JP7462338B2 - Anti-fatigue - Google Patents

Description

The present invention relates to an anti-fatigue agent, and more specifically, to an anti-fatigue agent containing ornithine or a salt thereof (hereinafter sometimes simply referred to as ornithines) and other specific ingredients as active ingredients.

In recent years, physical and mental fatigue can easily accumulate due to long working hours and excessive stress, and there has been active development of medicines and other products aimed at improving this fatigue.

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

Republished Patent Publication No. 2007-142286 JP 2014-193903 A

The objective of the present invention is to provide an anti-fatigue agent that is highly effective in reducing fatigue.

The inventors conducted extensive research and studies into the fatigue-reducing effect of ornithine, and discovered that a high fatigue-reducing effect can be achieved by combining ornithine with other specific ingredients, leading to the completion of the present invention. Specifically, they discovered that by combining ornithine with other specific ingredients that have little or no fatigue-reducing ability, it is possible to synergistically improve the fatigue-reducing ability.

That is, the present invention relates to an anti-fatigue agent characterized by containing ornithine or a salt thereof and at least one component selected from the group consisting of the following (a) to (d) as active ingredients:
(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; and (d) at least one vitamin and mineral selected from vitamin B1, vitamin B6, vitamin B12, vitamin E, niacin, folic acid, vitamin K, and zinc.

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

The anti-fatigue agent of the present invention preferably has a mass ratio of ornithine or a salt thereof to other active ingredients in the range of 0.5:1 to 70:1. It is also preferable that the agent is in the form of a tablet, capsule, powder, granule, or liquid.

The present invention further relates to a method for reducing fatigue (excluding medical procedures) that comprises ingesting the above-mentioned anti-fatigue agent.

The anti-fatigue agent of the present invention can provide a high fatigue reduction effect.

This is a diagram showing the cell viability of mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + plant material) is applied. The left graph is for pine as the plant material, and the right graph is for rice (rice bran) as the plant material. This is a diagram showing the cell viability of mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + sweetener) is applied. The graph on the upper left shows the results when aspartame is used as a sweetener, the graph on the upper right shows the results when trehalose is used as a sweetener, and the graph on the lower left shows the results when reduced palatinose is used as a sweetener. Fig. 1 shows the cell viability of mouse myoblast cell line when the anti-fatigue agent (ornithine + amino acids) of the present invention is applied.The graph on the upper left shows the graph using glutamine as amino acid, the graph on the upper right shows the graph using glutamic acid as amino acid, the graph on the lower left shows the graph using glycine as amino acid, and the graph on the lower right shows the graph using histidine as amino acid. This is a diagram showing the cell viability of 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. FIG. 1 shows the cell viability of mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + amino acids) is applied. The graph on the upper left shows the graph using phenylalanine as amino acid, the graph on the upper right shows the graph using tyrosine as amino acid, and the graph on the lower left shows the graph using anserine as amino acid. This is a diagram showing the cell viability of mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + vitamins and minerals) is applied.The upper left graph shows the vitamin B1 used as vitamin, the upper right graph shows the vitamin B6 used as vitamin, the lower left graph shows the vitamin B12 used as vitamin, and the lower right graph shows the vitamin E used as vitamin. This is a diagram showing the cell viability of mouse myoblast cell line when the anti-fatigue agent of the present invention (ornithine + vitamins and minerals) is applied. The upper left graph shows the results of using niacin as vitamins, the upper right graph shows the results of using folic acid as vitamins, and the lower left graph shows the results of using vitamin K as vitamins. FIG. 1 is a graph showing the cell survival rate 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 minerals.

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

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 working, a fatigue prevention effect is obtained in which the occurrence of fatigue is suppressed (making it difficult to get tired) during work after taking the agent, and by taking the agent after work, a fatigue improvement effect is obtained in which fatigue caused by work is improved (recovered). In addition, by reducing muscle fatigue during sleep, a relaxing effect during sleep can be obtained.

[Ornithine]
Ornithine, which is the active ingredient of the anti-fatigue agent of the present invention, may be L-ornithine or D-ornithine, but is preferably L-ornithine. Ornithine may be obtained by chemical synthesis, fermentation, or any other method of production. In addition, the salt of ornithine is not particularly limited as long as it is a pharmacologic acceptable salt, and examples thereof include inorganic acid salts, organic acid salts, and metal salts. Ornithine is commercially available as a pharmaceutical product, a reagent, and the like, and these commercially available products can be used.

[Other ingredients]

(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 together with ornithine or a salt thereof as an active ingredient.

These plant materials may be any part of the plant, such as leaves, stems, roots, flowers, fruits, trunks, branches, etc., and in addition to the plant materials themselves (including dried products), processed plant materials such as crushed products, juice, extracts, etc. can be used. Examples of crushed products include powders and granules. The juice and extracts may be in liquid form, but can also be used in the form of a paste or dried powder. Extracts can be obtained by extraction using a suitable solvent, and examples of the solvent that can be used include water (hot water), ethanol, and aqueous ethanol. These plant materials can be commercially available.

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

Rice is a plant of the genus Oryza in the family Poaceae. The parts of the plant used as the plant material of the present invention are preferably the outer husk and embryo of brown rice, and more specifically, it is preferable to use rice bran, which is obtained as a by-product when brown rice is polished. There are no particular limitations on the type of rice, and examples include the japonica and indica varieties.

(b) Sweetener 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 one that exhibits sweetness, and is not limited to the purpose of use as a sweetener.

(c) Amino acids In the anti-fatigue agent of the present invention, it is preferable to use 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 together with ornithine or a salt thereof. Examples of the salt include sodium salt and hydrochloride.

(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 and 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 of the present invention includes the form of a compound containing zinc.

The anti-fatigue agent of the present invention is not particularly limited as long as it contains ornithine or a salt thereof and a specified other ingredient, and can be distinguished from other products in terms of its use for anti-fatigue. For example, the scope of the present invention includes products that display the anti-fatigue function on the main body, packaging, instructions, or advertising materials of the product according to the present invention. Examples of the anti-fatigue agent include so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods such as specified health foods, nutritional functional foods, and functional foods whose efficacy has been approved by a specified organization, and feed. Examples of so-called health foods include those that display the following: "For continued fatigue," "For daily fatigue," "Supports high physical and mental performance," "Improves fatigue," "Improves stress," "Improves sleep," "Improves sleep," and "For those who get tired easily." The anti-fatigue agent of the present invention can be taken by anyone who is concerned about the above effects, regardless of gender or age, but it is preferable for healthy people, excluding those with illnesses, to take it in order to enjoy the effects of the anti-fatigue agent of the present invention more effectively. In addition, since a relaxing effect during sleep can be obtained by reducing muscle fatigue during sleep, it is preferable to take it at night, and even more preferable to take it before sleep.

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, chewables, and sticks. Among these, tablets, capsules, powders, granules, and liquids are particularly preferred. Specific examples include supplements, packaged beverages filled in PET bottles, cans, bottles, and the like, and instant powdered beverages and instant granular beverages that are dissolved in water (hot water), milk, fruit juice, green juice, and the like before drinking. These are preferred because they are easy to drink during meals and can increase palatability.

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 effect is exhibited.

In general, when the anti-fatigue agent of the present invention is a medicine 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 mass calculated on a dry weight basis.

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

When the anti-fatigue agent of the present invention is an instant powdered beverage (powder) or an instant granular beverage (granule), 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 calculated on a dry weight basis.

In order to more effectively exert the effects of the present invention, the active ingredient is preferably contained in an amount of 80% or more of the entire anti-fatigue agent of the present invention (excluding water) calculated on a dry mass basis, 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 only of the active ingredient of the present invention. In other words, when the anti-fatigue agent of the present invention contains, for example, component (a) (a plant material), it is preferable that the composition does not contain any plant material other than pine or rice.

There is no particular limit to the amount of intake of the anti-fatigue agent of the present invention, but from the viewpoint of more significantly exerting the effects of the present invention, it is preferable to take the active ingredient so that the daily intake 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, and 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 multiple containers, for example, 2 to 3, so that the daily intake is the above-mentioned amount.

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.

The anti-fatigue agent of the present invention can be produced by known formulation methods by adding, as necessary, additives acceptable for oral use and ingredients other than the active ingredient.

The anti-fatigue agent of the present invention may be an anti-fatigue food containing the active ingredient, or an anti-fatigue food obtained by adding the active ingredient to a food, such as a food in which the content of the active ingredient of the present invention is increased compared to normal foods (including natural foods), or a food that does 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.

Examples of the anti-fatigue foods 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, jellies, jams, creams, baked goods, and bread; processed seafood and livestock foods such as kamaboko, ham, and sausages; processed milk, fermented milk, Examples include dairy products such as yogurt; fats and oils such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing, and processed foods; seasonings such as sauces and soy sauce; 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.

The fatigue reduction method of the present invention is characterized by ingesting the anti-fatigue agent of the present invention described above, but does not include medical procedures. The anti-fatigue agent of the present invention can be ingested by anyone who is concerned about the above-mentioned effects, regardless of gender or age, but it is preferable for healthy people, excluding those with illnesses, to ingest the agent, since the effects of the anti-fatigue agent of the present invention can be enjoyed more effectively. In addition, since reducing muscle fatigue during sleep provides a relaxing effect during sleep, it is preferable to ingest the agent at night, and even more preferable to ingest the agent 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 establishment.

The present invention will be described below with reference to examples.
[Example 1]
(1) Mouse myoblast cell line C2C12 was seeded into a 96-well plate at 5×10 ³ cells/well.
(2) After pre-incubation overnight, the culture supernatant was removed and samples were added as shown in Tables 1 and 2 below.

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

The prepared stock solution was further diluted with 10% FBS-DMEM to adjust the concentration to twice the desired final concentration. The hydrophobic sample was adjusted to twice the desired final concentration and to 1% DMSO-10% FBS-DMEM.

For ornithine, commercially available L-ornithine hydrochloride was used. As other ingredients used together with ornithine, the substances shown in Tables 3 to 6 were used.

(3) 24 hours after the addition of the samples, 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.

After removing the culture supernatant, each well was washed once with PBS, and 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.

The results are shown in Tables 3 to 6 and Figures 1 to 8. The graphs in the figures show, from left to right, the results for "control (no addition)", "ornithine (O) added alone", "other components added alone", and "ornithine + other components added". The numbers in the explanations below the graphs indicate the sample concentrations; for example, "O_0.25" in the graph on the left of Figure 1 indicates ornithine 0.25 (μg/mL). The concentration units for added components are μg/mL in all graphs.

For pine, a hot water extract (dried powder) of French maritime pine bark was used.
For rice (rice bran), a commercially available product was used.
For mugwort, finely ground fresh leaves were used.

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.

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

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

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

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

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

Take 5 capsules a day with water without chewing.

[Example 4] (Preparation of granules)
The following ingredients were mixed and prepared into granules (3,000 mg) in a conventional manner.

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

Take one packet of the above granules daily with water etc.

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

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 of water Remainder

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

Claims (3)

A food composition comprising ornithine or a salt thereof and aspartame (excluding the oral compositions (1) to (3) below).
(1) An oral composition for muscle building containing dextrose monohydrate, maltodextrin, creatine monohydrate, creatine malate, creatine taurate, L-lysine hydrochloride, N-acetyl-L-valine, L-valine α-ketoglutarate, L-valine ethyl ester hydrochloride, L-isoleucine pyroglutamate, L-isoleucine ethyl ester hydrochloride, N-acetyl-L-phenylalanine, L-threonine, L-histidine, L-histidine α-ketoglutarate, and L-methionine. (2) A diet drink containing coenzyme Q10, hyaluronic acid, ornithine hydrochloride, polyphenols, and dietary fiber. (3) An oral composition containing ornithine or a salt thereof, aspartame, and vinegar. A food composition comprising ornithine or a salt thereof and trehalose (excluding the oral compositions (1) to ( 5 ) below).
(1) A cosmetic beverage containing astaxanthin, cysteine peptide, vitamin C and ceramide. (2) A cheese containing ornithine. (3) An oral composition for preventing or treating hemoglobinuria or myoglobinuria containing a branched chain amino acid or a salt thereof, ornithine or a salt thereof, glutamine or a salt thereof, and trehalose.
(4) Food composition containing nameko
(5) Food composition containing Bunashimeji A food composition comprising ornithine or a salt thereof and reduced palatinose (excluding the oral compositions of (1) and (2) below).
(1) A supplement containing ornithine, curcumin and kudzu flowers. (2) A diet drink containing coenzyme Q10, hyaluronic acid, ornithine hydrochloride, polyphenols and dietary fiber.