JP2021122224A - Stress reducing agent and stress reducing composition - Google Patents

Abstract

To provide a novel stress reducing agent and a novel stress reducing composition.SOLUTION: A stress reducing agent and a stress reducing composition include glutamic acid or salt thereof, potassium salt, and sugar alcohol.SELECTED DRAWING: None

Description

The present invention relates to a stress reducing agent and a stress reducing composition.

In modern society, people are exposed to various types of physical, chemical, psychological and social stress. In particular, in recent years, work and human relationships have tended to become more complicated, and the proportion of people suffering from psychological stress is increasing regardless of generation. Continued exposure to such stress can adversely affect organs throughout the body, resulting in severe psychosomatic disorder, depression, gastric ulcer, hypertension and the like.

Japanese Patent Application Laid-Open No. 2000-319177 (Patent Document 1) is characterized by containing one or more amino acids selected from the group consisting of biotin and histidine, arginine, methionine, and glutamic acid as an active ingredient. Stress improvers are listed.

Japanese Unexamined Patent Publication No. 2000-319177

An object of the present invention is to provide a novel stress reducing agent and a stress reducing composition.

[1] A stress reducing agent containing glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol.
[2] The stress reducing agent according to [1], wherein the sugar alcohol is mannitol.
[3] The stress reducing agent according to [1] or [2], which is a food composition.
[4] A stress-reducing composition containing glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol.
[5] The stress-reducing composition according to [4], which is a seasoning.

The stress response can be reduced by administering the stress reducing agent and the stress reducing composition of the present invention.

It is a graph which shows the concentration of corticosterone in serum in a restraint stress test.

<Stress reducer>
The stress reducing agent of the present invention contains glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol. By administering the stress reducing agent of the present invention, the effect of reducing the stress response can be obtained. The subjects to which the stress reducing agent of the present invention is administered include individuals capable of causing a stress response (for example, humans; domestic animals and poultry such as cows, horses, pigs, sheep, dogs and birds; experimental animals such as mice and rats; and Animals for aquatic farming, etc.).

The stress response can occur when various external stimuli (stresses) act as loads. In humans, stresses that cause stress reactions include physical ones such as heat and cold, noise and congestion, pollutants, drugs, oxygen deficiency / excess, chemical ones such as carbon monoxide, starvation, and infection. There are various biological things such as overwork and lack of sleep, and social things such as nervousness, anxiety, fear, and excitement. In livestock and aquaculture animals, the stress that causes a stress reaction includes external stimuli such as transportation and transportation, and high-density breeding or aquaculture in a narrow breeding farm or farm.

Stress reactions include psychological reactions such as decreased vitality, irritability, anxiety, and depression (depression, decreased interest / interest), pain in the body, headache, stiff shoulders, lower back pain, tired eyes, palpitation and shortness of breath. , Stomach pain, loss of appetite, physical reactions such as constipation and diarrhea, insomnia, and behavioral reactions such as increased drinking and smoking. In addition, the stress response includes the onset of stress-related diseases such as anxiety disorder, somatic symptom disorder, mood disorder, digestive motility abnormality, irritable bowel syndrome and digestive ulcer.

The effects of reducing the stress response by administering the stress reducing agent of the present invention include a preventive effect that can reduce the stress response that occurs when stress is applied and a reduction of the stress response that occurs. There is an improving effect that can be done. The method of administering the stress reducing agent of the present invention is oral or enteral.

As a method for evaluating the effect of reducing the stress response, in the present specification, a change in corticosterone concentration in serum, which is known to correlate with the stress response by applying stress to small animals such as rats and mice. Is used to measure and evaluate.

(Glutamic acid or its salt)
As the glutamic acid, any of natural ones derived from animals and plants, or those obtained by a chemical synthesis method, a fermentation method, or a genetic recombination method may be used. Further, in glutamic acid, any of L-form, D-form, and a mixture thereof (for example, racemic form) may be used, but L-form is preferably used.

Examples of the salt of glutamic acid in the present invention include those designated as food additives, such as salts with inorganic bases and amino acid salts. Salts with inorganic bases include salts with alkali metals such as sodium and potassium, salts with alkaline earth metals such as calcium and magnesium, salts with ammonium, etc., and amino acid salts include algining glutamic acid and resingle tamate. And so on.

As the glutamic acid or a salt thereof contained in the stress reducing agent of the present invention, glutamic acid, sodium L-glutamate, and sodium D-glutamate are preferable, and glutamic acid and sodium L-glutamate are more preferable. The stress reducing agent of the present invention may contain only one component or two or more components as glutamic acid or a salt thereof.

(Potassium salt)
The potassium salt is designated as a food additive and may be any of an inorganic acid salt, an organic acid salt and an amino acid salt, and the number of potassium ions is monovalent or divalent or higher. May be good. Specific examples include potassium chloride, potassium sulfate, tripotassium phosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, potassium lactate, potassium gluconate, monopotassium citrate, potassium hydrogen tartrate, potassium glutamate, and the like. NS. Among these, potassium chloride is preferable. The stress reducing agent of the present invention may contain only one kind of component or two or more kinds of components as the potassium salt.

In the stress reducing agent, the potassium salt may be a solid such as crystalline, powdery or granular, or may be dissolved in a liquid.

In the stress reducing agent, the number of moles of potassium per 1 mole of glutamic acid is preferably 2.5 to 20.

(Sugar alcohol)
As the sugar alcohol, either a natural sugar alcohol derived from an animal or a plant or a sugar alcohol obtained by a chemical synthesis method may be used. Specific examples of sugar alcohols include erythritol, xylitol, sorbitol (D-glucitol), mannitol, glycerin, erythritol, maltitol, arabinitol, rythritol, iditol, boremitol, perseitor, galactitol, reduced candy, reduced palatinose, etc. Maltitol and lactitol are exemplified. Of these, mannitol is preferable. The stress reducing agent of the present invention may contain only one kind of component or two or more kinds of components as the sugar alcohol.

In the stress reducing agent, the number of moles of sugar alcohol per 1 mole of glutamic acid is preferably 1.2 to 63.

(dose)
The dose of the stress-reducing agent varies depending on the gender, age, body weight, diet, form of administration, stress symptoms, degree of exposure to stress, etc., but for example, daily administration to an adult (assuming a body weight of 60 kg). The amount of glutamic acid in the stress reducing agent is preferably 0.01 to 5 g, more preferably 0.1 to 2 g.

<Stress reduction composition>
The stress-reducing composition of the present invention contains glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol, and specifically contains the above-mentioned stress-reducing agent. The stress reducing agent itself may be the stress reducing composition of the present invention. The above description of the stress reducing agent is applied to the stress reducing agent contained in the stress reducing composition of the present invention. The stress-reducing composition of the present invention is preferably a food composition or a pharmaceutical composition.

(Food composition)
Examples of the food composition of the present invention include seasonings, foods (including nutritionally functional foods, foods for specified health uses, etc.), dietary supplements, nutritional supplements, beverages, feeds, and the like.

When glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol contained in the food composition of the present invention are present at the same time, it is known to have a kelp soup stock (kelp extract) -like taste (for example, patent). Application Publication No. 5-59690). Therefore, the food composition of the present invention is suitably used as a seasoning. The form of the seasoning is not particularly limited, and examples thereof include powder, granules, tablets, liquids, and gels.

In order to have a kelp soup stock-like taste in the food composition of the present invention, the molar ratio of each component is glutamic acid: potassium salt: sugar alcohol = 1: 2.5 to 20: 1.2 to 63. Is preferable. In the food composition of the present invention, it is preferable to use sodium glutamate as a raw material for glutamic acid, potassium chloride as a raw material for potassium salt, and mannitol as a raw material for sugar alcohol from the viewpoint of having a better taste like kelp soup stock.

Examples of the seasoning include an umami seasoning obtained by mixing glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol with other food materials; and the like.

Specific examples of foods and drinks include supplements such as nutritionally functional foods; and beverages such as tea, soft drinks, energy drinks, and beauty drinks.

The food composition of the present invention can be produced, for example, by adding glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol, respectively.

When the food composition of the present invention is a dietary supplement or a nutritional supplement, the dosage form thereof includes, for example, tablets, capsules, granules, powders, fine granules, chewable tablets, pills, troches. Examples thereof include agents, jelly agents, syrups, and liquid agents.

The preparation of these formulations includes non-toxic excipients, binders, lubricants, disintegrants, preservatives, isotonic agents, stabilizers, dispersants, antioxidants, colorants, flavoring agents, buffers. It can be carried out by a known method using additives such as a pH adjuster and a thickening agent. Non-toxic additives contained in these preparations include, for example, starch, gelatin, glucose, lactose, fructose, maltose, magnesium carbonate, silicon dioxide, talc, magnesium stearate, calcium stearate, methyl cellulose, carboxymethyl cellulose, cellulose, and the like. Examples thereof include gum arabic, polyethylene glycol, propylene glycol, petrolatum, glycerin, ethanol, syrup, sodium chloride, sodium sulfite, sodium phosphate, citric acid, polyvinylpyrrolidone, water, shelac, carnauba wax and the like. In addition, in order to reinforce or enhance the usefulness of the present invention, the formulation may contain other components, drugs and the like.

The food composition of the present invention may contain various additives as components other than the above-mentioned glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol, depending on the type of the food composition. Additives include sweeteners, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, magnesium stearate, steer. Cellulous derivatives such as calcium phosphate and hydroxypropyl cellulose, crystalline cellulose, silicon dioxide, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, arabic gum, carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide. , Calcium pantothenate, fatty acids (excluding the above-mentioned glutamate acid or its salts), calcium salts, pigments, fragrances and the like.

(Pharmaceutical composition)
Examples of the pharmaceutical composition of the present invention include veterinary drugs, quasi-drugs, pharmaceuticals, therapeutic agents, preventive agents and the like.

The dose of the pharmaceutical composition varies depending on the sex, age, body weight, diet, mode of administration, stress symptoms, degree of exposure to stress, etc. of the subject to be administered, but for example, daily administration to an adult (assuming a body weight of 60 kg). The amount of glutamic acid in the pharmaceutical composition is preferably 0.01 to 5 g, more preferably 0.1 to 2 g. Such a dose can be administered once or in several divided doses.

In the present invention, the stress response can be reduced by administering the above dose to the administration subject, but in that case, only the active ingredients of glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol are used as they are or as a pharmaceutical carrier. Tablets, capsules, granules, powders, syrups, chewable tablets, pills, troches, etc. It can be orally or enterally administered as a pharmaceutical preparation such as a jelly preparation, a syrup, a liquid preparation, a gum preparation, and a drops preparation. As the administration method, oral administration is preferable, and a drug sustained-release form is preferable. Examples of the sustained-release form include usual sustained-release agents such as gel-coated preparations and multi-coated preparations, as well as gum preparations and drops preparations.

Further, the present invention also includes a form in which the active ingredients of glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol are formulated in two or more portions and mixed at the time of administration, or taken at the same time at the time of administration.

The above-mentioned pharmaceutical carrier is one that is pharmaceutically acceptable and has as little pharmaceutical action as possible in the body. Examples of the pharmaceutical carrier when orally administered include binders such as hydroxypropyl cellulose, traganth gum, arabic rubber, corn starch and gelatin; excipients such as dicalcium phosphate; partially pregelatinized starch, corn starch, potato starch, alginic acid and the like. Disintegrants; starches such as magnesium stearate; pigments; fragrances such as orange flavor; solvents such as water, ethanol and glycerol; nutrients such as proteins, amino acids, vitamins, lipids and glucose can be appropriately used. .. Further, as a pharmaceutical carrier, pharmaceutically acceptable antioxidants such as cysteine, glutathione, ascorbic acid, sodium metasulfate, and sodium bicarbonate, and acid neutralizers such as calcium carbonate, aluminum hydroxide gel, and aluminum silicate are used. Can be mentioned. One or more of these can be used.

When the stress-reducing composition of the present invention is a food composition such as a dietary supplement or a nutritional supplement, or a pharmaceutical composition, the content of the active ingredient in the composition is preferably 0.1% by mass to 100% by mass. It is mass%, more preferably 10% by mass to 90% by mass, still more preferably 40% by mass to 80% by mass.

The present invention will be described in more detail with reference to Examples. However, the present invention is not limited to these examples.

[Experimental Example 1]
(Mouse used)
Experiments were performed using 4-week-old male ICR mice. By stressing mice, the stress-reducing effect of monosodium glutamate (hereinafter sometimes abbreviated as "MSG") alone, the stress-reducing effect of a combination of two components of potassium chloride and mannitol, and the stress-reducing effect of MSG, potassium chloride and mannitol. The stress-reducing effect of the combination of the three components was verified. The mice used in the test were 6 mice in 1 group, divided into 5 groups (A to E), and fed with food and beverage to carry out the experiment.

(Beverage)
As ingredients contained in the beverage (food composition), sodium glutamate (Fujifilm Wako Pure Chemical Industries, Ltd.), potassium chloride (Nakaraitesku Co., Ltd.) and mannitol (Fujifilm Wako Pure Chemical Industries, Ltd.) are used, and distilled water is further added. Using. Table 1 shows the amount of each component added in a total of 100 mL for the beverage used in the restraint stress test. Among the beverages shown in Table 1, the three-component simulated soup stock is a food composition according to the present invention containing monosodium glutamate (MSG), potassium chloride, and mannitol.

(Food)
A commercially available diet (Oriental Yeast Co., Ltd., "MF") was used.

(Restricted stress test)
Group A is a control, with free intake of food and water (beverage) on days 1 to 5 (acclimation period), and food and water (test period) on days 6 to 8 (test period) without stress. Beverages) were taken freely. On the 9th day, dissection and blood sampling were performed, and the concentration of corticosterone in serum was measured.
In group B, food and water (beverage) were freely ingested on the 1st to 5th days (acclimation period), and restraint stress was applied for 5 hours a day on the 6th to 8th days (test period), and the 6th day. Until the restraint stress on the 8th day was released, food and water (drinks) were freely ingested, and after the restraint stress on the 8th day was released, fasting was performed. On day 9, restraint stress was applied, then dissection and blood sampling were performed to measure serum corticosterone levels.
In group C, the diet and the two-component simulated drink (beverage) were freely ingested on the 1st to 5th days (acclimation period), and the restraint stress was applied for 5 hours a day on the 6th to 8th days (test period). From the 6th day to the 8th day until the restraint stress was released, the diet and the two-component simulated drink (beverage) were freely ingested, and after the restraint stress was released on the 8th day, fasting was performed. On day 9, restraint stress was applied, then dissection and blood sampling were performed to measure serum corticosterone levels.
In Group D, the diet and 3-component simulated drink (beverage) were freely ingested on the 1st to 5th days (acclimation period), and the restraint stress was applied for 5 hours a day on the 6th to 8th days (test period). From the 6th day to the 8th day until the restraint stress was released, the diet and the 3-component simulated drink (beverage) were freely ingested, and after the restraint stress was released on the 8th day, fasting was performed. On day 9, restraint stress was applied, then dissection and blood sampling were performed to measure serum corticosterone levels.
In group E, the diet and one-component simulated drink (beverage) were freely ingested on the 1st to 5th days (acclimation period), and the restraint stress was applied for 5 hours a day on the 6th to 8th days (test period). From the 6th day to the 8th day until the restraint stress was released, the diet and 1-component simulated drink (beverage) were freely ingested, and after the restraint stress was released on the 8th day, fasting was performed. On day 9, restraint stress was applied, then dissection and blood sampling were performed to measure serum corticosterone levels.
The body weights of groups A to E were measured on the 1st, 6th, and 9th days.
Table 2 shows the mean and standard deviation of 6 corticosterone concentrations in serum measured on day 9 for groups A to E, and 6 animals weighing on days 1, 6, and 9. Shows the average value of. FIG. 1 is a graph showing the measurement results of the concentration of corticosterone in the serum shown in Table 2.

Based on the results shown in Table 2 and FIG. 1, the following considerations could be made.
Comparison between group A and group B: It was found that corticosterone in serum increased by applying restraint stress.
Comparison between group B and group D: It was found that oral ingestion of 3-component simulated soup stock reduced serum corticosterone, that is, reduced stress response.
Comparison between D group and C group or E group: According to the three-component simulated soup stock, it was found that the effect of reducing corticosterone in serum was higher than that of the two-component simulated soup stock or the one-component simulated soup stock.

Claims (5)

A stress-reducing agent containing glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol. The stress reducing agent according to claim 1, wherein the sugar alcohol is mannitol. The stress reducing agent according to claim 1 or 2, which is a food composition. A stress-reducing composition containing glutamic acid or a salt thereof, a potassium salt, and a sugar alcohol. The stress-reducing composition according to claim 4, which is a seasoning.

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