Anti-fatigue agent

Abstract

To provide an anti-fatigue agent having a high fatigue-reducing effect. SOLUTION: The anti-fatigue agent is characterized by containing ornithine or a salt thereof and a specific component such as vitamin B1 as active ingredients.

Description

[Technical Field]

[0001] The present invention relates to an anti-fatigue agent, and more particularly to an anti-fatigue agent containing ornithine or a salt thereof (hereinafter sometimes simply referred to as an ornithine) and other specific ingredients as active ingredients. [Background technology]

[0002] In recent years, long working hours and excessive stress have led to the accumulation of physical and mental fatigue, and there has been active development of drugs and other treatments aimed at alleviating this fatigue.

[0003] For example, a fatigue-reducing agent containing ornithine or its salt, and glutathione or its salt as active ingredients (Patent Document 1) and an anti-fatigue agent containing a dioxabicyclo[3.3.0]octane derivative such as sesamin, which is represented by a specific structural formula, as an active ingredient (Patent Document 2) have been proposed. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Re-table No. 2007-142286 [Patent Document 2] Japanese Patent Application Laid-Open No. 2014-193903 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide an anti-fatigue agent that has a high fatigue-reducing effect. [Means for solving the problem]

[0006] The present inventors have conducted extensive research and studies into the fatigue-reducing effect of ornithine, and have found that a high fatigue-reducing effect can be achieved by combining ornithine with specific other components, leading to the completion of the present invention. Specifically, they have found that the fatigue-reducing ability can be synergistically improved by combining ornithine with specific other components that have little or no fatigue-reducing ability.

[0007] That is, the present invention relates to an anti-fatigue agent characterized by containing, as active ingredients, ornithine or a salt thereof and at least one component selected from the group consisting of the following (a) to (d): (a) at least one plant material selected from pine and rice (b) at least one sweetener selected from aspartame, trehalose, and reduced palatinose; (c) at least one amino acid selected from glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, tyrosine, and anserine; (d) at least one vitamin or mineral selected from vitamin B1, vitamin B6, vitamin B12, vitamin E, niacin, folic acid, vitamin K, and zinc;

[0008] The anti-fatigue agent of the present invention may be obtained by adding an active ingredient comprising ornithine or a salt thereof and at least one component selected from the group consisting of (a) to (d).

[0009] Furthermore, the anti-fatigue agent of the present invention preferably has a blending mass ratio of ornithine or a salt thereof to other active ingredients in the range of 0.5: 1 to 70: 1. Furthermore, the agent is preferably in the form of a tablet, capsule, powder, granule, or liquid.

[0010] Furthermore, the present invention relates to a method for reducing fatigue (excluding medical procedures) which comprises ingesting the anti-fatigue agent. [Effects of the Invention]

[0011] The anti-fatigue agent of the present invention can provide a high fatigue-reducing effect. [Brief explanation of the drawings]

[0012] [Figure 1] This shows the cell viability of a mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + plant material) was applied. The graph on the left shows the results when pine was used as the plant material, and the graph on the right shows the results when rice (rice bran) was used as the plant material. [Figure 2] This is a graph showing the cell viability of a mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + sweetener) was applied. The graph on the upper left shows the results when aspartame was used as the sweetener, the graph on the upper right shows the results when trehalose was used as the sweetener, and the graph on the lower left shows the results when reduced palatinose was used as the sweetener. [Figure 3] This is a diagram showing the cell viability of a mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + amino acids) is applied. The upper left graph is for the case where glutamine is used as an amino acid, the upper right graph is for the case where glutamic acid is used as an amino acid, the lower left graph is for the case where glycine is used as an amino acid, and the lower right graph is for the case where histidine is used as an amino acid. [Figure 4] This is a diagram showing the cell viability of a mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + amino acids) is applied. The upper left graph is for the case where isoleucine is used as the amino acid, the upper right graph is for the case where leucine is used as the amino acid, the lower left graph is for the case where lysine hydrochloride is used as the amino acid, and the lower right graph is for the case where methionine is used as the amino acid. [Figure 5] This is a diagram showing the cell viability of a mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + amino acids) is applied. The graph on the upper left is for when phenylalanine is used as the amino acid, the graph on the upper right is for when tyrosine is used as the amino acid, and the graph on the lower left is for when anserine is used as the amino acid. [Figure 6] This is a graph showing the cell viability of a mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + vitamins and minerals) was applied. The upper left graph is for when vitamin B1 was used as the vitamin, the upper right graph is for when vitamin B6 was used as the vitamin, the lower left graph is for when vitamin B12 was used as the vitamin, and the lower right graph is for when vitamin E was used as the vitamin. [Figure 7] This is a graph showing the cell viability of a mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + vitamins and minerals) was applied. The graph on the top left shows the results when niacin was used as the vitamin, the graph on the top right shows the results when folic acid was used as the vitamin, and the graph on the bottom left shows the results when vitamin K was used as the vitamin. [Figure 8] FIG. 1 is a graph showing the cell viability of a mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + vitamins and minerals) was applied, and zinc was used as the mineral. DETAILED DESCRIPTION OF THE INVENTION

[0013] The anti-fatigue agent of the present invention is characterized by containing, as active ingredients, ornithine or a salt thereof and at least one component (hereinafter sometimes referred to as "other component") selected from the group consisting of the following (a) to (d):

[0014] The anti-fatigue agent of the present invention can reduce physical fatigue and mental fatigue caused by physical fatigue, and specifically can prevent and improve fatigue. That is, by taking the anti-fatigue agent of the present invention before work, a fatigue prevention effect is obtained, in which the occurrence of fatigue during work after taking the agent is suppressed (making fatigue less likely to occur), and by taking the agent after work, a fatigue improvement effect is obtained, in which fatigue caused by work is improved (recovered). Furthermore, by reducing muscle fatigue during sleep, a relaxing effect during sleep can be achieved.

[0015] [Ornithine] Ornithine as the active ingredient of the anti-fatigue agent of the present invention can be L-ornithine or D-ornithine, but preferably L-ornithine.Ornithine can be obtained by chemical synthesis, or by fermentation, and its manufacturing method is not limited.In addition, as long as it is a pharmaceutically acceptable salt, the salt of ornithine is not particularly limited, and can include, for example, inorganic acid salt, organic acid salt, and metal salt.Ornithine is commercially available as medicine, reagent, etc., and these commercially available products can be used.

[0016] [Other ingredients]

[0017] (a) Plant material In the anti-fatigue agent of the present invention, it is preferable to use at least one plant material selected from pine and rice as an active ingredient together with ornithine or a salt thereof.

[0018] These plant materials may be any part of the plant, such as leaves, stems, roots, flowers, fruits, trunks, or branches. In addition to the plant material itself (including dried products), processed plant material products such as crushed products, juice, and extracts can be used. Examples of crushed products include powders and granules. Juices and extracts may be in liquid form, but can also be used as pastes or dry powders. Extracts can be obtained by extraction using an appropriate solvent, and examples of solvents that can be used include water (hot water), ethanol, and aqueous ethanol. These plant materials can be commercially available.

[0019] Examples of pine include French maritime pine (Pinus Martima), larch, black pine, red pine, etc., among which French maritime pine (Pinus Martima), which is rich in proanthocyanidins, is preferred. The part used as the plant material of the present invention is preferably bark, and an extract obtained from this pine bark is particularly preferred. This extract contains high concentrations of proanthocyanidins as well as oligomeric proanthocyanidins, and for example, it is preferred that the extract contains 20% by mass or more of oligomeric proanthocyanidins based on the dry mass of the extract.

[0020] Rice is a plant of the genus Oryza in the family Poaceae. The parts used as the plant material of the present invention are preferably the husk and embryo of brown rice, and more specifically, rice bran, which is obtained as a by-product during the polishing of brown rice, is preferably used. The type of rice is not particularly limited, and examples include japonica and indica varieties.

[0021] (b) sweeteners In the anti-fatigue agent of the present invention, it is preferable to use at least one sweetener selected from aspartame, trehalose, and reduced palatinose as an active ingredient together with ornithine or a salt thereof. The sweetener of the present invention means an agent that exhibits sweetness, and is not limited to being used as a sweetener.

[0022] (c) Amino acids In the anti-fatigue agent of the present invention, it is preferable to use, together with ornithine or its salt, at least one amino acid (including a salt) selected from glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, tyrosine, and anserine as an active ingredient. Examples of the salt include sodium salt and hydrochloride.

[0023] (d) Vitamins and minerals In the anti-fatigue agent of the present invention, it is preferable to use, together with ornithine or a salt thereof, at least one vitamin / mineral selected from vitamin B1, vitamin B6, vitamin B12, vitamin E, niacin, folic acid, vitamin K, and zinc as an active ingredient. Note that zinc as a mineral in the present invention includes the form of a compound containing zinc.

[0024] The anti-fatigue agent of the present invention is not particularly limited as long as it contains ornithine or a salt thereof and other specified ingredients and can be distinguished from other products in terms of its anti-fatigue properties. For example, the scope of the present invention includes products that display an anti-fatigue function on the product itself, packaging, instructions, or promotional materials. Examples of such products include so-called health foods, such as pharmaceuticals (including quasi-drugs), functional foods designated as foods for specified health uses, nutritional functional foods, and functional food products whose efficacy has been recognized by designated organizations, as well as animal feed. Examples of so-called health foods include those labeled with claims such as "for persistent fatigue," "for daily fatigue," "supports high physical and mental performance," "improves fatigue," "improves stress," "improves sleep," "improves sleep," and "for those who easily get tired." While the anti-fatigue agent of the present invention can be taken by anyone concerned about the above-mentioned effects, regardless of gender or age, it is recommended that healthy individuals, excluding those with illnesses, take the agent to more effectively enjoy the effects of the anti-fatigue agent of the present invention. Furthermore, since reducing muscle fatigue during sleep provides a relaxing effect during sleep, it is recommended that the agent be taken at night, and even more preferably before sleep.

[0025] Examples of the form of the anti-fatigue agent of the present invention include tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, pills, pastes, creams, caplets, gels, chewable tablets, and sticks. Among these, tablets, capsules, powders, granules, and liquids are particularly preferred. Specific examples include supplements, packaged beverages filled in PET bottles, cans, jars, etc., and instant powdered beverages and instant granular beverages that can be dissolved in water (hot water), milk, fruit juice, green juice, etc. for consumption. These are preferred because they are easy to drink during meals and can enhance palatability.

[0026] The content of ornithine and other ingredients (active ingredients) in the anti-fatigue agent of the present invention may be appropriately determined within the range in which the effects thereof are exhibited.

[0027] Generally, when the anti-fatigue agent of the present invention is a pharmaceutical or supplement (tablet, capsule), the active ingredient is preferably contained in an amount of 0.01 to 100% by mass, more preferably 0.1 to 85% by mass, and even more preferably 0.5 to 70% by mass, of the total amount converted to dry mass.

[0028] When the anti-fatigue agent of the present invention is a packaged beverage (liquid), the active ingredient is preferably contained in an amount of 0.01 to 10 mass % of the total amount, calculated as dry mass, more preferably 0.03 to 6 mass %, and even more preferably 0.05 to 4 mass %.

[0029] Furthermore, when the anti-fatigue agent of the present invention is an instant powdered drink (powder) or an instant granular drink (granules), the active ingredient is preferably contained in an amount of 1 to 100% by mass, more preferably 5 to 90% by mass, and even more preferably 10 to 80% by mass, of the total amount converted to dry mass.

[0030] To more effectively exert the effects of the present invention, the active ingredient preferably accounts for 80% or more of the total amount of the anti-fatigue agent of the present invention (excluding water) in terms of dry mass, more preferably 90% or more, even more preferably 95% or more, and particularly preferably 100%. Furthermore, when the anti-fatigue agent of the present invention contains any of components (a) to (d), it is preferable that the contained components consist solely of the active ingredient of the present invention. That is, when the anti-fatigue agent of the present invention contains, for example, component (a) (plant material), it is preferable that it is composed so as not to contain plant materials other than pine and rice.

[0031] The intake amount of the anti-fatigue agent of the present invention is not particularly limited, but from the viewpoint of more significantly exhibiting the effects of the present invention, it is preferable that the daily intake amount of the active ingredient is 100 mg / day or more, more preferably 200 mg / day or more, and even more preferably 300 mg / day or more. The upper limit is not particularly limited, but is, for example, 2 g / day, preferably 3 g / day. The anti-fatigue agent of the present invention can be stored as a daily dose in one container or divided into, for example, 2 to 3 multiple containers so that the daily intake amount is the above-mentioned intake amount.

[0032] The blending mass ratio of ornithines and other components is preferably in the range of 0.5:1 to 70:1, more preferably in the range of 0.75:1 to 60:1, even more preferably in the range of 1:1 to 60:1, and particularly preferably in the range of 1:1 to 50:1, in terms of dry mass. By having the blending ratio of ornithines and other components in the above range, the effects of the present invention can be more effectively exhibited.

[0033] The anti-fatigue agent of the present invention can be produced by a known formulation method by adding, as necessary, orally acceptable additives and ingredients other than the active ingredient.

[0034] Furthermore, examples of the anti-fatigue agent of the present invention include anti-fatigue foods containing the active ingredient, as well as anti-fatigue foods obtained by adding the active ingredient to a food, such as foods in which the content of the active ingredient of the present invention has been increased compared to ordinary foods (including natural foods), and foods that do not normally contain the active ingredient of the present invention to which the active ingredient has been added. The active ingredients may be added separately or simultaneously, or together with other ingredients other than the active ingredient.

[0035] Examples of the anti-fatigue food of the present invention include beverages such as carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, smoothies, and green juice; frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba, udon, harusame, Chinese noodles, and instant noodles; sweets such as candy, candy, gum, chocolate, tablet sweets, snacks, biscuits, jelly, jam, cream, baked goods, and bread; processed seafood and livestock foods such as kamaboko, ham, and sausage; processed milk, fermented milk, Examples include dairy products such as yogurt; oils and fats such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing, and processed foods thereof; seasonings such as sauces and soy sauce; and retort pouch foods such as curry, stew, oyakodon, rice porridge, porridge, Chinese rice bowl, katsudon, tempura bowl, beef bowl, hayashi rice, omelet rice, oden, mapo dolphin, gyoza, shumai, hamburger steak, meatballs, various sauces, and various soups.

[0036] The fatigue-reducing method of the present invention is characterized by ingesting the anti-fatigue agent of the present invention as described above, but does not constitute a medical procedure. The anti-fatigue agent of the present invention can be administered to anyone concerned about the above-mentioned effects, regardless of gender or age. However, since the effects of the anti-fatigue agent of the present invention can be more effectively enjoyed, it is preferable for healthy people, excluding those with illnesses, to ingest it. Furthermore, since reducing muscle fatigue during sleep provides a relaxing effect during sleep, it is preferable to ingest it at night, and even more preferable to ingest it before sleep. An example of the method of the present invention is a method of reducing fatigue by providing the anti-fatigue food of the present invention in a restaurant or other eating and drinking establishment. [Example]

[0037] The present invention will be described below based on examples. [Example 1] (1) Mouse myoblast cell line C2C12 was cultured at 5 × 10 3 The cells were seeded onto a 96-well plate at 100 cells / well. (2) After overnight pre-culture and removal of the culture supernatant, samples were added as shown in Tables 1 and 2 below.

[0038] Each sample was prepared as follows. Each sample was dissolved in 10% FBS-DMEM at 5 mg / mL (or 1.28 mg / mL), stirred by inversion for 1 hour, and then filtered to prepare the stock solution. However, the hydrophobic sample was dissolved in DMSO at 50 mg / mL to prepare the stock solution.

[0039] The prepared stock solution was further diluted with 10% FBS-DMEM to a concentration twice the desired final concentration. The hydrophobic sample was adjusted to a concentration twice the desired final concentration in 1% DMSO-10% FBS-DMEM.

[0040] As for ornithine, commercially available L-ornithine hydrochloride was used. As other components used together with ornithine, the substances shown in Tables 3 to 6 were used.

[0041] [Table 1]

[0042] [Table 2]

[0043] (3) 24 hours after the addition of the sample, the cell viability was measured using Cell Counting Kit-8. The reagents were adjusted so that the ratio of DMEM medium to WST-8 solution was 20:1.

[0044] After removing the culture supernatant, each well was washed once with PBS. After removing the PBS, 150 μL of the above WST-8 preparation solution was dispensed into each well. As soon as color developed (approximately 15 minutes later), the absorbance at 450 nm was measured.

[0045] The results are shown in Tables 3 to 6 and Figures 1 to 8. Each graph in the figure represents, from left to right, the results of "control (no addition)," "ornithine (O) alone added," "other components alone added," and "ornithine + other components added." The numerical values ​​in the legend below the graphs indicate the sample concentrations; for example, "O_0.25" in the left graph of Figure 1 indicates 0.25 μg / mL of ornithine. The concentration units of the added components are μg / mL in all graphs.

[0046] [Table 3]

[0047] For pine, a hot water extract (dried powder) of the bark of French maritime pine was used. Commercially available rice bran was used. For mugwort, finely ground fresh leaves were used.

[0048] [Table 4]

[0049] [Table 5]

[0050] [Table 6]

[0051] As shown in Tables 3 to 6 and Figures 1 to 8, muscle cells were activated synergistically by combining ornithine with other specific components of the present invention. Therefore, the anti-fatigue agent of the present invention can more effectively alleviate fatigue.

[0052] [Example 2] (Production of tablets) Tablets were prepared consisting of the following ingredients:

[0053] L-ornithine hydrochloride 130mg (100mg as ornithine) Fructooligosaccharides 20mg Pine bark extract 10mg Arginine 20mg Isoleucine 5mg Leucine 5mg Lysine 2mg Vitamin E 1mg Silicon dioxide 30mg Shellac 20mg

[0054] Take 5 to 10 tablets a day with water without chewing.

[0055] [Example 3] (Production of capsules) 400 mg of the following mixture was encapsulated in a soft capsule to prepare a capsule preparation.

[0056] L-ornithine hydrochloride 260mg (200mg as ornithine) Arginine 60mg Lysine 8mg Folic acid 10mg Vitamin B1 10mg Niacin 10mg Glycerin fatty acid ester 5mg Silicon dioxide 37mg

[0057] Take five capsules a day with water without chewing.

[0058] [Example 4] (Production of Granules) The following ingredients were mixed and prepared into granules (3000 mg) in a conventional manner.

[0059] L-ornithine hydrochloride 2600mg (2000mg as ornithine) Rice bran extract 200mg Glutamine 60mg Glutamic acid 40mg Vitamin B12 10mg Zinc gluconate 5mg Lactose 50mg Indigestible dextrin 25mg Sucrose fatty acid ester 10mg

[0060] The granules are taken once a day with water.

[0061] [Example 5] (Production of liquid formulation) A liquid formulation (100 mL) consisting of the following components was prepared.

[0062] Aspartame 500mg Trehalose 400mg L-ornithine hydrochloride 400mg Pine bark extract 100mg Niacin 60mg Folic acid 50mg Vitamin C 50mg Vitamin B12 30mg Citric acid 20mg Fragrance (appropriate amount) water remainder [Industrial Applicability]

[0063] The anti-fatigue agent of the present invention has a fatigue-reducing effect and can be used as an oral preparation, and therefore the present invention is highly industrially useful.

Claims

[Claim 1] A food composition comprising ornithine or a salt thereof and at least one free amino acid selected from isoleucine and leucine.

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