Nerve-soothing composition

Abstract

The present invention relates to a composition for improving, preventing or treating anxiety disorders and a composition for stabilizing the nervous system.

Description

[Technical field]

[0001] The present invention relates to a composition for improving, preventing or treating anxiety disorders and a composition for stabilizing the nervous system. [Background technology]

[0002] Anxiety is a kind of defense system to protect the human body, and it excites the autonomic nervous system. When we are often anxious, we become tired, and when the sympathetic nervous system is overactivated due to stress and overwork, we are always anxious, which can interfere with our daily lives and lead to anxiety disorders. Anxiety disorders include post-traumatic stress disorder, obsessive-compulsive disorder, social phobia, and generalized anxiety disorder, and anxiety is also involved in other mental disorders such as depression and substance abuse. In particular, the latter, social phobia and generalized anxiety disorder, are not well known, but they plague many people.

[0003] Anxiety disorder is a general term for mental illnesses that cause various types of abnormal or pathological anxiety and fear to interfere with daily life. Anxiety and fear are normal emotional responses, but if they exceed the normal range, they can cause mental distress and physical symptoms. Anxiety stimulates the sympathetic nervous system, causing physical symptoms such as headaches, increased heart rate, increased respiratory rate, and gastrointestinal abnormalities, which are inconvenient and make it difficult to carry out daily activities such as home life, work life, and schoolwork. There are various diagnoses for anxiety disorders, each with its own characteristic definition and diagnostic criteria. Diseases that fall under the category of anxiety disorder include panic disorder, specific phobias (such as acrophobia, blood phobia, and snake phobia), social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and acute stress disorder. Anxiety disorders include many mental illnesses of different natures and are complex, so it is difficult to define the cause in a single word.

[0004] In general, pathological anxiety can be caused by a deficiency or excess of neurotransmitters in the brain nerves responsible for emotional aspects such as anxiety and depression, genetic predisposition, functional or structural changes in the brain identified through brain imaging research, social psychology aspects, and even cognitive behavioral aspects that analyze and judge past experiences and currently received information. In particular, post-traumatic stress disorder and acute stress disorder are mainly caused by accidents or disasters that cause serious mental shock.

[0005] Anxiety is a normal psychological reaction, and it is impossible to completely eliminate anxiety. However, although treatment can reduce the level of anxiety and restore normality, in many cases it recurs and the course can become chronic. Anxiety disorders are often accompanied by depression, and frequent drinking to reduce anxiety can lead to addictive disorders such as alcoholism.

[0006] Representative anti-anxiety drugs currently available commercially include benzodiazepine drugs, such as diazepam, oxazepam, prazepam, lorazepam, alprazolam, helazepam, and clonazepam, and these drugs are also used primarily for the purposes of sedation and sleep induction.

[0007] Benzodiazepine drugs have the advantage of being effective quickly, and are the most commonly prescribed drugs in Korea. The mechanism of action of these drugs is known to be increasing the affinity of gamma-aminobutyric acid (GABA) receptors, a representative inhibitory neurotransmitter in the central nervous system, and opening adjacent Cl- channels more frequently to increase Cl- ion permeability. Benzodiazepine drugs are effective quickly, but they have the disadvantage of being addictive and habit-forming. If the drug is not used according to the treatment of a specialist, symptoms may recur or withdrawal symptoms may appear. Other side effects include drowsiness, ataxia, orthostatic hypotension, respiratory depression, headache, chronic sleep disorder, and liver disease.

[0008] On the other hand, buspirone-based drugs have been attracting attention recently because, although the therapeutic effects appear somewhat slowly, they are not addictive or dependent, and prescriptions are increasing due to their advantage of not causing impairment of cognitive abilities such as memory or motor skills.

[0009] In addition, some serotonin reuptake inhibitors (SSRIs) are sometimes used as anti-anxiety drugs, but it takes several weeks for these drugs to take effect, and they can cause side effects such as weight gain and sexual dysfunction, and are only effective in one-third of patients. Furthermore, in some patients, SSRIs can worsen anxiety. For this reason, there is a need to develop drugs with a new structure that have fewer side effects and are not addictive or addictive. Summary of the Invention [Problem to be solved by the invention]

[0010] An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of anxiety disorders.

[0011] Another object of the present invention is to provide a food composition for preventing or ameliorating anxiety disorders.

[0012] It is yet another object of the present invention to provide a pharmaceutical composition for neuroleptics.

[0013] It is yet another object of the present invention to provide a neurostimulating food composition. [Means for solving the problem]

[0014] The present invention relates to a composition for improving, preventing or treating anxiety disorders and a composition for stabilizing the nervous system.

[0015] The present invention will now be described in more detail.

[0016] One example of the present invention relates to a pharmaceutical composition for preventing or treating anxiety disorders, comprising one or more extracts selected from the group consisting of White Scarlet Wheat Root, Shaoxing Green Tea and Angelica Root.

[0017] In the present invention, the anxiety disorder may be, but is not limited to, separation or isolation anxiety disorder, paranoia, panphobia, panobsessive-compulsive disorder, dysphoria, or panic disorder.

[0018] Another embodiment of the present invention relates to a pharmaceutical composition for stabilizing nerves, comprising one or more extracts selected from the group consisting of White Scarlet Wheat, Shaoxing Green Tea and Angelica dahurica.

[0019] In the present invention, the pharmaceutical composition for neuroleptics may be for treating or preventing manic-depressive illness, neurasthenia or dysphagia, but is not limited thereto.

[0020] White-headed cuckoo is also called white-headed cuckoo, but its original plant, ikema, also known as koikema, is a vine that grows in sunny areas at the foot of mountains or on slopes by the sea. The roots are harvested from autumn to winter, dried and used as medicine. White-headed cuckoo has a sweet and slightly bitter taste and is warm. In traditional Chinese medicine, this herb replenishes the liver and kidneys, strengthens muscles and bones, improves the digestive system, and has the function of detoxification. These effects can be used to treat liver and kidney deficiency, erectile dysfunction, nocturnal emission, soreness in the lower and knees, spleen deficiency and bad luck, abdominal distension, diarrhea, early gray hair, and insufficient breast milk after childbirth.

[0021] Phlomis umbrosa TURCZ. is a perennial herbaceous plant of the Lamiaceae family. It is a Chinese herbal medicine, originally made from the dried roots of the Dipsus flower, but nowadays, the Dipsus flower is rare, so Phlomis umbrosa TURCZ., which is also from the Lamiaceae family, is used instead. Phlomis umbrosa TURCZ. is named after its ability to treat fractures. Its ingredients include alkaloids, essential oils, and vitamin E. Its medicinal properties are mild and bitter in taste. It is effective for lower back pain caused by weak liver and kidney function, and for poor movement of the bones and muscles of the legs. It is also effective for arthritis and rheumatism, and is often used for discs and bruises in the lower back. For women, taking it during pregnancy can prevent miscarriage, and it is also effective in stopping bleeding when there is heavy menstruation or severe uterine bleeding. For the elderly, it is often used when they have difficulty walking due to lack of strength in the lower body, when they are unable to bend and stretch well, or when they have numbness or pain. It is better to avoid using it with Zhijie Huang, and it should not be used for diarrhea. A typical prescription is Jakdangan. Leaf buds are also eaten as a namul dish.

[0022] In Korea, Angelica gigas Nakai refers to the dried root of the Apiaceae plant, while in China, Angelica sinensis (Oliv.) Diels refers to the dried root of the Apiaceae plant. In Japan, the dried root of the Apiaceae plant, Angelica acutiloba (Siebold.&Zucc.) Kitag. or North Sea Angelica (Angelica acutiloba (Siebold.&Zucc.) Kitag. var. sugiyamae Hikino) is used. It is said that the name "Angelica" was given to the plant with the hope that the husband would return home. This comes from the ancient Chinese custom of wives placing Angelica in the bosoms of their husbands who were going to battle out of concern for them, and it was believed that eating Angelica on the battlefield would help them recover and return home. One theory is that it was named because "if you eat this medicine, your qi and blood will return to normal." This herb has a warm medicinal nature and a sweet but spicy taste, but generally Korean Angelica is less sweet and more spicy than Chinese Angelica or Japanese Angelica. The main effect of Angelica is to make blood when there is a lack of blood. Angelica made from the roots of Chinese Angelica or Japanese Angelica is excellent at making blood. However, Angelica made from the roots of Korean Angelica is relatively better at activating blood circulation, rather than making blood, and has strong anti-cancer and blood pressure lowering effects. Pharmacologically, diabetes promotes blood flow in the coronary artery and stimulates the production of red blood cells. Korean Angelica is also called Earth Angelica, Chongkenso, and Joseon Angelica, Chinese Angelica is also called Angelica, Wengui, Qiangui, Daseri, Elephant Horse, and Earth Immortal, and Japanese Angelica is also called Nihon Honki.

[0023] In the present invention, the composition may contain one or more extracts selected from the group consisting of White-sleeved Urea, Intermittent Oleander, and Angelica Root, for example, a mixed extract of White-sleeved Urea, Intermittent Oleander, and Angelica Root, or a mixture of White-sleeved Urea extract, Intermittent Oleander extract, and Angelica Root extract.

[0024] In the present invention, the white-necked oak extract may be an extract produced using one or more selected from the group consisting of its roots, stems, and leaves, for example, an extract produced using the roots, but is not limited thereto.

[0025] In the present invention, the intermittent extract may be an extract produced using one or more selected from the group consisting of the roots, stems, and leaves, for example, an extract produced using the roots, but is not limited thereto.

[0026] In the present invention, the Angelica extract may be an extract produced using one or more selected from the group consisting of its roots, stems, and leaves, for example, an extract produced using the roots, but is not limited thereto.

[0027] The extract of the present invention may be a crude extract obtained by extraction with one or more solvents selected from the group consisting of water and linear or branched alcohols having 1 to 4 carbon atoms, for example, a crude extract obtained by extraction using water as a solvent.

[0028] When a mixture of water and alcohol is used as the solvent for producing the crude extract of the present invention, the mixture may be an aqueous solution of a straight-chain or branched alcohol having 1 to 4 carbon atoms, the solution being 10% or more and less than 100% (v / v), 20% or more and less than 100% (v / v), 30% or more and less than 100% (v / v), 40% or more and less than 100% (v / v), 50% or more and less than 100% (v / v), 60% or more and less than 100% (v / v), or 70% or more and less than 100% (v / v).

[0029] In the present invention, the aqueous alcohol solution may be one or more selected from the group consisting of an aqueous methanol solution, an aqueous ethanol solution, an aqueous propanol solution, and an aqueous butanol solution, but is not limited thereto.

[0030] The extract according to the present invention may be a solvent fraction obtained by fractionating a solvent crude extract with an additional solvent.

[0031] In the present invention, the solvent fraction may be a solvent fraction using one or more solvents selected from the group consisting of ethyl ether, ethyl acetate, and butanol, for example, a solvent fraction using butanol as a solvent.

[0032] The content of the extract as an active ingredient in the composition according to the present invention can be appropriately adjusted depending on the form and purpose of use, the condition of the patient, and the type and severity of symptoms, and may be, but is not limited to, 0.001 to 99.9 wt. % or 0.1 to 99.9 wt. %, preferably 0.1 to 50 wt. % or 0.1 to 40 wt. %, based on the solid content weight.

[0033] The composition of the present invention may be administered to mammals, including humans, via various routes. The administration method may be any commonly used method, such as oral, cutaneous, intravenous, intramuscular, subcutaneous, etc., and is preferably administered orally.

[0034] Each of the compositions of the present invention can be formulated by a conventional method into oral dosage forms such as powders, granules, tablets, capsules, ointments, suspensions, emulsions, syrups, aerosols, etc., or parenteral dosage forms such as transdermal agents, suppositories, and sterile injection solutions.

[0035] In addition to the mixed extract, the composition of the present invention may further contain auxiliary substances such as pharma-ceutical compatible and physiologically acceptable carriers, excipients and diluents.

[0036] Carriers, excipients and diluents that may be included in the compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate and mineral oil.

[0037] When preparing the formulation, diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. can be used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid formulations can be prepared by mixing the extract with at least one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used.

[0038] Oral preparations include suspensions, resistant solutions, emulsions, syrups, ointments, and the like, and may contain various excipients such as wetting agents, sweeteners, flavorings, preservatives, etc. in addition to water and liquid paraffin, which are commonly used simple diluents.

[0039] Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, oil solutions, freeze-dried preparations, suppositories, transdermal preparations, etc. For non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. may be used.

[0040] For the preparation of suppositories, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin, etc. may be used.

[0041] In embodiments in which the compositions of the invention are administered to humans, the compositions of the invention may be administered alone, but generally will be administered in admixture with a pharmaceutical carrier selected having regard to the mode of administration and standard pharmaceutical practice.

[0042] For example, the compositions of the present invention may be administered orally, bucally or sublingually in the form of tablets containing starch or lactose, or in the form of capsules alone or containing excipients, or in the form of elixirs or suspensions containing flavoring or coloring chemicals. Such liquid preparations may be formulated with pharma- ceutically acceptable excipients such as suspending agents (e.g., methylcellulose, semi-synthetic glycerides such as witepsol, or glyceride mixtures such as a mixture of apricot kernel oil and PEG-6 esters, or a mixture of PEG-8 and kaffiric / kaffiric glycerides).

[0043] The dosage of the composition of the present invention may vary depending on the age, weight, sex, dosage form, health condition and degree of disease of the patient. It may be administered once a day or in several divided doses at regular intervals according to the judgment of a doctor or pharmacist. For example, the daily dosage may be 0.1 to 500 mg / kg, preferably 0.5 to 300 mg / kg, based on the content of the active ingredient. This dosage is an example of an average case, and the dosage may be increased or decreased for each individual.

[0044] If the daily dose of the composition of the present invention is less than the above-mentioned dosage volume, it is difficult to obtain a significant effect, and if it exceeds this amount, it is not only uneconomical but also exceeds the range of the usual dose, and there is a risk of undesirable side effects. Therefore, it is preferable to set it within the above-mentioned range.

[0045] In the present invention, the composition induces adenosine A1 agonist activity and exerts a prophylactic or therapeutic effect on anxiety disorders, or a neurostabilizing effect.

[0046] GPCR is a group of receptors that are target proteins of various ligands and respond to various signaling substances such as neurotransmitters and hormones, and plays an important role in regulating most physiological functions such as human reproduction, metabolism, immunity, and psychological functions. Therefore, GPCR profiling was used to screen GPCRs that the composition of the present invention affects, and dose response verification and mechanism of action tracing evaluation were performed on adenosine A1, adrenoceptor beta3, adenosine A2A, and GABAA ion channels, which are known to have mechanisms of action related to neurostabilization. As a result, it was confirmed that the extract of the present invention can improve anxiety disorders by inducing concentration-dependent adenosine A1 agonist activity, and is not related to other adenosine A2A, adrenoceptor beta3, and GABAA ion channels.

[0047] Yet another embodiment of the present invention relates to a food composition for preventing or improving anxiety disorders, comprising one or more extracts selected from the group consisting of White-shou-uu, Jang-dan and Angelica dahurica.

[0048] In the present invention, the anxiety disorder may be, but is not limited to, separation or isolation anxiety disorder, paranoia, panphobia, panobsessive-compulsive disorder, dysphoria, or panic disorder.

[0049] Yet another embodiment of the present invention relates to a food composition for stabilizing the nerves, comprising one or more extracts selected from the group consisting of White-sleeved ginger, Jang-dan, and Angelica dahurica.

[0050] In the present invention, the food composition for stabilizing the nerves may be for preventing or improving manic-depressive illness, neurasthenia, or dysphagia, but is not limited thereto.

[0051] The extract has already been explained, and the explanation thereof will be omitted.

[0052] The health functional food may be various foods, beverages, food additives, etc.

[0053] The content of the herbal extract as an active ingredient contained in the health functional food can be appropriately added depending on the form of the food, the desired use, etc., and is not particularly limited, but can be added at, for example, 0.01 to 15 wt% of the total food weight, and the health drink composition can be added at a ratio of 0.02 to 10 g, preferably 0.3 to 1 g, based on 100 ml.

[0054] The health drink composition of the present invention contains the above extract as an essential ingredient in the indicated ratio, but there are no particular limitations on the liquid ingredients, and it can contain various flavorings or natural carbohydrates as additional ingredients like ordinary beverages.

[0055] The natural carbohydrates are common sugars, such as monosaccharides, e.g., glucose, fructose, etc.; disaccharides, e.g., maltose, sucrose, etc.; polysaccharides, e.g., dextrin, cyclodextrin, etc.; and sugar alcohols, such as xylitol, sorbitol, erythritol, etc.

[0056] In addition to the above, natural flavors (thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavoring agents. The ratio of the natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g, per 100 ml of the composition of the present invention.

[0057] In addition to the above, the composition of the present invention may contain various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectinic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated drinks, etc. In addition, the composition of the present invention may contain natural fruit juices, and fruit pulp for the production of fruit juice drinks and vegetable drinks. Such ingredients may be used independently or in combination. The ratio of such additives is not critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

[0058] In particular, when the extract of the present invention is administered to the human body, due to the general characteristics of natural extracts, it is believed that there is no need to worry about side effects compared to other synthetic medicines. In fact, the results of toxicity tests on standardized herbal compositions have revealed that the extract has no effect on the living body.

[0059] The process for preparing the extract of the present invention is described in more detail as follows:

[0060] At least one selected from the group consisting of white-necked oak, scutellaria, and angelica is cut, washed with water to remove contamination, dried, and then reflux-extracted with an extraction solvent of about 5 to 20 volume times, preferably 7 to 15 volume times, the weight of the at least one selected from the group consisting of white-necked oak, scutellaria, and angelica. After extraction, the filtrate is collected by filtration. The extraction temperature is not particularly limited, but is preferably 40 to 110°C, and preferably 55 to 105°C.

[0061] The extraction process may be repeated once or several times, and in a preferred embodiment of the present invention, a method of performing re-extraction after the first extraction is adopted, in order to prevent a decrease in extraction efficiency with only the first extraction, since the herb itself has a high water content and loss occurs even if it is effectively filtered when mass-producing herb extract. Also, as a result of verifying the extraction efficiency at each stage, it was found that about 80-90% of the total amount of extraction was extracted by the second extraction.

[0062] In one embodiment of the present invention, when the extraction process is repeated twice, the obtained residue is refluxed with about 5 to 15 volume times, preferably 8 to 12 volume times, of the extraction solvent. After extraction, the mixture is filtered and mixed with the previously obtained filtrate, followed by vacuum concentration to produce the extract of the present invention.

[0063] Although the efficiency of extraction can be increased by performing two-stage extraction and mixing the filtrates obtained after each extraction, the extract of the present invention is not limited by the number of extractions.

[0064] If the amount of solvent used in producing the extract of the present invention is too small, stirring becomes difficult, the solubility of the extract decreases, and the extraction efficiency decreases. Conversely, if the amount of solvent used is too large, a large amount of solvent will be used in the next purification step, which is uneconomical and may cause problems in handling. Therefore, it is preferable to keep the amount of solvent used within the above range.

[0065] The filtered extract thus obtained is subjected to azeotropic concentration 1 to 5 times, preferably 2 to 3 times, with about 10 to 30 times, preferably 15 to 25 times, more preferably about 20 times by weight of water of the total weight of the concentrate in order to adjust the content of the remaining lower alcohol so as to facilitate use as a raw material for pharmaceuticals or foods, and then the same amount of water is added again to homogeneously suspend the extract, followed by freeze-drying and / or spray-drying to produce an extract in a powder form.

[0066] The extraction method used in the present invention may be any commonly used method, such as cold immersion, hot water extraction, ultrasonic extraction or reflux cooling extraction, for example, hot water extraction, but is not limited thereto. Effect of the Invention

[0067] The present invention can provide a composition for improving, preventing or treating anxiety disorders and a composition for stabilizing the nervous system. [Brief description of the drawings]

[0068] [Figure 1] FIG. 2 is a schematic diagram showing the production of a fraction according to one embodiment of the present invention.

[0069] [Diagram 2] 1 is a graph showing the measurement results of the neurostabilizing induction time of a crude extract according to an embodiment of the present invention.

[0070] [Diagram 3] 1 is a graph showing the measurement results of the neurostable induction time of a butanol fraction according to an embodiment of the present invention.

[0071] [Figure 4]1 is a graph showing the measurement results of the neurostabilization duration of a crude extract according to an embodiment of the present invention.

[0072] [Diagram 5] 1 is a graph showing the measurement results of neurostabilization duration of a butanol fraction according to an embodiment of the present invention.

[0073] [Figure 6] 1 is a graph showing the results of evaluating anxiety disorders for a crude extract and a butanol fraction according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0074] A pharmaceutical composition for preventing or treating anxiety disorders, comprising one or more extracts selected from the group consisting of White-shou-uu, Jang-dan and Angelica acutiloba. EXAMPLES

[0075] The present invention will now be described in more detail with reference to the following examples, but these examples are merely for the purpose of illustrating the present invention and are not intended to limit the scope of the present invention.

[0076] Example 1. Preparation of crude extract

[0077] Natural herbal medicines Cynanchum wilfordii root, Phlomis umbrosa root, and Angelica gigas root were mixed in a weight ratio of 1:1:1.08, and then extracted by heating in 10x water at 95~105℃ for 8 hours. The filtrate was then filtrated and freeze-dried at -80℃ to obtain a crude extract in powder form.

[0078] Example 2. Preparation of butanol fraction of crude extract

[0079] 2 kg of the powdered crude extract of Example 1 was dissolved in water to 10-15 brix, and then placed in a large stirrer and stirred at 400 rpm for 6 hours to obtain an aqueous solution of the crude extract. Then, n-butanol equivalent to twice the volume (v / v) of the aqueous solution of the crude extract was added, stirred at about 400 rpm for 2 hours, and left at room temperature for 24 hours or more to carry out liquid-liquid fractionation. After liquid-liquid fractionation, the n-butanol layer in the supernatant was carefully collected, and the liquid-liquid fractionation and recovery process was repeated twice more for the lower aqueous layer. Then, only the n-butanol layer was collected, the solvent was completely removed in a vacuum concentrator to 30-33 brix, and then the solution was sufficiently dissolved in distilled water to 13-15 brix and freeze-dried. After freeze-drying was completed, the obtained powder was pulverized in a mixer and homogenized by passing it through a 500 mesh sieve, left in a vacuum desiccator (25°C, -0.76 mbar) for 8 hours or more, and then double-packed and stored.

[0080] Experimental example 1. Neurostabilization induction time measurement

[0081] 1-1. Crude extract

[0082] The efficacy was demonstrated using a pentobarbital-induced neurostabilization model using mice. Specifically, after a one-week habituation period, the composition of Example 1 was repeatedly administered once a day for a total of four weeks. The composition of the example was administered at 100 or 300 mg / kg. 30 minutes after the last intake, 40 mg / kg of pentobarbital, a neurostabilization inducer, was administered to measure the neurostabilization induction time, and the results are shown in FIG. 2 and Table 1.

[0083] [Table 1]

[0084] Statistically significant comparison with control group *:p<0.05, **:p<0.01

[0085] As can be seen from FIG. 2 and Table 1, when compared to the control group, it was confirmed that the neurostabilization induction time was statistically significantly reduced in both dose groups of the composition of Example 1 (100 mg / kg intake group: p<0.01, 300 mg / kg intake group: p<0.05).

[0086] 1-2. Butanol fraction

[0087] The efficacy was demonstrated using a pentobarbital-induced neurostabilization model using mice. Specifically, after a one-week habituation period, the composition of Example 2 was repeatedly administered once a day for a total of two weeks. The composition of Example 2 was administered at 200 or 400 mg / kg. 45 minutes after the last intake, 45 mg / kg of pentobarbital, a neurostabilization inducer, was administered to measure the neurostabilization induction time, and the results are shown in FIG. 3 and Table 2.

[0088] [Table 2]

[0089] Statistically significant comparison with control group *:p<0.05, **:p<0.01

[0090] As can be seen from FIG. 3 and Table 2, the neurostabilization induction time was statistically significantly reduced in both the 200 mg / kg and 400 mg / kg dose groups of Example 2 compared to the control group (p<0.05).

[0091] Experimental Example 2. Neurostabilization Duration Measurement

[0092] 2-1. Crude extract

[0093] In Experimental Example 1-1, after nerve safety induction, the time during which nerves were activated was measured for each group, and thus the nerve stability duration was measured. The results are shown in FIG.

[0094] [Table 3]

[0095] Statistically significant comparison with control group *:p<0.05, **:p<0.01

[0096] As can be seen from FIG. 4 and Table 3, the duration of neuronal stability was also statistically significantly increased in both dose groups of the composition of the present invention (p<0.01).

[0097] 2-2. Butanol fraction

[0098] In Experimental Example 1-2, after nerve safety induction, the time during which nerves were activated was measured for each group, and thus the nerve stability duration was measured. The results are shown in FIG.

[0099] [Table 4]

[0100] Statistically significant comparison with control group *:p<0.05, **:p<0.01

[0101] As can be seen from FIG. 5 and Table 4, the neurostabilization duration was statistically significantly increased in both dose groups in Example 2 (p<0.05).

[0102] Experimental Example 3. Evaluation of neurostabilization induction below titer

[0103] Pentobarbital, a neuroleptic inducer, was administered at 30 mg / kg, which is below its potency, to evaluate the degree of neuroleptic induction in the neuroleptic borderline state. The results are shown in Table 5.

[0104] [Table 5]

[0105] Stability (%) = number of neurally activated individuals / total number of individuals x 100

[0106] As can be seen from Table 5, in the untreated group, neurostabilization was induced by about 20%, while in the group administered 100 mg / kg or more of the composition of the embodiment, the neurostabilization induction rate was 60-50%. In particular, it was confirmed that the composition had an excellent effect of increasing the duration of neurostabilization, and thus had an effect of inducing neurostabilization.

[0107] In conclusion, the composition of the embodiment was found to be highly effective in improving anxiety disorders by statistically significantly improving the relevant markers, neurostabilization induction time and neurostabilization duration, in a neurostabilization induction animal model using pentobarbital, compared to the control group.

[0108] Experimental Example 4. Evaluation of neurostabilizing-related mechanism of action (GPCR)

[0109] To determine the mechanism of action of improving anxiety disorders, profiling assays were performed to explore the mechanism of action by analyzing GPCR activity patterns associated with neuronal stability.

[0110] GPCR is a group of receptors that are target proteins of various ligands and respond to various signal transmitters such as neurotransmitters and hormones, and play an important role in regulating most physiological functions such as human reproduction, metabolism, immunity, and psychological functions. Therefore, using GPCR profiling, GPCRs affected by the composition of the embodiment were screened, and dose response verification and mechanism of action tracing evaluation were performed for adenosine A1, adrenergic receptor beta3, adenosine A2A, and GABAA ion channels, which are known to have mechanisms of action related to neurostabilization.

[0111] Specifically, to examine the dose-response activity of the extract, it was serially diluted to 8 concentrations up to 100μg / ml and tested. The effective maximum value of the reference agonist for each known receptor was calculated as 100% and the activity was converted to a percentage (%), confirming that the extract has agonist activity for GPCRs with 50% or more activity. The adenosine A1 receptor was evaluated by calcium fluorimetry assay in human recombinant BA / F3 cells in which the A1 receptor was stably expressed, and the activity was evaluated by comparing it with the effective maximum value of CPA, an adenosine A1 receptor agonist, calculated as 100%. The results are shown in FIG. 6 and Table 6.

[0112] [Table 6]

[0113] As can be seen from FIG. 6 and Table 6, the extract of Example 1 and its butanol fraction of Example 2 showed concentration-dependent agonist activity as the concentration increased to 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 μg / ml, and the extract of Example 1 showed high activity of 50% or more at concentrations of 3 μg / ml or more and the extract of Example 2 showed high activity of 50% or more. Among the neurostabilization-related action mechanisms, the composition of the Example can improve anxiety disorder by inducing concentration-dependent adenosine A1 agonist activity, and it was confirmed that it is not related to adenosine A2A, adrenergic receptor beta3, or GABAA ion channels, and the action mechanism for improving anxiety disorder was secured. It was also confirmed that it had strong agonist activity against adenosine A1 receptor, and the 50% effective concentration (EC50) was confirmed to be 2.15 μg / ml for the composition of Example 1 and 0.33 μg / ml for the composition of Example 2. [Industrial Applicability]

[0114] The present invention relates to a composition for improving, preventing or treating anxiety disorders and a composition for stabilizing the nervous system.

Claims

1. Contains a mixture of extracts of white sclerotinia, jade, and angelica. The mixed extract is a solvent fraction obtained by extracting a crude extract obtained by extracting the white-shou wu, the jade root and the angelica root in a weight ratio of 1:1:1.08 with one or more solvents selected from the group consisting of water and a linear or branched alcohol having 1 to 4 carbon atoms, and the crude extract is fractionated using one or more solvents selected from the group consisting of ethyl ether, ethyl acetate and butanol; A pharmaceutical composition for preventing or treating anxiety disorders, characterized in that the mixed extract activates adenosine A1 receptors.

2. 2. The pharmaceutical composition of claim 1, wherein the anxiety disorder is separation or isolation anxiety disorder, paranoia, panphobia, panobsessive-compulsive disorder, dysphoria, or panic disorder.

3. Contains a mixture of extracts of white sclerotinia, jade, and angelica. The mixed extract is a solvent fraction obtained by extracting a crude extract obtained by extracting the white-shou wu, the jade root and the angelica root in a weight ratio of 1:1:1.08 with one or more solvents selected from the group consisting of water and a linear or branched alcohol having 1 to 4 carbon atoms, and the crude extract is fractionated using one or more solvents selected from the group consisting of ethyl ether, ethyl acetate and butanol; The food composition for preventing or improving anxiety disorders, characterized in that the mixed extract activates adenosine A1 receptors.

4. The food composition of claim 3, wherein the anxiety disorder is separation or isolation anxiety disorder, paranoia, panphobia, panobsessive-compulsive disorder, dysphoria, or panic disorder.

5. Contains a mixture of extracts of white sclerotinia, jade, and angelica. The mixed extract is a solvent fraction obtained by extracting a crude extract obtained by extracting the white-shou wu, the jade root and the angelica root in a weight ratio of 1:1:1.08 with one or more solvents selected from the group consisting of water and a linear or branched alcohol having 1 to 4 carbon atoms, and the crude extract is fractionated using one or more solvents selected from the group consisting of ethyl ether, ethyl acetate and butanol; The mixed extract is characterized in that it activates adenosine A1 receptors and is a pharmaceutical composition for neuroleptics.

6. The pharmaceutical composition according to claim 5, wherein the neuroleptic pharmaceutical composition is for the treatment or prevention of manic-depressive illness, neurasthenia or dysthymia.

7. Contains a mixture of extracts of white sclerotinia, jade, and angelica. The mixed extract is a solvent fraction obtained by extracting a crude extract obtained by extracting the white-shou wu, the jade root and the angelica root in a weight ratio of 1:1:1.08 with one or more solvents selected from the group consisting of water and a linear or branched alcohol having 1 to 4 carbon atoms, and the crude extract is fractionated using one or more solvents selected from the group consisting of ethyl ether, ethyl acetate and butanol; The mixed extract is characterized by activating adenosine A1 receptors.

8. The food composition according to claim 7, wherein the food composition is for the treatment or prevention of manic-depressive illness, neurasthenia or dysphagia.

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