JP2019194246A - Anti-fatigue agent - Google Patents

Abstract

To provide an anti-fatigue agent having a high fatigue alleviation effect.SOLUTION: An anti-fatigue agent contains ornithine or a salt thereof, and at least one component selected from the group consisting of the following (a)-(d) as active ingredients: (a) rice, (b) at least one sweetener selected from aspartame, trehalose, and reduction 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.SELECTED DRAWING: Figure 1

Description

  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 ornithine) and a specific other component as an active ingredient.

  Under the circumstances of long working hours and excessive stress in recent years, physical and mental fatigue is likely to accumulate, and the development of drugs and the like for the purpose of improving fatigue of these fatigues has been actively conducted.

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

No. 2007-142286 JP 2014-193903 A

  The subject of this invention is providing the anti-fatigue agent with a high fatigue reduction effect.

  The present inventors diligently investigated and studied the fatigue-reducing effect of ornithine, and found that a combination of ornithine and a specific other component can provide a high fatigue-reducing effect, leading to the completion of the present invention. It was. Specifically, the present inventors have found that the ability to reduce fatigue can be synergistically improved by combining ornithine with other specific components that have little or no ability to reduce fatigue.

That is, the present invention relates to an anti-fatigue agent comprising 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) glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, At least one amino acid selected from lysine, methionine, phenylalanine, tyrosine, and anserine (d) at least one amino acid selected from vitamin B1, vitamin B6, vitamin B12, vitamin E, niacin, folic acid, vitamin K, and zinc Vitamins and minerals

  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).

  In the anti-fatigue agent of the present invention, the blending mass ratio of ornithine or a salt thereof and another active ingredient is preferably in the range of 0.5: 1 to 70: 1. Moreover, it is preferable that they are a tablet, a capsule, a powder agent, a granule, or a liquid agent.

  Furthermore, this invention relates to the fatigue reduction method (however, except medical practice) characterized by ingesting the said anti-fatigue agent.

  According to the anti-fatigue agent of the present invention, a high fatigue reduction effect can be obtained.

It is a figure which shows the cell survival rate of a mouse | mouth myoblast cell strain at the time of applying the anti-fatigue agent (ornithine + plant material) of this invention. The graph on the left uses pine as the plant material, and the graph on the right uses rice (rice bran) as the plant material. It is a figure which shows the cell viability of a mouse | mouth myoblast cell line at the time of applying the anti-fatigue agent (ornithine + sweetener) of this invention. The upper left graph uses aspartame as a sweetener, the upper right graph uses trehalose as a sweetener, and the lower left graph uses reduced palatinose as a sweetener. It is a figure which shows the cell survival rate of a mouse | mouth myoblast cell line at the time of applying the anti-fatigue agent (ornithine + amino acids) of this invention. The upper left graph uses glutamine as the amino acid, the upper right graph uses glutamic acid as the amino acid, the lower left graph uses glycine as the amino acid, and the lower right This graph uses histidine as an amino acid. It is a figure which shows the cell survival rate of a mouse | mouth myoblast cell line at the time of applying the anti-fatigue agent (ornithine + amino acids) of this invention. The upper left graph uses isoleucine as the amino acid, the upper right graph uses leucine as the amino acid, and the lower left graph uses lysine-hydrochloride as the amino acid. The lower right graph uses methionine as an amino acid. It is a figure which shows the cell survival rate of a mouse | mouth myoblast cell line at the time of applying the anti-fatigue agent (ornithine + amino acids) of this invention. The upper left graph uses phenylalanine as the amino acid, the upper right graph uses tyrosine as the amino acid, and the lower left graph uses anserine as the amino acid. It is a figure which shows the cell survival rate of a mouse | mouth myoblast cell strain at the time of applying the anti-fatigue agent (ornithine + vitamin-mineral) of this invention. The upper left graph uses vitamin B1 as vitamins, the upper right graph uses vitamin B6 as vitamins, and the lower left graph uses vitamin B12 as vitamins. The lower right graph uses vitamin E as vitamins. It is a figure which shows the cell survival rate of a mouse | mouth myoblast cell strain at the time of applying the anti-fatigue agent (ornithine + vitamin-mineral) of this invention. The upper left graph uses niacin as vitamins, the upper right graph uses folic acid as vitamins, and the lower left graph uses vitamin K as vitamins. It is a figure which shows the cell viability of a mouse | mouth myoblast cell line at the time of applying the anti-fatigue agent (ornithine + vitamin-minerals) of this invention, and uses zinc as minerals.

  The anti-fatigue agent of the present invention contains 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 other components) as active ingredients. It is characterized by that.

  The anti-fatigue agent of the present invention can reduce physical fatigue and mental fatigue resulting from physical fatigue. Specifically, fatigue can be prevented and improved. That is, by taking the anti-fatigue agent of the present invention before work, the fatigue prevention effect that suppresses the occurrence of fatigue in the work after ingestion (to reduce fatigue) is obtained, and by taking after work, The fatigue improvement effect which improves (recovers) the fatigue caused by is obtained. Moreover, the relaxation effect during sleep is acquired by reducing muscle fatigue during sleep.

[Ornithine]
The ornithine as an active ingredient of the anti-fatigue agent of the present invention may be L-ornithine or D-ornithine, but is preferably L-ornithine. Ornithine can be produced by any method, such as those obtained by chemical synthesis and those obtained by fermentation. The ornithine salt is not particularly limited as long as it is a pharmaceutically acceptable salt, and examples thereof include inorganic acid salts, organic acid salts, and metal salts. Ornithine is commercially available as pharmaceuticals, reagents, etc., and these commercially available products can be used.

[Other ingredients]

(A) Plant material In the anti-fatigue agent of this invention, it is preferable to use at least 1 sort of plant material chosen from a pine and a rice as an active ingredient with ornithine or its salt.

  These plant materials may be any part of the plant such as leaves, stems, roots, flowers, fruits, trunks, branches, etc. In addition to the plant materials themselves (including dried products), pulverized products, juices In addition, a processed plant material such as an extract can be used. Examples of the pulverized product include powder and granules. The juice or extract may be liquid, but can also be used as a paste or dry powder. The extract can be obtained by extraction using an appropriate solvent. As the solvent, for example, water (hot water), ethanol, or hydrous ethanol can be used. As these plant materials, commercially available products can be used.

  Examples of the pine include French coastal pine (Pinus Martina), larch, black pine, and red pine. Among these, French coastal pine (Pinus Martina) rich in proanthocyanidins is preferable. The bark is preferred as the site used as the plant material of the present invention, and an extract obtained from this pine bark is particularly preferred. This extract contains a high concentration of oligomeric proanthocyanidins in addition to proanthocyanidins. For example, it is preferable that the extract contains 20% by mass or more of oligomeric proanthocyanidins with respect to the dry mass of the extract.

  Rice is a plant belonging to the genus Gramineae. The part used as the plant material of the present invention is preferably brown rice hulls or embryos. Specifically, it is preferable to use rice bran obtained as a by-product when white rice is refined. There is no restriction | limiting in particular as a kind of rice, A japonica seed | species, an indica seed | species, etc. can be mentioned.

(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 a sweetener and is not limited to the purpose of use as a sweetener.

(C) Amino acids In the anti-fatigue agent of the present invention, together with ornithine or a salt thereof, as an active ingredient, at least selected from glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, tyrosine, and anserine One amino acid (including a salt) is preferably used. Examples of the salt include sodium salt and hydrochloride.

(D) Vitamins and minerals The anti-fatigue agent of the present invention is selected from vitamin B1, vitamin B6, vitamin B12, vitamin E, niacin, folic acid, vitamin K, and zinc as an active ingredient together with ornithine or a salt thereof. It is preferable to use at least one vitamin / mineral. In addition, zinc as minerals of this invention contains the form of the compound containing zinc.

  The anti-fatigue agent of the present invention is particularly limited as long as it contains ornithine or a salt thereof and a predetermined other component and can be distinguished from other products as a product in terms of being used for anti-fatigue. Instead, for example, the display of the fact that any of the main body, packaging, instructions, and promotional material of the product according to the present invention has an anti-fatigue function is included in the scope of the present invention. For example, so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods for which the indication of efficacy has been approved by specified organizations such as foods for specified health use, functional nutritional foods, functional labeling foods, feed, etc. Can be mentioned. In so-called health foods, “for continued fatigue”, “for daily fatigue”, “supporting high physical and mental performance”, “improvement of fatigue”, “improvement of stress”, “improvement of sleep”, Examples of the display are “enhancing sleep”, “to easily get tired”, and the like. The anti-fatigue agent of the present invention can be taken regardless of gender and age as long as the above-mentioned effects are concerned, because the effect of the anti-fatigue agent of the present invention can be enjoyed more effectively. It is desirable for healthy people except sick people to take. Moreover, since the relaxation effect during sleep can be obtained by reducing muscle fatigue during sleep, it is desirable to take it at night, and more desirably before sleep.

  Examples of the anti-fatigue agent of the present invention include tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, rounds, and pastes. Agents, cream agents, caplet agents, gel agents, chewable agents, stick agents and the like. Among these, the forms of tablets, capsules, powders, granules, and liquids are particularly preferable. Specifically, supplements, container-packed beverages filled in PET bottles, cans, bottles, etc., instant powder beverages and instant granule beverages for dissolving and drinking in water (hot water), milk, fruit juice, green juice, etc. Can be illustrated. These are preferable in that they can be easily taken at the time of eating and the like, and can enhance palatability.

  The contents of ornithine and other components (active ingredients) in the anti-fatigue agent of the present invention may be appropriately contained within the range where the effects are exerted.

  In general, when the anti-fatigue agent of the present invention is a pharmaceutical or a supplement (tablet, capsule), the active ingredient is preferably contained in an amount of 0.01 to 100% by mass in terms of dry mass, It is more preferable that 0.1-85 mass% is contained, and it is further more preferable that 0.5-70 mass% is contained.

  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% by mass in terms of dry mass, and 0.03 to 6% by mass. More preferably, it is more preferably contained in an amount of 0.05 to 4% by mass.

  Moreover, when the anti-fatigue agent of this invention is an instant powdered drink (powder) and an instant granule drink (granule), 1-100 mass% of active ingredients may be contained in dry mass conversion. Preferably, 5 to 90% by mass is contained, and 10 to 80% by mass is more preferred.

  In order to exhibit the effect of the present invention more effectively, it is preferable that 80% or more of the whole anti-fatigue agent of the present invention (excluding moisture) is contained in terms of dry mass, and 90% or more is contained. More preferably, it is more preferably 95% or more, and particularly preferably 100%. Furthermore, when the anti-fatigue agent of this invention contains any of component (a)-(d), it is preferable that the component contained is comprised only with the active ingredient in this invention. That is, when the anti-fatigue agent of this invention contains a component (a) (plant material), it is preferable to comprise so that plant materials other than a pine and a rice may not be included.

  Although there is no restriction | limiting in particular as an intake of the anti-fatigue agent of this invention, From a viewpoint of exhibiting the effect of this invention more notably, it ingests so that the intake of the active ingredient per day may be 100 mg / day or more. It is preferable to take it so that it becomes 200 mg / day or more, and it is more preferable to take it so that it may become 300 mg / day or more. Although the upper limit in particular is not restrict | limited, For example, it is 2 g / day, Preferably it is 3 g / day. The anti-fatigue agent of the present invention can be stored in one container, or divided into a plurality of containers, for example, as one day so that the daily intake becomes the above-mentioned intake.

  The blending mass ratio of ornithine and other components is preferably in the range of 0.5: 1 to 70: 1 in terms of dry mass, and more preferably in the range of 0.75: 1 to 60: 1. Preferably, it is in the range of 1: 1 to 60: 1, more preferably in the range of 1: 1 to 50: 1. The effects of the present invention can be more effectively exhibited when the blending ratio of ornithine and other components is within the above range.

  The anti-fatigue agent of this invention can be manufactured by a well-known formulation method, adding the additive accept | permitted for oral use, and components other than an active ingredient as needed.

  Examples of the anti-fatigue agent of the present invention include anti-fatigue foods containing active ingredients, and anti-fatigue foods obtained by adding active ingredients to foods. For example, normal foods Examples include foods in which the content of the active ingredient of the present invention is increased compared to (including natural foods), and foods that do not normally contain the active ingredient of the present invention. For the addition of the active ingredients, the respective ingredients may be added separately, may be added simultaneously, or may be added together with other ingredients other than the active ingredients.

  Examples of the anti-fatigue food of the present invention include carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages, smoothies, green juice and other frozen desserts; ice cream, ice sherbet, shaved ice and other frozen desserts; Noodles such as noodles and instant noodles; sweets such as candy, candy, gum, chocolate, tablet confectionery, snack confectionery, biscuits, jelly, jam, cream, baked confectionery and bread; fishery and livestock processed foods such as kamaboko, ham and sausage Dairy products such as processed milk, fermented milk, yogurt; salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing and other fats and processed foods; seasonings such as sauces, soy sauce; curry, stew, oyakodon , Porridge, miscellaneous cooking, Chinese rice bowl, bonito, tempura bowl, beef bowl, hayashi rice, omelet rice, oden, mabodo , Mention may be made of dumplings, Shumai, hamburger, meatballs, various sources, retort pouch foods such as various soups and the like.

  The fatigue reducing method of the present invention is characterized by ingesting the anti-fatigue agent of the present invention described above, but does not include medical practice. The anti-fatigue agent of the present invention can be taken regardless of gender or age if it is a person who is concerned about the above-mentioned effect, but can enjoy the effect of the anti-fatigue agent of the present invention more effectively. It is desirable for healthy people except sick people to take them. Moreover, since the relaxation effect during sleep can be obtained by reducing muscle fatigue during sleep, it is preferably taken at night, and more preferably taken before sleep. Examples of the method of the present invention include a method for reducing fatigue by providing the anti-fatigue food of the present invention in a restaurant such as a restaurant.

Hereinafter, the present invention will be described based on examples.
[Example 1]
(1) A mouse myoblast cell line C2C12 was seeded on a 96-well plate so as to be 5 × 10 ³ cells / well.
(2) Pre-cultured overnight, and after removing the culture supernatant, 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 5 mg / mL (or 1.28 mg / mL), and after stirring for 1 h by inversion, filtering was performed as a stock solution. However, the hydrophobic sample was dissolved in DMSO so as to be 50 mg / mL as a stock solution.

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

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

(3) 24 hours after the sample addition, the cell viability was measured using Cell Counting Kit-8. At this time, the reagent was adjusted so that DMEM medium: WST-8 solution = 20: 1.

  After removing the culture supernatant, each well was washed once with PBS, and after removing PBS, 150 μL of the WST-8 preparation was dispensed. As soon as the color developed (after about 15 minutes), the absorbance at 450 nm was measured.

  The results are shown in Tables 3 to 6 and FIGS. Each graph in the figure represents the results of “control (no addition)”, “alone addition of ornithine (O)”, “single addition of other components”, and “addition of ornithine and other components” from the left. The numerical value in the description at the bottom of the graph indicates the sample concentration. For example, “O_0.25” in the left graph in FIG. 1 indicates ornithine 0.25 (μg / mL). The concentration unit of the additive component is μg / mL in all graphs.

As for pine, a hot water extract (dry powder) of bark of French coastal pine was used.
For rice (rice bran), a commercial product was used.
For mugwort, finely ground powder was used.

  As shown in Tables 3 to 6 and FIGS. 1 to 8, myocytes were activated synergistically by combining ornithine and specific other components of the present invention. Therefore, according to the anti-fatigue agent of the present invention, fatigue can be more effectively reduced.

[Example 2] (Manufacture of tablets)
A tablet comprising the following components was produced.

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

  Take the above tablets with water without chewing 5-10 tablets a day.

[Example 3] (Manufacture of capsules)
400 mg of the following mixture was enclosed in a soft capsule to produce a capsule.

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

  Take the above capsules with water without chewing 5 tablets a day.

[Example 4] (Production of granules)
The following ingredients were mixed to produce granules (3000 mg) by a conventional method.

L-ornithine hydrochloride 2600 mg (2000 mg 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

  Take one granule together with water etc. a day.

[Example 5] (Manufacture of solution)
A liquid (100 mL) comprising the following components was produced.

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
Perfume appropriate amount water balance

  Since the anti-fatigue agent of the present invention has a fatigue reducing effect and can be used as an oral agent, the industrial utility of the present invention is high.

Claims (1)

An anti-fatigue agent comprising 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) Rice (b) At least one sweetener selected from aspartame, trehalose, and reduced palatinose (c) Selected from glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, tyrosine, and anserine (D) at least one vitamin / mineral selected from vitamin B1, vitamin B6, vitamin B12, vitamin E, niacin, folic acid, vitamin K, and zinc