WO2020179890A1 - Anti-fatigue agent - Google Patents

Anti-fatigue agent Download PDF

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Publication number
WO2020179890A1
WO2020179890A1 PCT/JP2020/009531 JP2020009531W WO2020179890A1 WO 2020179890 A1 WO2020179890 A1 WO 2020179890A1 JP 2020009531 W JP2020009531 W JP 2020009531W WO 2020179890 A1 WO2020179890 A1 WO 2020179890A1
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Prior art keywords
fatigue
allylcysteine
fatigue agent
present
allium
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PCT/JP2020/009531
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French (fr)
Japanese (ja)
Inventor
勝彦 高柳
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株式会社ダイセル
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Priority to JP2021503654A priority Critical patent/JPWO2020179890A1/ja
Publication of WO2020179890A1 publication Critical patent/WO2020179890A1/en

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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17Amino acids, peptides or proteins
    • A23L33/175Amino acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/195Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • A61K31/198Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/896Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8962Allium, e.g. garden onion, leek, garlic or chives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism

Definitions

  • the present invention relates to an anti-fatigue agent.
  • the present invention also relates to foods and drinks for anti-fatigue, pharmaceuticals for anti-fatigue, food additives or seasonings using the anti-fatigue agent.
  • caffeine As a food ingredient with an anti-fatigue effect, caffeine has long been said to have an anti-fatigue effect, and is incorporated into drinks and the like (Patent Document 1).
  • Patent Document 1 the anti-fatigue effect of caffeine is due to the excitatory action and does not fundamentally relieve fatigue.
  • caution is required against excessive intake.
  • Non-Patent Document 1 the amount of intake that exerts an anti-fatigue effect is described as 400 mg, which is a difficult amount to take from supplements and the like.
  • Garlic is known as a food with anti-fatigue and nutritional tonic effects, and the anti-fatigue effect of garlic extract has been reported (Non-Patent Document 2).
  • Non-Patent Document 2 sugars, amino acids, sulfur compounds, etc. are described as the components contained in the extract, but it has not been clarified which component contributes to anti-fatigue.
  • Patent Document 2 black garlic, which is heat-aged garlic, has been widely recognized as a health food, and anti-fatigue foods used in combination with ginseng have been reported.
  • the intake period in this report is 2 days, and it has not been confirmed whether it can exert an anti-fatigue effect over a long period of time.
  • Patent Document 3 garlic that has been heat-aged by a unique method has an effect of preventing the accumulation of fatigue.
  • the intake that exhibits the anti-fatigue effect is described as 5 g per day as the heat-aged garlic extract, and it is difficult to easily ingest daily.
  • the effect of preventing the accumulation of fatigue is reported, and the effect of heat-aged garlic extract on recovery from fatigue has not been evaluated.
  • anti-fatigue effects such as garlic have been reported in the past, but it is not clear which component exerts the anti-fatigue effect, and among the anti-fatigue effects, the promotion of fatigue recovery is particularly promoted. The effect could not be enjoyed easily and sufficiently.
  • the main object of the present invention is to provide an anti-fatigue agent that can easily and sufficiently enjoy the fatigue recovery promoting effect.
  • 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 using the anti-fatigue agent.
  • the present inventors have conducted extensive studies on anti-fatigue components derived from garlic, and found that S-allylcysteine contained in aged garlic exerts an excellent fatigue recovery promoting effect.
  • the present invention is an invention completed by further studying based on these findings.
  • Item 1 An anti-fatigue agent containing S-allylcysteine as an active ingredient.
  • Item 2. The anti-fatigue agent according to Item 1, wherein the S-allylcysteine is derived from a plant belonging to the genus Allium.
  • Item 3. Item 2. The anti-fatigue agent according to Item 1 or 2, which promotes recovery from fatigue that occurs in daily life.
  • Item 4. An anti-fatigue food or drink containing the anti-fatigue agent according to any one of Items 1 to 3.
  • An anti-fatigue drug containing the anti-fatigue agent according to any one of Items 1 to 3.
  • Item 6. Item 4. A food additive or seasoning containing the anti-fatigue agent according to any one of items 1 to 3.
  • the present invention it is possible to provide an anti-fatigue agent that can easily and sufficiently enjoy the effect of promoting fatigue recovery.
  • the present invention can provide foods and drinks for anti-fatigue, pharmaceuticals for anti-fatigue, food additives or seasonings using the anti-fatigue agent.
  • the anti-fatigue agent of the present invention is characterized by containing S-allylcysteine as an active ingredient.
  • the anti-fatigue agent of the present invention can exert an effect of promoting recovery from fatigue.
  • the anti-fatigue agent of the present invention will be described.
  • the anti-fatigue agent of the present invention contains S-allyl cysteine as an active ingredient, and by ingesting it, the fatigue recovery promoting effect can be simply and sufficiently enjoyed.
  • the anti-fatigue agent of the present invention is particularly effective as an anti-fatigue agent that promotes recovery from fatigue.
  • S-allyl cysteine Natural products of S-allyl cysteine generally have a structure represented by the following general formula.
  • the S-allylcysteine contained in the anti-fatigue agent of the present invention may be an optical isomer of S-allylcysteine having the above structure, or may be a mixture of each optical isomer.
  • the S-allylcysteine contained in the anti-fatigue agent of the present invention may be derived from a plant of the genus Allium or the like, or may be chemically synthesized.
  • the plant of the genus Allium is not particularly limited, but since it contains a large amount of sulfur-containing amino acids such as alliin which is a raw material of S-allyl cysteine, garlic, onion, gyoja garlic, juniper, leek, kankeiira, itracchio, kii Itrakyo, Miyamarakkyo, Nobir, Yamarakkyo, Asatsuki, Ezonegi, Himeezonegi, Shibutuasatsuki, Shiroma Asatsuki, Izuasatsuki, Tree Onion, Negi, Wakegi, Riki, Rakkyo, Shimaraguki, Esharot, Ao Negi, Chives Can be mentioned.
  • alliin which is a raw material of S-allyl cysteine, garlic, onion, gyoja garlic, juniper, leek, kankeiira, itracchio, kii Itrakyo, Miyamarakkyo, Nobir, Yamarakky
  • garlic Allium sativum L.
  • onion Allium cepa L.
  • asatsuki Allium schoenoprasum L.
  • lacquer Allium chinense G.Don
  • S-allylcysteine may be derived from one type of plant belonging to the genus Allium, or may be derived from two or more types of plants belonging to the genus Allium.
  • the plants of the genus Allium themselves contain almost no S-allylcysteine
  • the plants of the genus Allium that have not been treated to increase S-allylcysteine are used as the anti-fatigue agent of the present invention. It is not possible.
  • S-allylcysteine is increased in the heat-aged garlic extract, it is necessary to ingest a large amount of the heat-aged garlic extract in order to exert an excellent fatigue recovery promoting effect. It is difficult to enjoy it easily and sufficiently.
  • the method for increasing the content of S-allylcysteine contained in plants of the genus Allium is not particularly limited, and a known method can be adopted.
  • the content of S-allylcysteine can be efficiently increased by allowing cysteine to act on alliin contained in plants of the genus Allium (Patent No. 5612786).
  • S-allylcysteine can also be increased by allowing allicin and L-cystine to coexist with alkaline earth metal hydroxides and alkaline earth metal oxides.
  • Plants of the genus Allium in which the content of S-allylcysteine is increased by such a method can be an excellent anti-fatigue agent containing S-allylcysteine as an active ingredient.
  • Alliin or allicin which is the raw material, is a type of sulfur-containing amino acid, and is widely contained in plants of the genus Allium such as garlic and onion.
  • a chemically synthesized product may be used as a raw material, or an industrially processed product such as an extract or a purified material containing alliin or allicin may be used as a raw material.
  • an industrially processed product such as an extract or a purified material containing alliin or allicin may be used as a raw material.
  • a pulverized product of a material containing alliin or allicin a primary processed product such as a paste may be used.
  • the material containing alliin or allicin is not particularly limited, but since the content of alliin or allicin is high, preferably allium plants, allium plant juices, allium plant extracts, and the like are used. Can be mentioned. As described later, it is desirable to use allium plants, allium plant juices, and allium plant extracts that maintain the intrinsic alliinase activity. That is, when a material containing alliin is used in the production method of the present invention, it is possible to use a plant of the genus Allium, a squeezed juice of a plant of the genus Allium, an extract of a plant of the genus Allium, etc., in which the underlying alliinase is maintained. preferable.
  • an alliin-containing material in which alliinase is inactivated it is preferable to mix it with a material having allyiner activity. More than 700 kinds of plants of the genus Allium are known, and any of those containing alliin or allicin may be used as a material.
  • plants of the genus Allium include garlic, onion, gyoja garlic, chives, leeks, kankei nira, itrakko, kiiitrakkyo, chives, nobil, yamarakyo, chives, leeks, leeks, chives, chives, leeks, chives, leeks, chives, leeks, chives Examples include tree onions, green onions, leeks, leek, rakkyo, shimarakko, eshalot, green onions, chives, yagura onions, and white onions.
  • garlic Allium sativum L.
  • onion Allium cepa L.
  • Asatsuki Allium schoenoprasum L.
  • Rakkyo Allium chinense G.
  • garlic Allium sativum L.
  • onion Allium cepa L.
  • Asatsuki Allium schoenoprasum L.
  • Rakkyo Allium chinense G.
  • garlic Allium sativum L.
  • onion Allium cepa L.
  • Asatsuki Allium schoenoprasum L.
  • Rakkyo Allium chinense G.
  • a plant of the genus Allium may be subjected to treatments such as cutting, crushing and grinding for the purpose of promoting the production of S-allyl cysteine and the like, and then subjected to the next step. Cuts, crushed products, and ground products of plants of the genus Allium are obtained, for example, by cutting, crushing, and grinding the plants using a crusher, a mixer, a food processor, a pulper fisher, or the like.
  • the juice of plants of the genus Allium can be prepared using, for example, a filter press, a juicer mixer, or the like. The juice can also be prepared by filtering the above-mentioned pyroclastic material using a filter cloth or the like.
  • Cuttings, shreds, grinds, and juices of Allium plants may be diluents or concentrates.
  • the diluted product include those obtained by diluting a cut product, a crushed product, a ground product, a juice, or the like of the plant with water about 1 to 50 times.
  • the concentrate include those obtained by concentrating a cut product, a crushed product, a ground product, a juice, or the like of the plant 1 to 100 times by freeze concentration, vacuum concentration, or the like.
  • the cuts, crushed materials, ground products, and squeezed products of Allium plants may be frozen.
  • An extract of a plant of the genus Allium can be obtained by extracting the above-mentioned plant of the genus Allium, the cut product, or the like with a solvent such as water.
  • the above-mentioned plants of the genus Allium and their processed products are placed in an environment of a temperature of 20 ° C. to 75 ° C. for 1 hour or more under alkaline conditions (incubation step), so that the conversion reaction from alliin to S-allylcysteine proceeds. , The content of S-allylcysteine can be increased.
  • the pH is preferably set to 8 or higher, more preferably 10 or higher, and even more preferably 11 or higher.
  • the method for adjusting the pH is not particularly limited, and examples thereof include a method of adding an acid component or an alkaline component to a plant of the genus Allium in which alliinase is inactivated.
  • the acid component is not particularly limited, and examples thereof include hydrochloric acid.
  • the alkaline component is not particularly limited, and examples thereof include alkaline liquids such as sodium hydroxide and potassium hydroxide. Further, solid substances such as alkaline earth metal hydroxide and alkaline earth metal oxide may be used.
  • the acid component and the alkaline component may be used individually by 1 type, or may be used in combination of 2 or more types.
  • the temperature in the incubation step is preferably about 20 ° C. to 75 ° C., more preferably about 25 ° C. to 65 ° C., and further preferably about 30 ° C. to 60 ° C.
  • the time for placing in the environment of the above-mentioned incubation step varies depending on the kind and amount of the raw material used, but is preferably about 0.1 to 48 hours, more preferably 0.2 to 24 hours, and further It is preferably 0.5 to 12 hours.
  • the production of S-allylcysteine may be carried out with stirring or may be carried out with standing still.
  • the stirring method is not particularly limited, and examples thereof include a method of stirring using stirring blades, a mixer, a stirrer, and the like.
  • enzymes and additives that promote the production of S-allylcysteine may be mixed before, during, and after the incubation step.
  • an enzyme or an additive for the purpose of improving the physical properties and handleability of the reaction product may be mixed as long as the production of S-allylcysteine and the stability of the produced S-allylcysteine are not impaired.
  • the enzyme is not particularly limited as long as it promotes the production of S-allylcysteine, and is preferably an enzyme having protease activity, lactase activity, peptidase activity, maceration activity, glutaminase activity, and ⁇ -glutamyl transpeptidase activity. Is mentioned. Among these, an enzyme having glutaminase activity or ⁇ -glutamyltranspeptidase activity as the main activity is preferable because it has a particularly high effect of promoting the production of S-allylcysteine.
  • the enzyme examples include “Violacta FN5", “Violacta N5", “Proleather FG-F”, “Protin SD-PC10F”, “Protin SD-AY10", “Protin SD-NY10”, and “Protin SD-NY10” manufactured by Amano Enzyme.
  • Protease M "peptidase R”, “pectinase A”, “neurase F3G”, “pancreatin F”, “protease A”, “lipase R”, “lipase A”, “protease P”, “protease N”.
  • the additive is not particularly limited as long as it has the activity of producing S-allylcysteine, and preferred examples thereof include cysteine, cystine, and glutathione.
  • Cysteine is a type of sulfur-containing amino acid and is 2-amino-3-sulfanylpropionic acid.
  • cysteine a material containing cysteine, an extract or a purified product of cysteine extracted from the material containing cysteine may be used.
  • the L-form widely exists, but in addition to the L-form, it may be an optical isomer (D-form) thereof or a mixture of each optical isomer. Further, chemically synthesized cysteine may be used, or a reduced cystine described later may be used.
  • cysteines from the viewpoint of availability, it is preferable to use a purified cysteine commercially available as a reagent, a pharmaceutical ingredient, a food ingredient, or the like.
  • 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.
  • cystine is obtained by reducing the cystine because it has a structure in which two molecules of cysteine are linked via a disulfide bond (-SS-) generated by oxidation of a thiol group (-SH). Cysteine may also be used.
  • cystine L-form
  • cystine may be an optical isomer (D-form) thereof, or a mixture of each optical isomer.
  • L-cystine is generally preferred because a purified product that can be used as a reagent, a pharmaceutical ingredient, a food ingredient, etc. is easily available.
  • Cystine is reduced and converted to cysteine by coexisting with a compound that lowers the redox potential or a compound having a reducing action.
  • a compound that lowers the oxidation-reduction potential include alkaline earth metal hydroxides and alkaline earth metal oxides
  • examples of the compound having a reducing action include glutathione.
  • Glutathione is a tripeptide consisting of three amino acids, glutamic acid, cysteine, and glycine.
  • Foods containing large amounts of glutathione include beef liver, pork belly, milk, oysters, sardines, cod, salmon, red shellfish, tomatoes, spinach, broccoli, peas, sprouts, raw cabbage, kiwifruit, avocado, rice germ. , Flour, baker's yeast, yeast, etc., and not only glutathione itself but all the above foods containing glutathione can be used.
  • yeast is preferable from the viewpoint of containing glutathione in a high concentration.
  • a material containing glutathione may be used as it is, or it may be subjected to steps such as water extraction, hot water extraction, and purification in order to further increase the concentration of glutathione.
  • glutathione There are two types of glutathione, a reduced type and an oxidized type (a disulfide bond of two reduced glutathione molecules), and both can be used, but the reduced type is preferable from the viewpoint of reactivity.
  • the reaction product in which S-allylcysteine is increased can be used as it is as an anti-fatigue agent, and the reaction product is further subjected to filtration, centrifugation, concentration, extraction, drying, etc. At least one step may be performed to further increase the content of S-allyl cysteine, and the anti-fatigue agent may be obtained. Further, in order to increase the purity of S-allylcysteine in the anti-fatigue agent, a purification step of purifying S-allylcysteine can also be performed by a normal purification operation such as column chromatography or recrystallization.
  • the reaction product can be dried by a known drying means such as freeze-drying and spray-drying to obtain a solid substance (powder, granules, etc.).
  • the anti-fatigue agent of the present invention preferably uses a reaction mixture containing S-allylcysteine or a purified product of S-allylcysteine as an anti-fatigue agent for pharmaceuticals, quasi-drugs, foods and drinks, feeds, health foods, etc. can do.
  • 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.
  • the content of S-allylcysteine contained in the anti-fatigue agent of the present invention is preferably 0.0001 g from the viewpoint of exerting an excellent fatigue recovery promoting effect. /100 g or more, more preferably 0.01 g/100 g or more, and still more preferably 0.10 g/100 g or more.
  • the upper limit of the content of S-allylcysteine contained in the anti-fatigue agent of the present invention is not particularly limited, but usually about 10 g/100 g can be mentioned.
  • the applied amount of the anti-fatigue agent of the present invention may be appropriately set according to the type of product used, the application, the expected effect, the application form, and the like.
  • the daily intake or dose 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.
  • the daily intake or dose of S-allylcysteine for adults should be within such a range, preferably 0.0001 g / 100 g or more, more preferably 0.01 g / 100 g or more, still more preferably 0.10 g / g. It is preferable to ingest or administer the anti-fatigue agent of the present invention containing a content of S-allylcysteine of 100 g or more.
  • the timing of ingesting the anti-fatigue agent of the present invention it is preferable to ingest it before an action that causes fatigue (for example, before exercise) from the viewpoint of exerting an excellent fatigue recovery promoting effect.
  • the anti-fatigue agent of the present invention can adjust the autonomic nerve function to a normal state by the action of S-allyl cysteine, and thus is preferably used for recovery from fatigue.
  • the anti-fatigue agent of the present invention can promote recovery from fatigue that occurs in daily life, and, for example, can suitably improve fatigue in healthy people.
  • the form of application of the anti-fatigue agent of the present invention is not particularly limited, but may be any of oral, transdermal, transintestinal, transmucosal, transvenous, transarterial, subcutaneous, intramuscular and the like. Although it can be used in an application form, oral application is preferable from the viewpoint of exerting an anti-fatigue effect more easily and effectively.
  • the anti-fatigue agent of the present invention can be used in any application form and exerts an anti-fatigue effect, it is used by blending it in various products such as foods and drinks, pharmaceuticals, food additives, seasonings, feeds, and pet foods. be able to. As described above, it is difficult to ingest 5 g of the heat-aged garlic extract daily as described in Patent Document 3, so that the anti-fatigue agent of the present invention does not include the heat-aged garlic extract. It is preferable that the heat-aged garlic extract is not included in foods and drinks containing the anti-fatigue agent of the present invention.
  • the dosage form of the product containing the anti-fatigue agent of the present invention may be solid, semi-solid, liquid or the like, and is appropriately set according to the type and application of the product.
  • the product containing the anti-fatigue agent of the present invention contains water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, depending on the form and the like, as long as the effects of the present invention are not impaired.
  • Esters, plant extracts, water-soluble polymers, surfactants, metal soaps, alcohols, polyhydric alcohols, pH regulators, antioxidants, UV inhibitors, preservatives, fragrances, powders, thickeners , Dyes, chelating agents and the like may be contained.
  • the product containing the anti-fatigue agent of the present invention may contain other components depending on its form, application, etc., as long as the effects of the present invention are not impaired.
  • Other components 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 , ⁇ -cryptoxanthin, lycopene, etc.), catechins (shrimp galocatechin gallate, etc.), polyphenols (anthocyanin, cacao polyphenols, etc.), peptides (imidazole dipeptide, BCAA, etc.), CoQ10, ⁇ -lipoic acid, and aminolevulin Examples include amino acids that are not simple amino acids, such as acids, GABA, and theanin. These blending amounts are not limited as long as the effects
  • S-allylcysteine is adjusted to a desired form as it is or in combination with other food materials and additive components to obtain the desired effect. It is provided as an item.
  • foods and drinks include general foods and drinks, foods for specified health use, dietary supplements, functional foods, foods for patients, and the like. Further, it can also be used as a food or drink containing the anti-fatigue agent of the present invention for recovering from fatigue or for reducing the feeling of fatigue.
  • the form of these foods and drinks is not particularly limited, but specifically, main dishes such as breads and noodles; side dishes such as cheese, ham, wieners and processed seafood; fruit juice drinks, sparkling drinks, lactic acid drinks and the like.
  • the amount of the anti-fatigue agent blended in the foods and drinks varies depending on the form of the foods and drinks, and for example, S-allylcysteine is 0.0001 to 10.
  • the mass ratio is preferably 0.005 to 5% by mass, more preferably 0.001 to 1% by mass.
  • the anti-fatigue agent of the present invention when used in the field of food and drink, the anti-fatigue agent of the present invention alone or in combination with other ingredients such as food additives and seasonings for anti-fatigue (hereinafter referred to as It can also be provided as a food additive, etc.).
  • the anti-fatigue agent of the present invention when used as a food additive, the content of S-allylcysteine in the food additive, the amount of the food additive added to the food or drink, and the like are the food and drink to be added. It may be appropriately set so that S-allylcysteine can satisfy the above-mentioned content in the product.
  • the anti-fatigue agent of the present invention may be used alone or in combination with other pharmacologically active ingredients, pharmaceutically acceptable bases, additive ingredients, etc. in a desired form. It is provided as an anti-fatigue drug that exerts the desired effect.
  • the form of such a drug is not particularly limited, but specifically, an orally-administered preparation such as a tablet, a granule, a powder, a capsule, a soft capsule, or a syrup; a liquid, an ointment, a cream, or a gel.
  • Preparations for percutaneous or transmucosal administration such as sprays, patches, inhalants, suppositories; injections and the like.
  • S -Allylcysteine is in the range of 0.0001 to 10% by mass, preferably 0.0005 to 5% by mass, and more preferably 0.001 to 1% by mass, in the case of transdermal or transmucosal preparations.
  • S-allylcysteine is 0.000000001 to 10% by mass, preferably 0.00001 to 10% by mass, and more preferably 0.0001 to 10% by mass can be mentioned.
  • the anti-fatigue agent of the present invention can be adjusted to a desired form alone or in combination with other feed components to obtain the desired effect.
  • feed ingredients used in the feed or pet food include, for example, grains such as corn, wheat, barley, and rye; bran such as bran and rice bran; corn gluten meal, meal such as corn jammeal; skim milk powder, Animal feeds such as whey, fish meal and bone meal; yeasts such as beer yeast; calcium such as calcium phosphate and calcium carbonate; vitamins; amino acids; sugars and the like.
  • the mixing ratio of the anti-fatigue agent to the feed or pet food varies depending on the form of the feed or pet food, and for example, S-allylcysteine. Is 0.000001 to 10% by mass, preferably 0.0001 to 5% by mass, and more preferably 0.001 to 1% by mass.
  • Example 1 Peel and remove the pedestal, add equal weight of ion-exchanged water to 250 g of garlic (variety name: Fukuchi White) divided into scales, and grind with a commercially available household juicer (SUNVIGOR juice mixer, SML-G22). And got a garlic paste.
  • garlic paste 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) are added, and ion-exchanged water is doubled by weight of garlic. The amount was added, and the mixture was heated to 50 to 55 ° C. and stirred.
  • Example 2 Using the powder prepared in Example 1, S-allyl cysteine-containing soft capsules having the composition of the test meal shown in Table 1 were prepared. The content was recovered from the soft capsules, and the SAC content in the recovered material was measured. As a result, 1.0 mg of S-allylcysteine was contained per particle (2.0 mg in total of 2 particles). The weight of one capsule is 632 mg.
  • Test Example 1 Using each of the test meals shown in Table 1 (a test meal having a daily intake of 2 tablets and a placebo), the fatigue recovery promoting effect of S-allyl cysteine was evaluated. Specifically, the human study was conducted as a randomized, double-blind, crossover study. The test food intake period was 4 weeks, and a washout period of 4 weeks was provided between the two test periods. In addition, in order to eliminate the seasonal effect, two groups were set, a group that first took the test meal and a group that first took the placebo.
  • This test was outsourced to the Institute of Medical Sciences Co., Ltd., and was conducted under the guidance and supervision of experts with the approval of the company's ethics committee.
  • Four weeks after ingestion a physical workload was performed on the day of the examination.
  • the anoxic work threshold (AT: Anaerobic Threshold) was measured in advance by gradually increasing the load of the bicycle ergometer, and a bicycle ergometer rowing was performed for 4 hours with 80% of the heart rate at AT as the target heart rate. After the load was completed, a recovery period of 4 hours was set.
  • the fatigue recovery promoting effect was evaluated for fatigue and autonomic nervous function.
  • Fatigue was evaluated on a visual analog scale (VAS) and measured during screening, before loading, 2 hours after loading, 4 hours after loading, 2 hours after recovery, and 4 hours after recovery.
  • VAS visual analog scale
  • the acceleration pulse wave was measured using Altet CDN (Umedica Co., Ltd.) before loading, 2 hours after loading, 4 hours after loading, 2 hours after recovery, and 4 hours after recovery.
  • Autonomic nerve function was evaluated by frequency analysis at a intervals.
  • LF mainly reflects sympathetic nerve activity and HF reflects parasympathetic nerve activity, and in a fatigued state, parasympathetic nerve activity does not increase even during the resting period, resulting in a predominant state of sympathetic nerve activity.
  • the test diet group was in a state of predominant sympathetic nerve activity in the active phase after 4 hours of loading, and was in a state of predominant parasympathetic nerve activity in the resting phase in the recovery phase. It is considered that the state of autonomic nervous function is adjusted to suit the situation. In addition, it is considered that the promotion of recovery of the feeling of fatigue during the recovery period, which is observed in VAS, is related to the regulatory action of autonomic nerve function.

Abstract

Provided is an anti-fatigue agent with which the fatigue recovery-promoting effects thereof can be simply and fully received. The anti-fatigue agent contains S-arylcysteine as an active ingredient.

Description

抗疲労剤Anti-fatigue agent
 本発明は、抗疲労剤に関する。また、本発明は、当該抗疲労剤を利用した、抗疲労用飲食品、抗疲労用医薬品、食品添加物又は調味料に関する。 The present invention relates to an anti-fatigue agent. The present invention also relates to foods and drinks for anti-fatigue, pharmaceuticals for anti-fatigue, food additives or seasonings using the anti-fatigue agent.
 厚生労働省が平成14年度に実施した労働者健康状況調査によると、「普段の仕事で疲れる」とする労働者は72.2%にのぼり、日本において多くの労働者が疲労を自覚していることが確認され、平成31年の現在においてもこの状況は変わっていない。疲労は作業能率の減退状態と定義されることからも、疲労に起因した社会的損失は大きく、疲労に効果のある食品を開発することの意義は非常に大きい。 According to the Worker Health Survey conducted by the Ministry of Health, Labor and Welfare in 2002, 72.2% of the workers said that they were "tired from their daily work", and many workers in Japan are aware of their fatigue. Has been confirmed, and this situation has not changed even as of 2019. Since fatigue is defined as a state in which work efficiency declines, the social loss caused by fatigue is large, and the significance of developing food products that are effective for fatigue is extremely significant.
 抗疲労作用のある食品成分としては、古くから、カフェインには抗疲労効果があるといわれ、ドリンク剤等に配合されている(特許文献1)。しかしカフェインの抗疲労効果は興奮作用によるものであり、根本的に疲労を回復させるものではない。またその興奮作用から、過剰な摂取に対する注意が必要という欠点がある。 As a food ingredient with an anti-fatigue effect, caffeine has long been said to have an anti-fatigue effect, and is incorporated into drinks and the like (Patent Document 1). However, the anti-fatigue effect of caffeine is due to the excitatory action and does not fundamentally relieve fatigue. In addition, due to its excitatory effect, there is a drawback that caution is required against excessive intake.
 また、近年ではイミダゾールジペプチドに抗疲労効果が発見され、例えば鯨肉由来のイミダゾールジペプチドの抗疲労効果が報告されている(非特許文献1)。しかし本報告では抗疲労効果を発揮する摂取量は400mgと記載されており、サプリメント等から摂取するには困難な量である。 Further, in recent years, an anti-fatigue effect has been discovered for imidazole dipeptide, and for example, an anti-fatigue effect of whale meat-derived imidazole dipeptide has been reported (Non-Patent Document 1). However, in this report, the amount of intake that exerts an anti-fatigue effect is described as 400 mg, which is a difficult amount to take from supplements and the like.
 抗疲労や滋養強壮効果のある食品としては、にんにくが知られており、にんにく抽出液の抗疲労効果を報告している(非特許文献2)。この報告では抽出液に含まれる成分として糖類、アミノ酸類、硫黄化合物などを記載しているが、どの成分が抗疲労に寄与しているかは明らかになっていなかった。 Garlic is known as a food with anti-fatigue and nutritional tonic effects, and the anti-fatigue effect of garlic extract has been reported (Non-Patent Document 2). In this report, sugars, amino acids, sulfur compounds, etc. are described as the components contained in the extract, but it has not been clarified which component contributes to anti-fatigue.
 また、近年、にんにくを加熱熟成させた黒にんにくが健康食品として認知を拡げており、高麗人参と併用した抗疲労食品が報告されている(特許文献2)。しかしながら、この報告での摂取期間は2日であり、長期に渡って抗疲労効果を発揮しうるものかは確認されていない。 In recent years, black garlic, which is heat-aged garlic, has been widely recognized as a health food, and anti-fatigue foods used in combination with ginseng have been reported (Patent Document 2). However, the intake period in this report is 2 days, and it has not been confirmed whether it can exert an anti-fatigue effect over a long period of time.
 また、にんにくを独自の方法で加熱熟成させたものに疲労感の蓄積予防効果が報告されている(特許文献3)。しかしながら、本報告では抗疲労効果を発揮する摂取量は、加熱熟成ニンニクエキスとして1日5gと記載されており、毎日、簡便に摂取することは困難である。また、本報告では、疲労感の蓄積予防効果が報告されているに過ぎず、加熱熟成ニンニクエキスについて、疲労からの回復させる効果があることについて評価されていない。 In addition, it has been reported that garlic that has been heat-aged by a unique method has an effect of preventing the accumulation of fatigue (Patent Document 3). However, in this report, the intake that exhibits the anti-fatigue effect is described as 5 g per day as the heat-aged garlic extract, and it is difficult to easily ingest daily. Moreover, in this report, only the effect of preventing the accumulation of fatigue is reported, and the effect of heat-aged garlic extract on recovery from fatigue has not been evaluated.
特開平09-059161号公報Japanese Patent Laid-Open No. 09-059161 特許第5601747号Patent No. 5601747 特開2018-70602号公報Japanese Patent Laid-Open No. 2018-70602
 前記の通り、従来、にんにくなどの抗疲労効果が報告されているが、具体的にどの成分が抗疲労効果を発揮しているのかが明らかではなく、また、抗疲労効果の中でも特に疲労回復促進効果を簡便且つ十分に享受することはできなかった。 As mentioned above, anti-fatigue effects such as garlic have been reported in the past, but it is not clear which component exerts the anti-fatigue effect, and among the anti-fatigue effects, the promotion of fatigue recovery is particularly promoted. The effect could not be enjoyed easily and sufficiently.
 本発明は、疲労回復促進効果を簡便且つ十分に享受し得る抗疲労剤を提供することを主な目的とする。また、本発明は、当該抗疲労剤を利用した、抗疲労用飲食品、抗疲労用医薬品、食品添加物又は調味料を提供することも目的とする。 The main object of the present invention is to provide an anti-fatigue agent that can easily and sufficiently enjoy the fatigue recovery promoting effect. 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 using the anti-fatigue agent.
 本発明者等は、にんにくに由来する抗疲労成分について鋭意検討を重ねたところ、熟成にんにく中に含まれるS-アリルシステインが、優れた疲労回復促進効果を発揮することを見出した。本発明は、これらの知見に基づいて、さらに検討を重ねることにより完成された発明である。 The present inventors have conducted extensive studies on anti-fatigue components derived from garlic, and found that S-allylcysteine contained in aged garlic exerts an excellent fatigue recovery promoting effect. The present invention is an invention completed by further studying based on these findings.
 すなわち、本発明は、下記に掲げる態様の発明を提供する。
項1. S-アリルシステインを有効成分とする、抗疲労剤。
項2. 前記S-アリルシステインがアリウム属植物に由来する、項1に記載の抗疲労剤。
項3. 日常生活で生じる疲労の回復を促進する、項1又は2に記載の抗疲労剤。
項4. 項1~3のいずれか1項に記載の抗疲労剤を含む、抗疲労用飲食品。
項5. 項1~3のいずれか1項に記載の抗疲労剤を含む、抗疲労用医薬品。
項6. 項1~3のいずれか1項に記載の抗疲労剤を含む、食品添加物又は調味料。
That is, the present invention provides the inventions of the following aspects.
Item 1. An anti-fatigue agent containing S-allylcysteine as an active ingredient.
Item 2. Item 2. The anti-fatigue agent according to Item 1, wherein the S-allylcysteine is derived from a plant belonging to the genus Allium.
Item 3. Item 2. The anti-fatigue agent according to Item 1 or 2, which promotes recovery from fatigue that occurs in daily life.
Item 4. An anti-fatigue food or drink containing the anti-fatigue agent according to any one of Items 1 to 3.
Item 5. An anti-fatigue drug containing the anti-fatigue agent according to any one of Items 1 to 3.
Item 6. Item 4. A food additive or seasoning containing the anti-fatigue agent according to any one of items 1 to 3.
 本発明によれば、疲労回復促進効果を簡便且つ十分に享受し得る抗疲労剤を提供することができる。また、本発明は、当該抗疲労剤を利用した、抗疲労用飲食品、抗疲労用医薬品、食品添加物又は調味料を提供することができる。 According to the present invention, it is possible to provide an anti-fatigue agent that can easily and sufficiently enjoy the effect of promoting fatigue recovery. In addition, the present invention can provide foods and drinks for anti-fatigue, pharmaceuticals for anti-fatigue, food additives or seasonings using the anti-fatigue agent.
試験例1におけるビジュアルアナログスケール(VAS)の評価結果を示すグラフである。It is a graph which shows the evaluation result of the visual analog scale (VAS) in Test Example 1.
 本発明の抗疲労剤は、S-アリルシステインを有効成分とすることを特徴とする。本発明の抗疲労剤は、疲労回復促進効果を発揮することができる。以下、本発明の抗疲労剤について説明する。 The anti-fatigue agent of the present invention is characterized by containing S-allylcysteine as an active ingredient. The anti-fatigue agent of the present invention can exert an effect of promoting recovery from fatigue. Hereinafter, the anti-fatigue agent of the present invention will be described.
 前述の通り、古くから、ニンニク等のアリウム属の植物には、疲労回復効果や精力向上効果があることなどが知られていたが、ニンニク等のアリウム属の植物に含まれるS-アリルシステインの含有量はごく微量である。これに対して、本発明の抗疲労剤は、S-アリルシステインを有効成分として含んでおり、これを摂取することで疲労回復促進効果を簡便且つ十分に享受し得る。本発明の抗疲労剤は、疲労回復を促進する抗疲労剤として特に有効である。 As mentioned above, it has long been known that plants of the genus Allium such as garlic have a fatigue recovery effect and an effect of improving energy, but S-allylcysteine contained in plants of the genus Allium such as garlic The content is very small. On the other hand, the anti-fatigue agent of the present invention contains S-allyl cysteine as an active ingredient, and by ingesting it, the fatigue recovery promoting effect can be simply and sufficiently enjoyed. The anti-fatigue agent of the present invention is particularly effective as an anti-fatigue agent that promotes recovery from fatigue.
S-アリルシステイン
 S-アリルシステインの天然物は、一般に、下記一般式で示される構造を有する。
Figure JPOXMLDOC01-appb-C000001
S-allyl cysteine Natural products of S-allyl cysteine generally have a structure represented by the following general formula.
Figure JPOXMLDOC01-appb-C000001
 本発明の抗疲労剤に含まれるS-アリルシステインは、上記構造を有するS-アリルシステインの他、これの光学異性体であってもよいし、各光学異性体の混合物であってもよい。 The S-allylcysteine contained in the anti-fatigue agent of the present invention may be an optical isomer of S-allylcysteine having the above structure, or may be a mixture of each optical isomer.
 本発明の抗疲労剤に含まれるS-アリルシステインは、アリウム属の植物等に由来するものであってもよいし、化学合成されたものであってもよい。 The S-allylcysteine contained in the anti-fatigue agent of the present invention may be derived from a plant of the genus Allium or the like, or may be chemically synthesized.
 アリウム属の植物としては、特に制限されないが、S-アリルシステインの原料となるアリインなどの含硫アミノ酸の含有量が多いことから、ニンニク、タマネギ、ギョウジャニンニク、ヒメニラ、ニラ、カンケイニラ、イトラッキョウ、キイイトラッキョウ、ミヤマラッキョウ、ノビル、ヤマラッキョウ、アサツキ、エゾネギ、ヒメエゾネギ、シブツアサツキ、シロウマアサツキ、イズアサツキ、ツリーオニオン、ネギ、ワケギ、リーキ、ラッキョウ、シマラッキョウ、エシャロット、青ネギ、チャイブ、ヤグラネギ、白ネギなどが挙げられる。これらの中でも、アリインなどの含硫アミノ酸を高濃度に含む観点から、ニンニク(Allium sativum L.)、タマネギ(Allium cepa L.)、アサツキ(Allium schoenoprasum L.)、ラッキョウ(Allium chinense G.Don)、ギョウジャニンニク(Allium victorialis subsp. platyphyllum)などが好ましく、ニンニク(Allium sativum L.)がより好ましい。S-アリルシステインは、1種類単独のアリウム属の植物に由来していてもよいし、2種類以上のアリウム属の植物に由来していてもよい。 The plant of the genus Allium is not particularly limited, but since it contains a large amount of sulfur-containing amino acids such as alliin which is a raw material of S-allyl cysteine, garlic, onion, gyoja garlic, juniper, leek, kankeiira, itracchio, kii Itrakyo, Miyamarakkyo, Nobir, Yamarakkyo, Asatsuki, Ezonegi, Himeezonegi, Shibutuasatsuki, Shiroma Asatsuki, Izuasatsuki, Tree Onion, Negi, Wakegi, Riki, Rakkyo, Shimaraguki, Esharot, Ao Negi, Chives Can be mentioned. Among them, garlic (Allium sativum L.), onion (Allium cepa L.), asatsuki (Allium schoenoprasum L.), and lacquer (Allium chinense G.Don) from the viewpoint of containing sulfur-containing amino acids such as alliin in a high concentration. , Gyojaninnik (Allium victorialis subsp. Platyphyllum) and the like are preferable, and garlic (Allium sativum L.) is more preferable. S-allylcysteine may be derived from one type of plant belonging to the genus Allium, or may be derived from two or more types of plants belonging to the genus Allium.
 前述の通り、アリウム属の植物自体には、S-アリルシステインはほとんど含まれていないため、S-アリルシステインを増加させる処理を施していないアリウム属の植物は、本発明の抗疲労剤とすることはできない。また、加熱熟成ニンニクエキスでは、S-アリルシステインが増加されているが、優れた疲労回復促進効果を発揮するためには、加熱熟成ニンニクエキスを多量に摂取する必要があり、疲労回復促進効果を簡便且つ十分に享受することは困難である。 As described above, since the plants of the genus Allium themselves contain almost no S-allylcysteine, the plants of the genus Allium that have not been treated to increase S-allylcysteine are used as the anti-fatigue agent of the present invention. It is not possible. In addition, although S-allylcysteine is increased in the heat-aged garlic extract, it is necessary to ingest a large amount of the heat-aged garlic extract in order to exert an excellent fatigue recovery promoting effect. It is difficult to enjoy it easily and sufficiently.
 アリウム属の植物に含まれるS-アリルシステインの含有量を増加させる方法としては、特に制限されず、公知の方法を採用することができる。例えばアリウム属の植物に含まれるアリインにシステインを作用させることでS-アリルシステインの含有量を効率的に増加させることができる(特許第5612786号)。またアリシンと、L-シスチンとを、アルカリ土類金属水酸化物及びアルカリ土類金属酸化物と共存させることでもS-アリルシステインを増加させることができる。このような方法によりS-アリルシステインの含有量が増加されたアリウム属の植物は、S-アリルシステインを有効成分とする優れた抗疲労剤とすることができる。 The method for increasing the content of S-allylcysteine contained in plants of the genus Allium is not particularly limited, and a known method can be adopted. For example, the content of S-allylcysteine can be efficiently increased by allowing cysteine to act on alliin contained in plants of the genus Allium (Patent No. 5612786). S-allylcysteine can also be increased by allowing allicin and L-cystine to coexist with alkaline earth metal hydroxides and alkaline earth metal oxides. Plants of the genus Allium in which the content of S-allylcysteine is increased by such a method can be an excellent anti-fatigue agent containing S-allylcysteine as an active ingredient.
 原料となるアリインまたはアリシンとは、含硫アミノ酸の一種であり、例えば、ニンニク、タマネギなどのアリウム属の植物に広く含まれている。アリインまたはアリシンとしては化学合成物を原料として用いてもよいし、アリインまたはアリシンを含む素材の抽出物、精製物といった工業的加工物などを原料として用いてもよい。さらに、アリインまたはアリシンを含む素材の粉砕物、ペーストなどの一次加工物を用いてもよい。 Alliin or allicin, which is the raw material, is a type of sulfur-containing amino acid, and is widely contained in plants of the genus Allium such as garlic and onion. As alliin or allicin, a chemically synthesized product may be used as a raw material, or an industrially processed product such as an extract or a purified material containing alliin or allicin may be used as a raw material. Further, a pulverized product of a material containing alliin or allicin, a primary processed product such as a paste may be used.
 アリインまたはアリシンを含む素材としては、特に制限されないが、アリインまたはアリシンの含有量が多いことから、好ましくはアリウム属の植物、アリウム属の植物の搾汁、及びアリウム属の植物の抽出物などが挙げられる。なお、アリウム属の植物、アリウム属の植物の搾汁、及びアリウム属の植物の抽出物は、後述の通り、内在するアリイナーゼ活性が維持されたもの用いることが望ましい。すなわち、本発明の製造方法において、アリインを含む素材を用いる場合、内在するアリイナーゼが維持された、アリウム属の植物、アリウム属の植物の搾汁、アリウム属の植物の抽出物などを用いることが好ましい。またアリイナーゼが不活化されたアリイン含有素材用いる場合には、アリイナー活性有する素材と混合することが好ましい。アリウム属の植物としては、700種類以上が知られており、アリインまたはアリシンを含むものであればいずれを素材として用いてもよい。アリウム属の植物の具体例としては、ニンニク、タマネギ、ギョウジャニンニク、ヒメニラ、ニラ、カンケイニラ、イトラッキョウ、キイイトラッキョウ、ミヤマラッキョウ、ノビル、ヤマラッキョウ、アサツキ、エゾネギ、ヒメエゾネギ、シブツアサツキ、シロウマアサツキ、イズアサツキ、ツリーオニオン、ネギ、ワケギ、リーキ、ラッキョウ、シマラッキョウ、エシャロット、青ネギ、チャイブ、ヤグラネギ、白ネギなどが挙げられる。これらの中でも、アリインまたはアリシンなどの含硫アミノ酸を高濃度に含む観点から、ニンニク(Allium sativum L.)、タマネギ(Allium cepa L.)、アサツキ(Allium schoenoprasum L.)、ラッキョウ(Allium chinense G.Don)、ギョウジャニンニク(Allium victorialis subsp. platyphyllum)などが好ましく、ニンニク(Allium sativum L.)がより好ましい。 The material containing alliin or allicin is not particularly limited, but since the content of alliin or allicin is high, preferably allium plants, allium plant juices, allium plant extracts, and the like are used. Can be mentioned. As described later, it is desirable to use allium plants, allium plant juices, and allium plant extracts that maintain the intrinsic alliinase activity. That is, when a material containing alliin is used in the production method of the present invention, it is possible to use a plant of the genus Allium, a squeezed juice of a plant of the genus Allium, an extract of a plant of the genus Allium, etc., in which the underlying alliinase is maintained. preferable. When an alliin-containing material in which alliinase is inactivated is used, it is preferable to mix it with a material having allyiner activity. More than 700 kinds of plants of the genus Allium are known, and any of those containing alliin or allicin may be used as a material. Specific examples of plants of the genus Allium include garlic, onion, gyoja garlic, chives, leeks, kankei nira, itrakko, kiiitrakkyo, chives, nobil, yamarakyo, chives, leeks, leeks, chives, chives, leeks, chives, leeks, chives Examples include tree onions, green onions, leeks, leek, rakkyo, shimarakko, eshalot, green onions, chives, yagura onions, and white onions. Among these, garlic (Allium sativum L.), onion (Allium cepa L.), Asatsuki (Allium schoenoprasum L.), and Rakkyo (Allium chinense G.) from the viewpoint of containing sulfur-containing amino acids such as alliin or allicin in a high concentration. Don), gyoja garlic (Allium victorialis subsp. platyphyllum) and the like are preferable, and garlic (Allium sativum L.) is more preferable.
 アリウム属の植物は、S-アリルシステインの生成を促進することなどを目的として、切断、破砕、磨砕等の処理をしてから、次工程に供してもよい。アリウム属の植物の切断物、破砕物、磨砕物は、例えば、当該植物をクラッシャー、ミキサー、フードプロセッサー、パルパーフィッシャーなどを用いて切断、破砕、磨砕することによって得られる。また、アリウム属の植物の搾汁は、例えばフィルタープレス、ジューサーミキサーなどを用いて調製することができる。搾汁は、上記磨砕物を、濾布などを用いて濾過することによっても調製することができる。アリウム属の植物の切断物、破砕物、磨砕物、及び搾汁は、希釈物または濃縮物であってもよい。希釈物としては、例えば、当該植物の切断物、破砕物、磨砕物、搾汁などを水で1~50倍程度に希釈したものが挙げられる。また、濃縮物としては、例えば、当該植物の切断物、破砕物、磨砕物、搾汁などを凍結濃縮、減圧濃縮などの手段によって1~100倍に濃縮したものなどが挙げられる。アリウム属の植物の切断物、破砕物、磨砕物、搾汁は、冷凍したものであってもよい。アリウム属の植物の抽出物は、前述のアリウム属の植物や当該切断物等を、例えば水などの溶媒により抽出することにより得ることができる。 A plant of the genus Allium may be subjected to treatments such as cutting, crushing and grinding for the purpose of promoting the production of S-allyl cysteine and the like, and then subjected to the next step. Cuts, crushed products, and ground products of plants of the genus Allium are obtained, for example, by cutting, crushing, and grinding the plants using a crusher, a mixer, a food processor, a pulper fisher, or the like. In addition, the juice of plants of the genus Allium can be prepared using, for example, a filter press, a juicer mixer, or the like. The juice can also be prepared by filtering the above-mentioned pyroclastic material using a filter cloth or the like. Cuttings, shreds, grinds, and juices of Allium plants may be diluents or concentrates. Examples of the diluted product include those obtained by diluting a cut product, a crushed product, a ground product, a juice, or the like of the plant with water about 1 to 50 times. Examples of the concentrate include those obtained by concentrating a cut product, a crushed product, a ground product, a juice, or the like of the plant 1 to 100 times by freeze concentration, vacuum concentration, or the like. The cuts, crushed materials, ground products, and squeezed products of Allium plants may be frozen. An extract of a plant of the genus Allium can be obtained by extracting the above-mentioned plant of the genus Allium, the cut product, or the like with a solvent such as water.
 上記のアリウム属の植物およびその加工物は、アルカリ性条件化で温度20℃~75℃の環境下に1時間以上置く(インキュベート工程)ことで、アリインからS-アリルシステインへの変換反応が進行し、S-アリルシステインの含有量を増加させることができる。 The above-mentioned plants of the genus Allium and their processed products are placed in an environment of a temperature of 20 ° C. to 75 ° C. for 1 hour or more under alkaline conditions (incubation step), so that the conversion reaction from alliin to S-allylcysteine proceeds. , The content of S-allylcysteine can be increased.
 インキュベート工程において、S-アリルシステインの生成をより一層向上させる観点から、pHを8以上にすることが好ましく、更に好ましくは10以上、より好ましくは11以上とすることが挙げられる。 In the incubation step, from the viewpoint of further improving the production of S-allyl cysteine, the pH is preferably set to 8 or higher, more preferably 10 or higher, and even more preferably 11 or higher.
 pHを調整する方法としては特に制限されないが、例えば、酸成分またはアルカリ成分を、アリイナーゼを失活させたアリウム属の植物に添加する方法などが挙げられる。酸成分としては、特に制限されず、塩酸などが挙げられる。また、アルカリ成分としては、特に制限されず、水酸化ナトリウム、水酸化カリウムなどのアルカリ性液体が挙げられる。またアルカリ土類金属水酸化物及びアルカリ土類金属酸化物などの固形物を用いてもよい。酸成分及びアルカリ成分は、それぞれ、1種類単独で使用してもよいし、2種類以上を組み合わせて使用してもよい。 The method for adjusting the pH is not particularly limited, and examples thereof include a method of adding an acid component or an alkaline component to a plant of the genus Allium in which alliinase is inactivated. The acid component is not particularly limited, and examples thereof include hydrochloric acid. The alkaline component is not particularly limited, and examples thereof include alkaline liquids such as sodium hydroxide and potassium hydroxide. Further, solid substances such as alkaline earth metal hydroxide and alkaline earth metal oxide may be used. The acid component and the alkaline component may be used individually by 1 type, or may be used in combination of 2 or more types.
 また、インキュベート工程における温度としては、好ましくは20℃~75℃程度、より好ましくは25℃~65℃程度、さらに好ましくは30℃~60℃程度が挙げられる。また、前述のインキュベート工程の環境下に置く時間としては、使用する原料の種類、量などによっても異なるが、好ましく0.1時間~48時間程度、より好ましくは0.2時間~24時間、更に好ましくは0.5時間から12時間程度が挙げられる。S-アリルシステインの生成は、攪拌しながら行ってもよいし、静置して行ってもよい。攪拌方法としては、特に制限されず、例えば、攪拌羽、ミキサー、スターラーなどを用いて攪拌する方法が挙げられる。 Further, the temperature in the incubation step is preferably about 20 ° C. to 75 ° C., more preferably about 25 ° C. to 65 ° C., and further preferably about 30 ° C. to 60 ° C. In addition, the time for placing in the environment of the above-mentioned incubation step varies depending on the kind and amount of the raw material used, but is preferably about 0.1 to 48 hours, more preferably 0.2 to 24 hours, and further It is preferably 0.5 to 12 hours. The production of S-allylcysteine may be carried out with stirring or may be carried out with standing still. The stirring method is not particularly limited, and examples thereof include a method of stirring using stirring blades, a mixer, a stirrer, and the like.
 さらに、インキュベート工程の前、工程中、工程後に、S-アリルシステインの生成を促進する酵素や添加剤を混合してよい。またS-アリルシステインの生成や生成したS-アリルシステインの安定性を損なわない範囲において、反応物の物性や取扱い性の改善を目的とした酵素や添加剤を混合してもよい。 Furthermore, enzymes and additives that promote the production of S-allylcysteine may be mixed before, during, and after the incubation step. In addition, an enzyme or an additive for the purpose of improving the physical properties and handleability of the reaction product may be mixed as long as the production of S-allylcysteine and the stability of the produced S-allylcysteine are not impaired.
 酵素としては、S-アリルシステインの生成を促進するものであれば特に限定されず、好ましくは、プロテアーゼ活性、ラクターゼ活性、ペプチダーゼ活性、マセレーション活性、グルタミナーゼ活性、γ-グルタミルトランスペプチダーゼ活性を有する酵素が挙げられる。これらの中でも、グルタミナーゼ活性またはγ-グルタミルトランスペプチダーゼ活性を主たる活性とする酵素は、S-アリルシステインの生成を促進する効果が特に高いため好ましい。 The enzyme is not particularly limited as long as it promotes the production of S-allylcysteine, and is preferably an enzyme having protease activity, lactase activity, peptidase activity, maceration activity, glutaminase activity, and γ-glutamyl transpeptidase activity. Is mentioned. Among these, an enzyme having glutaminase activity or γ-glutamyltranspeptidase activity as the main activity is preferable because it has a particularly high effect of promoting the production of S-allylcysteine.
 酵素の具体例としては、天野エンザイム製「ビオラクタFN5」、「ビオラクタN5」、「プロレザーFG-F」、「プロチンSD-PC10F」、「プロチンSD-AY10」、「プロチンSD-NY10」、「プロテアーゼM」、「ペプチダーゼR」、「ペクチナーゼA」、「ニューラーゼF3G」、「パンクレアチンF」、「プロテアーゼA」、「リパーゼR」、「リパーゼA」、「プロテアーゼP」、「プロテアーゼN」、「プロテアーゼS」、「プロチンAC10F」、「グルタミナーゼ」、キッコーマン製「ペクトリアーゼ」、協和化成製「セルラーゼTP2協和」、合同酒精製「GODO AGI-EC」、三菱化学フーズ製「コクラーゼ」、シイベルヘグナー製「Rapidase」、新日本化学工業製「スミチームAGS-L」、「スミチームAC-L」、「スミチームCTS」、「スミチームCM-G」、「スミチームKDC」、「スミチームC6000」、「スミチームAP」、「スミチームFP」、「スミチームLPL」、「スミチームLP50」、「スミチームBGT」、「スミチームRP」、「スミチームGML」、「スミチームTG」、エイチ・ビイ・アイ製「オリエンターゼ22BF」、「セルロシンAC40」、「セルロシンHC100」、「セルロシンTP25」、「セルロシンHC」、「オリエンターゼ20A」、「オリエンターゼ5BL」、(株)日本生物.科学研究所製「納豆菌培養エキスNSK-SD」、ノボザイム製「ガマナーゼ」、ペプチド研究所製「WSCDHCL」、ヤクルト薬品工業製「ペクチナーゼHL」、「セルラーゼY-NC」、「セルラーゼオノヅカRS」、「セルラーゼオノヅカR-10」、「マセロチームR-10」などが挙げられる。酵素は、1種類単独で使用してもよいし、2種類以上を組み合わせて使用してもよい。 Specific examples of the enzyme include "Violacta FN5", "Violacta N5", "Proleather FG-F", "Protin SD-PC10F", "Protin SD-AY10", "Protin SD-NY10", and "Protin SD-NY10" manufactured by Amano Enzyme. Protease M", "peptidase R", "pectinase A", "neurase F3G", "pancreatin F", "protease A", "lipase R", "lipase A", "protease P", "protease N". , "Protease S", "Protin AC10F", "Glutaminase", Kikkoman "Pectinase", Kyowa Kasei "Cellulase TP2 Kyowa", Joint Sake Purification "GODO AGI-EC", Mitsubishi Chemical Foods "Coclase", Sibel Hegner "Rapidase", "Sumiteam AGS-L", "Sumiteam AC-L", "Sumiteam CTS", "Sumiteam CM-G", "Sumiteam KDC", "Sumiteam C6000", "Sumiteam AP", manufactured by Shin Nippon Chemical Industry Co., Ltd. "Sumiteam FP", "Sumiteam LPL", "Sumiteam LP50", "Sumiteam BGT", "Sumiteam RP", "Sumiteam GML", "Sumiteam TG", HBI "Orientase 22BF", "Cellulase AC40" , "Cellulase HC100", "Cellulase TP25", "Cellulase HC", "Orientase 20A", "Orientase 5BL", Nippon Biology Co., Ltd. Scientific Research Institute "Natto Culture Extract NSK-SD", Novozyme "Gamanase", Peptide Laboratory "WSCDHCL", Yakult Pharmaceutical Industry "Pectinase HL", "Cellulase Y-NC", "Cellulase Onozuka RS" , "Cellulase Onozuka R-10", "Maceroteam R-10" and the like. One type of enzyme may be used alone, or two or more types may be used in combination.
 また、添加剤としては、S-アリルシステインの生成活性を有するものであれば特に限定されず、好ましくは、システイン、シスチン、グルタチオンなどが挙げられる。 Further, the additive is not particularly limited as long as it has the activity of producing S-allylcysteine, and preferred examples thereof include cysteine, cystine, and glutathione.
 システインとは含硫アミノ酸の一種であり、2-アミノ-3-スルファニルプロピオン酸である。システインとしてはシステインを含む素材、システインを含む素材から抽出したシステインの抽出物若しくは精製物を用いてもよい。天然に存在するシステインとしては、L体が広く存在するが、L体の他、これの光学異性体(D体)であってもよいし、各光学異性体の混合物であってもよい。また、化学合成されたシステインを用いてもよいし、後述するシスチンを還元したものを用いてもよい。 Cysteine is a type of sulfur-containing amino acid and is 2-amino-3-sulfanylpropionic acid. As the cysteine, a material containing cysteine, an extract or a purified product of cysteine extracted from the material containing cysteine may be used. As the naturally-occurring cysteine, the L-form widely exists, but in addition to the L-form, it may be an optical isomer (D-form) thereof or a mixture of each optical isomer. Further, chemically synthesized cysteine may be used, or a reduced cystine described later may be used.
 上記システインのうち、入手容易性の観点から、試薬、医薬品成分、食品成分などとして市販されているシステインの精製物を用いることが好ましい。なお、システインを含む素材としては、システインを含むものであれば特に制限されないが、例えば、オート麦、小麦胚芽、芽キャベツ、ブロッコリーなどが挙げられる。 Among the above cysteines, from the viewpoint of availability, it is preferable to use a purified cysteine commercially available as a reagent, a pharmaceutical ingredient, a food ingredient, or the like. 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.
 また、シスチンは、2分子のシステインがチオール基(-SH)の酸化によって生成するジスルフィド結合(-S-S-)を介してつながった構造を有することから、該シスチンを還元することにより得られたシステインを用いてもよい。また、シスチンは、シスチン(L体)の他、これの光学異性体(D体)であってもよいし、各光学異性体の混合物であってもよい。 In addition, cystine is obtained by reducing the cystine because it has a structure in which two molecules of cysteine are linked via a disulfide bond (-SS-) generated by oxidation of a thiol group (-SH). Cysteine may also be used. In addition to cystine (L-form), cystine may be an optical isomer (D-form) thereof, or a mixture of each optical isomer.
 L-シスチンは、一般的に、試薬、医薬品成分、食品成分などに使用可能な精製物が容易に入手可能であり好ましい。 L-cystine is generally preferred because a purified product that can be used as a reagent, a pharmaceutical ingredient, a food ingredient, etc. is easily available.
 シスチンは、酸化還元電位を下げるような化合物や還元作用を有する化合物と共存させることにより還元されてシステインに変換される。酸化還元電位を下げるような化合物としてはアルカリ土類金属水酸化物やアルカリ土類金属酸化物などが、還元作用を有する化合物としてはグルタチオンなどがあげられる。 Cystine is reduced and converted to cysteine by coexisting with a compound that lowers the redox potential or a compound having a reducing action. Examples of the compound that lowers the oxidation-reduction potential include alkaline earth metal hydroxides and alkaline earth metal oxides, and examples of the compound having a reducing action include glutathione.
 グルタチオンは、グルタミン酸、システイン、グリシンの3つのアミノ酸からなるトリペプチドである。グルタチオンを多量に含有する食品としては、牛レバー、豚バラ肉、牛乳、カキ、イワシ、マダラ、シャケ、赤貝、トマト、ホウレンソウ、ブロッコリー、エンドウマメ、芽キャベツ、生キャベツ、キウイフルーツ、アボカド、米胚芽、小麦粉、パン酵母、酵母などがあり、グルタチオン自体だけでなく、グルタチオンを含む上記食品すべてを用いることができる。中でも、グルタチオンを高濃度に含むという観点から、酵母が好ましい。グルタチオンの形態としては、グルタチオンを含む素材をそのまま用いても良いし、さらにグルタチオンの濃度を高めるために、水抽出、熱水抽出、精製などの工程を経たものでもよい。 Glutathione is a tripeptide consisting of three amino acids, glutamic acid, cysteine, and glycine. Foods containing large amounts of glutathione include beef liver, pork belly, milk, oysters, sardines, cod, salmon, red shellfish, tomatoes, spinach, broccoli, peas, sprouts, raw cabbage, kiwifruit, avocado, rice germ. , Flour, baker's yeast, yeast, etc., and not only glutathione itself but all the above foods containing glutathione can be used. Among them, yeast is preferable from the viewpoint of containing glutathione in a high concentration. As the form of glutathione, a material containing glutathione may be used as it is, or it may be subjected to steps such as water extraction, hot water extraction, and purification in order to further increase the concentration of glutathione.
 グルタチオンには、還元型と酸化型(還元型グルタチオン2分子がジスルフィド結合したもの)があり、いずれも用いることができるが、反応性の観点から、還元型が好ましい。 There are two types of glutathione, a reduced type and an oxidized type (a disulfide bond of two reduced glutathione molecules), and both can be used, but the reduced type is preferable from the viewpoint of reactivity.
 以上例示された酵素または添加剤を用いる場合、それぞれ単独で用いてもよいし、これらを併用してもよい。 When the enzymes or additives exemplified above are used, they may be used alone or in combination.
 本発明においては、S-アリルシステインを増加させた反応生成物をそのまま抗疲労剤とすることもできるし、反応生成物に対して、さらに、濾過、遠心分離、濃縮、抽出、乾燥等のうち少なくとも1つの工程を行って、S-アリルシステインの含有量をさらに高める工程を行い、抗疲労剤としてもよい。また、抗疲労剤中のS-アリルシステインの純度を高めるために、カラムクロマトグラフィー、再結晶等の通常の精製操作によって、S-アリルシステインを精製する精製工程を行うこともできる。さらに、反応生成物を、フリーズドライ、スプレードライなどの公知の乾燥手段によって乾燥させて固形物(粉末、顆粒など)とすることもできる。本発明の抗疲労剤は、S-アリルシステインを含む反応混合物や、S-アリルシステインの精製物を、医薬品、医薬部外品、飲食品、飼料、健康食品などの抗疲労剤として好適に使用することができる。 In the present invention, the reaction product in which S-allylcysteine is increased can be used as it is as an anti-fatigue agent, and the reaction product is further subjected to filtration, centrifugation, concentration, extraction, drying, etc. At least one step may be performed to further increase the content of S-allyl cysteine, and the anti-fatigue agent may be obtained. Further, in order to increase the purity of S-allylcysteine in the anti-fatigue agent, a purification step of purifying S-allylcysteine can also be performed by a normal purification operation such as column chromatography or recrystallization. Further, the reaction product can be dried by a known drying means such as freeze-drying and spray-drying to obtain a solid substance (powder, granules, etc.). The anti-fatigue agent of the present invention preferably uses a reaction mixture containing S-allylcysteine or a purified product of S-allylcysteine as an anti-fatigue agent for pharmaceuticals, quasi-drugs, foods and drinks, feeds, health foods, etc. can do.
 また、本発明において、S-アリルシステインを有効成分として含む抗疲労剤は、S-アリルシステインを有効成分として含む身体機能回復剤等としても、好適に使用することができる。 Further, 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.
S-アリルシステインの含有量、適用量、摂取するタイミング
 本発明の抗疲労剤に含まれるS-アリルシステインの含有量としては、優れた疲労回復促進効果を発揮する観点から、好ましくは0.0001g/100g以上、より好ましくは0.01g/100g以上、さらに好ましくは0.10g/100g以上が挙げられる。なお、本発明の抗疲労剤に含まれるS-アリルシステインの含有量の上限値としては、特に制限されないが、通常、10g/100g程度が挙げられる。
Content, application amount, and timing of ingestion of S-allylcysteine The content of S-allylcysteine contained in the anti-fatigue agent of the present invention is preferably 0.0001 g from the viewpoint of exerting an excellent fatigue recovery promoting effect. /100 g or more, more preferably 0.01 g/100 g or more, and still more preferably 0.10 g/100 g or more. The upper limit of the content of S-allylcysteine contained in the anti-fatigue agent of the present invention is not particularly limited, but usually about 10 g/100 g can be mentioned.
 また、本発明の抗疲労剤の適用量については、使用される製品の種類、用途、期待される効果、適用形態等に応じて適宜設定すればよい。例えば、S-アリルシステインの成人1日当たりの摂取又は投与量が0.0001~3g、好ましくは0.0005~2g、さらに好ましくは0.001~1gとなるように設定すればよい。S-アリルシステインの成人1日当たりの摂取又は投与量がこのような範囲になるようにして、好ましくは0.0001g/100g以上、より好ましくは0.01g/100g以上、さらに好ましくは0.10g/100g以上のS-アリルシステインの含有量が含まれる本発明の抗疲労剤を摂取又は投与することが好ましい。 Further, the applied amount of the anti-fatigue agent of the present invention may be appropriately set according to the type of product used, the application, the expected effect, the application form, and the like. For example, the daily intake or dose 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. The daily intake or dose of S-allylcysteine for adults should be within such a range, preferably 0.0001 g / 100 g or more, more preferably 0.01 g / 100 g or more, still more preferably 0.10 g / g. It is preferable to ingest or administer the anti-fatigue agent of the present invention containing a content of S-allylcysteine of 100 g or more.
 また、本発明の抗疲労剤を摂取するタイミングについては、優れた疲労回復促進効果を発揮する観点から、疲労を生じさせる行動の前(例えば、運動前)の摂取が好ましい。 In addition, regarding the timing of ingesting the anti-fatigue agent of the present invention, it is preferable to ingest it before an action that causes fatigue (for example, before exercise) from the viewpoint of exerting an excellent fatigue recovery promoting effect.
抗疲労剤の用途
 本発明の抗疲労剤は、S-アリルシステインの作用によって、自律神経機能を正常な状態に調整することができるので、疲労からの回復に好適に使用される。本発明の抗疲労剤は、日常生活で生じる疲労の回復を促進することができ、例えば健常者の疲労を好適に改善することができる。
Use of Anti-Fatigue Agent The anti-fatigue agent of the present invention can adjust the autonomic nerve function to a normal state by the action of S-allyl cysteine, and thus is preferably used for recovery from fatigue. The anti-fatigue agent of the present invention can promote recovery from fatigue that occurs in daily life, and, for example, can suitably improve fatigue in healthy people.
抗疲労剤の使用形態
 本発明の抗疲労剤の適用形態については、特に制限されないが、例えば、経口、経皮、経腸、経粘膜、経静脈、経動脈、皮下、筋肉内等の任意の適用形態で使用できるが、抗疲労作用をより簡便かつ有効に発揮させるという観点から、好ましくは、経口適用が挙げられる。
Form of Use of Anti-Fatigue Agent The form of application of the anti-fatigue agent of the present invention is not particularly limited, but may be any of oral, transdermal, transintestinal, transmucosal, transvenous, transarterial, subcutaneous, intramuscular and the like. Although it can be used in an application form, oral application is preferable from the viewpoint of exerting an anti-fatigue effect more easily and effectively.
 本発明の抗疲労剤は、任意の適用形態で使用して抗疲労作用を発揮できるので、飲食品、医薬品、食品添加物、調味料、飼料、ペットフード等の各種製品に配合して使用することができる。なお、前記の通り、特許文献3に記載されたような、加熱熟成ニンニクエキスを、毎日5gも摂取することは困難であるため、本発明の抗疲労剤には加熱熟成ニンニクエキスは包含されないことが好ましく、また、本発明の抗疲労剤を含む飲食品などにも、加熱熟成ニンニクエキスは包含されないことが好ましい。 Since the anti-fatigue agent of the present invention can be used in any application form and exerts an anti-fatigue effect, it is used by blending it in various products such as foods and drinks, pharmaceuticals, food additives, seasonings, feeds, and pet foods. be able to. As described above, it is difficult to ingest 5 g of the heat-aged garlic extract daily as described in Patent Document 3, so that the anti-fatigue agent of the present invention does not include the heat-aged garlic extract. It is preferable that the heat-aged garlic extract is not included in foods and drinks containing the anti-fatigue agent of the present invention.
 また、本発明の抗疲労剤が配合される製品の剤型は、固形状、半固形状、液状等のいずれであってもよく、当該製品の種類や用途に応じて適宜設定される。本発明の抗疲労剤が配合される製品には、その形態等に応じて、本発明の効果を損なわない範囲内で、水、油脂類、ロウ類、炭化水素類、脂肪酸類、高級アルコール類、エステル類、植物抽出エキス類、水溶性高分子、界面活性剤、金属石鹸、アルコール、多価アルコール、pH調整剤、酸化防止剤、紫外線防止剤、防腐剤、香料、粉体、増粘剤、色素、キレート剤等の添加剤を含有しても良い。また、本発明の抗疲労剤が配合される製品には、その形態や用途等に応じて、本発明の効果を損なわない範囲で、他の成分を配合しても良い。他の成分としては、例えば、スクワラン、ナイアシン、ナイアシンアミド、長鎖ヒアルロン酸、プラセンタエキス、ソルビトール、キチン、キトサン、各種植物抽出物、クエン酸、ビタミンA,C,E,P、カロテノイド類(アスタキサンチン、β-クリプトキサンチン、リコペンなど)、カテキン類(エビガロカテキンガレートなど)、ポリフェノール類(アントシアニン、カカオポリフェノールなど)、ペプチド類(イミダゾールジペプチド、BCAAなど)、CoQ10、α-リポ酸の他、アミノレブリン酸・GABA・テアニンなど、単純アミノ酸でないアミノ酸類等が挙げられる。これらの配合量については、本発明の効果を損なわない限り限定されない。 The dosage form of the product containing the anti-fatigue agent of the present invention may be solid, semi-solid, liquid or the like, and is appropriately set according to the type and application of the product. The product containing the anti-fatigue agent of the present invention contains water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, depending on the form and the like, as long as the effects of the present invention are not impaired. , Esters, plant extracts, water-soluble polymers, surfactants, metal soaps, alcohols, polyhydric alcohols, pH regulators, antioxidants, UV inhibitors, preservatives, fragrances, powders, thickeners , Dyes, chelating agents and the like may be contained. In addition, the product containing the anti-fatigue agent of the present invention may contain other components depending on its form, application, etc., as long as the effects of the present invention are not impaired. Other components 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 galocatechin gallate, etc.), polyphenols (anthocyanin, cacao polyphenols, etc.), peptides (imidazole dipeptide, BCAA, etc.), CoQ10, α-lipoic acid, and aminolevulin Examples include amino acids that are not simple amino acids, such as acids, GABA, and theanin. These blending amounts are not limited as long as the effects of the present invention are not impaired.
 本発明の抗疲労剤を飲食品に使用する場合、S-アリルシステインを、そのまま又は他の食品素材や添加成分と組み合わせて所望の形態に調整して、前記所望の効果を奏する抗疲労用飲食品として提供される。このような飲食品としては、一般の飲食品の他、特定保健用食品、栄養補助食品、機能性食品、病者用食品等が挙げられる。また、本発明の抗疲労剤を含む、疲労回復用や疲労感の低減用の飲食品などとすることもできる。これらの飲食品の形態として、特に制限されないが、具体的にはパン類、麺類等の主菜;チーズ、ハム、ウインナー、魚介加工品等の副菜;果汁飲料、炭酸飲料、乳酸飲料等の飲料;クッキー、ケーキ、ゼリー、アイス、プリン、キャンディー、ヨーグルト等の嗜好品;錠剤、顆粒、粉剤、カプセル、ソフトカプセル、栄養ドリンク等のサプリメント等が例示される。これらの飲食品は、前述する用途に供することが出来る。また、前記病者用食品は、疲労の治療が必要とされる患者用として提供される。 When the anti-fatigue agent of the present invention is used in foods and drinks, S-allylcysteine is adjusted to a desired form as it is or in combination with other food materials and additive components to obtain the desired effect. It is provided as an item. Examples of such foods and drinks include general foods and drinks, foods for specified health use, dietary supplements, functional foods, foods for patients, and the like. Further, it can also be used as a food or drink containing the anti-fatigue agent of the present invention for recovering from fatigue or for reducing the feeling of fatigue. The form of these foods and drinks is not particularly limited, but specifically, main dishes such as breads and noodles; side dishes such as cheese, ham, wieners and processed seafood; fruit juice drinks, sparkling drinks, lactic acid drinks and the like. Beverages; luxury items such as cookies, cakes, jellies, ice cream, puddings, candies, yogurts; supplements such as tablets, granules, powders, capsules, soft capsules, energy drinks, etc. are exemplified. These foods and drinks can be used for the above-mentioned purposes. In addition, the food for the sick is provided for patients who need treatment for fatigue.
 本発明の抗疲労剤を飲食品に使用する場合、飲食品に対する該抗疲労剤の配合量については、飲食品の形態等に応じて異なるが、例えば、S-アリルシステインが0.0001~10質量%、好ましくは0.005~5質量%、更に好ましくは0.001~1質量%となる範囲が挙げられる。 When the anti-fatigue agent of the present invention is used in foods and drinks, the amount of the anti-fatigue agent blended in the foods and drinks varies depending on the form of the foods and drinks, and for example, S-allylcysteine is 0.0001 to 10. The mass ratio is preferably 0.005 to 5% by mass, more preferably 0.001 to 1% by mass.
 更に、本発明の抗疲労剤を飲食品の分野で使用する場合、本発明の抗疲労剤を単独で、又は他の成分と組み合わせて、抗疲労用の食品添加物や調味料など(以下、食品添加物等)として提供することもできる。本発明の抗疲労剤を食品添加物等として使用する場合、当該食品添加物等中のS-アリルシステインの含有量、飲食品に対する当該食品添加物等の添加量等は、添加対象となる飲食品中でS-アリルシステインが前述する含有量を充足できるように適宜設定すればよい。 Furthermore, when the anti-fatigue agent of the present invention is used in the field of food and drink, the anti-fatigue agent of the present invention alone or in combination with other ingredients such as food additives and seasonings for anti-fatigue (hereinafter referred to as It can also be provided as a food additive, etc.). When the anti-fatigue agent of the present invention is used as a food additive, the content of S-allylcysteine in the food additive, the amount of the food additive added to the food or drink, and the like are the food and drink to be added. It may be appropriately set so that S-allylcysteine can satisfy the above-mentioned content in the product.
 また、本発明の抗疲労剤を医薬品に使用する場合、本発明の抗疲労剤を単独で、又は他の薬理活性成分、薬学的に許容される基剤や添加成分等と組み合わせて所望の形態に調整して、前記所望の効果を奏する抗疲労用医薬品として提供される。このような医薬品の形態としては、特に制限されないが、具体的には、錠剤、顆粒剤、粉剤、カプセル剤、ソフトカプセル剤、シロップ剤等の経口投与製剤;液剤、軟膏剤、クリーム剤、ゲル剤、噴霧剤、貼付剤、吸入剤、坐剤等の経皮又は経粘膜投与製剤;注射剤等が挙げられる。 When the anti-fatigue agent of the present invention is used in a pharmaceutical product, the anti-fatigue agent of the present invention may be used alone or in combination with other pharmacologically active ingredients, pharmaceutically acceptable bases, additive ingredients, etc. in a desired form. It is provided as an anti-fatigue drug that exerts the desired effect. The form of such a drug is not particularly limited, but specifically, an orally-administered preparation such as a tablet, a granule, a powder, a capsule, a soft capsule, or a syrup; a liquid, an ointment, a cream, or a gel. , Preparations for percutaneous or transmucosal administration such as sprays, patches, inhalants, suppositories; injections and the like.
 本発明の抗疲労剤を医薬品として使用する場合、医薬品に対する該抗疲労剤の配合割合については、医薬品の形態等に応じて異なるが、例えば、経口投与製剤又は注射剤の場合であれば、S-アリルシステインが0.0001~10質量%、好ましくは0.0005~5質量%、更に好ましくは0.001~1質量%となる範囲が挙げられ、経皮又は経粘膜投与製剤の場合であれば、S-アリルシステインが0.0000001~10質量%、好ましくは0.00001~10質量%、更に好ましくは0.0001~10質量%となる範囲が挙げられる。 When the anti-fatigue agent of the present invention is used as a drug, the mixing ratio of the anti-fatigue agent to the drug varies depending on the form of the drug, etc., but in the case of an orally administered preparation or an injection, S -Allylcysteine is in the range of 0.0001 to 10% by mass, preferably 0.0005 to 5% by mass, and more preferably 0.001 to 1% by mass, in the case of transdermal or transmucosal preparations. For example, the range in which S-allylcysteine is 0.000000001 to 10% by mass, preferably 0.00001 to 10% by mass, and more preferably 0.0001 to 10% by mass can be mentioned.
 また本発明の抗疲労剤を飼料又はペットフードに使用する場合、本発明の抗疲労剤を単独で又は他の飼料成分と組み合わせて所望の形態に調整して、前記所望の効果を奏する飼料又はペットフードとして提供される。該飼料又はペットフードに使用される飼料成分としては、例えば、トウモロコシ、小麦、大麦、ライ麦等の穀類;ふすま、米ぬか等のぬか類;コーングルテンミール、コーンジャムミール等の粕類;脱脂粉乳、ホエー、魚粉、骨粉等の動物性飼料類;ビール酵母等の酵母類;リン酸カルシウム、炭酸カルシウム等のカルシウム類;ビタミン類;アミノ酸類;糖類等が挙げられる。 When the anti-fatigue agent of the present invention is used in a feed or pet food, the anti-fatigue agent of the present invention can be adjusted to a desired form alone or in combination with other feed components to obtain the desired effect. Served as pet food. Examples of feed ingredients used in the feed or pet food include, for example, grains such as corn, wheat, barley, and rye; bran such as bran and rice bran; corn gluten meal, meal such as corn jammeal; skim milk powder, Animal feeds such as whey, fish meal and bone meal; yeasts such as beer yeast; calcium such as calcium phosphate and calcium carbonate; vitamins; amino acids; sugars and the like.
 本発明の抗疲労剤を飼料又はペットフードとして使用する場合、飼料又はペットフードに対する該抗疲労剤の配合割合については、飼料又はペットフードの形態等に応じて異なるが、例えば、S-アリルシステインが0.000001~10質量%、好ましくは0.0001~5質量%、更に好ましくは0.001~1質量%となる範囲が挙げられる。 When the anti-fatigue agent of the present invention is used as a feed or pet food, the mixing ratio of the anti-fatigue agent to the feed or pet food varies depending on the form of the feed or pet food, and for example, S-allylcysteine. Is 0.000001 to 10% by mass, preferably 0.0001 to 5% by mass, and more preferably 0.001 to 1% by mass.
 以下に、実施例及び比較例を示して本発明を詳細に説明する。ただし、本発明は、実施例に限定されない。実施例及び比較例中の測定方法は次の通りである。 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.
(HPLC分析条件)
カラム:Unison US-C18 5μm (250mm×4.6mm) インタクト株式会社製
カラム温度:45℃
移動相:[A液]10mM りん酸2水素カリウム緩衝液(pH2.5/りん酸)、[B液]アセトニトリル
流速:1mL/min
測定波長:210nm
(HPLC analysis conditions)
Column: Unison US-C18 5 μm (250 mm×4.6 mm) Intact Co. column temperature: 45° C.
Mobile phase: [Solution A] 10 mM potassium dihydrogen phosphate buffer (pH 2.5/phosphoric acid), [Solution B] Acetonitrile flow rate: 1 mL/min
Measurement wavelength: 210 nm
(実施例1)
 皮をむいて台座を除去し、鱗片に分けたにんにく(品種名:福地ホワイト)250gに、等重量のイオン交換水を加えて市販の家庭用ジューサー(SUNVIGOR ジュースミキサー,SML-G22)で摩砕し、にんにくペーストを得た。にんにくペースト100質量部に対して、酸化マグネシウム(ナカライテスク製)6質量部と、L-シスチン(プロテインケミカル製)4質量部を、それぞれ添加し、更にイオン交換水をにんにく重量に対して2倍量を添加し、50~55℃に加温して攪拌した。酸化マグネシウム及びL-シスチン添加から6時間目にサンプリングを行い、サンプリング液中のS-アリルシステインの含有量をHPLC法で分析したところ、1.00g/kgのS-アリルシステイン(SAC)が生成していた。上記ペーストをろ過した後、ろ液に38gのマルトデキストリン(松谷化学工業株式会社)を添加して噴霧乾燥し、140gの粉末を得た。この粉末のS-アリルシステイン含有量を測定したところ、0.68g/100gであった。
(Example 1)
Peel and remove the pedestal, add equal weight of ion-exchanged water to 250 g of garlic (variety name: Fukuchi White) divided into scales, and grind with a commercially available household juicer (SUNVIGOR juice mixer, SML-G22). And got a garlic paste. 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) are added, and ion-exchanged water is doubled by weight of garlic. The amount was added, and the mixture was heated to 50 to 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 sampling solution was analyzed by the HPLC method. As a result, 1.00 g / kg of S-allylcysteine (SAC) was produced. Was. After filtering the paste, 38 g of maltodextrin (Matsuya 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.
(実施例2)
 実施例1で製造した粉末を用い、表1の被験食の組成を有するS-アリルシステイン含有ソフトカプセルを製造した。ソフトカプセルから内容物を回収し、回収物中のSAC含有量を測定した結果、1粒当たり、S-アリルシステインが1.0mg(2粒合計で2.0mg)含有されていた。なお、カプセル1粒の重量は、632mgである。
(Example 2)
Using the powder prepared in Example 1, S-allyl cysteine-containing soft capsules having the composition of the test meal shown in Table 1 were prepared. The content was recovered from the soft capsules, and the SAC content in the recovered material was measured. As a result, 1.0 mg of S-allylcysteine was contained per particle (2.0 mg in total of 2 particles). The weight of one capsule is 632 mg.
(比較例1)
 表1のプラセボの組成を有するS-アリルシステイン非含有ソフトカプセルを製造した。ソフトカプセルから内容物を回収し、回収物中のS-アリルシステイン含有量を測定した結果、S-アリルシステインは検出されなかった。
(Comparative example 1)
S-allylcysteine-free soft capsules having the placebo composition shown in Table 1 were produced. As a result of recovering the content from the soft capsule and measuring the S-allylcysteine content in the recovered product, S-allylcysteine was not detected.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
(試験例1)
 表1に示された各試験食(1日摂取量2粒の被験食及びプラセボ)を用いて、S-アリルシステインの疲労回復促進効果を評価した。具体的には、ヒト試験を、ランダム化二重盲検クロスオーバー試験として実施した。試験食摂取期間は4週間とし、2度の試験期間の間に4週間のウォッシュアウト期間を設けた。また季節効果を排除するため、試験食を先に摂取するグループとプラセボを先に摂取するグループの2群を設定した。
(Test Example 1)
Using each of the test meals shown in Table 1 (a test meal having a daily intake of 2 tablets and a placebo), the fatigue recovery promoting effect of S-allyl cysteine was evaluated. Specifically, the human study was conducted as a randomized, double-blind, crossover study. The test food intake period was 4 weeks, and a washout period of 4 weeks was provided between the two test periods. In addition, in order to eliminate the seasonal effect, two groups were set, a group that first took the test meal and a group that first took the placebo.
 本試験では30歳以上60歳以下の健常な男女24名を被験者とし、ランダムに2グループに割り付けた。2グループの性別、年齢、スクリーニング時のVAS(疲労感)スコア、身体作業負荷における負荷強度(Watt)は2グループ間で有意差はみられなかった。 In this test, 24 healthy men and women aged 30 to 60 were randomly assigned to two groups. There was no significant difference between the two groups in the sex, age, VAS (fatigue) score at screening, and load intensity (Watt) in the physical work load of the two groups.
 本試験は、株式会社総合医科学研究所に委託し、同社の倫理委員会承認を得て専門家の指導・監督下で実施された。摂取4週間後検査日には身体作業負荷を実施した。身体作業負荷は予め自転車エルゴメーターの漸増負荷により無酸素性作業閾値(AT: Anaerobic Threshold)を測定し、AT時心拍数の80%を目標心拍数とした4時間の自転車エルゴメーター漕ぎを実施し、負荷終了後には4時間の回復期間を設定した。 This test was outsourced to the Institute of Medical Sciences Co., Ltd., and was conducted under the guidance and supervision of experts with the approval of the company's ethics committee. Four weeks after ingestion, a physical workload was performed on the day of the examination. For the physical work load, the anoxic work threshold (AT: Anaerobic Threshold) was measured in advance by gradually increasing the load of the bicycle ergometer, and a bicycle ergometer rowing was performed for 4 hours with 80% of the heart rate at AT as the target heart rate. After the load was completed, a recovery period of 4 hours was set.
 なお、運動の強さと量に関し、厚生労働省「健康づくりのための運動指針2006」では、運動の強さを「メッツ」、メッツに時間を乗じたものを運動量「エクササイズ(Ex)」として簡易的に定量化し、強度4メッツ以上の活発な身体活動(運動・生活活動)を週23Ex以上実施することを推奨している。本試験では、運動量は、軽い自転車漕ぎであり、強度は3.0~4.0メッツに相当する。また、運動量は、4時間の運動であることから12~16Exとなる。これはゴルフの1ラウンドや、草むしり、犬の散歩の合計で2.5~3時間程度に相当する運動量であり、誰もが日常的に経験する程度の運動量である。 Regarding the strength and amount of exercise, the Ministry of Health, Labor and Welfare's "Exercise Guidelines for Health Promotion 2006" refers to the strength of exercise as "Mets" and the time multiplied by Mets as "Exercise (Ex)". It is recommended to carry out active physical activity (exercise / life activity) with an intensity of 4 mets or more at 23 Ex or more per week. In this test, the amount of exercise is light bicycle rowing, and the intensity corresponds to 3.0 to 4.0 mets. In addition, the amount of exercise is 12 to 16 Ex because it is exercise for 4 hours. This is an amount of exercise equivalent to about 2.5 to 3 hours in total for one round of golf, weeding, and walking of dogs, and is an amount of exercise that anyone experiences on a daily basis.
 疲労回復促進効果は、疲労感及び自律神経機能について評価した。疲労感は、ビジュアルアナログスケール(VAS)で評価し、スクリーニング時、運動負荷試験の負荷前、負荷2時間後、負荷4時間後、回復2時間後、回復4時間後に測定した。また、自律神経機能評価は、負荷前、負荷2時間後、負荷4時間後、回復2時間後および回復4時間後に、アルテットCDN((株)ユメディカ)を用いて加速度脈波を測定しa-a間隔の周波数解析により自律神経機能を評価した。 The fatigue recovery promoting effect was evaluated for fatigue and autonomic nervous function. Fatigue was evaluated on a visual analog scale (VAS) and measured during screening, before loading, 2 hours after loading, 4 hours after loading, 2 hours after recovery, and 4 hours after recovery. In the evaluation of autonomic nervous function, the acceleration pulse wave was measured using Altet CDN (Umedica Co., Ltd.) before loading, 2 hours after loading, 4 hours after loading, 2 hours after recovery, and 4 hours after recovery. Autonomic nerve function was evaluated by frequency analysis at a intervals.
<結果1:評価対象者>
 24名のうち、自己都合脱落1名、身体作業負荷中の体調不良による試験中止1名、身体作業負荷4時間の前後でVASの疲労感の上昇がみられなかった1名、抗疲労の関与成分であるS-アリルシステインの血中レベルの上昇がみられなかった1名の4名を有効性評価の解析から除外し、20名を有効性評価の解析対象者とした。
<Result 1: Evaluation target>
Of the 24 patients, 1 was dropped out due to personal reasons, 1 was discontinued due to poor physical condition during physical workload, 1 was not showing an increase in VAS fatigue around 4 hours of physical workload, and anti-fatigue was involved. Four subjects, one of whom did not show an increase in the blood level of S-allylcysteine as a component, were excluded from the analysis of efficacy evaluation, and 20 subjects were analyzed.
<結果2:ビジュアルアナログスケール(VAS)による疲労感の評価>
 摂取4週間後検査日の負荷試験において、負荷開始前からのVAS変化を比較したところ、被験食群はプラセボ群と比較して、回復2時間後の疲労感が有意に低値であった(図1)。
<Result 2: Evaluation of fatigue by visual analog scale (VAS)>
In the load test on the test day 4 weeks after ingestion, when the VAS change from before the start of loading was compared, the feeling of fatigue 2 hours after recovery was significantly lower in the test diet group than in the placebo group (). Figure 1).
<結果3:自律神経機能>
 自律神経機能評価において、被験食群はプラセボ群と比較して、LF-MEM、LF-FFTが負荷4時間後で有意な高値、HF-MEM、HF-FFTが回復4時間後で有意な低値であった(下表2:自律神経機能評価(加速度脈波a-a間隔の周波数解析)絶対値、下表3:自律神経機能評価(加速度脈波a-a間隔の周波数解析) 摂取4週間後来院時からの変化)。また負荷4時間後からの変化においてもLF/HF-FFTが回復2時間後で有意な低下、HF%-FFTが回復4時間後で有意な上昇がみられた(下表4:自律神経機能評価(加速度脈波a-a間隔の周波数解析)摂取4週間後検査日負荷4時間後からの変化)。
<Result 3: Autonomic nervous function>
In the evaluation of autonomic nervous function, the test diet group had significantly higher values for LF-MEM and LF-FFT 4 hours after loading, and significantly lower values for HF-MEM and HF-FFT 4 hours after recovery, compared with the placebo group. It was a value (Table 2 below: Absolute nerve function evaluation (frequency analysis of acceleration pulse wave aa interval)) Absolute value, Table 3 below: Autonomic nerve function evaluation (frequency analysis of acceleration pulse wave aa interval) Changes from the time of visit after a week). In addition, the change after 4 hours of loading also showed a significant decrease in LF / HF-FFT 2 hours after recovery and a significant increase in HF% -FFT 4 hours after recovery (Table 4: Autonomic nerve function below). Evaluation (frequency analysis of acceleration pulse wave aa interval) 4 weeks after intake, change from 4 hours after test day load).
 LFは主に交感神経活動、HFは副交感神経活動を反映し、疲労状態では休息期にあっても副交感神経活動が上昇しないことによる交感神経活動優位な状態となることが報告されている。被験食群は、負荷4時間後で活動期に有利な交感神経活動優位な状態にあり、さらに回復期には休息期に有利は副交感神経活動優位な状態にあることから、被験食摂取によりそれぞれの状況に適した自律神経機能の状態に調節されていると考えられる。また、VASで認められた回復期における疲労感の回復促進は、自律神経機能の調節作用が関連していると考えられる。 It has been reported that LF mainly reflects sympathetic nerve activity and HF reflects parasympathetic nerve activity, and in a fatigued state, parasympathetic nerve activity does not increase even during the resting period, resulting in a predominant state of sympathetic nerve activity. The test diet group was in a state of predominant sympathetic nerve activity in the active phase after 4 hours of loading, and was in a state of predominant parasympathetic nerve activity in the resting phase in the recovery phase. It is considered that the state of autonomic nervous function is adjusted to suit the situation. In addition, it is considered that the promotion of recovery of the feeling of fatigue during the recovery period, which is observed in VAS, is related to the regulatory action of autonomic nerve function.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005

Claims (6)

  1.  S-アリルシステインを有効成分とする、抗疲労剤。 An anti-fatigue agent containing S-allylcysteine as an active ingredient.
  2.  前記S-アリルシステインがアリウム属植物に由来する、請求項1に記載の抗疲労剤。 The anti-fatigue agent according to claim 1, wherein the S-allylcysteine is derived from a plant belonging to the genus Allium.
  3.  日常生活で生じる疲労の回復を促進する、請求項1又は2に記載の抗疲労剤。 The anti-fatigue agent according to claim 1 or 2, which promotes recovery from fatigue that occurs in daily life.
  4.  請求項1~3のいずれか1項に記載の抗疲労剤を含む、抗疲労用飲食品。 An anti-fatigue food or drink containing the anti-fatigue agent according to any one of claims 1 to 3.
  5.  請求項1~3のいずれか1項に記載の抗疲労剤を含む、抗疲労用医薬品。 An anti-fatigue drug containing the anti-fatigue agent according to any one of claims 1 to 3.
  6.  請求項1~3のいずれか1項に記載の抗疲労剤を含む、食品添加物又は調味料。 A food additive or seasoning containing the anti-fatigue agent according to any one of claims 1 to 3.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101731606A (en) * 2008-11-21 2010-06-16 宁月宝 Black garlic health product and preparation method thereof
KR20160066809A (en) * 2014-12-03 2016-06-13 광주여자대학교 산학협력단 Method of producing a health tea
JP2017088549A (en) * 2015-11-11 2017-05-25 株式会社ダイセル Endurance enhancers

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101731606A (en) * 2008-11-21 2010-06-16 宁月宝 Black garlic health product and preparation method thereof
KR20160066809A (en) * 2014-12-03 2016-06-13 광주여자대학교 산학협력단 Method of producing a health tea
JP2017088549A (en) * 2015-11-11 2017-05-25 株式会社ダイセル Endurance enhancers

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
TAKAYANAGI, KATSUHIKO ET AL.: "Somatic Fatigue Alleviation Effect of S-Allyl cysteine", JAPANESE PHARMACOLOGY AND THERAPEUTICS, vol. 47, no. 4, April 2019 (2019-04-01), pages 607 - 619 *

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