WO2019132061A1 - Composition for preventing and alleviating stress- and fatigue-related diseases - Google Patents

Abstract

The present invention relates to composition for preventing and alleviating stress- and fatigue-related diseases. According to one embodiment of the present invention, a composition for preventing and alleviating stress- and fatigue-related diseases contains any one selected from the plant extract group consisting of an Aconitum villosum Rchb. extract, a Pulsatilla cernua (Thunb.) Bercht. & J. Presl extract, an Aconitum volubile Pall. extract, an Adonis ramosa Franch. extract, an Aconitum monanthum Nakai extract, a Ranunculus ternatus Thunb. extract, a Ranunculus tachiroei Franch. & Sav. extract, a Clematis terniflora extract, a Thalictrum aquilegifolium L. var. sibiricum Regel & Tiling extract, a Ranunculus japonicus Thunb. extract, a Ranunculus silerifolius H. Lév. extract, an Adonis amurensis Regel & Radde extract, a Clematis apiifolia DC. extract, a Pulsatilla koreana extract, an Anemone narcissiflora L. extract and a mixture thereof.

Description

Composition for prevention and improvement of stress and fatigue related diseases

The present invention relates to a composition having the effect of preventing and improving stress and fatigue-related diseases using natural extracts. More specifically, the present invention relates to a method for producing a compound of formula (I), which comprises a compound represented by the formula (I) of the Buttercup Family, a fine hawthorn, And a composition for prevention and improvement of stress and fatigue-related diseases, which comprises any one selected from the group consisting of herbaceous plants, herbaceous plants, lavender, windblown flowers, and mixtures thereof.

Nowadays society is rapidly developing and diversified and it demands various roles for modern people. As a result, people are anxious about anxiety disorders and mental disorders due to various stresses.

Given the recent trend of increasing mental illnesses due to excessive school-age or various stresses, various stresses and related mental disorders are gradually increasing.

Here, briefly examining the mechanisms of stress-related neurotransmitters and hormones, external stimuli and stress are responsible for the secretion of neurotransmitters and hormones in the hypothalamus of the body. The signals from the hypothalamus to the central nervous system Neurotransmitters such as dopamine, noradrenaline, and serotonin are controlled to be liberated at each nerve end, and physiological activities such as emotional state, heart rate, blood pressure, and skeletal muscle blood flow are controlled. 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 in the corticosterone and water quality and 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 posttraumatic stress disorder. In general, generalized anxiety disorder, which occupies the largest portion of the anxiety disorder, is an excessive and widespread feeling of anxiety, And autonomic hypersensitivity are the most important features.

Depression (depression) is a disease that changes the function of the brain that controls emotions and causes 'negative emotions.' It is a disease that affects more than 100 million people all over the world. The nature of depression is a physiological and anatomical issue, and negative emotions are the consequences of such changes in body structure. It is said to feel depressed temporarily for 'depression'. The causes of depression are interpersonal stress and economic problems.

In general, 'fatigue' is defined as' a state in which work efficiency deteriorates when performing work ',' a state in which confusion of homeostasis occurs', or a state in which cortical restraint occurs, 'a decrease in ability to perform physical and mental activities '.

Such fatigue is generally caused by fatigue and fatigue, and it is a disease accompanied by a variety of symptoms such as sleep disturbance or insufficient desire. Fatigue or malaise is one of the important alarm signals to inform the body of an abnormality. It is awakened to intense exercise even in a healthy normal state, to a case of long working hours, or to a situation of excessive stress. This physiological fatigue usually restores the original normal state by resting on the body and does not last long.

Recently, diseases that become Chronic Fatigue Syndrome (CFS) are becoming a topic of intractable diseases. This represents the basic symptoms of long-term systemic fatigue, malaise, fever, lymphadenopathy, myalgia, arthralgia, mental neuropathy, which may interfere with daily life.

These fatigue symptoms are a source of panic disease, leading to obesity or excessive weight loss, leading to health problems and can be overdone if chronic fatigue is severe. It is defined as sudden death by overwork and overwork for a long time. The problem of overwork is recognized as being very important in medical, economic and social terms, and it can be regarded as a disease that occurs due to excessive accumulation of fatigue.

Serotonin is a neuro-metabolite found in cerebrospinal fluid, circulating the brain and acting neurotransmitter. The serotonin is closely related to the expression of emotions. When the substance is insufficient, emotion is unstable, causing anxiety and anxiety and impulsive tendency. Because the serotonin deficiency is closely related to depression, there are many drugs that are currently being used to treat depression, such as preventing serotonin from being reabsorbed and staying in the brain for longer. Meanwhile, the depression referred to in the present invention is defined to include anxiety or anxiety disorder as well as the lexical meaning of depression.

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) receptors 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 this regard, referring to the specific prior art, Prior Art 1 (KR 10-2010-0106062 A) discloses grapefruit oil; And fragrance composition containing bergamot oil, which provides stress relief and soothing effects, and can be used in a variety of applications in the fields of cosmetics and cosmetics. However, the stress in the prior art 1 does not substantially mitigate mental stress by providing a momentary refreshing sensation. That is, the term 'stress' is used in various ways, and the term 'pleasant feeling' is taken in a broad sense, and it is different from the mitigation of mental stress for the purpose of the present invention in the present invention.

The present invention relates to an anti-depressant / antisstress agent and a composition containing the same, and more particularly, to a composition comprising an unsaturated hydrocarbon contained in a specific formula, And an anti-depressant, an anti-stress agent and a composition containing the same, which act on an animal's central nervous system. However, this is not a natural product but a synthetic hydrocarbon compound. Therefore, there is a need to develop a composition for prevention and improvement of stress-related diseases that does not have side effects with high stability and long-term use by using extracts derived from natural materials.

Prior art 3 (KR 10-1595515 B1) discloses a composition comprising a one-year bar extract as an active ingredient and improving fatigue syndrome.

Prior Art 4 (KR 10-2014-0146378 A) relates to a composition containing an extract of a crude drug mixture comprising Sauce, Manchus, Corn oil, Sulfur Sulfur and Scutellum, wherein the composition containing the extract of the herbal mixture Maintenance ability, and fatigue recovery improvement effect.

An object of the present invention is to provide a composition for preventing and ameliorating stress and fatigue-related diseases by using an extract derived from a natural product.

The present invention provides a composition for preventing and ameliorating stress and fatigue-related diseases by preventing serotonin from being inhibited and suppressing the secretion of dopamine.

The present invention provides a composition for prevention and improvement of fatigue, which has anti-fatigue effect by preventing the inhibition of serotonin, suppressing dopamine and suppressing stress as well as reducing the concentrations of lactic acid, ammonia and inorganic phosphate in blood.

The present invention provides a composition for preventing and ameliorating depression or insomnia by preventing serotonin from being inhibited and suppressing the secretion of dopamine.

The present invention provides a composition for prevention and improvement of fatigue caused by an increase in glycogen concentration of muscles so as to produce an anti-fatigue effect.

Another object of the present invention is to provide a food composition having high palatability to the extent that can be provided with a high flavor by removing a spicy taste of a natural product belonging to the Buttercup Family.

In order to achieve the above object, a composition for preventing and improving stress and fatigue-related diseases according to an embodiment of the present invention may comprise at least one selected from the group consisting of a gherkin extract, a gherkin extract, a gherkin extract, a gherkin extract, Any one selected from the group consisting of plant extracts consisting of frog extract, frog extract, mint extract, pheasant leg extract, buttercup extract, chopstick grass extract, herbal extract, lavender extract, .

The composition for preventing and ameliorating stress and fatigue related diseases may be one which inhibits dopamine and prevents serotonin from being inhibited.

The stress-related disease may be any one selected from the group consisting of stress, depression, and insomnia.

The fatigue related disorder may be chronic fatigue syndrome.

The plant extract may be any one selected from the group consisting of water, organic solvents having 1 to 10 carbon atoms, subcritical fluids, supercritical fluids, and mixtures thereof.

The food composition according to another embodiment of the present invention may include a composition for preventing and ameliorating the stress and fatigue related diseases.

Hereinafter, the present invention will be described in more detail.

The composition for prevention and improvement of stress and fatigue related diseases according to one embodiment of the present invention is a composition for preventing and improving stress and fatigue related diseases, which comprises at least one member selected from the group consisting of a gherkin extract, a gherkin extract, a gherkin extract, a gherkin extract, , Plant extracts consisting of mint extract, pheasant leg extract, buttercup extract, chopstick grass extract, herbal extract, lavender extract, wiltwort extract, chrysanthemum extract, and mixtures thereof.

The Aconitum volubile Pall. Is a perennial plant belonging to the family Ranunculaceae, which belongs to the family Ranunculaceae. The country of origin is Korea, and it is mainly distributed in Gangwon-do or Hamkyung-do. Its roots grow to the side as a vine.

Pulsatilla cernua has many root leaves gathered on the ground. It is a double leaf, with 5 small leaves and 2 small leaves on the bottom. The tip of the split leaf on the apex is pointed, there is no hair on the front, but there are hairs like silk on the back.

Aconitum volubile Pall is a perennial plant belonging to the family Ranunculaceae, The country of origin is Korea, and it is mainly distributed in Gangwon-do or Hamkyung-do. Its roots grow to the side as a vine.

Adonis ramosa Franch is a perennial plant that grows in the mountains. Stems stand upright, have a lot of branches, and are 10-30 cm high. At the bottom of the stem there are scaly leaves. Leaves are alternate phyllotaxis, 2-3 folds. The petiole is 4-7cm long and has hairs when it is young, but grows gradually. Flowers bloom in April, one at each end of stem and branch, and yellow. Calyxes and petals spread horizontally. Fruits are achene, wide obovate, short hairs on the surface. It grows wild throughout the country. It is distributed in Russia, Japan and China.

The nitum monanthum is a perennial plant with a buttercup butterfly. The height is about 25cm, the leaves are staggered and the petiole is long. The roots are thick and the stems are delicate and straight. From July to August, dark purple flowers bloom 1 to 3 at the end of the stem. Poisonous plant that grows in valleys of high mountains, and is distributed in the back of the mountains of North Ham.

The frog gull (Ranunculus ternatus) has no hairs throughout. There are fusiform roots and beard roots with sharp ends at both ends. It is used for edible and medicinal purposes. Young leaves are poisoned and edible.

A frog buttercup (Ranunculus tachiroei) is a perennial plant that grows in a lowland wetland. The stem stands upright, reaching 1m in height, with spreading hairs on the lower part and loose hairs on the upper part. Leaves under roots and stems are long petiole. Blades are divided into 3 branches, 2 with irregular sawtooth on the edge. Flowers bloom from June to July, hanging from the tips of branches and branches, and yellow. The calyx leaves are 5 pieces and they are bent backward by ovate. The petals are five and are oval. Fruits are aquatic, rounded and run. It grows wild throughout the country. It is distributed in Russia, Japan and China.

Clematis (Clematis terniflora) is a haploid leaf composed of five to seven small leaves. Small leaf is ovate with plain edge, narrow end, round bottom or wedge shape. There are no hairs on both sides and it is glazed. The petiole is bent like a tendril.

The pheasant's leg (Thalictrum aquilegifolium) is entirely hairless. The stem stands straight and branches, it is hollow, ridged, and white or white on a green or purple background. The shape of the leaf is similar to that of three leaves.

Ranunculus japonicus is a perennial plant commonly found in mountains and fields throughout the country, and is distributed in China, Taiwan and Japan. Whole hairy white. Stems stand upright, 50 to 70 cm high. Root leaves are deeply divided into 3 to 5 branches, and petiole is long. The stem leaf has petiole on the lower part, but not on the upper part. The bottom of the stem and petiole are firmly hairs. The flower is hanging at the end of the stem in May or June, and it is yellow. Calyx has 5 sheets, oval, hairy. The petal is 5 sheets, yellow, about twice the length of calyx. There are many pistils and stamens.

Why chopsticks grass (Ranunculus quelpaertensis) grows as seeds with 2-year or perennial herbs. It is distributed in the southern part of the country and grows in mountainous marsh wetlands. The stem grows about 20 to 60 cm in height and has little hair. Leaflet has long petiole, three leaflets, and three deeply cracked leaves. Leaves are short, 3-bifurcated, and upper part is merely divided into 3 pieces. It blooms in July or August. The pedicel is 2 to 6 cm long and has yellow flowers. The bract is round, with short hairs on the stout, and the achene is flat oval with a length of about 3.5mm and the style is turned backward.

Adonis amurensis is a perennial plant that grows nationwide except Jeju Island. It is distributed worldwide in China, Japan, and northeastern Russia. The stem grows up to 5 to 15 cm when bloomed, but later grows to 30 to 40 cm. Usually, the branches do not split, but they also split. Leaves are alternate, folded with three or four quadrants. The lower petiole is long but becomes shorter as it goes upwards. Flowers bloom one at the end of the trunks in March and April, and it is yellow. The calyx leaf is usually 8 or 9 leaves, similar in length to the petals, or slightly longer, and dark brown. There are 10 to 30 petals and many stamens and pistils.

Clematis apiifolia is a deciduous semi-shrub vine plant that grows into rhizomes or seeds. It is distributed in the southern part of the country and grows in mountainous areas. The vine stalks are about 2 to 4 meters long and have small hairs on the branches. Leaves grow 3 or 2 times, and lobules are 4 ~ 7cm long ovate lanceolate with sawtooth on the acute angle and fine hairs on the back vein. It blooms from July to September. The flower that hangs on the acupuncture is white. Achenia has five to ten hairs, with hairy, long style with white or light brown hairs.

Pulsatilla koreana (Pulsatilla koreana) is composed of long leaf stalk and five small leaf-like compound leaves. The small leaf is 3-4cm long and is deeply divided into 3 pieces. The top piece is 6 ~ 8mm wide and its tip is dull. The front side is dark green and has no hairs, but there are many white hairs on the back side.

Anemone narcissiflora is named after 'the daughter of the wind' and has a place close to the wind. Most of the kinds of wind flowers in Korea are blooming in spring, but only the flower of today is the only flower in summer.

It is used to inhibit dopamine. It is used to inhibit dopamine and to inhibit dopamine, and to inhibit dopamine, to inhibit dopamine It has an effect of preventing the serotonin from being inhibited, and can have an effect on the improvement of the stress disease and the anti-fatigue activity.

Preferably, the plant extracts are selected from the group consisting of ginseng extract, ginseng extract, ginseng extract, ginseng extract, ginseng extract, ginseng extract, frog ginseng extract, pheasant ginseng extract, , A herbal extract, a lavender extract, a wiltwort extract, a chrysanthemum extract, and a mixture thereof, and a mignard extract.

More preferably, the plant extract may be a myrtle extract.

Fragrant Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Frog Leaf Extract, Frog Leaf Extract, Frog Leaf Extract, Pheasant Leaf Extract Extracts, Lycopersicon esculentum extracts, Rhizomelia sp. Extracts, and Windy flower extracts were found to inhibit dopamine and inhibit serotonin. As a result, it was confirmed that dopamine inhibition and serotonin concentration of each individual extract were maintained, and the effect was remarkably high when using mignard extract.

Therefore, it was investigated whether the mint extract and other plant extracts showed synergistic effect. The extracts of the ginseng root extracts, the ginseng extract, the ginseng extract, the ginseng extract, the ginseng extract, Mixed extracts of Fagaceae Extract, Pheasant Leg Extract, Butterfly Extract, Why Chopsticks Full Extract, Herb Extract, Lycopersicon esculentum Extract, Lycopersicon esculentum Extract, The extracts of Rhizoctonia japonica L., Leaf Rhizoma Extract, Leaf Rhizoma Extract, Leaf Extract of Frog, Leaf Extract of Frog, Leaf Extract of Pheasant, Extract of Buttercup Larvae, Why Chopsticks Extract, Leaf Extract, Leaf Extract, Dopamine inhibition and serotonin Nine maintenance effect was superior, but the effect was lower than that of mignard extract alone.

Therefore, it was confirmed that the use of mignard extract alone is most effective in preventing and ameliorating stress and fatigue related diseases, because it has the best effect of suppressing dopamine and maintaining serotonin.

On the other hand, the fatigue used throughout the specification of the present invention is defined to include not only fatigue but also chronic fatigue syndrome or hyperactivity as a preliminary meaning.

The anti-fatigue activity used throughout the specification of the present invention refers to an activity of reducing fatigue or restoring fatigue, specifically, improving the functioning duration of the exercise or the functioning site (including the brain) , And to suppress the increase of fatigue material at the same momentum or action amount (endurance enhancement, physical strength enhancement), to improve the fatigue detection state of the brain or nerve even though the exercise or the affected part is not fatigued, and This refers to the effect of promoting the recovery of the fatigue state of the exercised or operated part to the normal state.

In addition, chronic fatigue syndrome referred to in the present invention refers to basic symptoms such as long-term systemic fatigue, malaise, fever, lymphadenopathy, myalgia, arthralgia, and mental neuropathy which may interfere with daily life.

The composition for prevention and improvement of fatigue-related diseases of the present invention can treat chronic fatigue syndrome, that is, alleviate each symptom of chronic fatigue syndrome and transit to a normal state.

In addition, the overesponses of the composition for prevention and improvement of fatigue-related diseases of the present invention means that, even in the case of severe overwork, the fatigue can not be felt sufficiently, As a result, it means cerebrovascular disease or heart disease leading to permanent labor incapacity or death. The anti-fatigue agent of the present invention can treat chronic fatigue syndrome, thereby preventing overwork.

The composition for preventing and ameliorating stress and fatigue related diseases may be one which inhibits dopamine and prevents serotonin from being inhibited. When the plant extracts are used, secretion of neurotransmitters (hormones) such as dopamine, noradrenaline, corticosterone, etc. which are secreted by the singal from the hypothalamus to the central nervous system during stress can be further reduced, Since the levels can further increase the secretion of decreasing serotonin, it can exert excellent efficacy in stress reduction or relief and anti-fatigue. Furthermore, since the plant extract is a natural physiologically active substance, there is no need to worry about side effects or toxicity during ingestion or administration of an animal. In particular, there is no risk of drowsiness or drug dependence due to excessive relaxation by drug treatment, Also, it can be safe for human body even if it is administered for a long time or in large doses.

The stress-related disease may be any one selected from the group consisting of stress, depression, and insomnia.

When dopamine is inhibited, it is effective for prevention and improvement of depression. In the case of insomnia, it can inhibit dopamine and inhibit lowering of serotonin, thereby preventing and improving.

The plant extract may be any one selected from the group consisting of water, organic solvents having 1 to 10 carbon atoms, subcritical fluids, supercritical fluids, and mixtures thereof.

Preferably, the solvent is water or an alcohol solvent having 1 to 4 carbon atoms. The plants and the solvent to be extracted may be mixed at a weight ratio of 1: 1 to 1:15. In the above range, it may be advantageous to obtain an effective substance having a dopamine-inhibiting activity.

Preferably, the solvent is a mixture of water and ethanol in a weight ratio of 1: 10 to 10: 1, and the plant extract is prepared by mixing the plant and the solvent in a weight ratio of 1: 5 to 1:10, For 2 to 12 hours and 2 to 7 times repeatedly.

By the above range, it is not only advantageous for obtaining the effective substance but also toxic for mignard and has a strong spicy taste. Therefore, if it is within the above range, the toxicity is lowered to solve the problem of side effect and to remove strong spicy taste .

The food composition according to another embodiment of the present invention may include a composition for preventing and ameliorating the stress and fatigue related diseases.

Since the food composition has anti-fatigue activity and anti-stress activity, it can provide a functional food for relieving the chronic fatigue syndrome associated with it, overwork, depression or insomnia, and can be used for a long period of time It has the advantage of not having any side effects.

Preferably, the food composition contains 0.03% to 0.8% by weight of mignury extract. When the mignard extract is contained in an amount of less than 0.03%, the effect of suppressing dopamine secretion and maintaining the serotonin concentration is insignificant. When the mignard extract is contained in an amount of more than 0.8% by weight, There is a problem that it can not be used as a food composition depending on the toxicity contained in the middlings.

The composition for preventing and improving stress and fatigue-related diseases according to the present invention can be used for a long period of time without any adverse effect by using an extract derived from a natural product.

The composition for prevention and improvement of stress and fatigue-related diseases according to the present invention has an excellent anti-fatigue effect by preventing the inhibition of serotonin, suppressing dopamine and suppressing stress as well as reducing the concentrations of lactic acid, ammonia and inorganic phosphate in blood .

The composition for prevention and improvement of depression according to the present invention prevents serotonin from being inhibited and suppresses the secretion of dopamine, thereby preventing and improving depression. In addition, the glycogen concentration of the muscle can be increased to produce an anti-fatigue effect.

The food composition according to the present invention has a pungent flavor of natural products belonging to the Buttercup Family and has high palatability to the extent that it can be provided with a high flavor and has an effect of preventing and improving stress diseases.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a graph showing results of weight and organ weights according to an embodiment of the present invention. FIG.

2 is a graph showing the results of weight and organ weights according to an embodiment of the present invention.

FIG. 3 is a graph showing the results of an experiment for improving stress response behavior according to an embodiment of the present invention.

FIG. 4 is a graph showing results of stress response behavior improvement experiments according to an embodiment of the present invention.

5 shows results of serotonin measurement experiment according to an embodiment of the present invention.

FIG. 6 shows experimental results of dopamine measurement according to an embodiment of the present invention.

FIG. 7 is a graph showing results of a clinical test for improving stress symptoms according to an embodiment of the present invention.

FIG. 8 relates to clinical test results for improving stress symptoms according to an embodiment of the present invention.

9 is a graph showing a test result of measuring glycogen concentration in muscle according to an embodiment of the present invention.

10 is a clinical test for improving fatigue symptoms according to an embodiment of the present invention.

The present invention relates to a composition for preventing or treating chondroparial disorders, which comprises extracts of ginseng, ginseng extract, ginseng extract, ginseng extract, extracts of ginseng extract, extracts of frog ginseng, extracts of frog ginseng, extracts of ginseng, The present invention relates to a composition for preventing and improving stress and fatigue-related diseases, which comprises any one selected from the group consisting of extracts, herbal extracts, lavender extracts, persimmon extracts, flavor extracts and mixtures thereof.

Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily carry out the present invention. The present invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.

[Production Example: Preparation of Extract]

Fragrant Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Frog Leaf Extract, Frog Leaf Extract, Frog Leaf Extract, Pheasant Leaf Extract Each plant was screened, pulverized, mixed with water and ethanol mixed solvent at a weight ratio of 1: 5 to 1:10 to prepare an extract.

On the other hand, in the case of the mignoli extract having the best anti-fatigue activity and antistress activity, the Minderian extract was separately ground and pulverized, and then the solvent in which the pulverized Mindari was mixed with water and ethanol was diluted with 1: 5 to 1:10, and the extract is repeated 2 to 7 times at an extraction temperature of 50 to 100 캜 for 2 to 7 hours. The extract is filtered with a filter, concentrated in vacuo, mixed with the extract and dextrin And then spray-dried to prepare an extract of Minderian.

[Test Example 1: Test for measuring weight and organ weight]

The adrenal gland is a stress-sensitive organ that secretes cortisol in response to stress in the adrenal cortex and catecholamine hormone in the adrenal gland in response to stress. Therefore, the adrenal hypertrophy and adrenal weight are increased due to stress, and the spleen associated with immunity is contracted by stress and the spleen weight is decreased.

In order to confirm the effect of preventing and improving the stress of the composition of the present invention, the composition prepared according to the above Preparation Example was administered to experimental animals to confirm adrenal and spleen weight changes. In addition, we observed changes in body weight of experimental animals due to stress.

A nine-week-old Sparague-Dawley-rat (Samtako) was used and subjected to a one-week adaptation period and used in the experiment. The animals were housed in a controlled room with a room temperature of 23 degrees, in which the lights were turned off in 12 hour increments. The feeds used were solid feeds and the water used was disinfected water. Feed and water were not restricted.

After extracting the extract of Mugwang organs of the above preparation example in distilled water, it was orally administered (50 mg / kg) once a day for 1 month continuously at 14-15 hours. The experimental group consisted of 3 groups, the stressed control group, the muguri herb extract group, and the normal control group, which did not give both the stress and the extract. For each experimental group, five rats were used. From 7 days after administration, the rats were placed in a cylinder of 6 cm in width and 14 cm in length, and fixed at an inclination of 45 degrees to induce stress for 3 weeks. The body weight was measured once a week, and the body weight was finally measured immediately before the sacrifice of the experimental animals to check the stress and the weight change of the experimental animals due to administration of the composition of the present invention.

The rats were anesthetized with 4% isoflurane to remove the adrenal gland and the spleen was weighed. Results were compared with mean and standard error for the weight, spleen, and adrenal mass of the normal controls. Statistical analysis using Student's t-test was used to compare the results of the mignori-treated group and the stress-control group, and it was regarded as significant at p <0.05. The results of each experimental group are shown in Fig. 1 and Fig.

Referring to FIGS. 1 and 2, it can be seen that stressed experimental animals have decreased body weight, adrenal weight, and spleen weight, respectively, as compared with the normal control group. However, it was confirmed that the weight loss was suppressed in the group administered with the extract of Moglii extract and the adrenal and spleen weights were maintained to a similar level to that of the normal control group.

Therefore, it can be seen that the composition effectively suppresses weight loss, adrenal enlargement and spleen atrophy by stress, maintains hormonal balance from stress, and maintains the health of the immune system related organ.

[Experimental Example 2: Stress Response Behavior Improvement Test - Forced Swimming Test]

The following experiment was conducted to confirm the effect of the stress-induced behavioral change on the extract of Mindygum extract according to the present invention.

After 4 weeks of ICR male mice (Samtaco Bio Korea, Inc.), the lights were turned on and off repeatedly every 12 hours after the adaptation period of one week, and the room temperature was maintained at 18 to 23 ° C and humidity was maintained at 60% . The feeds were fed solid feed and there were no restrictions on feeding and watering except in the process of inducing stress.

The extract of Mugwang organs of the above Preparation Example was dissolved in distilled water and then orally administered (40 mg / kg) once a day for 1 month continuously at 14-15 hours. The experimental group consisted of 3 groups, the stressed control group, the muguri herb extract group, and the normal control group, which did not give both the stress and the extract. For each experimental group, 5 animals were used, and daily stress for 4 weeks was induced from 7 days after administration. The stress-inducing method is modified by the method of Willner et al. (Wilner et al., Reduction of sucrose preference by chronic unpredictable mild stress, 1987). Specifically, fasting, dietary restriction after fasting , Creating an unexpected variety of mental stress situations such as providing an empty water bottle after the singularity, leaning a kennel, breeding a large number of laboratory animals in a kennel, flashing lights, cold rooms, and constant light.

A forced swimming test was performed on test animals. A cylindrical transparent water tank (14 cm in diameter, 20 cm in height) was filled with water at 23 to 25 ° C so that the water depth was 15 cm, and then one test animal was placed in the water tank. All test animals were forced to swim in a cylindrical water bath for 6 minutes. 2 minutes after the start of the experiment, the total time (hereinafter referred to as &quot; floating time &quot;) in which the experimental animal did not move in the cylindrical water tank was measured and recorded for 4 minutes before the end. Specifically, the term "immovable time" refers to a state in which there is no movement (immobility), except for a small movement of the head over the surface of the water. Immobility is one of the depression indicators of depression and is common in stress laboratory animals.

Results were expressed as mean and standard error. Statistical significance was verified by statistical analysis using Student's t-test to compare the results of the middlery treatment group and the stress control group, and the results were expressed as being significant at p <0.05. The results are shown in Fig.

Referring to FIG. 3, it can be seen that stressed experimental animals have a longer floating time than stressed control animals in comparison to the normal control group. However, it was found that the immobilization time was shorter in the group administered with the extract of Angelica gigas Nakai than in the negative control group.

Therefore, it can be understood that the above-mentioned composition improves the behavior such as depression and despair caused by stress, thereby preventing and improving stress.

[Experimental Example 3: Stress Response Behavior Improvement Test - Tail Suspension Method]

The test animals of Experimental Example 3 were subjected to the tail suspension method. The test animals were held at a height of 15 cm from the bottom and 1 cm of the tail was held for 6 minutes to observe the movement of the test animals. The initial 2 minutes was considered as the adaptation period and the time when the animal did not move for 4 minutes before the end was measured and recorded.

* 90 Results were expressed as mean and standard error. Statistical significance was verified by statistical analysis using Student's t-test. The results were compared between the middlery treatment group and the stress control group, and were considered to be significant at p <0.05. The results are shown in Fig.

Referring to FIG. 4, it can be seen that the stressed animal is immersed in the inverted state of the tail, and the immobility time is longer than that of the normal control. However, in the group treated with Muguri herb extract, more immobility was observed than in the stress control group.

Therefore, it can be seen that the above-mentioned composition improves the lethargy and frustration caused by the stress, thereby preventing and improving the stress.

[Experimental Example 4: Serotonin measurement experiment]

Serotonin is a neurotransmitter involved in mood, behavior, appetite, sleep, and muscle contraction. Serotonin depresses symptoms such as depression and decreases serotonin in stress situations.

The test animals in which the experiments of Experimental Examples 2 and 3 were completed were sacrificed by cervical dislocation and brains were harvested and hippocampal tissues were rapidly cooled in a coldly cooled tube. Each tissue sample was sonicated by treatment with 0.4 M perchloric acid and centrifuged at 12,000 rpm (4 ° C) for centrifugation. For the analysis, Qi and other methods were slightly modified and high performance liquid chromatography with electrochemical detection (HPLC-ECD) method was used.

Results are expressed as mean and standard error (% of control) compared to serotonin concentration in normal control. Statistical significance was tested by Student's t-test to compare significance of p <0.05 compared to control group. The results are shown in Fig.

Referring to FIG. 5, it can be seen that the serotonin measured in the hippocampus of the stressed test animal is significantly lower than that of the normal control group. However, the serotonin level was maintained higher in the group administered with the extract of Moguri Herbal Extract than in the stress control group.

Therefore, it can be seen that the composition inhibits the decrease of serotonin due to stress, thereby preventing and improving stress.

[Experimental Example 5: Experiment for Measuring Dopamine]

Dopamine is a neurotransmitter of the central nervous system and is a precursor to norepinephrine, and is involved in cognition and attention concentration, compensation, and control of motor function. Since it is known that dopamine secretion is suppressed in a chronic stress situation, dopamine measurement experiments have confirmed the effect of preventing and improving stress due to the composition of the present invention.

Dopamine concentration was measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD) method in the same manner as in Experimental Example 4 of the test animals in which the experiments of Experimental Examples 2 and 3 were completed.

Results are expressed as mean and standard error (% of control) compared to dopamine concentration in normal control. Statistical significance was tested by Student's t-test to compare significance of p <0.05 compared to control group. The results are shown in Fig.

Referring to FIG. 6, it can be seen that the concentration of dopamine measured in the hippocampus of a stressed test animal is significantly lower than that of a normal control. However, the concentration of dopamine was maintained higher in the group administered with the extract of Moguri Herbal Extract than in the stress control group.

Therefore, it can be seen that the composition prevents and reduces stress by suppressing the decrease of dopamine due to stress.

[Experimental Example 6: Clinical trial for improving stress symptoms]

The composition of the present invention was encapsulated and clinical studies were conducted. Adults and boys aged 19 years and over were randomly assigned to 20 placebo-controlled and experimental groups, and stress-symptomatic trials were conducted. In the experimental group, the composition of the present invention, 400 mg / capsule of Angelica gigante Herbarium extract, was taken per day for 30 days per day, and the placebo control group received the same placebo capsules. Evaluation of improvement of stress symptoms was carried out before the start of administration and after 30 days of administration.

The Symptom Checklist-Revised (SCL-90-R) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate stress symptoms. SCL-90-R is a test method developed by Derogatis (1997). It is used for evaluation of physical and mental symptoms due to stress. Kim, Kwang-il et al. (1984) is widely used in Korea as well. This test has 90 items and each item is classified into nine sub - dimensions such as somatization, obsessive - compulsive, interpersonal sensitivity, depression, anxiety, hostility, fear anxiety, paranoia, psychiatric scale. According to the degree of symptom, it uses 5 points from 'no (0) point' to 'very severe (4) point'.

The results were expressed as mean symptom improvement ratio by comparing scores before and after ingestion of 9 sub - dimensions. The results are shown in Fig.

7, about 30% to 58% of symptom improvement effect was observed in all items of stress-induced somatization, obsessive compulsive disorder, interpersonal sensitivity, depression, anxiety, hostility, fear anxiety, paranoia, there was. On the other hand, no significant symptom improvement was seen in the placebo-controlled group.

In order to evaluate the sleep disturbance caused by stress, Pittsburgh sleep test instrument test was performed. As shown in Table 2, this test is a total of 19 items. The score is scored on a 4-point scale from 0 to 3 for the quality of sleep during the past month. The greater the total score, the higher the severity of sleep disturbance.

The results showed percent reduction of PSQI before and after ingestion, ie improvement of sleep disturbance. Statistical significance was tested by Student's t-test, and it was considered as significant at p <0.05 compared with before consumption. The results are shown in Fig.

8, there was a 46% improvement in the sleep disturbance compared to the dose before the administration in the group receiving the extract of Mindi herb extract. On the other hand, no significant symptom improvement was seen in the placebo-controlled group.

Therefore, it can be seen that the composition improves various anti-body and mental symptoms due to stress and sleep disorder.

number	Question
One	In the past month, what time did you usually go to bed
2	In the last month, how many minutes did it take to sleep after going to bed?
3	During the past month, what time did you usually wake up?
4	During the past month, how many hours did you sleep at night?
5-14	During the past month, how often have you experienced the following problems?
5	I could not fall asleep within 30 minutes.
6	I woke up in the middle of the night or woke up too early in the morning.
7	I woke up sleeping in the bathroom.
8	When I was sleeping, I could not breathe comfortably.
9	When I was sleeping, I coughed or snorted very badly.
10	When I slept, it was too cold.
11	When sleeping, it was too hot.
12	I had a bad dream.
13	When I slept, my body hurt.
14	If there is any reason for sleeping other than 5 ~ 13 please write down specifically.
15	How often have you experienced 5 to 15 problems?
16	How do you rate your sleep status overall during your last month?
17	During the past month, how often did you take your medicine to fall asleep?
18	How often have you been awake during the last month, driving, eating, or doing other social activities?
19	During the past month, how difficult were you to get involved and work?

[Experimental Example 7: Experimental animal fatigue induction-treadmill]

A 6-week-old male Sprague-Dawley-rat (Samtako) was used and subjected to a one-week adaptation period and used in the experiment. The animals were housed in a controlled room with a room temperature of 23 degrees, in which the lights were turned off in 12 hour increments. The feeds used were solid feeds and the water used was disinfected water. Feed and water were not restricted.

After extracting the extract of Mugwang organs of the above preparation example in distilled water, it was orally administered (50 mg / kg) once a day for 1 month continuously at 14-15 hours. The experimental group consisted of two control groups which induced fatigue, only physiological saline solution, and the group which ingested fatigue induction and Mindygarii extract.

After one week of administration, fatigue induction test animals were exercised once a day for three weeks using a small animal treadmill. In the first week, exercise was carried out at a speed of 15 m / min for 20 minutes, and fatigue was induced by exercise for 60 minutes at a rate of 30 m / min on the day of sacrifice by gradually increasing the speed and time. Respectively.

[Experimental Example 8: Measurement of Lactic Acid Concentration]

Lactic acid is the final product of anaerobic action. When fatigue accumulates, lactic acid accumulates in muscles, and when lactic acid accumulates, the body becomes acidified and fatigue is further induced. Therefore, in order to evaluate the fatigue improving effect of the composition of the present invention, the concentration of lactic acid in the blood of the test animal of Experimental Example 7 was measured.

Before the sacrifice of the experimental animal of Experimental Example 7, the blood was collected through the abdominal subcortical vein and centrifuged at 1,500 xg at 4 ° C for 15 minutes to separate plasma and used for the analysis. Plasma lactate concentrations were analyzed using an automated biochemical analyzer (Hitachi 7060, Hitachi, Japan).

Results were expressed as mean and standard error. Significance was tested by statistical analysis using Student's T-test, and it was regarded as significant at p <0.05 compared with fatigue control. The results are shown in Table 2.

[Experimental Example 9: Ammonia Concentration Measurement]

Ammonia causes the production of lactic acid and causes a rapid decline of glycogen, resulting in local fatigue in the muscles, and is transmitted through the blood to the brain, causing toxicity to the central nervous system.

Plasma separated from Experimental Example 8 was measured for blood ammonia concentration using an automatic biochemical analyzer (Hitachi 7060, Hitachi).

Results were expressed as mean and standard error. Significance was tested by statistical analysis using Student's T-test, and it was regarded as significant at p <0.05 compared with fatigue control. The results are shown in Table 2.

[Experimental Example 10: Measurement of Inorganic Phosphate Concentration]

In muscle contraction, the concentration of inorganic phosphate increases, and this increased inorganic phosphate interferes with the ATPase action and inhibits energy production. Particularly during intensive exercise, accumulation of inorganic phosphate due to ATP hydrolysis increases the formation of acidic inorganic phosphate (H2PO4-) due to the accumulation of hydrogen ions. Therefore, as the fatigue accumulates, the concentration of inorganic phosphoric acid in blood increases, and when fatigue improves, the concentration of inorganic phosphate in blood decreases.

Plasma isolated from Experimental Example 8 was measured for blood phosphorus phosphate concentration using an automatic biochemical analyzer (Hitachi 7060, Hitachi).

Results were expressed as mean and standard error. Significance was tested by statistical analysis using Student's T-test, and it was regarded as significant at p <0.05 compared with fatigue control. The results are shown in Table 2.

	Fatigue control	Fatigue + mind girly
Lactate (mg / dl)	38 ± 2.4	29 ± 1.8 *
Ammonia (占 퐂 / dl)	429 ± 19.5	287 ± 8.6 *
Inorganic phosphorus (mg / dl)	6.5 ± 0.2	5.3 ± 0.1 *

Referring to Table 2, it can be seen that blood concentrations of lactic acid, ammonia, and inorganic phosphate increased due to fatigue in the group treated with Mignerium extract were statistically lower than those in the control group.

[Experimental Example 11: Measurement of glycogen concentration in muscles]

Glycogen concentration was measured by the Anthrone method. The muscle was dissolved in 30% KOH solution, and the mixture was boiled in boiling water at 100 ° C for 20 minutes, and left at room temperature for 20 minutes. 96% ethanol was added thereto and centrifuged at 2000 x g for 10 minutes. After washing the precipitate with distilled water, distilled water and Anthrone reagent were added and reacted at 100 ° C for 20 minutes. Absorbance was measured at 620 nm and compared with glucose standard solution.

Results are expressed as mean and standard error (% of control) compared to glycogen levels in fatigue control. Statistical significance was assessed by Student's t-test to compare significance of p <0.05 compared to control group. The results are shown in Fig.

Referring to FIG. 9, it was found that the glycogen concentration of the energy source muscle was increased by 60% or more in the group treated with the extract of Minderium herb extracts compared to the fat control group. Therefore, it can be seen that fatigue is improved by keeping the energy source decreasing due to fatigue high by the composition.

[Experimental Example 12: Clinical trial for improving fatigue symptoms]

The composition of the present invention was encapsulated and clinical studies were conducted. Adults and boys aged 19 years and over were randomly assigned to 20 placebo-controlled and experimental groups, respectively. In the experimental group, the composition of the present invention, 400 mg / capsule of Angelica gigante Herbarium extract, was taken per day for 30 days per day, and the placebo control group received the same placebo capsules. Evaluation of improvement of fatigue symptoms was carried out before the start of administration and after 30 days of administration.

Fatigue evaluation was performed using Multidimensional Fatigue Scale (MFS). The MFS is a reconstruction of the FAI (Fatigue Assessment Inventory) developed by Schwartz et al., And is designed to answer the fatigue level of each question from one to five points for the past two weeks. The higher the score, the higher the fatigue.

The results showed percent reduction of total MFS before and after ingestion, that is, fatigue improvement rate. Statistical significance was tested by Student's t-test, and it was considered as significant at p <0.05 compared with before consumption. The results are shown in Fig.

Referring to FIG. 10, there was an improvement of 38% in the group receiving the extract of Mindi herb extracts compared to that before administration. On the other hand, no significant symptom improvement was seen in the placebo-controlled group.

Thus, it can be understood that the composition improves the physical and mental fatigue.

[Experimental Example 13: Preparation of Food Composition]

The mignal extracts were mixed as shown in the following Table 2 to prepare Examples 1 to 6 as tea beverage compositions as follows.

	Example 1	Example 2	Example 3	Example 4	Example 5	Example 6
Mint extract concentration (% by weight)	0.02	0.03	0.1	0.3	0.8	1.0

The tea beverage composition according to Examples 1 to 6 was tested for 10 persons, and the taste, flavor, and palatability were evaluated in an index of 1 to 10, and the results are shown in Table 3 below .

	Example 1	Example 2	Example 3	Example 4	Example 5	Example 6
flavor	One	6.5	7	7	5	-
Flavor	One	6	8	7	7	-
Purity	One	6.5	7.5	7	6	-

It was found that the spicy taste of the intestines of the Examples 2 to 5 was weak and the taste was relatively high.

However, according to Example 1, the taste and aroma could hardly be felt. According to Example 6, there was almost no taste, and an objective evaluation of the tasting was performed in which a portion of the subject experienced a small oscillation due to toxicity There was a difficult problem.

Accordingly, when the composition is used as a food composition, the composition of the present invention can be provided as a food composition having high palatability when it is contained in an amount of 0.03 to 0.8% by weight based on the total amount of the food composition. And can be provided as a variety of functional food compositions.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, Of the right.

The present invention relates to a composition having the effect of preventing and improving stress and fatigue-related diseases using natural extracts. More specifically, the present invention relates to a method for producing a compound of formula (I), which comprises a compound represented by the formula (I) of the Buttercup Family, a fine hawthorn, And a composition for prevention and improvement of stress and fatigue-related diseases, which comprises any one selected from the group consisting of herbaceous plants, herbaceous plants, lavender, windblown flowers, and mixtures thereof.

Claims (6)

1. Fragrant Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Thistle Leaf Extract, Frog Leaf Extract, Frog Leaf Extract, Frog Leaf Extract, Pheasant Leaf Extract A plant extract consisting of an extract, a lavender extract, a wiltwort extract, a chrysanthemum extract, and a mixture thereof,

   A composition for preventing and improving stress and fatigue related diseases.
2. The method according to claim 1,

   The composition for prevention and improvement of stress and fatigue related diseases

   It inhibits dopamine and prevents serotonin from being suppressed.

   A composition for preventing and improving stress and fatigue related diseases.
3. The method according to claim 1,

   Wherein said stress-related disease is any one selected from the group consisting of stress, depression, and insomnia

   A composition for preventing and improving stress and fatigue related diseases.
4. The method according to claim 1,

   Wherein said fatigue-related disease is chronic fatigue syndrome

   A composition for preventing and improving stress and fatigue related diseases.
5. The method according to claim 1,

   The plant extract may be any one selected from the group consisting of water, an organic solvent having 1 to 10 carbon atoms, a subcritical fluid, a supercritical fluid, and a mixture thereof,

   A composition for preventing and improving stress and fatigue related diseases.
6. A composition for preventing and ameliorating stress and fatigue-related diseases according to any one of claims 1 to 5

   Food composition.

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