Anti-fatigue agent

Abstract

To provide an anti-fatigue agent with which the fatigue recovery-promoting effects thereof can be simply and fully received.SOLUTION: An anti-fatigue agent contains S-arylcysteine as an active ingredient.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an anti-fatigue agent. The present invention also relates to an anti-fatigue food or drink, an anti-fatigue drug, a food additive, or a seasoning that utilizes the anti-fatigue agent. [Background technology]

[0002] According to a survey on worker health conditions conducted by the Ministry of Health, Labor and Welfare in fiscal 2002, 72.2% of workers stated that they "get tired from their regular work," confirming that many workers in Japan are aware of fatigue, and this situation has not changed even now in 2019. Given that fatigue is defined as a state of reduced work efficiency, the social loss caused by fatigue is significant, and the development of foods that are effective against fatigue is extremely significant.

[0003] As a food ingredient with anti-fatigue properties, caffeine has long been said to have anti-fatigue effects and is included in energy drinks and the like (Patent Document 1). However, the anti-fatigue effects of caffeine are due to its stimulating effect, and it does not fundamentally relieve fatigue. In addition, due to its stimulating effect, it has the disadvantage that caution is required against excessive intake.

[0004] In recent years, imidazole dipeptides have been found to have anti-fatigue effects, and for example, the anti-fatigue effects of imidazole dipeptides derived from whale meat have been reported (Non-Patent Document 1). However, this report states that the intake amount required to exert the anti-fatigue effect is 400 mg, which is an amount that is difficult to ingest from supplements, etc.

[0005] Garlic is known as a food with anti-fatigue and nutritional tonic effects, and the anti-fatigue effects of garlic extract have been reported (Non-Patent Document 2). This report lists sugars, amino acids, sulfur compounds, etc. as components contained in the extract, but it was not clear which components contributed to the anti-fatigue effects.

[0006] In recent years, black garlic, which is made by heating and aging garlic, has been gaining recognition as a health food, and its use in combination with Korean ginseng as an anti-fatigue food has been reported (Patent Document 2). However, the period of intake in this report was two days, and it has not been confirmed whether it can exert an anti-fatigue effect over the long term.

[0007] In addition, it has been reported that garlic aged by heat using a unique method has an effect of preventing the accumulation of fatigue (Patent Document 3). However, this report states that the intake amount required to exert an anti-fatigue effect is 5g per day as heat-aged garlic extract, which is difficult to take every day. In addition, this report only reports the effect of preventing the accumulation of fatigue, and does not evaluate the effect of heat-aged garlic extract in recovering from fatigue. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Japanese Patent Application Publication No. 09-059161 [Patent Document 2] Patent No. 5601747 [Patent Document 3] JP 2018-70602 A [Non-patent literature]

[0009] [Non-Patent Document 1] Pharmacology and Therapy, 41, p879 [Non-Patent Document 2] Basic and Clinical Studies 20(16) 111-127 Summary of the Invention [Problem to be solved by the invention]

[0010] As mentioned above, the anti-fatigue effects of garlic and other ingredients have been reported in the past, but it has not been clear which specific components are responsible for the anti-fatigue effects, and it has not been possible to easily and fully enjoy the anti-fatigue effects, particularly the effect of promoting recovery from fatigue.

[0011] The main object of the present invention is to provide an anti-fatigue agent that can easily and fully enjoy the effect of promoting recovery from fatigue. Another object of the present invention is to provide an anti-fatigue food or drink, an anti-fatigue drug, a food additive, or a seasoning that utilizes the anti-fatigue agent. [Means for solving the problem]

[0012] The present inventors have conducted extensive research into anti-fatigue components derived from garlic and have found that S-allylcysteine ​​contained in aged garlic has an excellent effect of promoting fatigue recovery. Based on these findings, the present invention was completed through further research.

[0013] That is, the present invention provides the following aspects. Item 1. An anti-fatigue agent whose active ingredient is S-allylcysteine. Item 2. The anti-fatigue agent according to Item 1, wherein the S-allylcysteine ​​is derived from an Allium plant. Item 3. An anti-fatigue agent according to Item 1 or 2, which promotes recovery from fatigue occurring in daily life. Item 4. An anti-fatigue food or drink comprising the anti-fatigue agent according to any one of items 1 to 3. Item 5. An anti-fatigue drug comprising the anti-fatigue agent according to any one of items 1 to 3. Item 6. A food additive or seasoning comprising the anti-fatigue agent according to any one of items 1 to 3. Effect of the Invention

[0014] According to the present invention, it is possible to provide an anti-fatigue agent that can easily and fully enjoy the effect of promoting recovery from fatigue. Furthermore, the present invention can provide an anti-fatigue food or drink, an anti-fatigue medicine, a food additive, or a seasoning that utilizes the anti-fatigue agent. [Brief description of the drawings]

[0015] [Figure 1] 1 is a graph showing the evaluation results of the visual analog scale (VAS) in Test Example 1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] The anti-fatigue agent of the present invention is characterized in that it contains S-allylcysteine ​​as an active ingredient. The anti-fatigue agent of the present invention can exhibit an effect of promoting recovery from fatigue. The anti-fatigue agent of the present invention will be described below.

[0017] As mentioned above, it has been known for a long time that Allium plants such as garlic have fatigue recovery and energy-boosting effects, but the amount of S-allylcysteine ​​contained in Allium plants such as garlic is very small. In contrast, the anti-fatigue agent of the present invention contains S-allylcysteine ​​as an active ingredient, and by taking it, the fatigue recovery promotion effect can be easily and fully enjoyed. The anti-fatigue agent of the present invention is particularly effective as an anti-fatigue agent that promotes fatigue recovery.

[0018] S-allyl cysteine Natural S-allylcysteine ​​generally has a structure represented by the following general formula: [ka]

[0019] The S-allylcysteine ​​contained in the anti-fatigue agent of the present invention may be S-allylcysteine ​​having the above structure, or an optical isomer thereof, or a mixture of the optical isomers.

[0020] The S-allylcysteine ​​contained in the anti-fatigue agent of the present invention may be derived from a plant of the genus Allium or may be chemically synthesized.

[0021] Plants of the Allium genus are not particularly limited, but due to their high content of sulfur-containing amino acids such as alliin, which is a raw material for S-allylcysteine, examples include garlic, onion, wild garlic, Chinese chive, Chinese chive, Japanese chive, yellow ita-kkyo, mountain rakkyo, Nobiru, mountain rakkyo, chives, Scallion, Scallion, Himezo-nike, Shibutsua-satsuki, Shirou-ma-satsuki, Izu-satsuki, tree onion, green onion, scallion, leek, scallion, Shima-rakkyo, shallot, green onion, chive, Yagura-se-ki, and white onion. Among these, from the viewpoint of containing sulfur-containing amino acids such as alliin at high concentrations, garlic (Allium sativum L.), onion (Allium cepa L.), chives (Allium schoenoprasum L.), scallions (Allium chinense G.Don), wild garlic (Allium victorialis subsp. platyphyllum), etc. are preferred, and garlic (Allium sativum L.) is more preferred. S-allylcysteine ​​may be derived from a single type of Allium plant, or may be derived from two or more types of Allium plants.

[0022] As mentioned above, Allium genus plants themselves contain almost no S-allyl cysteine, so Allium genus plants that are not treated to increase S-allyl cysteine ​​cannot be used as the anti-fatigue agent of the present invention.In addition, although S-allyl cysteine ​​is increased in heat-ripened garlic extract, in order to exhibit excellent fatigue recovery promotion effect, it is necessary to take a large amount of heat-ripened garlic extract, and it is difficult to easily and fully enjoy fatigue recovery promotion effect.

[0023] The method for increasing the content of S-allylcysteine ​​contained in Allium plants is not particularly limited, and known methods can be adopted. For example, the content of S-allylcysteine ​​can be efficiently increased by reacting cysteine ​​with alliin contained in Allium plants (Patent No. 5612786). S-allylcysteine ​​can also be increased by coexisting allicin and L-cystine with an alkaline earth metal hydroxide and an alkaline earth metal oxide. An Allium plant in which the content of S-allylcysteine ​​has been increased by such a method can be used as an excellent anti-fatigue agent containing S-allylcysteine ​​as an active ingredient.

[0024] The raw material alliin or allicin is a type of sulfur-containing amino acid, and is widely contained in plants of the Allium genus, such as garlic and onion. Alliin or allicin may be a chemically synthesized product, or may be an industrially processed product such as an extract or purified product of a material containing alliin or allicin. Furthermore, primary processed products such as crushed material or paste containing alliin or allicin may be used.

[0025] The material containing alliin or allicin is not particularly limited, but since it has a high content of alliin or allicin, it is preferable to use Allium plants, Allium plant juice, and Allium plant extracts, etc. In addition, as described below, it is preferable to use Allium plants, Allium plant juice, and Allium plant extracts that maintain the inherent alliinase activity. That is, when using a material containing alliin in the production method of the present invention, it is preferable to use Allium plants, Allium plant juice, and Allium plant extracts that maintain the inherent alliinase. In addition, when using an alliin-containing material in which alliinase is inactivated, it is preferable to mix it with a material having alliiner activity. More than 700 types of Allium plants are known, and any of them may be used as the material as long as they contain alliin or allicin. Specific examples of plants in the Allium genus include garlic, onion, wild garlic, Chinese chive, Chinese chive, Japanese chive, yellow itakyo, mountain scallion, wild lettuce, mountain scallion, chives, chives, Japanese chives, asatsuki, Siberian leek, dwarf Siberian leek, asatsuki, white asatsuki, asatsuki, tree onion, green onion, scallion, leek, scallion, Shimarakkyo, shallot, green onion, chives, Yagura leek, and white onion. Among these, garlic (Allium sativum L.), onion (Allium cepa L.), chives (Allium schoenoprasum L.), scallions (Allium chinense G. Don), and wild garlic (Allium victorialis subsp. platyphyllum) are preferred from the viewpoint of containing high concentrations of sulfur-containing amino acids such as alliin or allicin, and garlic (Allium sativum L.) is more preferred.

[0026] The Allium plant may be subjected to a process such as cutting, crushing, grinding, etc., for the purpose of promoting the production of S-allylcysteine, etc., before being subjected to the next process. The Allium plant cut, crushed, or ground product may be obtained, for example, by cutting, crushing, or grinding the plant using a crusher, mixer, food processor, pulper fisher, or the like. The Allium plant juice may be prepared, for example, by using a filter press, juicer mixer, or the like. The ground product may also be prepared by filtering the ground product using a filter cloth or the like. The Allium plant cut, crushed, ground, or ground product may be diluted or concentrated. Examples of the diluted product include cut, crushed, ground, or ground product of the plant diluted about 1 to 50 times with water. Examples of the concentrated product include cut, crushed, ground, or ground product of the plant concentrated 1 to 100 times by means of freeze concentration, vacuum concentration, or the like. The cut, crushed, ground, or juice of the Allium plant may be frozen. The Allium plant extract can be obtained by extracting the Allium plant or its cut with a solvent such as water.

[0027] By placing the above-mentioned Allium plants and their processed products in an alkaline environment at a temperature of 20°C to 75°C for more than one hour (incubation process), the conversion reaction from alliin to S-allylcysteine ​​progresses, and the content of S-allylcysteine ​​can be increased.

[0028] In the incubation step, from the viewpoint of further improving the production of S-allylcysteine, the pH is preferably 8 or higher, more preferably 10 or higher, and even more preferably 11 or higher.

[0029] The method for adjusting the pH is not particularly limited, and may be, for example, a method of adding an acid component or an alkaline component to an Allium plant in which alliinase has been inactivated. The acid component is not particularly limited, and may be hydrochloric acid. The alkaline component is not particularly limited, and may be an alkaline liquid such as sodium hydroxide or potassium hydroxide. Solids such as alkaline earth metal hydroxides and alkaline earth metal oxides may also be used. The acid component and the alkaline component may each be used alone or in combination of two or more.

[0030] The temperature in the incubation step is preferably about 20°C to 75°C, more preferably about 25°C to 65°C, and even more preferably about 30°C to 60°C. The time for placing in the environment of the incubation step varies depending on the type and amount of the raw material used, but is preferably about 0.1 hours to 48 hours, more preferably about 0.2 hours to 24 hours, and even more preferably about 0.5 hours to 12 hours. The production of S-allylcysteine ​​may be performed with stirring or may be performed by leaving it to stand. The stirring method is not particularly limited, and examples thereof include a method of stirring using a stirring blade, a mixer, a stirrer, etc.

[0031] Furthermore, before, during, or after the incubation step, an enzyme or additive that promotes the production of S-allylcysteine ​​may be mixed in. Furthermore, an enzyme or additive for improving the physical properties or handling of the reaction product may be mixed in so far as it does not impair the production of S-allylcysteine ​​or the stability of the produced S-allylcysteine.

[0032] The enzyme is not particularly limited as long as it promotes the production of S-allylcysteine, and preferably includes enzymes having protease activity, lactase activity, peptidase activity, maceration activity, glutaminase activity, and γ-glutamyltranspeptidase activity. Among these, enzymes whose main activity is glutaminase activity or γ-glutamyltranspeptidase activity are preferred because they are particularly effective in promoting the production of S-allylcysteine.

[0033] Specific examples of enzymes include Amano Enzyme's "Biolacta FN5", "Biolacta N5", "Proleather FG-F", "Protin SD-PC10F", "Protin SD-AY10", "Protin SD-NY10", "Protease M", "Peptidase R", "Pectinase A", "Neurase F3G", "Pancreatin F", "Protease A", "Lipase R", "Lipase A", "Protease P", "Protease N", "Protease S", "Protin AC10F", and "Glutaminase", as well as Kikkoman's "Pectolyase", Kyowa Kasei's "Cellulase TP2 Kyowa", and Godo Shu Seizo's "GODO AGI-EC, Mitsubishi Chemical Foods' "Kokurase", SiberHegner's "Rapidase", Shinnihon Chemical Industry's "Sumiteam AGS-L", "Sumiteam AC-L", "Sumiteam CTS", "Sumiteam CM-G", "Sumiteam KDC", "Sumiteam C6000", "Sumiteam AP", "Sumiteam FP", "Sumiteam LPL", "Sumiteam LP50", "Sumiteam BGT", "Sumiteam RP", "Sumiteam GML", "Sumiteam TG", HBI's "Orienter Examples of the enzyme include "Cellulose 22BF", "Cellulose AC40", "Cellulose HC100", "Cellulose TP25", "Cellulose HC", "Orientase 20A", "Orientase 5BL", "Natto Bacillus Culture Extract NSK-SD" manufactured by Japan Bioscience Laboratories Co., Ltd., "Gamanase" manufactured by Novozymes, "WSCDHCL" manufactured by Peptide Institute, "Pectinase HL", "Cellulase Y-NC", "Cellulase Onozuka RS", "Cellulase Onozuka R-10", and "Macerozyme R-10" manufactured by Yakult Pharmaceutical Co., Ltd. One type of enzyme may be used alone, or two or more types may be used in combination.

[0034] The additive is not particularly limited as long as it has the activity of generating S-allylcysteine, and preferred examples include cysteine, cystine, and glutathione.

[0035] Cysteine ​​is a type of sulfur-containing amino acid, 2-amino-3-sulfanylpropionic acid. As the cysteine, a material containing cysteine, an extract of cysteine ​​extracted from a material containing cysteine, or a purified product thereof may be used. As naturally occurring cysteine, the L-form is widely present, but in addition to the L-form, its optical isomer (D-form) or a mixture of the optical isomers may also be used. In addition, chemically synthesized cysteine ​​or reduced cystine, which will be described later, may also be used.

[0036] Of the above cysteines, from the viewpoint of easy availability, it is preferable to use purified cysteine ​​that is commercially available as a reagent, pharmaceutical ingredient, food ingredient, etc. The material containing cysteine ​​is not particularly limited as long as it contains cysteine, and examples thereof include oats, wheat germ, Brussels sprouts, and broccoli.

[0037] In addition, since cystine has a structure in which two molecules of cysteine ​​are linked via a disulfide bond (-SS-) formed by oxidation of a thiol group (-SH), cysteine ​​obtained by reducing said cystine may be used. In addition, cystine may be cystine (L-form), or an optical isomer (D-form) thereof, or a mixture of the optical isomers.

[0038] L-cystine is generally preferred because purified products that can be used as a reagent, pharmaceutical ingredient, food ingredient, and the like are readily available.

[0039] Cystine is reduced to cysteine ​​when it is coexisted with a compound that lowers the redox potential or a compound that has a reducing effect. Examples of compounds that lower the redox potential include alkaline earth metal hydroxides and alkaline earth metal oxides, and examples of compounds that have a reducing effect include glutathione.

[0040] Glutathione is a tripeptide consisting of three amino acids, glutamic acid, cysteine, and glycine. Foods that contain a large amount of glutathione include beef liver, pork belly, milk, oysters, sardines, Pacific cod, salmon, ark shell, tomato, spinach, broccoli, peas, Brussels sprouts, raw cabbage, kiwi fruit, avocado, rice germ, wheat flour, baker's yeast, yeast, etc., and not only glutathione itself but also all of the above foods containing glutathione can be used. Among them, yeast is preferable from the viewpoint of containing glutathione at a high concentration. As for the form of glutathione, a material containing glutathione may be used as it is, or it may be one that has been subjected to a process such as water extraction, hot water extraction, and purification in order to further increase the concentration of glutathione.

[0041] Glutathione exists in reduced and oxidized forms (two reduced glutathione molecules formed by a disulfide bond), and either can be used, but the reduced form is preferred from the standpoint of reactivity.

[0042] When the enzymes or additives exemplified above are used, they may be used alone or in combination.

[0043] In the present invention, the reaction product with increased S-allylcysteine ​​can be used as an anti-fatigue agent as it is, or the reaction product can be further subjected to at least one of filtration, centrifugation, concentration, extraction, drying, etc., to further increase the content of S-allylcysteine, and can be used as an anti-fatigue agent. In addition, in order to increase the purity of S-allylcysteine ​​in the anti-fatigue agent, a purification step of purifying S-allylcysteine ​​by a normal purification operation such as column chromatography or recrystallization can be performed. Furthermore, the reaction product can be dried by a known drying method such as freeze drying or spray drying to form a solid (powder, granules, etc.). The anti-fatigue agent of the present invention can be suitably used as an anti-fatigue agent for drugs, quasi-drugs, foods and beverages, feed, health foods, etc.

[0044] In addition, in the present invention, the anti-fatigue agent containing S-allylcysteine ​​as an active ingredient can also be suitably used as a physical function recovery agent containing S-allylcysteine ​​as an active ingredient.

[0045] S-allylcysteine ​​content, dosage, and timing of intake The content of S-allylcysteine ​​contained in the anti-fatigue agent of the present invention is preferably 0.0001 g / 100 g or more, more preferably 0.01 g / 100 g or more, and even more preferably 0.10 g / 100 g or more, from the viewpoint of exhibiting an excellent effect of promoting recovery from fatigue. The upper limit of the content of S-allylcysteine ​​contained in the anti-fatigue agent of the present invention is not particularly limited, but is usually about 10 g / 100 g.

[0046] The application amount of the anti-fatigue agent of the present invention may be appropriately set according to the type of product used, the purpose, the expected effect, the application form, etc. For example, the daily intake or administration amount of S-allylcysteine ​​for an adult may be set to 0.0001 to 3 g, preferably 0.0005 to 2 g, and more preferably 0.001 to 1 g. It is preferable to ingest or administer the anti-fatigue agent of the present invention, which contains S-allylcysteine ​​in an amount of preferably 0.0001 g / 100 g or more, more preferably 0.01 g / 100 g or more, and even more preferably 0.10 g / 100 g or more, so that the daily intake or administration amount of S-allylcysteine ​​for an adult is within such range.

[0047] Regarding the timing of taking the anti-fatigue agent of the present invention, it is preferable to take it before an action that causes fatigue (for example, before exercise) in order to exert an excellent effect of promoting recovery from fatigue.

[0048] Anti-fatigue agent uses The anti-fatigue agent of the present invention can regulate the autonomic nervous function to a normal state by the action of S-allylcysteine, and is therefore suitable for use in recovering from fatigue. The anti-fatigue agent of the present invention can promote recovery from fatigue caused in daily life, and can suitably improve the fatigue of, for example, healthy people.

[0049] Usage of anti-fatigue agents The application form of the anti-fatigue agent of the present invention is not particularly limited, and it can be used in any application form, such as oral, transdermal, enteral, transmucosal, intravenous, intraarterial, subcutaneous, or intramuscular. From the viewpoint of exerting the anti-fatigue effect more simply and effectively, however, oral application is preferred.

[0050] The anti-fatigue agent of the present invention can be used in any application form to exert its anti-fatigue effect, and can be used by being blended in various products such as food and beverages, medicines, food additives, seasonings, feed, pet food, etc. As described above, since it is difficult to ingest 5 g of heat-aged garlic extract every day as described in Patent Document 3, it is preferable that the heat-aged garlic extract is not included in the anti-fatigue agent of the present invention, and it is also preferable that the heat-aged garlic extract is not included in the food and beverages containing the anti-fatigue agent of the present invention.

[0051] In addition, the dosage form of the product containing the anti-fatigue agent of the present invention may be any of solid, semi-solid, liquid, etc., and is appropriately set according to the type and use of the product. The product containing the anti-fatigue agent of the present invention may contain additives such as water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, plant extracts, water-soluble polymers, surfactants, metal soaps, alcohols, polyhydric alcohols, pH adjusters, antioxidants, UV inhibitors, preservatives, fragrances, powders, thickeners, pigments, and chelating agents, depending on the form, etc., within the range that does not impair the effects of the present invention. In addition, the product containing the anti-fatigue agent of the present invention may contain other ingredients depending on the form, use, etc., within the range that does not impair the effects of the present invention. Other ingredients include, for example, squalane, niacin, niacinamide, long-chain hyaluronic acid, placenta extract, sorbitol, chitin, chitosan, various plant extracts, citric acid, vitamins A, C, E, P, carotenoids (astaxanthin, β-cryptoxanthin, lycopene, etc.), catechins (shrimp gallocatechin gallate, etc.), polyphenols (anthocyanin, cacao polyphenol, etc.), peptides (imidazole dipeptide, BCAA, etc.), CoQ10, α-lipoic acid, and non-simple amino acids such as aminolevulinic acid, GABA, and theanine. The amounts of these ingredients are not limited as long as they do not impair the effects of the present invention.

[0052] When the anti-fatigue agent of the present invention is used in food and drink, S-allylcysteine ​​is prepared as it is or in combination with other food materials or additives into a desired form, and is provided as an anti-fatigue food and drink that exhibits the desired effect. Such food and drink can be general food and drink, as well as specific health foods, nutritional supplements, functional foods, and foods for the sick. In addition, the anti-fatigue agent of the present invention can be used as a food and drink for fatigue recovery or reduction. The form of these foods and drinks is not particularly limited, but specifically includes main dishes such as bread and noodles; side dishes such as cheese, ham, sausages, and seafood products; beverages such as fruit juice drinks, carbonated drinks, and lactic acid drinks; luxury items such as cookies, cakes, jellies, ice cream, puddings, candies, and yogurt; and supplements such as tablets, granules, powders, capsules, soft capsules, and nutritional drinks. These foods and drinks can be used for the above-mentioned purposes. In addition, the foods for the sick are provided for patients who require treatment for fatigue.

[0053] When the anti-fatigue agent of the present invention is used in food and beverages, the amount of the anti-fatigue agent to be blended in the food and beverage will vary depending on the form of the food and beverage, but for example, the range is 0.0001 to 10% by mass of S-allylcysteine, preferably 0.005 to 5% by mass, and more preferably 0.001 to 1% by mass.

[0054] Furthermore, when the anti-fatigue agent of the present invention is used in the field of food and beverages, the anti-fatigue agent of the present invention can be provided alone or in combination with other ingredients as an anti-fatigue food additive, seasoning, etc. (hereinafter referred to as food additive, etc.) When the anti-fatigue agent of the present invention is used as a food additive, etc., the content of S-allylcysteine ​​in the food additive, etc., the amount of the food additive, etc. added to the food and beverage may be appropriately set so that the above-mentioned content of S-allylcysteine ​​is satisfied in the food and beverage to which the anti-fatigue agent of the present invention is added.

[0055] Furthermore, when the anti-fatigue agent of the present invention is used in a pharmaceutical product, the anti-fatigue agent of the present invention is prepared into a desired form either alone or in combination with other pharmacologically active ingredients, pharma- ceutically acceptable bases, additives, etc., and provided as an anti-fatigue pharmaceutical product that exerts the desired effect. The form of such pharmaceutical products is not particularly limited, but specific examples thereof include oral preparations such as tablets, granules, powders, capsules, soft capsules, and syrups; transdermal or transmucosal preparations such as liquids, ointments, creams, gels, sprays, patches, inhalants, and suppositories; and injections.

[0056] When the anti-fatigue agent of the present invention is used as a pharmaceutical, the blending ratio of the anti-fatigue agent to the pharmaceutical varies depending on the form of the pharmaceutical, etc., but for example, in the case of an oral formulation or an injection, the range of S-allylcysteine ​​is 0.0001 to 10 mass%, preferably 0.0005 to 5 mass%, and more preferably 0.001 to 1 mass%, and in the case of a transdermal or transmucosal formulation, the range of S-allylcysteine ​​is 0.0000001 to 10 mass%, preferably 0.00001 to 10 mass%, and more preferably 0.0001 to 10 mass%.

[0057] When the anti-fatigue agent of the present invention is used in feed or pet food, the anti-fatigue agent of the present invention is prepared into a desired form alone or in combination with other feed ingredients, and provided as feed or pet food that exhibits the desired effect. Examples of feed ingredients used in the feed or pet food include cereals such as corn, wheat, barley, rye, etc.; bran, rice bran, etc.; corn gluten meal, corn jam meal, etc.; animal feeds such as skim milk powder, whey, fish meal, bone meal, etc.; yeasts such as brewer's yeast; calcium phosphate, calcium carbonate, etc.; vitamins; amino acids; sugars, etc.

[0058] When the anti-fatigue agent of the present invention is used as feed or pet food, the blending ratio of the anti-fatigue agent to the feed or pet food will vary depending on the form of the feed or pet food, but can be, for example, in the range of 0.000001 to 10 mass% of S-allylcysteine, preferably 0.0001 to 5 mass%, and more preferably 0.001 to 1 mass%. EXAMPLES

[0059] The present invention will be described in detail below with reference to examples and comparative examples. However, the present invention is not limited to the examples. The measurement methods in the examples and comparative examples are as follows.

[0060] (HPLC analysis conditions) Column: Unison US-C18 5μm (250mm×4.6mm) manufactured by Intact Co., Ltd. Column temperature: 45℃ Mobile phase: [Solution A] 10 mM potassium dihydrogen phosphate buffer (pH 2.5 / phosphoric acid), [Solution B] acetonitrile Flow rate: 1mL / min Measurement wavelength: 210nm

[0061] Example 1 Garlic paste was obtained by adding an equal weight of ion-exchanged water to 250 g of garlic (variety: Fukuchi White) that had been peeled, the base removed, and separated into cloves, and grinding the mixture with a commercially available household juicer (SUNVIGOR Juice Mixer, SML-G22). To 100 parts by mass of garlic paste, 6 parts by mass of magnesium oxide (manufactured by Nacalai Tesque) and 4 parts by mass of L-cystine (manufactured by Protein Chemical) were added, and ion-exchanged water was added in an amount twice the weight of the garlic, heated to 50-55°C, and stirred. Sampling was performed 6 hours after the addition of magnesium oxide and L-cystine, and the content of S-allylcysteine ​​in the sampled liquid was analyzed by HPLC, and 1.00 g / kg of S-allylcysteine ​​(SAC) was produced. After filtering the paste, 38 g of maltodextrin (Matsutani Chemical Industry Co., Ltd.) was added to the filtrate and spray-dried to obtain 140 g of powder. The S-allylcysteine ​​content of this powder was measured and found to be 0.68 g / 100 g.

[0062] Example 2 Using the powder produced in Example 1, soft capsules containing S-allylcysteine ​​were produced, which had the composition of the test food in Table 1. The contents were collected from the soft capsules, and the SAC content in the collected contents was measured. As a result, each capsule contained 1.0 mg of S-allylcysteine ​​(2.0 mg in total for two capsules). The weight of one capsule was 632 mg.

[0063] Comparative Example 1 Soft capsules not containing S-allylcysteine ​​were manufactured having the placebo composition shown in Table 1. The contents were recovered from the soft capsules, and the S-allylcysteine ​​content in the recovered contents was measured. As a result, no S-allylcysteine ​​was detected.

[0064] [Table 1]

[0065] (Test Example 1) The effect of S-allylcysteine ​​in promoting fatigue recovery was evaluated using each test food (test food with a daily intake of two tablets and placebo) shown in Table 1. Specifically, the human test was conducted as a randomized double-blind crossover study. The test food intake period was four weeks, with a four-week washout period between the two test periods. In addition, to eliminate seasonal effects, two groups were set up: one group that took the test food first and one group that took the placebo first.

[0066] In this study, 24 healthy men and women aged 30 to 60 years were randomly assigned to two groups. There were no significant differences between the two groups in terms of gender, age, VAS (fatigue sensation) score at screening, or physical workload intensity (Watts).

[0067] This test was outsourced to Sogo Medical Science Institute Co., Ltd., and was carried out under the guidance and supervision of experts with the approval of the company's ethics committee. On the test day four weeks after intake, a physical workload was carried out. The physical workload was measured in advance by gradually increasing the load on a bicycle ergometer to measure the anaerobic threshold (AT), and participants cycled on the bicycle ergometer for four hours with a target heart rate of 80% of the AT heart rate, and a four-hour recovery period was set after the load had ended.

[0068] Regarding the intensity and amount of exercise, the Ministry of Health, Labor and Welfare's "Guidelines for Exercise for Health Promotion 2006" quantifies the intensity of exercise in "METs" and the amount of exercise "exercise (Ex)" as the MET multiplied by time, and recommends performing vigorous physical activity (exercise / daily activities) with an intensity of 4 METs or more for 23 Ex or more per week. In this test, the amount of exercise was light cycling, with an intensity of 3.0-4.0 METs. The amount of exercise was 12-16 Ex, as it was 4 hours of exercise. This is the amount of exercise equivalent to a round of golf, weeding, and walking a dog for a total of about 2.5-3 hours, which is the amount of exercise that everyone experiences on a daily basis.

[0069] The effect of promoting fatigue recovery was evaluated based on fatigue sensation and autonomic nervous function. Fatigue sensation was evaluated using a visual analog scale (VAS) and was measured at screening, before the exercise stress test, 2 hours after stress, 4 hours after stress, 2 hours after recovery, and 4 hours after recovery. Autonomic nervous function was also evaluated by measuring accelerated pulse waves using an Artet CDN (Umedica Co., Ltd.) and analyzing the frequency of aa intervals before stress, 2 hours after stress, 4 hours after stress, 2 hours after recovery, and 4 hours after recovery.

[0070] <Result 1: Evaluation subjects> Of the 24 subjects, four were excluded from the analysis of efficacy evaluation: one subject dropped out for personal reasons, one subject discontinued the study due to poor health during the physical workload, one subject showed no increase in fatigue on the VAS before and after 4 hours of physical workload, and one subject showed no increase in blood levels of S-allylcysteine, an ingredient involved in anti-fatigue. Thus, 20 subjects were included in the analysis of efficacy evaluation.

[0071] <Result 2: Evaluation of fatigue using a visual analog scale (VAS)> In a loading test conducted on the test day four weeks after intake, the change in VAS from before the start of the loading test was compared. The test food group had a significantly lower sense of fatigue two hours after recovery than the placebo group (Figure 1).

[0072] <Result 3: Autonomic nervous function> In the evaluation of autonomic nervous function, the test food group showed significantly higher LF-MEM and LF-FFT values ​​4 hours after loading, and significantly lower HF-MEM and HF-FFT values ​​4 hours after recovery, compared to the placebo group (Table 2 below: Evaluation of autonomic nervous function (frequency analysis of accelerated pulse wave aa intervals) absolute values, Table 3 below: Evaluation of autonomic nervous function (frequency analysis of accelerated pulse wave aa intervals) changes from visit 4 weeks after ingestion). In addition, in the changes from 4 hours after loading, LF / HF-FFT showed a significant decrease 2 hours after recovery, and HF%-FFT showed a significant increase 4 hours after recovery (Table 4 below: Evaluation of autonomic nervous function (frequency analysis of accelerated pulse wave aa intervals) changes from 4 hours after loading on the test day 4 weeks after ingestion).

[0073] It has been reported that LF mainly reflects sympathetic nervous activity, and HF reflects parasympathetic nervous activity, and that in a state of fatigue, sympathetic nervous activity dominates even during the resting period, as parasympathetic nervous activity does not increase. The test food group was in a state of sympathetic nervous activity dominates, which is favorable for the active period, 4 hours after loading, and furthermore in a state of parasympathetic nervous activity dominates, which is favorable for the resting period, during the recovery period, so it is thought that the intake of the test food adjusted the autonomic nervous function to a state suitable for each situation. In addition, the promotion of recovery from fatigue during the recovery period, as observed by VAS, is thought to be related to the regulating effect of autonomic nervous function.

[0074] [Table 2]

[0075] [Table 3]

[0076] [Table 4]

Claims

1. An anti-fatigue agent containing S-allylcysteine ​​(excluding S-allylcysteine ​​contained in aged garlic or its extract) as an active ingredient.

2. The anti-fatigue agent according to claim 1, wherein the S-allylcysteine ​​is derived from an Allium plant.

3. 3. The anti-fatigue agent according to claim 1 or 2, which promotes recovery from fatigue occurring in daily life.

4. An anti-fatigue food or drink comprising the anti-fatigue agent according to any one of claims 1 to 3.

5. An anti-fatigue drug comprising the anti-fatigue agent according to any one of claims 1 to 3.

6. A food additive comprising the anti-fatigue agent according to any one of claims 1 to 3.

7. A seasoning comprising an anti-fatigue agent described in any one of claims 1 to 3.

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