KR101568044B1 - Composition reducing anxiety and stress - Google Patents

Abstract

The present invention provides a composition for relieving anxiety and stress comprising a mixture of (a) a theanine, and (b) an extract of green tea, red ginseng, and a sage extract.

Stress, anxiety

Description

TECHNICAL FIELD [0001] The present invention relates to compositions for relieving anxiety and stress,

The present invention relates to a composition for relieving anxiety and stress, comprising a mixture of at least one of green tea extract, red ginseng extract and Sasa extract, and a mixture of theanine.

Nowadays society is rapidly developing and diversified and it demands various roles for modern people. As a result, people who complain of generalized anxiety disorder and mental illness due to various stresses are increasing. According to the 2006 Mental State Epidemiology Survey released by the Ministry of Health and Welfare, the prevalence rate of mental illness, one of the mental illnesses experienced in one year in 2006, is one in six adults aged 18 to 64, 17.1 %. As of 2006, the lifetime prevalence of mental illness, which is the proportion of people experiencing one or more mental illnesses during their lifetime, was also 30%, one in three adults. In addition, the prevalence of the total population is much higher, considering the trend of increasing youth mental disorders due to excessive academic heat or various stresses.

Here, briefly examining the mechanism of stress-related neurotransmitter and hormone changes, it regulates the secretion of neurotransmitters and hormones from the hypothalamus to external stimuli and stress, and signals from the hypothalamus to the central nervous system A neurotransmitter such as dopamine, noradrenaline, and serotonin is regulated to be liberated at each nerve end, thereby controlling physiological activities such as emotional state, heart rate, blood pressure, and skeletal muscle blood flow . In addition, hormones are released into the blood through the hypothalamic-pituitary-adrenal (HPA) axis system, which is a circulation system of hormones that connect the pituitary-adrenal gland to the pituitary. If a person is exposed to external stimuli or stress, the corticotropin-releasing factor (CRF, corticotropin releasing factor) is released from the hypothalamus of the body. Then, when the secreted CRF binds to a receptor specifically binding to CRF of the pituitary gland, adrenocorticotropic hormone (ACTH, corticotropin-releasing hormone) is secreted. When the secreted ACTH reaches the adrenal gland through the blood and lymph nodes, corticosterone-like steroid hormones and hormones of catecholamines are released into the blood and thus are involved in the regulation of heart rate, blood pressure and energy metabolism , And negative regulation of the secretion of these factors.

Anxiety is a mental disease that usually lasts for more than six months and is characterized by nervousness, tension, and anxiety that are not recovered. This is generally caused by structural and functional abnormalities of the brain and by sustained stress. Especially in children and adolescents, anxiety and depression can be linked to anxiety and attention deficit hyperactivity disorder (ADHD). Anxiety disorders are classified into four types: generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, and post-traumatic stress disorder. In general, generalized anxiety disorder, which occupies the largest portion of the anxiety disorder is excessive and extensive, And autonomic hypersensitivity are the most important features.

Currently, treatment of anxiety in clinical practice is combined with long-term psychotherapy in addition to medication treatment. In the case of drug therapy, benzodiazepine antibiotics such as diazepam, lorazepam, clonazepam, and alprazolam are mainly used, and azapirone-type buspirone acts as a partial efficacy drug at the serotonin receptor, It is being used as a drug. In addition, imidazopyridine drugs such as zolpidem have been used to treat short-term insomnia due to anxiety.

However, drugs used for anxiety disorders and mental illness are mostly classified as psychotropic drugs, and benzodiazepine drugs act directly on the central nervous gamma-aminobutyric acid (GABA) receptor to inhibit the central nervous system Excessive sedation, and GABA inhibition is enhanced, depression, muscle relaxation, hypnosis, such as strengthening of the central suppression can appear. In addition, drugs used in anxiety disorders and psychiatric disorders are psychologically and physically dependent, which implies the risk of drug abuse.

Therefore, it is necessary to develop drugs that have an effect on mental disorders, do not cause excessive sedation and drowsiness, and do not cause dependence, or health functional foods that can prevent the development of stress stimuli into mental diseases.

In addition to theanine, the present inventors have found that when the extract of at least one of Green tea extract, Red ginseng extract and Sasa extract is used in combination with each other, the interaction between theanine and the extract can reduce or relieve anxiety and stress, It is possible to exert a more effective effect in the case of the present invention.

The present invention is based on this.

The present invention provides a composition for relieving anxiety and stress comprising a mixture of (a) a theanine, and (b) an extract of green tea, red ginseng, and a sage extract.

According to the present invention, a composition containing a mixture of at least one of green tea extract, red ginseng extract and Sasa extract in addition to theanine reduces the levels of dopamine, noradrenaline, and corticosterone, which are increased during stress, Or can be solved, further increasing the level of serotonin to prevent anxiety due to the decrease in the level of serotonin.

Hereinafter, the present invention will be described in detail.

In the present invention, the 'composition for relieving anxiety and stress' means a composition containing the mixture according to the present invention, which has an effect of reducing or eliminating stress, as well as reducing or eliminating anxiety or mental stability.

In the present invention, the 'mixture' is a mixture of theanine, an extract of at least one of green tea extract, red ginseng extract and Sasa extract, and each component is alternatively contained in the composition, or And includes all the components contained in the composition in a mixed state.

The present inventors have found that when mixing substances having a unique mechanism of reducing or eliminating (mental stabilizing) anxiety or reducing or eliminating stresses in an appropriate ratio, they are more effective in relieving anxiety and stress than using each substance alone And the effect is expected to be higher or antagonistic. As a result, it was found that a mixture of the extract of green tea, the extract of red ginseng and the extract of Sasa extract and theanine was obtained as a result of an animal experiment in which each substance known to exhibit the effect of reducing or eliminating the known anxiety and stress was combined The inventors of the present invention have found that the above-mentioned compositions exhibit a much higher degree of anxiety and stress relief or relieving effects than the above-mentioned respective substances alone.

Specifically, when the extract of at least one of Green tea extract, Red ginseng extract and Sasa extract is used in combination with theanine, the synergistic or antagonistic action of each substance causes stress The secretion of neurotransmitters (hormones) such as dopamine, noradrenaline, and corticosterone, which are secreted by the singal from the hypothalamus to the central nervous system, can be further reduced, and secretion of serotonin, Can be further increased, thereby exerting an excellent effect in reducing or eliminating anxiety and stress. In addition, since theanine, green tea extract, red ginseng extract and Sasa extract are all natural physiologically active substances, there is no need to worry about side effects or toxicity during ingestion of the human body or administration of the animal. In particular, There is no risk of drowsiness or drug dependence, and even if administered for a long time or in a large amount, it can be safe for human body.

Accordingly, the present invention is characterized in that the composition for relieving anxiety and stress includes a mixture of (a) theanine and (b) an extract of at least one of green tea extract, red ginseng extract and Sasa extract.

Theanine (γ-glutamylethylamide) (a) of the present invention is rarely found in other plants, and is a natural free amino acid contained only in tea and some mushroom cultivars. It is particularly contained in green tea ( Camellia sinensis ). At this time, the content of theanine is about 50% by weight of the total amino acids contained in the green tea, and about 1 to 2% by weight is contained in the green tea leaves. Theanine contained in green tea is biosynthesized by enzymes from glutamine and ethylamine in roots, transferred to leaves and accumulated, and decomposed upon sunlight to finally be called polyphenol catechin.

These theanines affect the release of neurotransmitters in the brain neurons, and in particular reduce the levels of dopamine and corticosterone, which are stress-induced neurotransmitters, and also cause anxiety It can increase the level of serotonin, which is excellent for reducing anxiety and relieving stress. It is also known to increase the brain alpha (alpha) wave to relax mental relaxation, and to have other antioxidant, blood cholesterol lowering and blood pressure lowering effects.

In the present invention, theanine prepared by a method known in the art can be used. For example, theanine can be prepared by inoculating a microorganism producing theanine converting enzyme into a medium, or commercially available one can be used.

In the case of the present invention, the extract (b) of any one or more of green tea extract, red ginseng extract and Sasa extract, which can exert an excellent effect on anxiety and stress reduction or elimination effect by interacting with the above-mentioned theanine, ).

For example, the composition for relieving anxiety and stress of the present invention may be (a) a mixture of (a) a theanine and (b) a green tea extract, a red ginseng extract, (A) can be mixed with theanine, or (b) both green tea extract, red ginseng extract, and sage extract can be mixed with theanine (a).

Generally, green tea is dried leaves of tea (Camellia sinensis ), an evergreen tea tree, and has long been used as a favorite food. Green tea contains a large amount of catechins such as epicatechin, epicatechin galate, epigallocatechin, and epigallocatechin gallate, which are known to be useful for human body. In addition to catechins, green tea contains polyphenols, flavonoids, amino acids, vitamins, vegetable estrogens, and various minerals in addition to caffeine and organic acids. Green tea, which contains these components, has been used for preventing arteriosclerosis, cancer, and neurological diseases, and is known to be capable of antioxidative and anti-inflammatory actions. Particularly, the components contained in green tea, such as catechin and other flavonoids, are used synergistically to reduce the amount of lactic acid, which is increased by stress. In contrast, blood and liver Of vitamin B ₁ , and thus exerts excellent efficacy in reducing or eliminating stress.

Ginseng is a perennial herbaceous herbaceous plant belonging to the ginseng ( Panax ) of Araliaceae and has been used as an important medicinal herb in oriental medicine. In particular, red ginseng is a dried ginseng which is mixed with saponin, which is a typical active ingredient of ginseng, and chemical changes such as changes in amino acid and browning. These red ginsengs contain no saponin components such as ginsenosides Rg2, Rg3, Rh1 and Rh2. As a result, red ginseng is known to be capable of anticancer action, hypotensive action, cranial nerve cell protective action, and antioxidant action. Of these, red ginseng is known to have various adaptive effects (adaptogen) It is known that it increases the ability to defend against various stresses and so that the living body can adapt more easily.

Sasamorpha purpurascens (Hackel) Nakai var. Borealis (Hackel) Nakai is a blue-green bamboo, about 1 to 2 m high, with long oval or vermiform leaves. The leaves of Sasa berry are known to be effective in relieving stress and mental stability by acting to calm the nervous system. It is also known that the heart and fever (stomach fever) When thunderstorms grow, tongue breaks due to thirst, deep burns, paralysis stops the airflow of the phlegm, and when the mind is confused, the sea water and sputum due to waste heat (pulmonary heat), blood pressure, , Staphylococcus aureus, and gastrointestinal disorders such as nausea and vomiting.

In the present invention, the aforementioned green tea, red ginseng and / or bamboo extract are used. That is, at least one of the green tea extract (b1), the red ginseng extract (b2) and the Sasa extract (b3) is used in the present invention. Here, the green tea extract (b1) is extracted from green tea leaves or treated with an extracted solution, preferably in the form of powder. The red ginseng extract (b2) is extracted from red ginseng or processed into an extracted solution, preferably in the form of powder.

The sasa extract (b3) is not limited to any particular site such as leaves, stems, roots, and shoots of Sasa, but is extracted from each site or processed into an extracted solution, preferably in powder form .

The green tea extract, red ginseng extract and Sasa extract can be extracted using water, an organic solvent, or a mixed solvent thereof. When extracting with an organic solvent, it is possible to use ethanol, isopropanol, acetone, oxalic acid, ethyl acetate, carbon dioxide or an organic solvent which is a mixed solvent thereof. In the case where the active ingredient of green tea, red ginseng or soya bean is not destroyed or minimized It can be extracted at room temperature or warming. In this case, the extraction method used is not particularly limited. For example, it can be extracted using an extraction method such as a cold extraction, an ultrasonic extraction, a reflux cooling extraction, a hot water extraction, etc. Preferably, And the filtrate is concentrated under reduced pressure to obtain the extracts of the present invention.

For example, the green tea extract of the present invention may be obtained by extracting green tea leaves from hot tea or hot water for 3 to 10 hours at a temperature in the range of about 60 to 70 ° C, filtering the extract, Or the supernatant obtained by removing the green tea leaves and the suspension of the green tea leaves may be spray-dried to be in powder form. Here, it is appropriate that the green tea leaves and the extraction solvent are mixed in a weight ratio ranging from 1: 5 to 30.

In addition, the red ginseng extract of the present invention may be a supernatant obtained by filtering an extract obtained by hot water or hot water extraction at a temperature in the range of about 70 to 80 ° C for 20 to 24 hours, then removing red ginseng and its suspension, , Or a powder obtained by adding an excipient to the supernatant. Here, the red ginseng is a mixture of red ginseng roots and red ginseng roots, and the red ginseng roots and red ginseng roots can be mixed in a weight ratio ranging from 0.5: 1 to 3: 1. It is preferable that the red ginseng and the extraction solvent are mixed in a weight ratio ranging from 1:10 to 20.

The sage extract of the present invention may be a supernatant obtained by filtering the extract obtained by warming the sorbate at a temperature in the range of about 70 to 100 ° C for about 18 to 24 hours in an extraction solvent and then removing the supernatant and its suspension, It may be in the form of a solid which is concentrated by adding water to the supernatant. Here, it is appropriate that the sage and the extraction solvent are mixed in a weight ratio ranging from 1:25 to 100.

The composition for relieving anxiety and stress of the present invention comprises a mixture of (a) an extract of at least one of theanine and (b) green tea extract (b1), red ginseng extract (b2) and Sasa extract . At this time, the mixture should appropriately select the mixing ratio of theanine and the extract in consideration of the interaction between theanine and the extract (s). If an amount less than the recommended minimum amount of each ingredient is used, it is difficult to expect an anxiety and stress relieving effect due to mutual synergistic effect. On the other hand, when the recommended maximum use amount of each ingredient is used, So that the effect of relieving anxiety and stress is not increased, and thus may not be suitable.

For example, in the case of a mixture of theanine (a) and green tea extract (b1), the ratio of a: b1 = 10 to 90 parts by weight: 20 to 80 parts by weight, preferably a: b1 = Part: 20 to 50 parts by weight. In case of a mixture of theanine (a) and red ginseng extract (b2), a: b2 = 10 to 90 parts by weight: 5 to 75 parts by weight, preferably a: b2 = 50 to 90 parts by weight: 10 to 50 parts by weight. B3 = 10 to 90 parts by weight and 5 to 50 parts by weight, preferably a: b3 = 50 to 90 parts by weight, in the case of a mixture of theanine (a) and Sasa extract (b3) 10 to 30 parts by weight. When a mixture of theanine (a), green tea extract (b1) and red ginseng extract (b2) is mixed, a: b1: b2 = 10 to 90 parts by weight: 10 to 80 parts by weight: 5 to 75 parts by weight . A: b1: b3 = 10 to 90 parts by weight: 10 to 80 parts by weight: 5 to 40 parts by weight when a mixture of theanine (a), green tea extract (b1) and Sasa extract (b3) . A: b2: b3 = 10 to 90 parts by weight: 5 to 75 parts by weight: 5 to 50 parts by weight when a mixture of theanine (a), red ginseng extract (b2) and Sasa extract (b3) . When a mixture of theanine (a), green tea extract (b1), red ginseng extract (b2) and Sasa extract (b3) is mixed, a: b1: b2: b3 = 10 to 90 parts by weight: 10 to 80 parts by weight : 5 to 70 parts by weight: 5 to 45 parts by weight.

The mixture of the present invention in which the extracts of at least one of the green tea extract (b1), the red ginseng extract (b2) and the Sasa extract (b3), in addition to theanine (a) It is possible to reduce stress such as dopamine, noradrenaline, and corticosterone which increase when stress is generated due to a synergistic effect, thereby increasing the level of serotonin that causes anxiety when the level is lowered. Can be prevented.

The mixture of the theanine (a) and the extract (b) may be contained in an amount of about 0.2 to 100% by weight based on the total weight of the composition.

On the other hand, according to the present invention, a composition comprising a mixture of theanine (a), the green tea extract, the red ginseng extract and the extract (b) of at least one of the extracts of Sasa extract, , Green tea extract, red ginseng extract and Sasa extract are safe substances for the human body, they can be used as foods or pharmaceutical compositions because they exert excellent anxiety and stress reduction or solving effect even when they are ingested.

According to the present invention, a composition comprising a mixture of theanine (a) and an extract (b) of at least one of green tea extract, red ginseng extract and Sasa extract can be applied to various foods, beverages, gums, tea, vitamin complex, And the like. Specifically, the foods to which the composition of the present invention can be applied include food products such as meat products, processed fish products, tofu products, noodles, noodles, noodles such as noodles, health supplements, dairy products, confectionery products, yogurt products, Fermented foods such as kimchi, beverages, soybean beverages, beverages such as fermented beverages.

The food may contain other ingredients besides containing the mixture of the present invention as an active ingredient. At this time, other components that may be additionally contained in the food other than the mixture of the present invention may additionally contain various conventional flavors or natural carbohydrates, unless otherwise specified.

Examples of the natural carbohydrate include common sugars such as monosaccharides (e.g., glucose and fructose), disaccharides (e.g., maltose and sucrose), polysaccharides (e.g., dextrin and cyclodextrin) ; And sugar alcohols such as xylitol, sorbitol, erythritol and the like, but are not limited thereto. Natural flavors such as tau martin and stevia extract (ex. Rebaudioside A and glycyrrhizin) and synthetic flavors such as saccharin and aspartame may be advantageously used as the flavor other than the above-mentioned flavor. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In the present invention, the term "functional food" refers to a food which emphasizes the nutritional function, the symbolic function, and the biological control function of the food, by physical, biochemical and biotechnological methods, Is a food added with value added to express the food, which means the food has been designed and manufactured so that the components of the food sufficiently exhibit the body control function related to the regulation of the body defense and body rhythm, prevention and recovery of disease, and the like. Such a functional food may further include a food-acceptable food-aid additive, for example, a sweetener or a functional ingredient.

In addition, the food of the present invention may further contain a fruit or the like in a composition containing the mixture of theanine (a), the green tea extract, the red ginseng extract and the extract (b) Fruit juice drinks, vegetable drinks, and the like.

The food of the present invention can be prepared in the form of tablets, granules, powders, capsules, liquid solutions and circles according to a known production method, and the content of the mixture according to the present invention varies depending on the formulation, To about 100% by weight based on the total weight of the composition.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. These components may be used independently or in combination, and the ratio of the additives is not particularly limited, but may be suitably selected in the range of about 0 to 20 parts by weight, preferably about 0.001 to 20 parts by weight, per 100 parts by weight of the composition.

Meanwhile, the composition for relieving anxiety and stress of the present invention can be used as a pharmaceutical composition.

As a result of an animal experiment and a human body test for the mixture of theanine (a) according to the present invention and the extract (b) of at least one of green tea extract, red ginseng extract and Sasa extract, And are therefore suitable for use in pharmaceutical compositions (see Examples 1 to 3).

The pharmaceutical composition may be formulated into tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, aerosols and the like in the form of oral dosage forms and sterile injectable solutions according to a conventional method for treating excessive anxiety and stress symptoms Solution or the like.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, Or a mixture of lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Examples of liquid formulations for oral administration include suspensions, solutions, emulsions, syrups and the like, and various excipients such as wetting agents, sweetening agents, fragrances, preservatives and the like may be included in addition to commonly used simple diluents such as water and liquid paraffin. Agents for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, and lyophilized formulations. Non-aqueous solvents and suspensions may include vegetable oils such as propylene glycol, polyethylene glycol and olive oil, injectable esters such as ethyl oleate, and the like.

The pharmaceutical composition of the present invention may further comprise a carrier, excipient or diluent. Examples of the carrier, excipient or diluent include lactose, textol, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose , Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.

In addition, the pharmaceutical composition of the present invention may further comprise a composition having an anxiety and / or stress-related hormone such as noradrenaline, dopamine, serotonin, corticosterone modulating effect.

The preferable dosage of the pharmaceutical composition according to the present invention may be appropriately selected by a person skilled in the art depending on the condition and the weight of the patient, the sex of the patient, the age, the degree of the disease, the drug form, the administration route and the period. In the case of oral administration, about 1 to 500 mg, preferably about 50 to 100 mg, per kg of body weight can be administered once to several times a day, more preferably once to three times, , These dosages are not intended to limit the scope of the invention in any way.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like through various routes. All modes of administration may be expected, for example by oral, intravenous, intramuscular or subcutaneous injection.

Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples. It should be understood, however, that the following examples are intended to illustrate and not limit the present invention.

[Example 1]

1-1. Manufacture of green tea extract

1 kg of dried green tea leaves and 23 to 30 kg of purified water (water) were put into an extractor, and then extracted at a temperature of about 60 to 70 ° C for about 3 hours. After the extraction was completed, green tea leaf and its suspension were removed through a filtration apparatus and spray dried to obtain about 250 g of powdery green tea extract.

1-2. Production of red ginseng extract

1 kg of 6 - year - old red ginseng mixed with 30 g of red ginseng and 2: 1 of red ginseng and 20 kg of purified water (water) were added to the extractor and extracted at about 80 ° C. for about 24 hours. After the extraction was completed, red ginseng and its suspension were removed through a filtration apparatus to obtain red ginseng extract. The total saponin content in red ginseng was adjusted to be 70 mg / g in order to standardize the raw materials. Thereafter, the obtained red ginseng extract was spray-dried to obtain powdery red ginseng extract.

1-3. Preparation of Sasa extract

1 kg of dried sage and 30 kg of purified water (water) were put into an extractor and then extracted at a temperature of about 70 to 100 ° C for about 18 to 24 hours to elute the soluble matter. Thereafter, the sludge and its suspension were removed through a filtration apparatus, and purified water was added to the filtered purificated water to obtain about 200 g of a sage extract in the form of a solid.

1-4. Preparation of mixtures

The theanine (L- theanine ^®, Taiyo inter Korea) produced a 50% by weight, from 50% by weight of the green tea extract prepared in the above 1-1, and 0% by weight of the ginseng extract prepared in the above 1-2, and the 1-3 And 0% by weight of Sasa extract to prepare a mixture.

[Example 2] - [Example 6], [Comparative Examples 1] - [Comparative Example 4]

As shown in the following Table 1, a mixture was prepared in the same manner as in Example 1, except that the contents of theanine, green tea extract, red ginseng extract and Sasa extract were changed.

Theanine
(weight%) Green tea extract
(weight%) Red ginseng extract
(weight%) Sasa extract
(weight%) Example 1 50 50 0 0 Example 2 50 0 50 0 Example 3 50 0 0 50 Example 4 33.3 33.3 33.3 0 Example 5 33.3 33.3 0 33.3 Example 6 25 25 25 25 Comparative Example 1 100 0 0 0 Comparative Example 2 0 100 0 0 Comparative Example 3 0 0 100 0 Comparative Example 4 0 0 0 100

[ Experimental Example  1] - Measurement of neurotransmitter (hormone) concentration change

The following experiment was conducted to confirm the effect of reducing or eliminating stress and anxiety of the mixture according to the present invention.

Test materials 1 to 6 were prepared by dissolving the mixture prepared in Examples 1 to 6 in drinking water. The test materials 1 to 6 were orally administered to each mouse (experimental groups 1 to 6) for 4 weeks. After the administration of the test substance to each mouse was completed, stress was induced in each mouse by electric shock of 0.6 mA per second for 30 minutes at intervals of 5 seconds. Then, stress-induced mice were each autopsied to extract blood and brain tissue (cerebral cortex, hippocampus, and striatum), and dopamine and corticosterone (hormone) secreted from the extracted blood and brain tissue Hormone), noradrenaline and serotonin were analyzed by ELISA (enzyme-linked immunosorbent assay) and are shown in Table 2 below.

As a control group 1, stress-only mice were used without orally administering the test substance in which the mixture was dissolved in drinking water, wherein each stress-related neurotransmitter secreted from the blood and / or brain tissue of the mice Hormone) concentration to 100%.

In addition, as the control groups 2 to 5, test substances dissolved in drinking water were orally administered to the mixture prepared in Comparative Examples 1 to 4, and stress-induced mice were used.

Dopamine
density(%) Nor adrenaline
density(%) Serotonin
density(%) Corticosterone
density(%) Control 1 100 100 100 100 Control group 2 81.2 72.9 126.6 50.5 Control group 3 88.2 81.2 122.2 60.6 Control group 4 90.9 88.2 120.1 53.2 Control group 5 89.2 85.0 110.6 62.2 Experiment 1 72.0 62.5 137.8 34.2 Experiment 2 68.2 68.2 148.7 32.5 Experiment group 3 75.9 65.8 140.9 35.9 Experiment group 4 58.2 57.5 158.9 20.7 Experiment group 5 59.0 58.0 158.2 20.2 Experiment group 6 50.0 45.5 200.0 16.7

As a result, the concentration of dopamine and corticosterone in striae, and the concentration of noradrenaline and serotonin in hippocampus were the highest.

Specifically, in the case of dopamine, noradrenaline and corticosterone, the concentrations of the experimental group 1 to the experimental group 6 were lower than those of the control groups 1 to 5, and in the experimental group 6, the concentrations of dopamine and noradrenaline , And the concentration of corticosterone decreased to about 16% of the control (see Table 2).

In serotonin, the concentration of serotonin was almost twice as high as that of control group 1 (see Table 2), especially in experimental group 6, in experimental groups 1 to 6, compared to control groups 1 to 5.

From these experimental results, it was found that when a mixture of theanine, green tea extract, red ginseng extract and extract of Sasa extract was mixed, compared with the case where each substance was administered or the case where no such substance was administered (Hormone) secretion that induces stress and / or anxiety, thereby suppressing the occurrence of stress and / or anxiety.

[ Experimental Example  2] - Reduction or inhibition of anxiety by test animals

Based on the results of Experimental Example 1, theanine, green tea extract and red ginseng extract were mixed with theanine, green tea extract and red ginseng extract according to the mixing ratio of Example 4 Animal experiments were conducted as follows.

Theanine, green tea extract, and red ginseng extract was dissolved in drinking water to prepare a test material. The test substance was orally administered to mice for 4 weeks. At this time, mice were administered with 20 mg / kg of theanine, 20 mg / kg of green tea extract and 20 mg / kg of red ginseng extract.

After the administration of the test substance to the mouse was terminated, the mice (hereinafter referred to as "test group") were placed on an apparatus for causing anxiety (ex. Cruciform testing apparatus, hole plate testing apparatus and rotating rod testing apparatus) , The changes in behavioral patterns of the mice on the apparatus were observed to evaluate anxiety reduction or inhibitory effects of the mixture.

At this time, as a positive control, 30 minutes before the behavioral pharmacological test, mice in which diazepam was injected intraperitoneally with a dose of 2 mg per kg of body weight were used. As a negative control group, a mouse to which the test substance was not administered was used.

2-1. Cross-examination Elevated plus - maze test )

Each mouse of the experimental group, the negative control group and the positive control group was placed on the central neutral region of the following cruciform testing apparatus and the movement of each mouse was observed for 5 minutes. Of the total number of open and closed arms, (open arm entries / total entries,%), and the total time spent in each open arm and closed arm, the time spent on open arms ,%) Are shown in Table 3, respectively. At this time, anxiety is reduced or eliminated as the stay time in the open arm and the number of movements to the open arm increase.

As shown in Fig. 1, two open arms (30 cm x 5 cm) and two closed arms (30 cm x 5 cm) were crossed with each other, and a center neutral platform (5 cm x 5 cm). In this apparatus, the bottom of each arm is made of wood, the wall of the closed arm is made of transparent Plexiglas, and the height of the wall is 38 cm from the bottom.

Number of moves to open arm (%) Stay in Open Arm (%) Negative control group 2.3 5.0 Experimental group 7.9 17.2 Positive control group 8.1 21.2

As can be seen in Table 3, the experimental group (mice to which the test substance containing the mixture of theanine, green tea extract and red ginseng extract was orally administered) was compared with the negative control (mice not administered the above test substance) The number of movements and the stay time in the open arm increased about three times. In the experimental group, the number of movements to the open arm was similar to that of the positive control group (diazepam intraperitoneally), but the stay time in the open arm was about 80% of that in the positive control group.

From these test results, it was found that the use of a composition containing, as an active ingredient, a mixture in which at least one of theanine, green tea extract, red ginseng extract and Sasa extract is mixed according to the present invention can reduce anxiety in test animals .

2-2. Hole plate  exam( hole board test )

Each of the mice in the experimental group, the negative control group and the positive control group was placed in the center of the rectangular field of the test plate of the vial plate and the mice were observed for 5 minutes in total (hereinafter referred to as "head dipping behavior") Respectively. At this time, the stronger anxiety state of the animal suppresses the head dipping behavior of the mouse. When the mouse performs a head dipping action to the hole, the sensor mounted in the hole of the apparatus senses it and measures the number of head dipping. Table 4 shows the results. Here, the anti-anxiety efficacy of the test substance (mixture) was evaluated from the increase in the number of head dipping times.

≪ Borehole plate test apparatus > - As shown in Fig. 2, 16 holes each having a diameter of 3 cm are equidistantly installed in a rectangular field (50 cm x 50 cm) having a constant height.

Head dipping times (times) Negative control group 29.2 ± 2.3 Experimental group 51.6 ± 2.7 Positive control group 62.0 ± 2.1

As shown in Table 4, in the case of the test group (mice to which the test substance containing the mixture of theanine, green tea extract and red ginseng extract was orally administered), the number of head dipping was decreased in the positive control group (diazepam was administered intraperitoneally One mouse) showed about 80% level of efficacy. However, the experimental group significantly increased the number of head dipping times compared to the negative control (mice not administered the test substance).

From these test results, it was found that the use of a composition containing, as an active ingredient, a mixture in which at least one of theanine, green tea extract, red ginseng extract and Sasa extract is mixed according to the present invention can reduce anxiety in test animals .

2-3. Rotation bar  exam( Route rod test )

In order to confirm whether the composition containing the mixture according to the present invention is used for the relaxation of the muscles, a rotating rod test as described below was conducted. Here, muscle relaxation is a typical side effect due to the action of antianxiety drugs including nerve stabilizers on the central nervous system.

The experimental group, the negative control group, and the positive control group were placed on the rotation rod of a rota-rod apparatus (see FIG. 3) having a diameter of 3 cm by rotating the robot 10 times per minute so that the head of the mouse was opposite to the rotation direction of the rotation rod, The rotation time of the mouse for a maximum of 5 minutes was measured, and the time when the mouse was dropped, that is, the time of the rotation rod was measured. At this time, the shorter the dropping time of the mouse, the more likely it is that cooperative movement disorder due to muscle relaxation occurs, and indirectly, it is considered to have a nervous stability (anti-anxiety) effect.

Rotating bar stay time (seconds) Negative control group 245.9 ± 15.9 Experimental group 100.1 + - 9.2 Positive control group 18.1 ± 3.8

As shown in Table 5, in the case of the experimental group (mouse in which the test substance containing the mixture of theanine, green tea extract and red ginseng extract was orally administered), the time to stay on the rotating rod was the negative control , And it was found that there was a relaxation effect by the test substance. However, the time of the swivel rod that can detect the degree of muscle relaxation was remarkably increased as compared with that of the positive control group (diazepam-administered intraperitoneally), and drowsiness and other side effects due to excessive muscle relaxation that can be induced by the drug And the possibility of

[ Experimental Example  3] - Human test  Anxiety and stress relieving effect

Based on the ratio of Example 6 on the basis of Experimental Examples 1 and 2, a mixture of theanine, green tea extract and red ginseng extract was mixed with a hard capsule preparation (1 day Intake: 300 mg), and the human body test was carried out. At this time, the subjects were selected 20 persons who complain about anxiety and stress which lasted more than one month. The test subjects were given 2 capsules once a day for 1 week and the remaining 10 subjects were given placebo twice a day for 1 week for 1 week. . A double-blind, placebo-controlled, cross-over study was conducted in which the subjects were given a placebo and a placebo after a two-week rest period after the end of one week's intake.

As a tool for evaluating people's anxiety and stress, psychological states related to BAI (anxiety), Bepsi-K stress scale questionnaire (stress), and their anxiety, which have proved their general validity for Koreans, VAS (Visual Analog Scale) shown above was investigated. These results are shown in Tables 6 to 8, respectively.

Here, BAI is a total of 21 anxiety-related questionnaire items that are answered by 0 ~ 3 points, and the sum of the anxiety level is expressed as sum. If the total score is 22 or more, it indicates observation and intervention. The Bepsi-K Stress Scale Questionnaire is a questionnaire that answers 1 question (low stress) to 5 points (high stress) for each item on a total of 5 questions about the stress level of each individual, and expresses it as an average value. Indicating high stress. The VAS is defined as a state of no anxiety on the left side, a state of maximum anxiety on the right side, and a distance from the left side (mm). The higher the value, the higher the state of anxiety.

Before ingestion After ingestion Placebo group 22.0 ± 12.3 21.1 ± 8.1 Test drug group 21.9 ± 10.0 18.0 ± 5.2

Before ingestion After ingestion Placebo group 1.9 ± 0.4 1.8 ± 0.5 Test drug group 1.7 ± 1.0 1.1 ± 0.4

Before ingestion (mm) After ingestion (mm) Placebo group 35.8 ± 4.2 30.2 ± 3.2 Test drug group 36.7 ± 2.2 23.6 ± 2.9

As can be seen in Tables 6 to 8 above, in the test drug group, anxiety, stress, and subjective anxiety were reduced compared to the placebo group.

From these results, it can be seen that the composition containing the mixture of theanine, green tea extract, red ginseng extract and Sasa extract as an active ingredient according to the present invention has an effect of reducing the anxiety and stress of the human body there was.

[Example 7]

The hard capsules were prepared in the amounts shown in Table 9 using carbon dioxide and magnesium stearate, which are commonly used in hard capsules, as a main component and a mixture of theanine, green tea extract, red ginseng extract and Sasa extract.

Compounding ratio (% by weight) Content (mg) Theanine 40.0 200.0 Green tea extract 16.0 80.0 Red ginseng extract 8.0 40.0 Sasa extract 8.0 40.0 Silicon dioxide 27.0 135.0 Magnesium stearate 1.0 5.0 (Sum) 100 500

As shown in Table 7, the mixture of theanine, green tea extract, red ginseng extract and Sasa extract and the excipient were uniformly agitated in an agitator and granulated, and then injected into a hard capsule machine to prepare a conventional hard capsule.

Example 7 is a preparation example for producing a conventional hard capsule containing a composition for dietary intake having an effect of reducing anxiety and relieving stress, and does not limit the formulations and raw materials of the present invention.

[Example 8]

Tablets were prepared in the amounts shown in Table 10 using lactose powder, crystalline cellulose, magnesium stearate, and HPMC, which are excipients commonly used in tablets, as a main component and a mixture of theanine, green tea extract, red ginseng extract and Sasa extract .

Compounding ratio (% by weight) Content (mg) Theanine 20.0 100.0 Green tea extract 8.0 40.0 Red ginseng extract 4.0 20.0 Sasa extract 4.0 20.0 Lactose powder 31.2 156.0 Crystalline cellulose 31.2 156.0 Magnesium stearate 1.0 5.0 HPMC 0.6 3.0 (Sum) 100 500

As shown in Table 10, the mixture of theanine, green tea extract, red ginseng extract and Sasa extract and the excipient were uniformly agitated in an agitator to granulate the mixture, which was then injected into a tablet machine to prepare a conventional tablet.

The above Example 8 is a preparation example for producing a conventional tablet containing a composition for dietary intake having an effect of reducing anxiety and stress or eliminating the effects of the present invention, and does not limit the formulations and raw materials of the present invention.

[Example 9]

The beverage was prepared in the amounts shown in Table 11 using crystalline fructose, anhydrous citric acid, vitamin C, and purified water, which are excipients commonly used in beverages and a mixture of theanine, red ginseng extract and Sasa extract.

Compounding ratio (% by weight) Content (mg) Theanine 2.0 2.0 Sasa extract 0.8 0.8 Red ginseng extract 0.8 0.8 Crystalline fructose 10.0 10.0 Anhydrous citric acid 0.4 0.4 Vitamin C 0.1 0.1 Purified water 85.9 85.9 (Sum) 100.0 100.0

As shown in Table 11, the mixture of theanine, red ginseng extract and Sasa extract and the excipient were uniformly mixed using a high-speed stirrer, and then purified water was added thereto to uniformly mix with the mixture and the excipient. Thereafter, the mixture was subjected to pasteurization treatment and put into bottles or cans to prepare beverages.

The above-mentioned Example 9 is a preparation example for producing a conventional beverage containing a composition for dietary intake having an effect of reducing anxiety and stress, or solving the effect, and does not limit the formulations and raw materials of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a photograph showing a cruciform test apparatus for measuring anxiety suppression effect of a mixture according to the present invention. FIG.

2 is a photograph showing a device for testing a hole plate for measuring an anxiety suppressing effect of a mixture according to the present invention.

3 is a photograph showing a rotating bar tester for measuring the anxiety suppressing effect of the mixture according to the present invention.

Claims (7)

(a) theanine; (b1) green tea extract; (b2) red ginseng extract; And (b3) Sasa extract Containing this mixed mixture, A: b1: b2: b3 = 10 to 90 parts by weight: 10 to 80 parts by weight: 5 to 70 parts by weight of a mixture of theanine (a), green tea extract (b1), red ginseng extract (b2) And 5 to 45 parts by weight of the composition. delete The composition for anxiety and stress relief according to claim 1, wherein the mixture is contained in an amount ranging from 0.2 to 100% by weight based on the total weight of the composition. The composition for anxiety and stress relief according to claim 1, further comprising a flavoring agent, a natural carbohydrate, a pharmaceutically acceptable food-aid additive, an excipient, a carrier, an excipient and a diluent. The composition for relieving anxiety and stress according to any one of claims 1, 3, and 4, wherein the composition is used as a food or a pharmaceutical composition. [Claim 6] The composition for anxiety and stress relief according to claim 5, wherein the food is prepared from any one selected from the group consisting of tablets, granules, powders, capsules, liquid solutions and rings. The pharmaceutical composition according to claim 5, wherein the pharmaceutical composition is one selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, aerosols and columnar solutions / RTI > anxiety and stress.

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