JP2017088524A - Joint-range-of-motion increasing agent and muscle extension agent for oral ingestion, as well as oral ingestion compositions - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide compositions that can exert joint-range-of-motion increasing effect and/or muscle extension effect by oral ingestion.SOLUTION: The present invention relates to a joint-range-of-motion increasing agent or muscle extension agent for oral ingestion which contain arginine and citrulline as active ingredients. The invention also relates to a composition for oral ingestion containing 80-2,000 mg per oral dose of arginine and 80-2,000 mg per oral dose of citrulline.SELECTED DRAWING: Figure 2

Description

The present invention relates to a joint range-of-motion-enhancing agent having an action of increasing the range of joint motion when taken orally.
The present invention relates to a muscle stretcher having a muscle stretch action by oral ingestion.

  The present invention further relates to an orally ingestible composition that can be used as the above-mentioned range of motion enhancer and / or muscle stretcher.

  Arginine and citrulline are known as intermediates in the urea cycle.

  Patent Document 1 discloses that arginine has an action of dilating blood vessels, and as its action mechanism, nitric oxide synthase expressed in vascular endothelial cells synthesizes nitric oxide (NO) that dilates blood vessels from arginine. Is disclosed. In Patent Document 1, a composition containing arginine can increase blood flow in capillaries without lowering systemic blood pressure, and can prevent, reduce, or treat dementia, coldness, stiff shoulders, dullness, and muscle fatigue. Have been described.

  Patent Document 2 discloses that citrulline has physiological functions such as blood flow improvement by vasodilation, and citric acid and sodium citrate or Formulating with disodium hydrogen phosphate is disclosed.

  Patent document 3 also makes it a subject to solve the problem of off-flavor in a citrulline-containing composition, and discloses that pH is adjusted as a means therefor.

  Patent Document 4 discloses that citrulline is produced from arginine together with nitric oxide having a vasodilating action. Patent Document 4 discloses that muscle augmentation is expected by taking arginine. Patent Document 4 discloses that citrulline is used instead of arginine in order to exert the function of arginine, and that ingested citrulline is converted into arginine in the body.

  Patent Document 5 discloses an NO production enhancer containing citrulline and glutathione, and describes that symptoms associated with decreased blood flow (for example, decreased performance of exercise due to decreased skeletal muscle activity) can be prevented or improved. .

In Patent Document 6, it is disclosed in the background art column that vitamin B ₆ (pyridoxine), vitamin B ₂ (riboflavin) and the like have an action of promoting the synthesis of vascular endothelial nitric oxide.

Patent Document 7 describes that vitamin B type ₁ is used for joint pain and the like, and is particularly effective for relatively mild joint pain symptoms.

  On the other hand, as the factor that limits the range of motion of the joints such as the lumbar region and the hip joint, muscle is the largest, but besides muscle, skin, tendon, joint capsule, ligament, connective tissue and the like can be mentioned (Non-patent Document 1). Non-Patent Document 1 discloses that the joint movement limitation derived from a muscle is due to a decrease in the stretchability of the muscle.

  Non-Patent Document 2 discloses that, as an effect of stretching, blood flow volume increases due to stretching and muscle temperature rises, so that muscle hardness is reduced and extensibility is improved. Similarly, Non-Patent Document 3 discloses that muscle extensibility improves when blood flow increases.

Japanese Patent No. 5046174 WO2009 / 064004 Japanese Patent No. 4964793 Japanese Patent No. 5534806 WO2013 / 122188 JP 2007-186434 A JP 2002-145777 A

Sportsmedicine, 2011, No. 133, p. 15 Physiotherapy Science, 25 (5): 785-789, 2010 Blackwell et al., UNLV Theses / Dissertations / Professional Papers / Capstones, Paper 1328 (2012)

  Stretching when exercising is intended to prevent injury due to exercising, reduce fatigue, and the like. If muscle extension can be promoted and the range of motion of the joint can be increased, the effect of stretching can be enhanced.

  Conventionally, a technique for increasing the range of motion of joints by oral intake of a composition such as food has not been provided. In Non-Patent Documents 2 and 3, there is a description that muscle extensibility improves when blood flow increases, but muscle elongation and joint range of motion increase are combined in combination with various factors other than blood flow. As a result, in practice, muscle extension and joint range of motion increase are not always possible only by increasing blood flow. Conventionally, an orally ingested composition having an action of increasing blood flow is known, but it has not been studied at all whether it is effective in increasing the range of motion of the joint or stretching the muscle.

  Therefore, the present invention provides a range-of-motion-enhancing agent and a muscle extender that can exert an effect by oral intake, and a composition for oral intake that can be used as the above-mentioned range-of-motion enhancer and / or muscle extender. The purpose is to provide.

The present inventors have found that the following method is effective as means for solving the above problems, and have completed the present invention.
(1) A joint range-of-motion-enhancing agent for oral consumption, containing arginine and citrulline as active ingredients.
(2) The joint range of motion enhancer according to (1), further comprising vitamin B.
(3) A muscle stretcher for oral consumption containing arginine and citrulline as active ingredients.
(4) The muscle stretcher according to (3), further containing vitamin Bs.
(5) A composition for oral consumption, per oral intake,
The said composition containing 80-2,000 mg arginine and 80-2,000 mg citrulline.
(6) The composition according to (5), further containing 1.0 to 25 mg of vitamin B ₁ per single oral intake.
(7) The composition according to further contain vitamin _{B 2} in single oral intake per 0.3～8.0Mg (5) or (6).
(8) The composition according to any one of (5) to (7), further comprising 0.3 to 7.0 mg of vitamin B ₆ per oral intake.
(9) The composition according to any one of (5) to (8), further containing 0.5 to ₁₂ μg of vitamin B ₁₂ per oral intake.
(10) The composition according to any one of (5) to (9), further containing 3.0 to 75 mg of niacin per oral intake.
(11) The composition according to any one of (5) to (10), further containing 20 to 500 mg of vitamin C per oral intake.
(12) The composition according to any one of (5) to (11), further containing 1.3 to 33 mg of vitamin E per oral intake.
(13) The composition according to (5), further containing 5 to 115 mg of vitamin B per oral intake.
(14) per oral intake,
1.0-25 mg of vitamin B ₁ ,
Vitamin _B 2 of 0.3~8.0mg,
0.3-7.0 mg of vitamin B ₆ ,
0.5-12 μg vitamin B ₁₂ ,
3.0-75 mg niacin,
The composition according to (5), containing 20 to 500 mg of vitamin C and 1.3 to 33 mg of vitamin E.

  The joint range-of-motion-enhancing agent of the present invention can exert an effect of increasing the range of joint motion when taken orally.

The muscle stretcher of the present invention can exert a muscle stretch effect by ingestion.
The composition of the present invention can exhibit an effect of increasing the range of motion of joint and / or a muscle stretching effect by ingestion.

FIG. 1 shows a test schedule for evaluating the joint range-of-motion increasing effect of the composition of the present invention. FIG. 2 shows the results of a test for confirming the effect of increasing the range of motion of the composition of the present invention (test meal) and the placebo meal.

Hereinafter, the present invention will be described in detail.
In the following explanation, the joint range-of-motion-enhancing agent for oral intake according to the present invention and the muscle stretcher for oral intake are collectively referred to as “the agent of the present invention”, and the composition for oral intake according to the present invention is It may be referred to as “the composition of the invention”.

<Active ingredient>
As arginine contained in the agent or composition of the present invention, L-arginine or D-arginine can be used, and L-arginine is more preferably used. The terms arginine, L-arginine, and D-arginine include not only educts but also various forms such as salts and hydrates. The arginine in the form of a salt is not particularly limited as long as it is a salt that can be taken orally as food, pharmaceuticals, etc. For example, organic acid salts, inorganic acid salts, metal salts, amino acid salts, ammonium salts and the like can be used.

  As citrulline contained in the agent or composition of the present invention, L-citrulline or D-citrulline can be used, and L-citrulline is more preferably used. The terms citrulline, L-citrulline and D-citrulline include not only the free form but also various forms such as salts and hydrates. The salt form of citrulline is not particularly limited as long as it is a salt that can be ingested orally as food, pharmaceuticals, etc. For example, organic acid salts, inorganic acid salts, metal salts, amino acid salts, ammonium salts and the like can be used.

The agent or composition of the present invention may further contain vitamin Bs. B vitamins encompasses vitamin _{B 1,} vitamin _{B 2,} niacin (nicotinic acid), vitamin _{B 6,} pantothenic acid, folic acid, p- aminobenzoic acid, inositol, choline, biotin, vitamin _{B 12,} vitamin _{B 13,} etc. , Preferably at least one selected from the group consisting of these compounds, preferably a mixture of two or more. Vitamin B is more preferably at least one selected from the group consisting of vitamin B ₁ , vitamin B ₂ , niacin, vitamin B ₆ and vitamin B ₁₂ , preferably a mixture of two or more, more preferably A mixture of all the compounds to which it belongs is used. Each compound listed as vitamin B includes not only free compounds but also various forms such as salts and hydrates. Each compound mentioned as vitamin B in the form of a salt is not particularly limited as long as it is a salt that can be taken orally as a food, medicine or the like.

  The agent or composition of the present invention may further contain an antioxidant vitamin. Antioxidant vitamins include vitamin C (ascorbic acid) and / or vitamin E, and more preferably a mixture of vitamin C and vitamin E is used. The terms antioxidant vitamin, vitamin C, and vitamin E include not only free forms but also various forms such as salts, hydrates, and other derivatives. The salt is not particularly limited as long as it is a salt that can be taken orally as food, medicine, and the like. Examples of the salt form and derivative vitamin C (ascorbic acid) include sodium L-ascorbate, calcium L-ascorbate, L-ascorbic acid 2-glucoside, L-ascorbic acid palmitate, L-ascorbic acid stearic acid Examples of the vitamin E derivative include tocopherol acetate and d-α-tocopherol acetate.

Next, the compounding amount of each component in the agent or composition of the present invention will be described. Unless otherwise specified, the blending amount of each component in the present invention indicates the blending amount in terms of free form.
The agent or composition of the present invention contains arginine and citrulline, and the compounding amount thereof is not particularly limited, but the compounding amount of arginine is preferably 80 to 2 per one oral intake of the agent or composition of the present invention. 1,000 mg, more preferably 130-1,200 mg, more preferably 200-800 mg, more preferably 300-500 mg, and the amount of citrulline is preferably 80-2,000 mg, more preferably 130-1,200 mg, More preferably, it is 200-800 mg, More preferably, it is 300-500 mg. When the amounts of arginine and citrulline are within this range, the range of motion of the joint can be increased by ingesting the agent or composition of the present invention. This effect is presumed to be due to the promotion of muscle elongation.

  Here, the “single oral intake” is an amount appropriately set according to the form of the agent or composition of the present invention, and is not limited to the amount taken in one oral intake operation. In addition, the total intake amount when ingested by multiple oral ingestion operations performed at intervals of a short time (for example, 60 minutes or less, preferably 10 minutes or less, more preferably 5 minutes or less) is also included. The specific amount of “single oral intake” is not particularly limited and can be appropriately determined according to the form of the agent or composition of the present invention. In the case of a thing, it is the range of 0.1-500 mL). When the agent or composition of the present invention is a liquid such as a beverage or liquid food, the “single oral intake” is preferably 30 to 500 mL, more preferably 50 to 300 mL, more preferably 70 to 200 mL. It is. The agent or composition of the present invention has relatively small dimensions such as granules, tablets (tablets), candy, soft candy, gummi, chewing gum, etc. For example, the largest diameter is less than 5 cm, preferably less than 3 cm, more preferably less than 2 cm In the case of a solid or semi-solid form (the group of compositions in such a form is referred to as “Group A”), the “single oral intake” is preferably 0.1 to 30 g, more Preferably it is 0.1-10g, More preferably, it is 0.5-5g. A group A agent or composition is generally one of the smallest units (eg, 1 granule, 1 tablet, candy, soft candy, 1 gummy, 1 chewing gum) or multiple oral doses. Can be ingested by ingestion. When the agent or composition of the present invention is in the form of a solid or semi-solid material such as a waffle, cookie, biscuit or the like having a relatively large size, for example, the largest diameter of 4 cm or more, preferably 5 cm or more (such as The group of compositions in such a form is referred to as “Group B”), and the “single oral intake” is preferably 1 to 120 g, more preferably 2 to 80 g, and more preferably 3 to 60 g. Group B agents or compositions generally take one of its smallest units (eg, one of waffles, cookies, biscuits) in multiple ingestion actions. When the agent or composition of the present invention is in the form of a solid or semi-solid with high water content, such as jelly (the group of compositions in such a form is referred to as “Group C”), The “intake amount” is preferably 5 to 250 g, more preferably 10 to 200 g, and more preferably 15 to 150 g. The group C agent or composition may be in the form of taking one or more of its minimum units (for example, one block-like jelly, one jelly containing a cheapack) in a single oral ingestion operation, or multiple times It may be in the form of ingestion by oral ingestion operation. The above meanings and preferred examples for “single oral intake” apply equally to “single oral intake” in the rest of the specification and claims.

  The agent or composition of the present invention further contains vitamin Bs. By using arginine and citrulline together with vitamin B, the joint range of motion increasing action and the muscle stretching action of the agent or composition of the present invention are more remarkably exhibited. Although the compounding quantity of vitamin B is not specifically limited, As a total amount of vitamin B, it is preferable to mix | blend 5-115 mg per one oral intake of the agent or composition of this invention, and to mix | blend 8-70 mg. More preferred.

The agent or composition of the present invention preferably contains vitamin B ₁ as vitamin B, and the blended amount of vitamin B ₁ (in terms of thiamine hydrochloride. In other parts of the specification and claims of the present invention) Is also preferably 1.0 to 25 mg, more preferably 1.7 to 15 mg, and more preferably 2.5 to 10 mg per oral intake of the agent or composition of the present invention. More preferably, it is 3-7 mg. When the amount of vitamin B ₁ is within this range, increased activity and muscle extending activity range of motion due to agents or compositions of the present invention can be exhibited more remarkably.

The agent or composition of the present invention preferably contains vitamin B ₂ as vitamin B, and the blending amount of vitamin B ₂ is preferably 0.3 to 8 per single oral intake of the agent or composition of the present invention. 0.0 mg, more preferably 0.5 to 5 mg, more preferably 0.8 to 3.2 mg. When the amount of vitamin B ₂ is in this range, it increased action and muscle extending activity range of motion due to agents or compositions of the present invention can be exhibited more remarkably.

The agent or composition of the present invention preferably contains vitamin B ₆ as vitamin B, and the amount of vitamin B ₆ is preferably 0.3 to 7 per oral intake of the agent or composition of the present invention. It is 0.0 mg, More preferably, it is 0.5-5 mg, More preferably, it is 0.8-2.8 mg, More preferably, it is 1.0-1.8 mg. When the blending amount of vitamin B ₆ is within this range, the joint range of motion increasing action and muscle stretching action of the agent or composition of the present invention are more remarkably exhibited.

The agent or composition of the present invention preferably contains vitamin B ₁₂ as vitamin B, and the blended amount of vitamin B ₁₂ (in terms of cyanocobalamin. The same applies to other parts of the specification and claims of the present invention). ) Is preferably 0.5 to 12 μg, more preferably 0.8 to 7.3 μg, and more preferably 1.2 to 4.8 μg per single oral intake of the agent or composition of the present invention. It is. When the amount of vitamin B ₁₂ is in this range, it increased action and muscle extending activity range of motion due to agents or compositions of the present invention can be exhibited more remarkably.

  The agent or composition of the present invention preferably contains niacin as vitamin B, and the amount of niacin is preferably 3.0 to 75 mg per oral intake of the agent or composition of the present invention. Preferably it is 5-45 mg, More preferably, it is 7-30 mg, More preferably, it is 10-20 mg. When the blending amount of niacin is within this range, the joint range of motion increasing action and the muscle stretching action of the agent or composition of the present invention are more remarkably exhibited.

The agent or composition of the present invention preferably contains a combination of vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , and niacin as vitamin B, and the amount of each component is in the above range. It is more preferable.

The agent or composition of the present invention preferably further contains an antioxidant vitamin.
When the agent or composition of the present invention contains vitamin C as an antioxidant vitamin, the blending amount is preferably 20 to 500 mg, more preferably 30 to 500 mg per oral intake of the agent or composition of the present invention. 300 mg, more preferably 50-200 mg. When the blending amount of vitamin C is within this range, the joint range of motion increasing action and the muscle stretching action of the agent or composition of the present invention are more remarkably exhibited.

  When the agent or composition of the present invention contains vitamin E as an antioxidant vitamin, the blending amount is preferably 1.3 to 33 mg, more preferably per oral intake of the agent or composition of the present invention. It is 2-20 mg, More preferably, it is 3-13 mg, More preferably, it is 4-9 mg. When the blending amount of vitamin E is within this range, the joint range of motion increasing action and the muscle stretching action of the agent or composition of the present invention are more remarkably exhibited.

  The agent or composition of the present invention preferably contains a combination of vitamin C and vitamin E as antioxidant vitamins, and the amount of each component is more preferably in the above range.

<Form of composition>
The agent of the present invention is preferably formulated in the form of a composition formulated with at least one other component in addition to the above active ingredients.

  The composition in which the agent of the present invention is formulated and the composition of the present invention are not particularly limited as long as they can be orally ingested by humans, such as pharmaceuticals, foods and drinks, and food and drink additives. It can be in any form such as solid, semi-solid. As used herein, “oral intake” includes not only human beings taking the oral route into the body by voluntary intention, but also human beings taking the oral route through the oral route under the direction of a doctor or the like.

  Preferred forms of the agent or composition of the present invention include liquids, solids, semi-solids and the like. Examples of liquids include beverages and liquid foods. The beverage may be provided in the form of a powdered beverage. Powdered drinks are mixed with water and ingested as liquid drinks. “Single oral intake” of powdered drinks refers to a single oral intake in the state of a liquid drink mixed with water, A preferable blending amount of each component may be such that the weight per one oral intake as a liquid beverage after mixing with water falls within the above range. Examples of the solid or semi-solid form of the agent or composition of the present invention include the form of Group A such as granules, tablets (tablets), candy, soft candy, gummi, chewing gum, waffles, cookies, biscuits, etc. Examples of the form of the group B and the form of the group C such as jelly can be given.

  The agent or composition of the present invention can contain other components suitable for various forms in addition to the above-mentioned active ingredients. Other ingredients include, for example, other plant extracts, dietary fiber, fructose dextrose liquid sugar, dextrin, acidulant, thickener, pigment, inositol, flavor, cyclic oligosaccharide, sweetener, mineral, antioxidant, An emulsifier, water, etc. are mentioned.

<Method of oral intake>
There is no particular limitation on the timing of oral ingestion of the agent or composition of the present invention, but it is oral before the stretch before exercise, for example, the time until the start of the stretch is 1 hour or less, more preferably 30 minutes or less. Ingestion is preferable because the effect of stretching performed thereafter can be enhanced.

<Sample>
A beverage composition containing the following components per 100 mL (corresponding to one oral intake) was prepared as a test meal.

  As a placebo meal, a beverage composition having the same composition was prepared in the above test meal except that the ingredients described in the column of active ingredients were not blended.

<Test method>
Twelve subjects are divided into two groups of 6 each, the following test is performed with one as the test meal group and the other as the placebo group, and the test meal group and placebo group are exchanged on another day and the same test is performed. A crossover test was conducted.

In one test, as shown in FIG. 1, initial measurement for 10 minutes, drinking of test meal or placebo meal, rest for 20 minutes, stretch for 9 minutes, break for 1 minute, and effect confirmation measurement for 10 minutes were performed in this order.
In one test, 100 mL of each person drank a test meal or a placebo meal.

  As the stretch, two sets of dynamic stretches (stretches that move muscles rhythmically while applying light momentum) were performed 10 times each on the left, right, and back of the ankles, thighs, and hip joints.

<Measurement item>
Range of motion when raising the leg with the knee extended (SLR-ROM: straight leg range of motion): The tester lifts the leg while supporting the subject's knees and ankles while stretching the knee from the posture The angle was measured with an goniometer. The measured values of SLR-ROM after initial and stretch were compared between the groups.
Data from those who were later found to meet the exclusion criteria were excluded from the analysis.

<Test results>
The measurement result of SLR-ROM is shown in FIG. The values in the figure represent mean values ± standard deviation.
It was confirmed that the range of motion of the joint was expanded by stretching exercise after taking the test meal.

Claims (14)

  A joint range-of-motion-enhancing agent for oral consumption, containing arginine and citrulline as active ingredients.   The joint range-of-motion enhancer according to claim 1, further comprising vitamin Bs.   A muscle stretcher for oral consumption containing arginine and citrulline as active ingredients.   The muscle stretcher according to claim 3, further comprising vitamin Bs. A composition for oral consumption, per oral intake,
The said composition containing 80-2,000 mg arginine and 80-2,000 mg citrulline. The composition of claim 5 containing vitamin _{B 1} in a single oral intake per 1.0～25Mg. Further composition according to claim 5 or 6 containing one vitamin _{B 2} oral intake per 0.3～8.0Mg. The composition according to any one of claims 5 to 7, further comprising 0.3 to 7.0 mg of vitamin B ₆ per single oral intake. The composition according to any one of claims 5 to 8, further comprising 0.5 to ₁₂ µg of vitamin B ₁₂ per oral intake.   The composition according to any one of claims 5 to 9, further comprising 3.0 to 75 mg of niacin per oral intake.   The composition according to any one of claims 5 to 10, further comprising 20 to 500 mg of vitamin C per oral intake.   The composition according to any one of claims 5 to 11, further comprising 1.3 to 33 mg of vitamin E per single oral intake.   6. The composition according to claim 5, further comprising 5-115 mg of vitamin B per oral intake. Per oral intake,
1.0-25 mg of vitamin B ₁ ,
Vitamin _B 2 of 0.3~8.0mg,
0.3-7.0 mg of vitamin B ₆ ,
0.5-12 μg vitamin B ₁₂ ,
3.0-75 mg niacin,
The composition according to claim 5, comprising 20 to 500 mg of vitamin C and 1.3 to 33 mg of vitamin E.

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