimming load test. As a result, as shown in FIG. 9 , SOD and CAT activities in the liver were significantly increased in the group administered with euscapic acid compared to the control group not administered with euscapic acid. SOD and CAT activities in the liver, which were reduced by exercise load, were significantly increased by administration of euscapic acid, confirming that euscapic acid is effective in recovering from muscle fatigue.

CS (Citrate synthase) is an enzyme that catalyzes the synthesis of citric acid in the first step of the TCA cycle. If the TCA cycle does not run smoothly, lactic acid in the blood accumulates and causes fatigue.

Therefore, in another specific embodiment of the present invention, changes in intramuscular SOD activity and CS concentration according to Euscapic acid treatment were confirmed through a mouse forced swimming load test. As a result, as confirmed in FIG. 10 , it was found that the intramuscular SOD activity and CS concentration increased significantly in the group administered with euscapic acid compared to the control group not administered with euscapic acid. The intramuscular SOD activity and CS concentration, which were reduced due to exercise load, increased with the administration of euscapic acid, confirming that euscapic acid is effective in recovering from muscle fatigue.

As described above, increased cytokines due to exercise can cause an inflammatory response in muscle tissue.

Therefore, in another specific embodiment of the present invention, changes in the levels of TNF-α, IL-6, IL-1β, and IL-4 in the blood according to Euscapic acid treatment were confirmed through a mouse forced swimming load test. As a result, as confirmed in FIG. 11, compared to the control group not administered with Euscapic Acid, the group administered with Yuscapic Acid had a decrease in the level of TNF-α in the blood, IL-6, IL-1β, and IL-4. showed a significant decrease in the level of The levels of TNF-α, IL-6, IL-1β, and IL-4 in the blood increased by exercise load decreased with administration of Euscapic Acid, confirming that Yuscapic Acid is effective in recovering from fatigue. .

In the present invention, the term "functional health food" includes both the meanings of "functional food" and "health food".

In the present invention, the term "functional food" is the same term as food for special health use (FoSHU), and in addition to nutrient supply, medicine and medical effects processed to efficiently exhibit bioregulatory functions. Means high food.

In the present invention, the term "health food" refers to food having active health maintenance or effects compared to general food, and health supplement food refers to food for the purpose of supplementing health. In some cases, the terms functional food, health food, and health supplement food are used interchangeably. The food may be prepared in various forms such as tablets, capsules, powders, granules, liquids, and pills.

As a specific example of such a functional food, processed food with improved storage stability can be prepared by using the composition to modify the characteristics of agricultural products, livestock products, or aquatic products.

The health functional food composition of the present invention may also be prepared in the form of nutritional supplements and food additives, and is intended for consumption by humans.

Food compositions of this type can be prepared in various forms according to conventional methods known in the art. General foods include, but are not limited to, beverages (including alcoholic beverages), fruits and their processed foods (e.g. canned fruits, bottled products, jams, marmalades, etc.), fish, meat and their processed foods (e.g. ham, sausages) Corned beef, etc.), breads and noodles (e.g. udon, buckwheat noodles, ramen, spagate, macaroni, etc.), fruit juice, various drinks, cookies, taffy, dairy products (e.g. butter, cheese, etc.), edible vegetable oil, margarine , Vegetable protein, retort food, frozen food, and various seasonings (eg, soybean paste, soy sauce, sauce, etc.) can be prepared by adding eucalyptic acid.

In addition, nutritional supplements are not limited thereto, but can be prepared by adding euscapic acid to capsules, tablets, pills, and the like.

In addition, health functional foods are not limited thereto, but, for example, the uscapic acid is prepared in the form of tea, juice, and drink, and can be consumed by liquefying, granulating, encapsulating, and powdering so that it can be consumed (health drink). can In addition, in order to use the yuscapic acid in the form of a food additive, it may be prepared and used in the form of a powder or concentrate. In addition, the yuscapic acid may be prepared in the form of a composition by mixing it with a known active ingredient known to be effective in recovering from fatigue.

When the food composition of the present invention is used as a health beverage composition, the health beverage composition may contain various flavoring agents or natural carbohydrates as additional components, like conventional beverages. The aforementioned natural carbohydrates include monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrins and cyclodextrins; It may be a sugar alcohol such as xylitol, sorbitol, or erythritol. Sweeteners include natural sweeteners such as thaumatin and stevia extract; Synthetic sweeteners such as saccharin and aspartame may be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.

Euscapic acid may be contained as an active ingredient in a food composition for preventing or recovering from fatigue, in an amount effective to obtain the preventive or restorative effect, for example, 0.01 to 100% by weight based on the total weight of the composition. It is preferred, but is not particularly limited thereto.

In addition to the above, the health functional food of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH regulators, stabilizers, and preservatives. , glycerin, alcohol or carbonation agent, and the like. In addition, the health food of the present invention may contain fruit flesh for producing natural fruit juice, fruit juice beverage, or vegetable beverage. These components may be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

A second aspect of the present invention relates to a pharmaceutical composition for fatigue recovery comprising euscapic acid or a pharmaceutically acceptable salt thereof.

In the pharmaceutical composition of the present invention, the description of the active ingredient, euscapic acid, and its effects are the same as those described in the first aspect, so the description thereof will be omitted.

As used herein, the term "pharmaceutically acceptable" refers to one that is physiologically acceptable and does not usually cause an allergic reaction or similar reaction when administered to humans, and the salt includes a pharmaceutically acceptable free acid (free acid). acid) is preferred.

The pharmaceutically acceptable salt may be an acid addition salt formed using an organic acid or an inorganic acid, and the organic acid may be, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, maleic acid, Malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, glycolic acid, glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxy acetic acid, benzenesulfonic acid, p- toluenesulfonic acid or methanesulfonic acid. Inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid or boric acid. The acid addition salt may preferably be in the form of a hydrochloride salt or an acetate salt, more preferably in the form of a hydrochloride salt.

In addition, additionally saltable forms are gabacin salt, gabapentin salt, pregabalin salt, nicotate salt, adipate salt, hemimalonate salt, cysteine salt, acetylcysteine salt, methionine salt, arginine salt, lysine salt, ornithine salt, or aspartate. etc.

In addition, the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier. A pharmaceutically acceptable carrier may further include, for example, a carrier for oral administration or a carrier for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid and the like. Carriers for parenteral administration may include water, suitable oils, saline, aqueous glucose and glycols, and the like. In addition, a stabilizer and a preservative may be further included. Suitable stabilizers include antioxidants such as sodium bisulfite, sodium sulfite or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben and chlorobutanol. As other pharmaceutically acceptable carriers, reference may be made to those described in the following literature (Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).

The pharmaceutical composition of the present invention can be administered to mammals including humans by any method. For example, it can be administered orally or parenterally, and parenteral administration methods include, but are not limited to, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal , intranasal, enteral, topical, sublingual or rectal administration.

The pharmaceutical composition of the present invention may be formulated into a formulation for oral administration or parenteral administration according to the administration route as described above. When formulated, one or more buffers (e.g., saline or PBS), carbohydrates (e.g., glucose, mannose, sucrose, or dextran, etc.), antioxidants, bacteriostatic agents, chelating agents (e.g., EDTA or glutathione), fillers, bulking agents, binders, adjuvants (eg aluminum hydroxide), suspending agents, thickening agents, wetting agents, disintegrating agents or surfactants, diluents or excipients.

Solid preparations for oral administration include tablets, pills, powders, granules, solutions, gels, syrups, slurries, suspensions or capsules, etc. These solid preparations include at least one excipient in the pharmaceutical composition of the present invention, for example , starch (including corn starch, wheat starch, rice starch, potato starch, etc.), calcium carbonate, sucrose, lactose, dextrose, sorbitol, mannitol, xylitol, erythritol maltitol, cellulose , methyl cellulose, sodium carboxymethyl cellulose and hydroxypropylmethyl-cellulose or gelatin may be mixed and prepared. Tablets or dragees may be obtained, for example, by combining the active ingredient with a solid excipient which is then milled and processed into a mixture of granules after adding suitable auxiliaries.

In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, or syrups. In addition to water or liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, or preservatives may be included. .

In addition, cross-linked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may be added as a disintegrant, and may further include anti-agglomerating agents, lubricants, wetting agents, flavoring agents, emulsifiers, and preservatives. .

In the case of parenteral administration, the pharmaceutical composition of the present invention may be formulated according to a method known in the art in the form of injection, transdermal administration, and nasal inhalation with a suitable parenteral carrier. In the case of the injection, it must be sterilized and must be protected from contamination by microorganisms such as bacteria and fungi. Examples of suitable carriers for injections include, but are not limited to, water, ethanol, polyols (eg, glycerol, propylene glycol, liquid polyethylene glycol, etc.), mixtures thereof, and/or solvents or dispersion media containing vegetable oils. can More preferably, suitable carriers include Hanks' solution, Ringer's solution, phosphate buffered saline (PBS) with triethanolamine or isotonic solutions such as sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose. etc. can be used. In order to protect the injection from microbial contamination, various antibacterial and antifungal agents such as paraben, chlorobutanol, phenol, sorbic acid, and thimerosal may be further included. Also, in most cases, the injection may further include an isotonic agent such as sugar or sodium chloride.

Transdermal preparations include ointments, creams, lotions, gels, external solutions, pastas, liniments, air rolls, and the like. In the above, 'transdermal administration' means that an effective amount of the active ingredient contained in the pharmaceutical composition is delivered into the skin by topically administering the pharmaceutical composition to the skin.

For administration by inhalation, the compounds used according to the present invention may be administered in pressurized packs or with a suitable propellant, for example dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. It can be conveniently delivered in the form of an aerosol spray from a nebulizer. In the case of pressurized aerosols, dosage units may be determined by providing a valve that delivers a metered amount. For example, gelatin capsules and cartridges for use in inhalers or insufflators may be formulated to contain a powder mixture of the compound and a suitable powder base such as lactose or starch. Formulations for parenteral administration are described in all pharmaceutical chemistry generally known prescriptions, Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour.

The pharmaceutical composition of the present invention can provide a desirable fatigue recovery effect when it contains an effective amount of eucalyptus acid. As used herein, the term "effective amount" refers to an amount that exhibits a greater response than that of the negative control, preferably an amount sufficient to prevent or recover from fatigue. The pharmaceutical composition of the present invention may contain 0.01 to 99.9% of yuscapic acid, and the remaining amount may be occupied by a pharmaceutically acceptable carrier. The effective amount of the uscapic ester contained in the pharmaceutical composition of the present invention will vary depending on the form in which the composition is commercialized.

The total effective amount of the pharmaceutical composition of the present invention can be administered to the patient in a single dose, or by a fractionated treatment protocol in which multiple doses are administered over a long period of time. The pharmaceutical composition of the present invention may vary the content of the active ingredient according to the condition of the patient. For example, it may be divided into 1 to several times to be administered in an amount of preferably 0.001 to 100 mg, more preferably 0.01 to 10 mg per 1 kg of body weight per day based on Euscapic Acid. However, the effective dosage for the patient is determined by considering various factors such as the patient's age, weight, health condition, gender, severity of disease, diet and excretion rate, as well as the route of administration of the pharmaceutical composition and the number of treatments. Therefore, considering this point, those skilled in the art will be able to determine an appropriate effective dosage according to the specific use for preventing or recovering from fatigue. The pharmaceutical composition according to the present invention is not particularly limited in its formulation, administration route and administration method as long as it exhibits the effects of the present invention.

Additionally, a third aspect of the present invention relates to a quasi-drug composition for fatigue recovery containing euscapic acid.

In the quasi-drug composition of the present invention, since the description of the active ingredient, euscapic acid, and its effects are the same as those described in the first aspect, the description thereof will be omitted.

In the present invention, the term "quasi-drugs" refers to textiles, rubber products or similar products used for the purpose of treating, mitigating, treating or preventing diseases of humans or animals, products that have weak effects on the human body or do not directly act on the human body, and devices or non-machines and similar items, products falling under one of the agents used for sterilization, insecticidal, and similar purposes to prevent infectious diseases, for the purpose of diagnosing, treating, mitigating, treating, or preventing human or animal diseases It may refer to items other than instruments, machines or devices among items used and items other than instruments, machines or devices among items used for the purpose of pharmacologically affecting the structure and function of humans or animals. In addition, the quasi-drug may include external skin preparations and personal hygiene products. Preferably, it may be a disinfectant cleaner, shower foam, gargreen, wet tissue, detergent soap, hand wash, or ointment, but is not limited thereto.

When the composition according to the present invention is used as a quasi-drug additive, the composition may be added as it is or used together with other quasi-drugs or quasi-drug ingredients, and may be appropriately used according to a conventional method. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of use.

A fourth aspect of the present invention provides a method for recovering from fatigue, comprising administering an effective amount of yuscapic acid, or a pharmaceutically acceptable salt or pharmaceutically acceptable salt thereof, to a subject in need thereof.

In the fatigue recovery method of the present invention, the description of the properties and effects of the yuscapic acid, its food-acceptable salt or pharmaceutically-acceptable salt is the same as described above, so the description thereof will be omitted.

As used herein, the term "administration" means providing a given composition of the present invention to a subject by any suitable method.

The term "individual" used in the present invention includes, but is not limited to, mammals including humans.

The preferred dosage of the composition of the present invention varies depending on the condition and body weight of the subject, the degree of fatigue, the formulation form of Euscapic acid, or a pharmaceutically acceptable salt or pharmaceutically acceptable salt thereof, but the intended fatigue recovery effect can be selected appropriately to achieve.

As used herein, the term "effective amount" refers to symptoms related to physical fatigue or chronic fatigue by inducing any one or more of the following a) to h), for example, fatigue, decreased stamina, reduced agility or lethargy. muscle fatigue; and/or fatigue due to physical diseases such as cancer, tuberculosis, diabetes, liver disease, hyperthyroidism, heart failure, anemia, fatigue due to mental problems such as severe stress, depression, anxiety, sleep disorders, social maladjustment, or excessive body An amount of Euscapic Acid, or a food-acceptable salt or pharmaceutically-acceptable salt thereof, sufficient to reduce or completely recover chronic fatigue, in which fatigue due to activity lasts for 6 months or longer or exhibits recurrent symptoms: a) at least one effect selected from the group consisting of reducing lactate dehydrogenase (LDH) activity in blood, reducing blood urea nitrogen (BUN), reducing aspartate aminotransferase (AST) activity, and reducing alanine aminotransferse (ALT) activity; b) intramuscular glycogen increasing effect; c) any one or more effects selected from the group consisting of reducing blood glucose level, reducing lactate level, reducing cortisol level, and reducing CK (creatine kinase) level; d) any one or more effects selected from the group consisting of increasing the level of free fatty acid in the blood and increasing the level of SOD (Superoxide dismutase); e) reducing the level of Malondialdehyde (MDA) in the blood; f) any one or more effects selected from the group consisting of increased SOD (Superoxide dismutase) activity and increased catalase activity in the liver; g) any one or more effects selected from the group consisting of increased intramuscular SOD (Superoxide dismutase) activity and increased citrate synthase activity; and h) any one or more effects selected from the group consisting of reducing the level of TNF-α in the blood, reducing the level of IL-6, reducing the level of IL-1β and reducing the level of IL-4. For a desired effect, the composition containing the yuscapic acid of the present invention, or a pharmaceutically acceptable salt or pharmaceutically acceptable salt thereof, may be administered once or repeatedly several times at regular time intervals.

In the fatigue recovery method of the present invention, the composition containing the euscapic acid, or a food-acceptable salt or a pharmaceutically-acceptable salt thereof may be administered to a subject by various routes, preferably orally. can In addition, it can be used alone or in combination with other methods for recovery from fatigue.

A fifth aspect of the present invention provides use of euscapic acid, or a food-acceptable salt or pharmaceutically-acceptable salt thereof, in the preparation of a food or drug for recovery from fatigue.

Similarly, in the use of the present invention, the description of the characteristics and effects of the yuscapic acid, or its food-acceptable salt or pharmaceutically-acceptable salt is the same as described above, so the description thereof will be omitted.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for exemplifying the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.

[Example 1]

Confirmation of anti-inflammatory and antioxidant effects in muscle cell lines

1-1. sample preparation

After taking 10 mg of Euscapic Acid (BP1819, Biopurify Phytochemicals) and putting it in a 10 ml volumetric flask, methanol was added and sonicated for 30 minutes. Thereafter, the solution was filtered through a 0.45 μm membrane filter, diluted to an appropriate concentration, and then used in the experiment.

1-2. Confirmation of anti-inflammatory activity

The C2C12 muscle cell line (ATCC ^® CRL-1772™) was treated with H ₂ O ₂ and then treated with 1 μg/ml of Euscapic Acid to confirm changes in the levels of inflammatory markers TNF-α and IL-6. As shown in FIG. 1, both the levels of TNF-α and IL-6 were increased in the control group treated with H ₂ O ₂ compared to the normal group, but significantly decreased by the treatment of eucalyptus acid. It was confirmed that the anti-inflammatory effect was induced.

1-3. Antioxidant activity check

C2C12 muscle cell line (ATCC ^® CRL-1772™) was treated with H ₂ O ₂ and then treated with 1 μg/ml of euscapic acid to confirm changes in levels of antioxidant markers SOD, catalase, and MDA. As shown in FIG. 2, the levels of SOD and catalase in the control group treated with H ₂ O ₂ were significantly reduced and the level of MDA was significantly increased, compared to the normal group. The levels of SOD and catalase were significantly increased, and the level of MDA was significantly decreased, confirming that the antioxidant effect was induced by the treatment with euscapic acid.

[Example 2]

Mouse forced swimming test (FTS)

4-week-old ICR mice (Dae-Han Experimental Animal Center) were orally administered with 1 mg/kg of Euscapic Acid once a day for 4 weeks, and the time they remained immobile in water was measured and compared with the control group. Immobility time was measured weekly. As a result, as confirmed in FIG. 3, the immobility time began to decrease compared to the control group from the 3rd week after oral administration of Euscapic Acid, and significantly decreased at the 4th week.

[Example 3]

Confirm anti-fatigue effect

3-1. Identification of anti-fatigue-related indicators in blood

In Example 2, the blood levels of LDH, BUN, AST, and ALT, which are indicators related to fatigue recovery, were confirmed by sacrificing ICR mice orally administered with Euscapic Acid for 4 weeks. As shown in FIG. 4, the control group, which was not administered with Euscapic Acid, had markedly increased levels of LDH, BUN, AST and ALT in the blood compared to the normal group, but Yuscapic Acid was administered for 4 weeks. In the oral administration group, all indicators were significantly reduced, showing excellent anti-fatigue effect.

3-2. Identification of anti-fatigue-related indicators in muscle

In Example 2, ICR mice orally administered with Yuscapic Acid for 4 weeks were sacrificed to measure the level of glycogen in muscle tissue, which is an index related to fatigue recovery. As a result, as shown in FIG. 5, the control group to which Euscapic Acid was not administered had a reduced intramuscular glycogen level compared to the normal group, but the glycogen level in the group orally administered with Yuscapic Acid for 4 weeks It was confirmed that the anti-fatigue effect was induced by this increase.

[Example 4]

Identification of various biochemical indicators related to anti-fatigue in blood

4-1. Check glucose, lactate, cortisol and CK levels

In Example 2, blood levels of glucose, lactic acid, cortisol, and CK, which are biochemical indicators related to fatigue recovery, were measured by sacrificing ICR mice orally administered with Euscapic Acid for 4 weeks. As a result, as shown in FIG. 6, the control group to which Euscapic acid was not administered showed a sharp increase in blood glucose, lactic acid, cortisol, and CK levels compared to the normal group. In the weekly oral administration group, it was confirmed that the anti-fatigue effect was induced by reducing the blood glucose level and significantly reducing the levels of lactate, cortisol, and CK.

4-2. Check free fatty acid and SOD levels

In Example 2, the blood levels of free fatty acid (FFA) and SOD, which are other biochemical indicators related to fatigue recovery, were measured by sacrificing ICR mice orally administered with Yuscapic Acid for 4 weeks. As shown in FIG. 7, the level of FFA and SOD in blood was significantly reduced in the control group not administered with Euscapic Acid compared to the normal group, but in the group orally administered with Yuscapic Acid for 4 weeks, It was confirmed that the levels of FFA and SOD increased, and in particular, the level of FFA increased significantly.

4-3. MDA level check

In Example 2, the blood level of MDA, another biochemical index related to fatigue recovery, was measured by sacrificing ICR mice that had been orally administered with Yuscapic Acid for 4 weeks. As shown in FIG. 8, the control group to which Euscapic Acid was not administered significantly increased the level of MDA in the blood compared to the normal group, but in the group orally administered Yuscapic Acid for 4 weeks, the MDA level decreased. significantly decreased.

[Example 5]

Confirmation of antioxidant enzyme activity in the liver

In Example 2, ICR mice orally administered with Euscapic Acid for 4 weeks were sacrificed to measure the activity of the antioxidant enzymes SOD and catalase in the liver. As shown in FIG. 9, in the control group not administered with Euscapic Acid, SOD and catalase activity in the liver were significantly reduced compared to the normal group, but in the group administered orally with Yuscapic Acid for 4 weeks, SOD and catalase activity were significantly increased.

[Example 6]

Determination of SOD and citrate synthase concentrations in muscle

In Example 2, the intramuscular activity and concentration of antioxidant enzyme SOD and citrate synthase, a biochemical indicator related to anti-fatigue, were measured by sacrificing ICR mice orally administered with Euscapic Acid for 4 weeks. As a result, as shown in FIG. 10, the control group to which Euscapic Acid was not administered showed a significant decrease in SOD activity and a significant decrease in the concentration of citrate synthase compared to the normal group. In the group that orally administered capic acid for 4 weeks, SOD activity significantly increased and the concentration of citrate synthase increased.

[Example 7]

Confirmation of anti-inflammatory activity in blood

In Example 2, the blood levels of TNF-α, IL-6, IL-1β and IL-4, which are indicators related to inflammation, were measured by sacrificing ICR mice orally administered with Euscapic Acid for 4 weeks. As a result, as shown in FIG. 11, the control group to which Euscapic Acid was not administered had higher levels of TNF-α, IL-6, IL-1β, and IL-4 in the blood compared to the normal group. However, the levels of TNF-α, IL-6, IL-1β and IL-4 were all decreased in the group orally administered with Euscapic Acid for 4 weeks, especially IL-6, IL-1β and IL-4. level was significantly decreased.

Based on the above results, Yuscapic acid induces anti-fatigue and fatigue by regulating the sugar production process under physical fatigue, lactic acid metabolism during glycolysis, regulating antioxidant enzymes under oxidative stress, and cytokines increased during exercise. It was confirmed that it was effective in suppression.

Claims (21)

1. A food composition for fatigue recovery, comprising Euscaphic acid or a food chemically acceptable salt thereof.
2. The food composition for recovery from fatigue according to claim 1, wherein the fatigue includes physical fatigue or chronic fatigue.
3. The food composition for recovering from fatigue according to claim 2, wherein the physical fatigue includes muscle fatigue.
4. The food composition for recovering from fatigue according to claim 1, wherein the fatigue recovery effect is induced by an anti-inflammatory or antioxidant effect.
5. The food composition for fatigue recovery according to claim 1, which exhibits any one or more of the following effects from a) to h):

   a) at least one effect selected from the group consisting of reducing lactate dehydrogenase (LDH) activity in blood, reducing blood urea nitrogen (BUN), reducing aspartate aminotransferase (AST) activity, and reducing alanine aminotransferse (ALT) activity;

   b) intramuscular glycogen increasing effect;

   c) any one or more effects selected from the group consisting of reducing blood glucose level, reducing lactate level, reducing cortisol level, and reducing CK (creatine kinase) level;

   d) any one or more effects selected from the group consisting of increasing the level of free fatty acid in the blood and increasing the level of SOD (Superoxide dismutase);

   e) reducing the level of Malondialdehyde (MDA) in the blood;

   f) any one or more effects selected from the group consisting of increased SOD (Superoxide dismutase) activity and increased catalase activity in the liver;

   g) any one or more effects selected from the group consisting of increased intramuscular SOD (Superoxide dismutase) activity and increased citrate synthase activity; and

   h) at least one effect selected from the group consisting of reducing the level of TNF-α in the blood, reducing the level of IL-6, reducing the level of IL-1β and reducing the level of IL-4.
6. According to any one of claims 1 to 5, wherein the food composition is a health functional food composition, a food composition for recovery from fatigue.
7. A pharmaceutical composition for fatigue recovery comprising Euscaphic acid or a pharmaceutically acceptable salt thereof.
8. The pharmaceutical composition for recovery from fatigue according to claim 7, wherein the fatigue includes physical fatigue or chronic fatigue.
9. The pharmaceutical composition for recovery from fatigue according to claim 8, wherein the physical fatigue includes muscle fatigue.
10. The pharmaceutical composition for fatigue recovery according to claim 7, wherein the fatigue recovery effect is induced by anti-inflammatory or antioxidant effects.
11. The pharmaceutical composition for fatigue recovery according to claim 7, which exhibits any one or more of the following effects from a) to h):

    a) at least one effect selected from the group consisting of reducing lactate dehydrogenase (LDH) activity in blood, reducing blood urea nitrogen (BUN), reducing aspartate aminotransferase (AST) activity, and reducing alanine aminotransferse (ALT) activity;

    b) intramuscular glycogen increasing effect;

    c) any one or more effects selected from the group consisting of reducing blood glucose level, reducing lactate level, reducing cortisol level, and reducing CK (creatine kinase) level;

    d) any one or more effects selected from the group consisting of increasing the level of free fatty acid in the blood and increasing the level of SOD (Superoxide dismutase);

    e) reducing the level of Malondialdehyde (MDA) in the blood;

    f) any one or more effects selected from the group consisting of increased SOD (Superoxide dismutase) activity and increased catalase activity in the liver;

    g) any one or more effects selected from the group consisting of increased intramuscular SOD (Superoxide dismutase) activity and increased citrate synthase activity; and

    h) at least one effect selected from the group consisting of reducing the level of TNF-α in the blood, reducing the level of IL-6, reducing the level of IL-1β and reducing the level of IL-4.
12. A method for recovering from fatigue, comprising administering an effective amount of Euscaphic acid, or a food-acceptable salt or pharmaceutically-acceptable salt thereof, to a subject in need thereof.
13. The method of claim 12, wherein the fatigue includes physical fatigue or chronic fatigue.
14. 14. The method of claim 13, wherein the physical fatigue comprises muscle fatigue.
15. The method of claim 12, wherein the fatigue recovery effect is induced by an anti-inflammatory or antioxidant effect.
16. The method of claim 12, which exhibits any one or more of the following a) to h) effects:

    a) at least one effect selected from the group consisting of reducing lactate dehydrogenase (LDH) activity in blood, reducing blood urea nitrogen (BUN), reducing aspartate aminotransferase (AST) activity, and reducing alanine aminotransferse (ALT) activity;

    b) intramuscular glycogen increasing effect;

    c) any one or more effects selected from the group consisting of reducing blood glucose level, reducing lactate level, reducing cortisol level, and reducing CK (creatine kinase) level;

    d) any one or more effects selected from the group consisting of increasing the level of free fatty acid in the blood and increasing the level of SOD (Superoxide dismutase);

    e) reducing the level of Malondialdehyde (MDA) in the blood;

    f) any one or more effects selected from the group consisting of increased SOD (Superoxide dismutase) activity and increased catalase activity in the liver;

    g) any one or more effects selected from the group consisting of increased intramuscular SOD (Superoxide dismutase) activity and increased citrate synthase activity; and

    h) at least one effect selected from the group consisting of reducing the level of TNF-α in the blood, reducing the level of IL-6, reducing the level of IL-1β and reducing the level of IL-4.
17. Use of Euscaphic acid, or a food-acceptable salt or pharmaceutically-acceptable salt thereof, in the manufacture of food or medicine for fatigue recovery.
18. 18. The use according to claim 17, wherein said fatigue comprises physical fatigue or chronic fatigue.
19. 19. The use of claim 18, wherein the physical fatigue comprises muscle fatigue.
20. The use according to claim 17, wherein the fatigue recovery effect is induced by an anti-inflammatory or antioxidant effect.
21. The use according to claim 17, which exhibits any one or more of the following effects a) to h):

    a) at least one effect selected from the group consisting of reducing lactate dehydrogenase (LDH) activity in blood, reducing blood urea nitrogen (BUN), reducing aspartate aminotransferase (AST) activity, and reducing alanine aminotransferse (ALT) activity;

    b) intramuscular glycogen increasing effect;

    c) any one or more effects selected from the group consisting of reducing blood glucose level, reducing lactate level, reducing cortisol level, and reducing CK (creatine kinase) level;

    d) any one or more effects selected from the group consisting of increasing the level of free fatty acid in the blood and increasing the level of SOD (Superoxide dismutase);

    e) reducing the level of Malondialdehyde (MDA) in the blood;

    f) any one or more effects selected from the group consisting of increased SOD (Superoxide dismutase) activity and increased catalase activity in the liver;

    g) any one or more effects selected from the group consisting of increased intramuscular SOD (Superoxide dismutase) activity and increased citrate synthase activity; and

    h) at least one effect selected from the group consisting of reducing the level of TNF-α in the blood, reducing the level of IL-6, reducing the level of IL-1β and reducing the level of IL-4.

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