JP2023062249A - Composition for reducing stress - Google Patents

Abstract

To provide a novel composition for reducing stress.SOLUTION: The present invention relates to a novel composition for reducing stress that comprises taxifolin or a salt thereof as an active ingredient. The present invention also relates to a pharmaceutical composition or food composition useful for prevention, treatment or amelioration of symptoms or diseases caused by stress.SELECTED DRAWING: None

Description

The present invention relates to compositions for reducing stress. More specifically, the present invention provides a composition for reducing stress containing taxifolin or a salt thereof as an active ingredient, and a composition for preventing and/or treating (or improving) symptoms or diseases caused by stress. Regarding the composition.

In modern society, where we are forced to lead busy lives, various kinds of stress are generated due to study, desk work, mental tension in human relationships, and the like, and mental fatigue is increasing. Such stress and mental fatigue can lead to depression with subjective symptoms such as lack of motivation, inattentiveness, inability to concentrate, irritability, and irritability. In some cases, subjective symptoms such as a heavy head and general malaise are accompanied, and in some cases, stiff shoulders, lumbago, headache, etc. occur concurrently. Furthermore, severe stress and mental fatigue may even cause neurological disorders and the like. Physical fatigue can basically be expected to recover by taking a rest, but chronic stress and mental fatigue cause a decline in motivation, attention and concentration, work efficiency, etc., and further recovery. is not easy. Therefore, there is a demand for the development of pharmaceuticals or foods and drinks that can effectively improve stress and mental fatigue caused by it in the stage of presymptomatic illness (preliminary group that has not yet developed the disease).

Antipsychotic drugs, antidepressants, tranquilizers, antianxiety drugs, sleeping pills, psychostimulants, antiepileptic drugs, etc. have been used as drugs for alleviating mental disorders caused by stress. However, the above drugs show various side effects such as dry mouth, constipation, nasal congestion, difficulty urinating, palpitations, blurred vision, and lethargy. In addition, there is a problem that if the dosage and usage are incorrect, adverse effects are produced, and the period of administration is usually longer than one year.

In addition, caffeine is widely known as a compound that reduces fatigue. In addition to being less effective in improving physical fatigue, overdose may increase agitation and interfere with rest and sleep, which are necessary to improve stress and fatigue.

In order to overcome the above-mentioned problems of drugs and the like, stress reducing agents using foods or food additives have been reported. For example, a stress-relieving food combining glutathione and other antioxidants (Patent Document 1), a stress suppressant containing gluten hydrolyzate as an active ingredient (Patent Document 2), and a solvent extract of a plant belonging to the persimmon family are effective. An anti-stress composition (Patent Document 3) as a component, an anti-stress agent containing a pine bark extract (proanthocyanidins and catechins) (Patent Document 4), an anti-stress agent containing a wasabi leaf extract (Patent Document 5), a stress reducing agent containing Lactobacillus gazelli as an active ingredient (Patent Document 6), and the like are known. However, these stress-relieving agents were not necessarily sufficient in terms of their effects.

As described above, conventional medicines (pharmaceutical compositions) and foods (food compositions) for reducing stress have problems in terms of safety and efficacy, and therefore should be taken with confidence. There is an urgent need to develop a medicine or food for reducing stress in a safe and effective manner that can be sustained.

Taxifolin has the following formula (1):

It is a type of flavonoid that accounts for the majority (90% or more) of the active ingredient of diquevertine, a bioflavonoid complex isolated from the woody part of Dahria larch or Siberian larch (Non-Patent Document 1 ). Taxifolin has been reported to have antioxidant and capillary protective properties (Non-Patent Document 2) and has been approved by the Ministry of Health of the Russian Federation as a drug with capillary protective and antioxidant properties. As a functional food, it is also approved as a food additive that extends the shelf life of foods. Furthermore, taxifolin has recently been confirmed to be safe for ingestion (Non-Patent Document 3), and has antioxidant activity in acute pancreatitis model mice (Non-Patent Document 4) and blood glucose improving effect in type 1 diabetes model rats (Non-Patent Document 3). Document 5), dementia-improving effects such as suppression of amyloid β aggregation in Alzheimer's disease model mice, improvement of cerebral blood flow, and improvement of spatial recognition function of mice in a water maze test (Patent Document 7, Non-Patent Document 6), and A preventive or therapeutic effect on non-alcoholic steatohepatitis (NASH) has been confirmed (Patent Document 8).
However, there are no reports on the stress-relieving effect of taxifolin, nor is there any report on the use of taxifolin as a prophylactic and/or therapeutic agent for symptoms or diseases caused by stress.

JP-A-8-275752 JP-A-11-49697 Japanese Patent Publication No. 2000-136143 JP-A-2003-95964 JP-A-2008-230975 WO2014/132982 WO2017/199755 WO2020/262703

вён, 1998, 19 хйм-фарм. журн, 1995, 29, 9, 61-64 Int. J. Toxicol., 2015, 34(2), 162-181 J. Ethnopharmacol., 2018, 224, 261-272 J. Cell. Biochem., 2019, 120(1), 425-438 Acta Neuropathol. Commun., 2017, 5(1), 26, doi:10.1186/s40478-017-0429-5

Against this background, the development of novel pharmaceuticals or foods and drinks that target stress, especially mental stress, for which no safe and effective preventive or therapeutic method or alleviation (or amelioration) method has yet been established. is coveted.

An object of the present invention is to provide a composition for reducing stress. A further object of the present invention is to provide a pharmaceutical composition or food composition effective in preventing and/or treating (or improving) symptoms or diseases caused by stress.

Under such circumstances, the present inventors, as a result of intensive studies, found that taxifolin or a salt thereof exhibits an excellent stress-relieving effect, and the prevention and / or treatment of symptoms or diseases caused by stress (or Improvement), it was found for the first time that it can be a useful and safe pharmaceutical composition or food composition, and the present invention was completed.

That is, the present invention is as follows.
[1] A composition for reducing stress containing taxifolin or a salt thereof as an active ingredient.
[2] The composition according to [1] above, wherein the stress is mental stress.
[3] The composition according to [1] or [2] above, which is for prevention and/or treatment of symptoms or diseases caused by stress.
[4] The above [ 3].
[5] The composition according to any one of [1] to [4] above, further comprising vitamins and excipients.
[6] The composition according to any one of [1] to [5] above, which is a pharmaceutical composition (hereinafter also referred to as "pharmaceutical composition of the present invention" or "pharmaceutical of the present invention"). .
[7] The composition according to any one of the above [1] to [5], which is a food composition (hereinafter sometimes referred to as "food composition of the present invention" or "food and drink of the present invention". ).
[8] The composition according to [7] above, labeled with a function related to stress reduction.
[9] Function display is "prevent stress", "reduce stress", "relieve stress", "reduce mental fatigue", "recover mental fatigue", "nervous function The composition according to [8] above, which is selected from the group consisting of "increases concentration", "increases concentration", and "motivates".
[10] Any of the above [7] to [9], which is prepared as a supplement, functional food, health food, food for special uses, food with health claims, food for specified health uses, or food with nutrient function claims. The composition according to
[11] Any one of the above [6] to [10], which is prepared in the form of tablets, pills, capsules, powders, granules, fine granules, troches, or liquids. composition.
[12] A stress reducing agent containing taxifolin or a salt thereof as an active ingredient.
[13] A method for preventing and/or treating stress-induced symptoms or diseases, which comprises orally administering a prophylactically and/or therapeutically effective amount of taxifolin or a salt thereof to a subject.
[14] The above [ 13].
[15] taxifolin or a salt thereof for use in the prevention and/or treatment of symptoms or diseases caused by stress.
[16] A taxifolin-containing food composition for use in preventing and/or ameliorating symptoms caused by stress.
[17] Use of taxifolin or a salt thereof for the manufacture of a medicament for use in the prevention and/or treatment of symptoms or diseases caused by stress.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an excellent stress reducer (composition for reducing stress) characterized by containing taxifolin or a salt thereof, which is a safe plant-derived ingredient, as an active ingredient. In addition, according to the present invention, by administering or ingesting an effective amount of taxifolin or a salt thereof to a subject, it becomes less susceptible to stress, and even if stress is received, symptoms or diseases caused by stress (for example, mental (fatigue, neurological disorder, loss of motivation, lack of attention and concentration, etc.), so it is useful and safe in the prevention and/or treatment (or improvement) of symptoms or diseases caused by stress. A pharmaceutical or food composition can be provided.

FIG. 1 shows a schematic diagram of a test protocol showing the order of execution of a test example (brain activity test) on a test day in terms of time. (1) in FIG. 2 shows the number of answers and the number of correct answers in the Serial Threes subtraction task for 2 minutes after ingestion of the composition of the present invention or placebo; time) and the time required for the correct answer. (1) in FIG. 3 shows the number of answers and the number of correct answers for the Serial Sevens subtraction task in 2 minutes after ingestion of the composition of the present invention or placebo, and (2) shows the time required to enter numbers time) and the time required for the correct answer. FIG. 4 shows the time required for the test (VAS required time) (1) after ingestion of the composition of the present invention or placebo, and the subjective evaluation results of mental fatigue (mental stress) by participants (VAS questionnaire Result) (2) is shown.

Terms used in this specification are defined as follows.

In the present specification, “taxifolin” is a compound represented by the formula (1), and is the major active ingredient of diquevertine, a bioflavonoid complex isolated from the woody part of Dahria larch or Siberian larch (90%). %) is a kind of flavonoids.

As used herein, taxifolin salts include salts that can be easily formed by the action of a pharmaceutically acceptable base. Examples of such salts include alkali metal salts such as sodium salts and potassium salts.

Taxifolin derived from Siberian larch is an optically active form ((+)-taxifolin). The taxifolin of the present invention includes not only (+)-taxifolin, but also its enantiomer (−)-taxifolin, a compound with low optical purity (both optically pure enantiomers mixed in an appropriate blending ratio). ), and racemates are also included. In addition, the taxifolin of the present invention is a label body, that is, one or two or more atoms constituting taxifolin are isotopes (e.g., ² H, ³ H, ¹¹ C, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ O, Also included are compounds labeled with ¹⁸ F, ³⁵ S, etc.).

The optically active form of taxifolin or a salt thereof of the present invention can be produced by chemical synthesis by a method known per se, or by extraction and/or purification from the xylem of Dahria larch or Siberian larch. Specifically, by using an optically active synthetic intermediate, or the racemate of the final product by a conventional method (for example, J. Jacques et al., "Enantiomers, Racemates and Resolution, John Wiley And Sons, Inc." et al.), optically active forms can be obtained by optical resolution. As taxifolin or a salt thereof of the present invention, commercially available (+)-taxifolin can be used as it is, or a commercially available larch extract (dicvertine) containing (+)-taxifolin as a main component is used. You can also

Taxifolin or a salt thereof of the present invention may be in the form of a crystal, and both a single crystal form and a mixture of crystal forms are included in taxifolin or a salt thereof. Crystals can be produced by applying a crystallization method known per se to crystallize.

Taxifolin or a salt thereof of the present invention may also include solvates thereof. These solvates are prepared by coordinating taxifolin or a salt thereof with a solvent molecule, and hydrates are also included. For example, taxifolin or its salt hydrates, ethanolates, dimethylsulfoxide solutes and the like can be mentioned.

As used herein, the term "stress" refers to various reactions of a living body due to an extra chemical, physical, mental, verbal or exertional load applied to the mind and body of the living body. "Stress" also means various responses of a living body caused by a constant load from inside the living body. Although the composition for reducing stress of the present invention is not particularly limited, it is particularly suitable for coping with stress caused by mental load (ie, mental stress).

As used herein, the term "reduce stress" means reducing the degree of stress received from the future, and includes preventing, alleviating, or curing symptoms or diseases caused by stress.

As used herein, "symptoms or diseases caused by stress" means poor physical condition caused by stress. One or two or more selected from the group consisting of concentration defects.

As used herein, the term "autonomic neuropathy" means a state in which the balance between the sympathetic nervous system and the parasympathetic nervous system is disrupted due to mental stress or overwork. Tension, headache, ringing in the ears, palpitations, constipation, diarrhea, irregular menstruation, discomfort in the mouth and throat, frequent urination, feeling of residual urine, sweating, stiff shoulders, irritability, anxiety, depression, deterioration of memory and concentration , accompanied by psychiatric symptoms such as intense emotional ups and downs. "Autonomic neuropathy" is also called "dysautonomia".

As used herein, "prevention" includes preventing disease onset, delaying disease onset, and preventing pathology from occurring. A "prophylactically effective amount" refers to a dose of active ingredient sufficient to achieve a prophylactic purpose.

As used herein, "treatment" includes curing the disease, ameliorating the condition (eg, one or more symptoms) of the disease, and inhibiting the progression of (the severity of) the disease. A "therapeutically effective amount" refers to a dose of active ingredient sufficient to achieve its therapeutic purpose. Therefore, "improvement" is a concept encompassed by "treatment."

As used herein, the term "subject" refers to a subject to whom a drug or food containing an effective amount of active ingredient necessary to prevent and/or treat (or improve) a disease or the pathology of a disease is administered or fed. means. The "subject" includes human or non-human animals (particularly mammals (eg, mice, rats, guinea pigs, hamsters, rabbits, cats, dogs, cows, sheep, monkeys, etc.)).

Pharmaceutical composition of the present invention (or medicament of the present invention)
As shown in the test examples described later, taxifolin exhibits an excellent stress-relieving effect, and therefore taxifolin or a salt thereof, or a pharmaceutical composition containing it as an active ingredient, is effective in preventing symptoms or diseases caused by stress. and/or can be suitably used as a therapeutic drug.

The medicament of the present invention may be either a medicament consisting of taxifolin or a salt thereof alone or a medicament containing taxifolin or a salt thereof and a pharmaceutically acceptable carrier or the like. The medicament of the present invention can be orally administered to a subject in a prophylactically effective amount or a therapeutically effective amount.

Pharmaceutically acceptable carriers include excipients (e.g., starch, lactose, sugar, calcium carbonate, calcium phosphate, etc.), binders (e.g., starch, gum arabic, carboxymethylcellulose, hydroxypropylcellulose, crystalline cellulose, etc.), Lubricants (e.g., magnesium stearate, talc, etc.), disintegrants (e.g., carboxymethylcellulose, talc, etc.), solvents (e.g., water for injection, physiological saline, Ringer's solution, alcohol, propylene glycol, polyethylene glycol, sesame oil, corn oil, olive oil, cottonseed oil, hydrogenated rapeseed oil, etc.), solubilizers (e.g., polyethylene glycol, propylene glycol, D-mannitol, trehalose, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, sodium salicylate, sodium acetate, etc.), suspending agents (e.g., gum arabic, tragacanth, sodium carboxymethylcellulose, methylcellulose, sodium alginate, etc.), surfactants (e.g., stearyltriethanolamine, sodium lauryl sulfate, Laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glyceryl monostearate, polysorbates, polyoxyethylene hydrogenated castor oil, etc.), coating substrates (e.g., polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, etc.), tonicity agents (eg, sodium chloride, glycerin, D-mannitol, D-sorbitol, glucose, etc.), buffering agents (eg, phosphates, acetates, carbonates) , buffer solutions such as citrate), thickeners (e.g., sodium alginate, xanthan gum, sodium chondroitin sulfate, polyvinyl alcohol, povidone, etc.), preservatives (e.g., paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid, etc.), antioxidants (e.g., sulfites, etc.), coloring agents (e.g., water-soluble edible tar pigments (e.g., food red No. 2 and 3, food yellow No. 4 and 5 , food coloring such as food blue No. 1 and 2), water-insoluble lake coloring (e.g., aluminum salt of water-soluble edible tar coloring, etc.), natural coloring (e.g., β-carotene, chlorophyll, red iron oxide)), sweetness agents (for example, sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, etc.) and the like.

After the above ingredients are mixed, the pharmaceutical composition of the present invention can be prepared, for example, by mixing the mixture into tablets, pills, capsules (including hard capsules, soft capsules, and microcapsules), powders, granules, and fine particles. Oral preparations such as granules, troches, liquids (including syrups, emulsions and suspensions) can be prepared.

With respect to pharmaceutical compositions in the form of tablets, granules, and fine granules, for the purposes of taste masking, improvement of photostability, improvement of appearance, or enteric properties, a method known per se using the above coating base material is used. may be coated with

The content of taxifolin or a salt thereof in the medicament of the present invention varies depending on the form of the preparation, but is usually about 1 to 100% by weight, preferably about 5 to 100% by weight, more preferably about 5 to 100% by weight, based on the total preparation. , about 10-100% by weight.

The dosage of taxifolin or its salt (that is, the prophylactically effective amount or the therapeutically effective amount) varies depending on the administration subject, disease, symptom, dosage form, administration route, etc. For example, in the case of humans, adult patients (body weight When orally administered to a body weight of about 60 kg), the dose is usually 10 to 10,000 mg, preferably 30 to 1,000 mg, and more preferably 50 to 500 mg per day in terms of taxifolin, which is an active ingredient, in once to several divided doses per day. It can be administered before, after or between meals. The administration period is not particularly limited.

Taxifolin or a salt thereof can be used alone or in combination with other known agents that exhibit stress-relieving effects. By combined use with other drugs, it is possible to enhance the preventive and/or therapeutic effects of taxifolin or its salts on symptoms or diseases caused by stress. Other drugs include antianxiety drugs (e.g., chlordiazepoxide, oxazolam, diazepam, etc.), antidepressants (e.g., amoxapine, nortriptyline, amitriptyline, trimipramine, imipramine, clomipramine, dosulepin, lofepramine, maprotiline, fluvoxamine, paroxetine, sertraline, duloxetine, etc.), caffeine, vitamins (e.g., vitamin A, vitamin B1, vitamin B2, vitamin B6, niacinamide, pantothenic acid, vitamin B12, vitamin E, biotin, vitamin C, etc.). are preferred, and vitamin C, which exhibits excellent antioxidative activity and no side effects, is particularly preferred.

The timing of administration of the other drug (concomitant drug) is not limited, and they may be administered to the subject simultaneously with taxifolin or a salt thereof, or may be administered with a time lag. Alternatively, a single preparation containing taxifolin or a salt thereof and a concomitant drug in combination can be administered.

The dose of the concomitant drug can be appropriately selected based on the clinically used dose. In addition, the mixing ratio of taxifolin or a salt thereof and the concomitant drug can be appropriately selected according to the subject of administration, administration route, target disease, symptom, type of concomitant drug, and the like.

Food Composition of the Present Invention In the present specification, taxifolin or a salt thereof, or a food composition containing it as an active ingredient may be referred to as "the food composition of the present invention".
The food composition of the present invention may consist of taxifolin or a salt thereof alone, or may be a composition in which taxifolin or a salt thereof and food additives or the like are blended. The food composition of the present invention contains taxifolin or a salt thereof and can be orally ingested by a subject, and there are no particular restrictions on the type, shape, etc. of the food composition. In addition, as shown in the test examples described later, taxifolin exhibits an excellent stress-relieving effect, so the food composition of the present invention is suitable for use in preventing and/or improving various symptoms caused by stress. can be used.

Examples of the food composition of the present invention include confectionery such as drops, candies, soda pop, gummies, and chewing gum; Western confectionery such as cookies, crackers, biscuits, potato chips, bread, cakes, chocolate, donuts, puddings, and jelly; Japanese sweets such as yokan, daifuku, ohagi, steamed buns, and castella; frozen desserts such as ice cream, popsicles, sherbet, and gelato; breads such as bread, French bread, and croissants; noodles such as udon, soba, Chinese noodles, and kishimen; Fish paste products such as kamaboko, chikuwa, and fish sausages; meat products such as ham, sausages, hamburgers, and corned beef; salt, pepper, miso, soy sauce, sauces, dressings, mayonnaise, ketchup, sweeteners (e.g., sugar, honey, powder condiments such as candy, starch syrup, jam, marmalade, etc.) and spicy seasonings (e.g., mustard, pepper, etc.) Teppanyaki foods such as Akashiyaki, takoyaki, monjayaki, okonomiyaki, yakisoba, and yakiudon; cheese, butter, margarine , yogurt and other dairy products; natto, fried tofu, tofu, konjac, dumplings, pickles, tsukudani, dumplings, shumai, croquettes, sandwiches, pizza, hamburgers, salads and other side dishes; beef, pork, chicken and other livestock products; Marine products such as shrimp, scallops, seaweed, and kelp; Various powders made from vegetables, fruits, plants, yeast, algae, etc.; Drinks etc. are mentioned.

Beverages include food and drink such as soup and miso soup; powdered food and drink such as instant coffee, instant black tea, instant milk, instant soup and instant miso soup; Alcoholic beverages such as shochu, beer, non-alcoholic beer with an alcohol content of 1% or less, low-malt beer, and chuhai; fruit juice (e.g., apple, mandarin orange, grape, banana, pear, plum juice, etc.) beverages, vegetable juices (e.g., , tomato, carrot, celery, cucumber, watermelon juice, etc.) beverages, fruit and vegetable juice-containing beverages, soft drinks, milk, soy milk, dairy drinks, drink-type yogurt, coffee, cocoa, tea beverages (e.g., Black tea, green tea, barley tea, brown rice tea, sencha, gyokuro tea, roasted tea, oolong tea, turmeric tea, pu-erh tea, rooibos tea, rose tea, chrysanthemum tea, herbal tea (e.g., mint tea, jasmine tea), energy drinks, Examples include non-alcoholic beverages such as sports drinks and mineral water.

Suitable examples of such food compositions include jelly, tea beverages, alcoholic beverages, drops, candies, soda pop, cookies, crackers, biscuits, chocolate, cheese, butter, margarine, chewing gum and the like.

In addition, the food composition of the present invention may be prepared as a functional food, health food, food for specified health use, food for special uses (for example, food for sick people), supplement, etc. It is preferably prepared as a food or supplement.

Examples of the form of the food composition of the present invention include tablets, pills, capsules (including hard capsules, soft capsules, and microcapsules), powders, granules, fine granules, troches, or liquids (syrups, emulsions, including suspending agents), etc., and tablets or capsules are preferred.

The food composition of the present invention is preferably a food for specified health use, a food for special dietary use, or a supplement in the form of tablets or capsules.

As used herein, the term "supplement" means not only nutritional supplements, food with nutrient function claims, etc., but also functions useful for maintenance, recovery, promotion, etc. of health (particularly, It also means health supplements, health functional foods, etc., which have functions of preventing and/or improving various symptoms.

The food composition of the present invention can be produced, for example, by adding taxifolin or a salt thereof to food by a known method. Specifically, for example, the food composition of tablet, for example, taxifolin or a salt thereof, excipients (e.g., starch, lactose, sucrose, mannitol, etc.), sweeteners, flavoring agents, etc. , mixing, and applying pressure with a tableting machine or the like to form the shape of a tablet. If necessary, other materials (for example, vitamins such as vitamin C, minerals such as iron, other additives such as dietary fiber) can also be added. Capsule food compositions are prepared by, for example, filling liquid, suspension, paste, powder, or granular food compositions containing taxifolin or a salt thereof into capsules or encapsulating them with a capsule base. It can be manufactured by molding.

The food composition of the present invention contains commonly used food materials, food additives, various nutrients, vitamins, flavor substances (e.g., cheese, chocolate, etc.), as long as they do not inhibit the effects of the present invention. A legally acceptable carrier and the like can be added. As the physiologically acceptable carrier, various conventional organic or inorganic carrier substances are used, and excipients, binders, disintegrants, lubricants, colorants, sweeteners, preservatives, antioxidants, Thickeners, emulsifiers and the like are included. Food additives include coloring agents, sweetening agents, preservatives, antioxidants, flavoring agents, and the like. Furthermore, other materials such as minerals such as iron, dietary fibers such as pectin, carrageenan and mannan may be contained.

Excipients, binders, disintegrants, lubricants, solvents, solubilizers, suspending agents, buffers, thickeners, colorants, sweeteners, preservatives, and antioxidants are as described above. Examples thereof include those similar to those used in the medicament of the present invention.

Vitamins may be either water-soluble or fat-soluble, and examples include vitamin A, vitamin B1, vitamin B2, vitamin B6, niacinamide, pantothenic acid, vitamin B12, vitamin E, biotin, vitamin C, and the like. Among them, vitamin C, which exhibits excellent antioxidant activity and has no side effects, is preferred.

Food compositions in the form of tablets, granules, and fine granules are coated by a method known per se using a coating base for purposes such as taste masking, improved light stability, improved appearance, or enteric properties. May be coated. Examples of the coating substrate include the same substrates as those used for the pharmaceutical of the present invention, and the coating can be carried out in the same manner.

The content of taxifolin or a salt thereof in the food composition of the present invention is about 0.1 to 50% by weight, preferably about 0.5 to 30% by weight, more preferably about 1 to 20% by weight.

The food composition thus obtained is safe and can be continuously fed to subjects, particularly preferably humans.

The intake of the food composition of the present invention may be within the range of an effective amount of taxifolin or a salt thereof capable of reducing stress, or an effective amount of preventing and/or improving various symptoms caused by stress. For example, when the food composition of the present invention is ingested by adults for the purpose of reducing stress, the intake of taxifolin or its salt is generally In terms of taxifolin, which is an active ingredient, it can be ingested in an amount of usually 10 to 10000 mg, preferably 30 to 1000 mg, more preferably 50 to 500 mg, once or several times a day. In addition, the above intake amount is preferable also from the viewpoint that the effect is exhibited without affecting palatability and intake amount. Similar amounts can be ingested when the subject is another animal.

Furthermore, the food composition of the present invention may be used alone, but other drugs (concomitant drugs) described above, other foods exhibiting stress-reducing effects (for example, the above-mentioned Patent Documents 1 to 6) It may be used in combination with the described foods, etc.). By combining with other medicines or foods, it is possible to further enhance the effects of preventing and/or improving various symptoms caused by stress.

In addition, the food composition of the present invention may be used as a health food, a functional food, a food for specified health use, a food with health claims, a food labeled to reduce stress, or a food for special dietary use (for example, a food for sick people). Classifications are also included. Examples of stress reduction display include "prevent stress", "reduce stress", "relieve stress", "reduce mental fatigue", "recover mental fatigue", "nervous function Examples include displays such as "increase concentration", "increase concentration", and "motivate". Therefore, the food composition of the present invention contains, for example, taxifolin or a salt thereof, and is for reducing stress, preventing and/or improving various symptoms caused by stress, etc. Food and drink labeled with

Here, functional indications attached to these food compositions can be made on any of the main bodies, containers, packaging, instructions, package inserts, or promotional materials of the products.

Hereinafter, the present invention will be described in more detail based on test examples and formulation examples, but the present invention is not limited by test examples and formulation examples, and can be changed without departing from the scope of the present invention. good too. In addition, reagents, devices, materials, etc. used in the present invention are commercially available unless otherwise specified.

The following study examples were conducted according to a randomized, parallel-group, placebo-controlled, double-blind study design. Participants were randomized to receive tablets having the compositions listed in Table 1 below as a taxifolin-containing composition (test composition) and placebo (control composition), respectively.

Twenty-eight healthy men and women aged 20 to 26 participated in the following test example (brain activity test).

Test Example: Brain Activity Test (1) Method All tests were performed on a computer according to the protocol shown in FIG. It consists of four repetitions of an approximately 10-minute assessment that measures performance speed, accuracy and mental fatigue during a continuous cognitive demand task. Each approximately 10-minute cycle of this battery performed two consecutive subtraction tasks (Serial Threes—2 minutes and Serial Sevens—2 minutes), a Rapid Visual Information Processing (RVIP)—5 minutes) and a visual Includes an analog mental fatigue scale. Individual issues are described below.

(i) Serial Threes subtraction task (2 minutes):
Participants are asked to subtract 3 from a random starting number between 900 and 999 shown on the computer. Instruct participants to enter their answers as quickly and as accurately as possible using the computer's numeric keys. The starting digit is cleared from the screen when the participant enters the first answer. Each of the three subsequent numeric responses by the participant are shown on the screen. The participant hits the enter key to indicate the end of each answer, clearing the three numbers from the screen. The measurement items were the number of answers, the number of correct answers, the number of incorrect answers, the rate of correct answers, the number of times the numbers were re-entered, the time required for answering, and the time required for correct answers. The numbers used as answers can be re-entered any number of times until the enter key is pressed, and the number of re-inputs was counted as the number of re-inputs of numbers. The time taken to answer is the time from one answer to the next (it represents the time between pressing the enter key, i.e. the time required to enter a number, regardless of whether it is correct or wrong), and the time taken to answer correctly is the time it takes to enter the correct answer. time.

(ii) Serial Sevens subtraction task (2 minutes):
This task is identical to the Serial Threes subtraction task except that it asks the participant to subtract seven.

(iii) Rapid visual information processing task (RVIP-5 minutes):
RVIP presses the enter key specified when three consecutive arithmetic progressions with a tolerance of 2 are displayed among the numbers 1 to 9 displayed one by one on the screen at a speed of 100 per minute. push. The measurement items of RVIP are the number of correct answers, the number of incorrect answers, the rate of correct answers, the number of overlooked numbers (the number of times when three consecutive arithmetic progressions with a tolerance of 2 were displayed but the enter key was not pressed), and the reaction time (with a tolerance of 2). The time from the screen display of three consecutive arithmetic progressions (2) to the press of the enter key).

(iv) "Mental Exhaustion" Visual Analogue Scale (VAS):
Participants scored their subjective feelings of mental fatigue from 0 to 100, ranging from ``the best feeling of no fatigue'' to ``the worst feeling of being completely exhausted'' self-evaluation on a standard analog scale.

Statistical analysis: The primary endpoints were brain activity test performance and subjective assessment of mental fatigue.

Mental fatigue: A main effect of time on the subjective evaluation of mental fatigue was observed, and mental fatigue increased over time (see (2) in Figure 4).

(2) Results From the results of FIGS. 2 and 3, the taxifolin-containing composition (test composition) intake group was higher than the placebo intake group in the number of answers and the It was confirmed that the number of correct answers increased and the time required for answering (input time) was shortened.
According to (1) of FIG. 4, the taxifolin-containing composition (test composition) intake group is shorter than the placebo intake group VAS (Visual Analog Scale; visual analog scale) required time, decision making It was confirmed that the speed was improved. In addition, from the results of (2) in FIG. 4, the taxifolin-containing composition (test composition) intake group is more than the placebo intake group, the difference between the third and fourth brain activity test VAS scores (mental It was observed that the VAS variation of the degree of fatigue) tended to decrease.

From the above test results, it was confirmed that the composition of the present invention prevents and/or improves mental fatigue caused by stress.

Formulation example 1 (manufacture of tablets)
1) (+)-taxifolin 120 g
2) Starch 420 g
3) crystalline cellulose 600 g
4) Vitamin C 300g
5) Hardened rapeseed oil 60 g
1000 tablets total 1500 g
The entire amount of 1), 2) and 4) and 400 g of 3) are kneaded with water, vacuum dried, and granulated. 200 g of 3) and 60 g of 5) are mixed with this sieved powder and tableted with a tableting machine. 1000 tablets containing 120 mg of (+)-taxifolin per tablet are thus obtained.

Formulation Example 2 (manufacture of capsules)
1) (+)-taxifolin 50 mg
2) Micronized cellulose 10 mg
3) Lactose 19 mg
4) Magnesium stearate 1 mg
Total 80 mg
1), 2), 3) and 4) are mixed and filled into gelatin capsules.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an excellent stress reducer (composition for reducing stress) characterized by containing taxifolin or a salt thereof, which is a safe plant-derived ingredient, as an active ingredient. In addition, according to the present invention, by administering or ingesting an effective amount of taxifolin or a salt thereof to a subject, it becomes less susceptible to stress, and even if stress is received, symptoms or diseases caused by stress (for example, mental (fatigue, neurological disorder, loss of motivation, lack of attention and concentration, etc.), so it is useful and safe in the prevention and/or treatment (or improvement) of symptoms or diseases caused by stress. A pharmaceutical or food composition can be provided.

Claims (10)

A composition for relieving stress containing taxifolin or a salt thereof as an active ingredient. 2. The composition of Claim 1, wherein the stress is psychological stress. 3. The composition according to claim 1 or 2, which is used for prevention and/or treatment of symptoms or diseases caused by stress. 4. The symptom or disease caused by stress is one or more selected from the group consisting of mental fatigue, autonomic neuropathy, loss of motivation, general malaise, and attention and concentration deficit according to claim 3. composition. The composition according to any one of claims 1 to 4, further comprising vitamins and excipients. A composition according to any one of claims 1 to 5, which is a pharmaceutical composition. The composition according to any one of claims 1 to 5, which is a food composition. 8. The composition of claim 7 labeled with a function associated with stress reduction. The function display is "Prevent stress", "Reduce stress", "Relieve stress", "Reduce mental fatigue", "Recover mental fatigue", "Enhance nerve function" 9. The composition of claim 8, which is selected from the group consisting of: , "improve concentration" and "motivate". 10. The product according to any one of claims 7 to 9, which is prepared as a supplement, a functional food, a health food, a food for special uses, a food with health claims, a food for specified health uses, or a food with nutrient claims. Composition.

Images