JP6966066B2 - Muscle spasm threshold enhancer - Google Patents

Description

The present invention relates to a muscle spasm threshold enhancer that exerts an excellent effect in suppressing and / or preventing muscle spasm.

Muscle spasms are sudden, short-term contractions of muscles or groups of muscles that are usually painful. Muscle cramps occur even at rest, and are especially likely to occur during or after strenuous exercise. Causes of muscle cramps include, for example, insufficient blood flow, dehydration, magnesium deficiency, potassium deficiency, calcium deficiency, spinal nerve compression, alcohol poisoning, pregnancy, renal failure, thyroid disorders, drug side effects, fatigue and exercise. .. The frequency of muscle cramps increases with age and is one of the diseases that afflicts the elderly. Also, in relation to pregnancy, symptoms tend to worsen as the number of weeks progresses.

Although muscle spasms cause physical and mental disorders, the current situation is that it is difficult to fundamentally resolve them because the details of the pathological mechanism are not clear.

In view of the above problems, an object of the present invention is to provide an agent capable of suppressing and / or preventing muscle cramps by easily ingesting it as a food or drink on a daily basis.

The present inventors have muscle cramps by ingesting an agent containing sodium ions and glucose in a specific molar ratio range and sodium ions, potassium ions, magnesium ions, phosphorus and organic acids in a specific range. The present invention has been completed by finding that the threshold value of is increased.

That is, the present invention relates to the following.
(1) A muscle containing sodium ions and glucose so that the molar ratio of sodium ions to glucose is 1: 1.5 to 3.0, and containing components having the following composition. Cramp threshold enhancer.
Na ⁺ 40-60mEq / L
K ⁺ 16-24mEq / L
Mg ²⁺ 1.6-2.4mEq / L
Phosphorus 1.6-2.4 mmol / L
Organic acid 18-60mEq / L
(2) The muscle spasm threshold enhancer according to (1) above, wherein the organic acid is at least one of citric acid and lactic acid.
(3) The muscle spasm threshold enhancer according to (1) or (2) above, which is a beverage or jelly.

By having a specific composition, the muscle spasm threshold enhancer of the present invention is absorbed more quickly than the intestinal tract by oral ingestion or administration, and improves the muscle spasm threshold. As a result, even if a stimulus higher than the stimulus that causes muscle spasm is given in normal times, the stimulus below the improved threshold value does not cause muscle spasm, which is effective in suppressing and / or preventing muscle spasm.

The muscle cramp threshold enhancer of the present invention can be easily ingested as a food or drink such as a beverage or jelly on a daily basis, and not only can the risk of incorrect dilution ratio during preparation be avoided, but also it is necessary to prepare for errands. Since it is not available, it can be easily taken by children and the elderly, or it can be taken quickly even during intense sports and work. Due to these excellent advantages, the muscle spasm threshold enhancer of the present invention can be widely used for the purpose of suppressing and / or preventing muscle spasms.

FIG. 1 is a diagram showing an experimental protocol of Test Example 1. FIG. 2 is a diagram showing the results of measuring the muscle spasm threshold in Test Example 1. 3A to 3C are diagrams showing the results of measuring the muscle spasm threshold in Test Example 1. In FIGS. 3A to 3C, * indicates that there is a significant difference between the OS-1 intake group and the mineral water intake group (p <0.05, t-test), and # indicates that there is a significant difference between the start of exercise (Pre). Indicates that there is a significant difference (p <0.05, t-test). 4A to 4C are diagrams showing changes in serum sodium, potassium, and magnesium concentrations in Test Example 1, respectively. In FIGS. 4A to 4C, * indicates that there is a significant difference between the OS-1 intake group and the mineral water intake group (p <0.05, t-test), and # indicates that there is a significant difference between the start of exercise (Pre). Indicates that there is a significant difference (p <0.05, t-test). FIG. 5 is a diagram showing an experimental protocol of Test Example 2. FIG. 6 is a diagram showing the results of measuring the muscle spasm threshold in Test Example 2. 7A to 7C are diagrams showing the results of measuring the muscle spasm threshold in Test Example 2. In FIGS. 7A to 7C, * indicates that there is a significant difference between the OS-1 intake group and the mineral water intake group (p <0.05, t-test), and # indicates that there is a significant difference between the start of exercise (Pre). It is shown that there is a significant difference (p <0.05, t-test). 8A to 8C are diagrams showing changes in serum sodium, potassium, and magnesium concentrations in Test Example 2, respectively. In FIGS. 8A-8C, # indicates that there is a significant difference (p <0.05, t-test) from the start of exercise (Pre).

The muscle cramp threshold enhancer of the present invention contains sodium ions and glucose so that the molar ratio of sodium ions to glucose is 1: 1.5 to 3.0, and contains components having the following composition. It is characterized by that.
Na ⁺ 40-60mEq / L
K ⁺ 16-24mEq / L
Mg ²⁺ 1.6-2.4mEq / L
Phosphorus 1.6-2.4 mmol / L
Organic acid 18-60mEq / L

In the present invention, ^{as a source of Na +} , K ⁺ , Mg ²⁺ , phosphorus or an organic acid, those known per se may be used. Such an electrolyte component may be an inorganic electrolyte component or an organic electrolyte component. Examples of the inorganic electrolyte component include alkali metals such as chlorides, sulfates, carbon oxides, and phosphor oxides, or salts of alkaline earth metals. Examples of the organic electrolyte component include salts of citric acid and an alkali metal or an alkaline earth metal. These may be used alone or may be a mixture of two or more.

The concentration of sodium ions in the muscle spasm threshold enhancer of the present invention is 40 to 60 mEq / L, preferably 45 to 55 mEq / L, more preferably 47 to 53 mEq / L, and most preferably 50 mEq / L. Is. Examples of the source of sodium ions include sodium chloride, sodium sulfate, sodium lactate, sodium glycerophosphate, sodium acetate, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, and the like. Of these, sodium chloride, sodium lactate or sodium dihydrogen phosphate, or any mixture of two or more thereof is preferable.

The concentration of potassium ions in the muscle spasm threshold enhancer of the present invention is 16 to 24 mEq / L, preferably 18 to 22 mEq / L, more preferably 19 to 21 mEq / L, and most preferably 20 mEq / L. Is. Examples of the source of potassium ions include potassium chloride, potassium sulfate, potassium glycerophosphate, potassium lactate, potassium acetate, potassium phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, and the like. Of these, potassium chloride is preferable.

In the muscle spasm threshold enhancer of the present invention, calcium may be added. When calcium is added, the concentration of calcium ions is 0 to 3 mEq / L, preferably 1.9 to 2.1 mEq / L. Examples of the source of calcium ions include calcium chloride, calcium gluconate, calcium lactate, calcium glycerophosphate, calcium acetate and the like. Of these, calcium gluconate or calcium glycerophosphate is preferable, and calcium glycerophosphate is more preferable.

The concentration of magnesium ions in the muscle spasm threshold enhancer of the present invention is 1.6 to 2.4 mEq / L, preferably 1.8 to 2.2 mEq / L, and more preferably 1.9 to 2. It is 1 mEq / L, most preferably 2.0 mEq / L. Examples of the source of magnesium ions include magnesium chloride, magnesium sulfate, magnesium lactate, magnesium glycerophosphate, magnesium acetate and the like. Of these, magnesium sulfate is preferable.

The concentration of phosphorus in the muscle spasm threshold enhancer of the present invention is 1.6 to 2.4 mmol / L, preferably 1.8 to 2.2 mmol / L, and more preferably 1.9 to 2.1 mmol. / L, most preferably 2.0 mmol / L. Here, the phosphoric acid partially dissociates in the aqueous solution to give H ₂ PO ₄ ⁻ , HPO ₄ ^2- or PO ₄ ^3- . Therefore, in the present invention, the sum of these phosphorus is expressed as "mmol / L".

Examples of the source of phosphorus include phosphoric acid, or a salt of phosphoric acid and an alkali metal or an alkaline earth metal. Among them, sodium phosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium phosphate, potassium hydrogen phosphate, potassium dihydrogen phosphate, calcium phosphate or calcium hydrogen phosphate are preferable, and sodium dihydrogen phosphate is more preferable.

The concentration of the organic acid in the muscle spasm threshold enhancer of the present invention is 18 to 60 mEq / L, preferably 28 to 56 mEq / L, more preferably 38 to 52 mEq / L, and most preferably 41 to 49 mEq / L. Is.

Examples of the organic acid include citric acid, lactic acid, amino acids (for example, glutamate or aspartic acid), alginic acid, malic acid and gluconic acid, and citric acid or lactic acid is preferable, and citric acid is more preferable. These may be used alone or in combination of two or more.

When citric acid and lactic acid are used in combination, the total content of citric acid and lactic acid shall not exceed 60 mEq / L, most preferably 50 mEq / L.

When citric acid is used as the organic acid, its concentration is 18 to 60 mEq / L, preferably 28 to 56 mEq / L, more preferably 38 to 52 mEq / L, and most preferably 41 to 49 mEq / L. .. Examples of the source of citric acid include salts of citric acid and an alkali metal or an alkaline earth metal. Examples of the salts include trisodium citrate.

Sources of other organic acids include, for example, salts of lactic acid, amino acids (eg, glutamic acid or aspartic acid, etc.), alginic acid, malic acid or gluconic acid, and alkali metals or alkaline earth metals. These may be mixed in 2 or more types. Of these, lactic acid, sodium lactate, or a mixture thereof is preferable.

The molar ratio of sodium ion to glucose in the muscle spasm threshold enhancer of the present invention is 1: 1.5 to 3.0, preferably 1: 1.8 to 2.5. The glucose content in the muscle spasm threshold enhancer of the present invention can be determined immediately from the above.

The osmotic pressure of the muscle spasm threshold enhancer of the present invention is preferably 200 to 300 mOsm / L, more preferably 240 to 260 mOsm / L. By setting the osmotic pressure within the above range, the osmotic pressure becomes close to the osmotic pressure of the body fluid, and the absorption of the muscle spasm threshold enhancer in the body can be improved.

Foods and drinks can be mentioned as a form of the muscle spasm threshold enhancer of the present invention. As the form of the food or drink, for example, it can be arbitrarily molded into a liquid form, a paste form, a gel form, or a powder form for adding water to make a beverage. Beverages or jellies are preferable as foods and drinks.

Beverages include, for example, drinks, soups, non-alcoholic beverages, jelly-like beverages, functional beverages and the like. Non-alcoholic beverages include, for example, sports drinks, tea beverages, dairy beverages, soft drinks, coffee beverages, fruit juice-containing beverages, vegetable juice-containing beverages, fruit juice and vegetable juice beverages, carbonated beverages or alcohol-free beer-taste beverages. However, it is not limited to these. A beer beverage having an alcohol content of less than 1%, such as a non-alcoholic beer, may be used.

If desired, the beverage may contain various nutrients, vitamins, flavors such as synthetic flavors or natural flavors, colorants, flavor substances such as cheese and chocolate, or additives such as synthetic sweeteners in addition to the above ingredients. good.

The vitamins may be water-soluble or fat-soluble, and may be, for example, retinol palmitate, tocopherol, bisbenchamine, riboflavin, pyridoxin hydrochloride, cyanocobalamin, sodium ascorbate, choleciferol, nicotinic acid amide, etc. Examples include calcium pantothenate, folic acid, biotin or choline bitartrate. Further, since the beverage is a beverage containing fruit juice, a beverage containing vegetable juice, or a beverage containing fruit juice and vegetable juice, natural fruit juice, fruit meat, or the like may be added.

The above additives may be used alone or in combination of any two or more kinds. The blending ratio of the additive is not particularly limited, but for example, it can be selected from the range of usually 0 to 20 parts by weight with respect to 100 parts by weight of the beverage.

In the form of jelly, as a gelling agent, for example, agar, gelatin, carrageenan, gellan gum, xanthan gum, locust bean gum, pectin, sodium alginate, potassium alginate, and other commonly used thickening polysaccharides. The above can be used. Preferably, one or more of agar, carrageenan, xanthan gum and locust bean gum is used. The blending ratio of these gelling agents is preferably 2 parts by weight or less with respect to 100 parts by weight of the jelly.

When all the above ingredients are prepared as the beverage or jelly according to the present invention, the preparation method is not particularly limited, and all the ingredients may be mixed at the same time, or any of the ingredients may be mixed separately. Other components or a mixture of other components may be added and mixed with the prepared mixture to prepare the mixture. The mixing operation of each of the above components can be carried out at room temperature or slightly heated.

Since the muscle spasm threshold enhancer of the present invention exerts a muscle spasm threshold enhancing effect, it has an effect of suppressing and / or preventing muscle spasm when taken at rest, before exercise, during exercise, after exercise, and the like. can get. The muscle spasm threshold enhancer of the present invention is more likely to exert its effect when ingested preferably at least during or after exercise, more preferably during exercise.

The intake amount of the muscle cramp threshold enhancer of the present invention varies depending on the age, weight, degree of exercise, etc. of the person who takes it, so it cannot be said unconditionally, and since the toxicity is extremely low, the person who takes it should take as much as he / she wants. You may. Specifically, for example, it is preferable to ingest the beverage according to the present invention at a rate of 1 to 50 mL / kg / hour or 1 to 100 mL / kg / day.

Examples of typical intakes include 500-1000 ml / day for school children to adults (including the elderly) and 300-600 ml / day for infants or 30-50 ml / day per kg body weight. be able to.

[Example 1]
With the composition shown in Table 1, each component was dissolved in 800 mL of distilled water, and after stirring, further distilled water was added to make the total volume 1 L. The solution was sterilized at 115 ° C. for 30 seconds, cooled to 93 ° C., and then filled in a PET bottle to obtain a beverage according to the present invention. The obtained beverage is referred to as OS-1 in the following test examples.

[Example 2]
The powdered agar and the electrolytes, glucose and the like shown in Table 2 were dissolved in 800 mL of distilled water, and after stirring, further distilled water was added to bring the total volume to 1 L. The solution was melted at 80 ° C. for 5 minutes, then filled in a pouch with a spout and sterilized at 95 ° C. for 33 minutes to obtain an OS-1-like water electrolyte jelly according to the present invention.

[Example 3]
An appropriate amount of binder was added to the mixture having the composition shown in Table 3 and granulated by the method of fluidized bed granulation to obtain a powdery composition according to the present invention. This composition was dissolved in 800 mL of distilled water, and after stirring, distilled water was further added to bring the total volume to 1 L, whereby an OS-1-like liquid composition could be obtained.

[Test Example 1] Effect of ingestion of beverage after exercise on muscle cramp threshold According to the experimental protocol shown in FIG. 1, 10 subjects (Asian, average age 25 years, average height 173.8 cm, average weight 74.0 kg) ) At room temperature, downhill running until 2% by weight of the subject's body weight is lost by sweating, and OS-1 or minerals at 10, 15 and 20 minutes after the end of exercise. Water was ingested and the effect on each endpoint was investigated.

The meanings of the terms in the experimental protocol shown in FIG. 1 and the evaluation method are shown below.
-BM (Blood Measures, blood measurement): 7 ml of venous blood was centrifuged at 3000 rpm for 10 minutes, 3 ml of serum was collected and stored frozen at -60 ° C, and then the concentrations of sodium, potassium and magnesium were measured.
-BP (Blood Pressure, blood pressure): Blood pressure was measured with an upper arm sphygmomanometer.
-ETS (Electrical Training): Electrodes were attached to the back of the knee and ankle, and the frequency was increased every 2 Hz from 10 Hz to 44 Hz. The frequency at which a current of 18-60 mA was passed for 3 seconds (every 30 seconds) and the calf was in a state where muscle cramps were observed and could not be restored was defined as TF (Treshold frequency, muscle cramp threshold).
-Hb (Haemoglobin, hemoglobin): Measured from 1 ml venous blood using HemoCue (manufactured by Sweden).
-HR (Heart Rate, heart rate): Measured with a POLAR sports watch.
-Ht (Hematocrit): Measured from 1 ml venous blood using HemoCue (manufactured by Sweden).
-RPE (Rating of Perceived Exercise, subjective exercise intensity): Exercise intensity was examined from the Borg scale.
-TS (Thermal Sensation, temperature sensation): The temperature sensation was examined in 0.5 ° C increments from 0 to 8 ° C.
-TT (Typical Temp, intra-ear temperature): The eardrum temperature (° C.) was measured with a post-exercise ear thermometer.

Table 4 shows the characteristics of the subjects and the test design.

2 and 3A to 3C show the results of measuring the muscle spasm threshold, and FIGS. 4A to 4C show the results of measuring changes in serum sodium, potassium, and magnesium concentrations, respectively. The vertical axis of FIG. 3C shows a value obtained by subtracting each muscle spasm threshold at the start of exercise (Pre) from each muscle spasm threshold at 0 minutes, 50 minutes, and 80 minutes after the end of exercise. In FIGS. 4A to 4C, the vertical axis shows the ion concentration obtained by subtracting each ion concentration at the start of exercise (Pre) from each ion concentration at 0 minutes and 80 minutes after the end of exercise.

As a result of evaluating each item shown in FIG. 1, as shown in FIGS. 2 and 3A to 3C, there was a significant difference in the muscle spasm threshold between the mineral water intake group and the OS-1 intake group. It was found that ingestion increased the muscle spasm threshold and suppressed muscle spasms. On the other hand, it was found that the intake of mineral water after exercise lowers the muscle spasm threshold and makes muscle spasms more likely to occur. In addition, as shown in FIG. 4A, a significant difference was observed in the serum sodium concentration between the mineral water intake group and the OS-1 intake group.

As shown in FIGS. 4B and 4C, no significant difference was observed in the changes in potassium and magnesium concentrations between the mineral water intake group and the OS-1 intake group. In addition, no significant difference was observed in heart rate, RPE, temperature sensation, blood pressure, tympanic membrane temperature, hemoglobin amount, hematocrit amount, serum osmolality and chlorine amount between the mineral water intake group and the OS-1 intake group.

[Test Example 2]
According to the experimental protocol shown in FIG. 5, the same subjects as in Test Example 1 were subjected to downhill running at room temperature. Body weight was measured 20 minutes after the start of exercise and every 10 minutes thereafter, and the same amount of OS-1 or mineral water as the amount of decrease was ingested, and the cumulative amount of loss was continued until 2% by weight of the body weight was reached. In addition, at 30 to 35 minutes after the end of exercise, OS-1 or mineral water equivalent to the amount of weight loss was ingested, and the effect on each endpoint was examined. The meanings and evaluation methods of the terms in the experimental protocol shown in FIG. 5 are the same as those in Test Example 1.

Table 5 shows the study design and intake.

6 and 7A to 7C show the results of measuring the muscle spasm threshold, and FIGS. 8A to 8C show the results of measuring changes in serum sodium, potassium, and magnesium concentrations, respectively. The vertical axis of FIG. 7C shows a value obtained by subtracting each muscle spasm threshold at the start of exercise (Pre) from each muscle spasm threshold at 0 minutes, 30 minutes, and 65 minutes after the end of exercise. In FIGS. 8A to 8C, the vertical axis shows the ion concentration obtained by subtracting each ion concentration at the start of exercise (Pre) from each ion concentration at 0 minutes and 65 minutes after the end of exercise.

As a result of evaluating each item shown in FIG. 5, as shown in FIGS. 6 and 7A to 7C, there was a significant difference in the muscle spasm threshold between the mineral water intake group and the OS-1 intake group, and OS-1 was exercised. It was found that the muscle spasm threshold was enhanced and the muscle spasm was suppressed by ingesting it. On the other hand, it was found that ingestion of mineral water during exercise lowers the muscle spasm threshold and makes muscle spasms more likely to occur.

As shown in FIGS. 8A to 8C, no significant difference was observed in the changes in serum sodium, potassium and magnesium concentrations between the mineral water intake group and the OS-1 intake group. In addition, no significant difference was observed in heart rate, RPE, temperature sensation, blood pressure, tympanic membrane temperature, hemoglobin amount, hematocrit amount, serum osmolality and chlorine amount between the mineral water intake group and the OS-1 intake group.

From the above results, it was found that the muscle spasm threshold was improved by ingesting the muscle spasm threshold enhancer of the present invention during or after exercise. In addition, from the results of FIGS. 2, 3A to 3C, 6 and 7A to 7C, the muscle spasm threshold due to the muscle spasm threshold enhancer of the present invention was determined by the intake during exercise as compared with the intake after exercise. It was found that the improvement effect was further enhanced.

The reason why the muscle spasm threshold was improved by the intake of the muscle spasm threshold enhancer of the present invention was that the change in sodium concentration was significantly different from that of the mineral water intake group due to the intake of OS-1 after exercise. Since the intake of OS-1 did not show a significant difference from the mineral water intake group, it cannot be explained only by the change in the electrolyte concentration in the blood.

Claims (3)

The muscle spasm threshold enhancement is characterized by containing sodium ion and glucose so that the molar ratio of sodium ion and glucose is 1: 1.5 to 3.0, and containing a component having the following composition. Agent.
Na ⁺ 40-60mEq / L
K ⁺ 16-24mEq / L
Mg ²⁺ 1.6-2.4mEq / L
Phosphorus 1.6-2.4 mmol / L
Citric acid 18-60 mEq / L The muscle spasm threshold enhancer according to claim 1, which is a beverage or jelly. The muscle spasm threshold enhancer according to claim 1 or 2, which is ingested before the onset of muscle spasm.

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