KR101769972B1 - A composition for improving, preventing and treating pulmonary disease comprising herb extract - Google Patents

Abstract

The present invention relates to a composition for reducing, preventing and treating insomnia, which can reduce, prevent, and treat insomnia by comprising a mixed extract, as an active ingredient, which is composed of Polygonum multiflorum, Poria cocos, Alisma orientale, and Polygonum multiflorum. In addition, the composition of the present invention can be ingested in the form of food as the composition has no toxicity.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for improving insomnia, preventing and treating pulmonary disease comprising herb extract containing a herbal medicine extract (YJ05)

The invention mokdanpi (Paeonia suffruticosa , Poria cocos , Alisma orientale , and a polygonum multiflorum as an active ingredient. The present invention relates to a composition for improving, preventing or treating insomnia.

Insomnia is a symptom of difficulty falling asleep or unable to fall asleep and frequently awakening, and it is recorded as a loss of sleep, dullness, mildness, no sleep, low sleep, incompetence, and bad sleep.

In addition, the sleeping surface can be said to be included in the category of insomnia, such as difficulty in sleeping, repeated awakening during sleep, early rising at dawn, awakening from sleep and falling back to sleep.

In modern society, the stress caused by mental and social confusion is increasing, and the number of patients complaining of insomnia is also increasing. According to recent statistics, about one-third of the total population in Korea experience symptoms of sleeplessness, of which 10 to 15% suffer from chronic insomnia lasting more than a month.

Sleep disturbances can cause and aggravate physical health problems such as fatigue, sensory disturbance, and temporary embarrassment, increase depression, stress, and lower overall quality of life, thus requiring effective treatment.

Currently, drug therapy is the most important component of sleeplessness therapy, most of which are synthetic chemicals. However, these synthetic chemicals have disadvantages in that they are awakened too quickly depending on the half-life of the drug, and the performance of the weekly activity is deteriorated due to hangover effect and accumulation effect. The side effects are serious.

Thus, the development of a therapeutic agent for insomnia derived from natural materials has been progressed recently

As a result, Lemon balm, Valerian, Hops, Passionflower, Kava kava, Sprouted oats, Lavender, Chamomile, Johns wort, and Jasmine have been developed and widely used in the market. Of course, research on the improvement of insomnia among the natural products of oriental origin, such as Sanjian, Yongan, Yakju, Chungcheong, Chungkuk, Red ginseng and so on, has been studied, but relatively little research and product development is done.

Korean Patent No. 1457315 Korean Patent Publication No. 2004-0053701

An object of the present invention is mokdanpi (Paeonia suffruticosa , Poria cocos , Alisma oriental and polygonum multiflorum as an active ingredient to prevent or treat insomnia.

It is another object of the present invention mokdanpi (Paeonia suffruticosa , Poria cocos , Alisma oriental and polygonum multiflorum as an active ingredient to improve or prevent insomnia.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating insomnia, which comprises a mixed extract of Paeonia suffruticosa , Poria cocos , Alisma orientale , and Polygonum multiflorum as active ingredients ≪ / RTI >

The weight ratio of Paeonia suffruticosa , Poria cocos , Alisma orientale and Polygonum multiflorum is 1: 1-8: 1-8: 1-12, preferably 1: 1-5: : 1-5: 1-8.

The mixed extract may be extracted with water, a lower alcohol having 1 to 4 carbon atoms, ethylene glycol, ethyl ether, or a mixed solvent thereof.

In another aspect of the present invention, there is provided a food composition for preventing or ameliorating insomnia, which comprises a mixture of Paeonia suffruticosa , Poria cocos , Alisma orientale and Polygonum multiflorum , May be contained as an active ingredient.

Paeonia suffruticosa), baekbokryeong (Poria cocos), Alismataceae (Alisma orientale) and yagyo etc. (Polygonum multiflorum) is 1: 1-5: there may be mixed in a weight ratio of 1-8: 1-10.

The composition for improving, preventing or treating insomnia containing the mixed extract of the present invention as an active ingredient, which comprises a mixed extract made of the herbal composition of the present invention, Baekbokryeong , taxa , and a night school , is effective in improving or preventing insomnia by reducing awakening time and increasing REM sleep time and NREM sleep time. It is highly effective in treating and is effective for manufacturing competitive food compositions and pharmaceutical compositions.

FIG. 1 is a graph showing the binding potency of 5-HT2c receptor for each concentration of Cy5-Tryptamine and 5-HT2c receptor immobilized on a protein chip for a binding assay system based on a protein chip.
Figure 2 shows the antagonistic effect on the 5-HT2cR receptor according to the concentration of the extract prepared according to Example 1 using a protein chip-based binding assay system.

The invention mokdanpi (Paeonia suffruticosa , Poria cocos , Alisma prevention or treatment of insomnia comprising as an active ingredient, a mixed extract (referred to as YJ05) consisting of oriental , oriental and polygonum multiflorum .

Hereinafter, the present invention will be described in detail.

The composition for improving, preventing or treating insomnia according to the present invention comprises Paeonia suffruticosa , Poria cocos , Alisma orientale ) and ash ( Polygonum multiflorum ) as an active ingredient.

Paeonia Suffruticosa is a medicinal herb made of root peels of Paeonia suffruticosa Andrews and has analgesic, sedative, antipyretic, anticonvulsant, anti-inflammatory, anti-thrombotic, antiallergic, gastric secretion inhibition, .

In addition, Poria cocos is dried sclerotia of Poria cocas Wolf. It acts on diuretic action, lowering of blood sugar level, sedation, and immunity-resisting action.

The Alisma orientale is a perennial herbaceous plant belonging to the taxa. It is a herbaceous plant belonging to the taxa, and is a herbaceous plant which is known as a herbaceous disease, a hereditary disease, nephritis, cystitis, urethritis,渴), diabetes, hypertension, fat and liver.

Polygonum multiflorum is a root of Polygonaceae. It has effects of lowering cholesterol, inhibiting atherosclerosis, antivirals, tonic, blood, intestines, and alopecia.

Paeonia suffruticosa , Poria cocos , Alisma orientale ) and nightclubs ( Polygonum multiflorum ) is used in a weight ratio of 1: 1-8: 1-8: 1-12, preferably 1: 1-5: 1-5: 1-8, more preferably 1: 1-2: 1- 2: 1-3. When the content of Baekbokwolryeong, Taejak, and Hacchae is lower than the lower limit, the effect of improving, preventing or treating insomnia may be lower than that of each herbal medicine alone, and insomnia may be improved , The effect of preventing or treating can be reduced.

In the case of using alone or in combination of the above-mentioned herbs, Baekbokryeong, Taesa, and Hajeong, it shows 1.5 to 20 times lower efficacy than the case of using together herringbone, Baekbokryeong,

Paeonia suffruticosa , Poria cocos , Alisma orientale ) and nightclubs ( Polygonum multiflorum ) is mixed with an extraction solvent in a weight ratio of 1: 5 to 25, preferably 1: 8 to 15, and extracted at 60 to 90 ° C to prepare an extract. When the weight ratio of the extract to the extracts is in the above range, the extract may be extracted in an amount such that the active ingredient of the mixture such as Mulberry, Baekbokryeong, Taxa,

The extraction solvent for extracting each of the above extracts is water, a lower alcohol having 1 to 4 carbon atoms, ethylene glycol, ethyl ether, or a mixed solvent thereof. The extraction solvent is not particularly limited, but an extract extracted with water is preferably used for improving, preventing or treating insomnia.

The term 'extract' used herein to refer to a mixture of ganoderma, Baekbokryeong, taekwasa and azalea includes not only the crude extract obtained by treating the extraction solvent, but also the processed products of mixed extracts such as Mulberry, Baekbokryeong, For example, mixed extracts such as Mulberry, Baekbokgol, Taejak, and Hajik can be prepared in powder form by additional processes such as vacuum distillation and freeze drying or spray drying.

In addition, the mixed extract of the present invention can be administered to a mammal in such a manner that a mixture of a herbal composition such as a herringbone, a baekbokryeong, a taxa, and a horsetail can be administered to an animal, and a mixture of such herbicide, baekbokryeong, But also includes mixed powders such as workpieces, such as wood pulp, Baekbokryeong, tars, and hometown. Although the present invention has been carried out with a mixture of woody, baekbokryeong, taxa, and nightclubs, it is expected that a desired effect can be achieved in the form of a mixed workpiece such as a woodblock, Baekbokryeong, will be.

As used herein, the term " comprising as an active ingredient " means an amount sufficient to achieve the efficacy or activity of a mixed extract such as Mulberry, Baekbokgol, For example, the mixed extracts such as Mulberry, Baekbokryeong, Taxa, and Hacchae are used at a concentration of 10 to 1500 μg / ml, preferably 100 to 1000 μg / ml. Since the mixed extracts such as Momonji, Baekbokryeong, Taeka, and Hajik are natural products, there is no adverse effect on the human body even when administered in an excessive amount. Therefore, the quantitative upper limit of the mixed extracts of Momonji, Baekbokryeong, As shown in FIG.

The pharmaceutical composition of the present invention can be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned active ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, A lubricant or a flavoring agent can be used.

The pharmaceutical composition may be formulated into a pharmaceutical composition containing at least one pharmaceutically acceptable carrier in addition to the above-described active ingredients for administration.

The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, liquids, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a mixture. Suitable binders include, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, natural and synthetic gums such as corn sweeteners, acacia, tracker candles or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like.

Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile water and sterile water suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.

Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.

The pharmaceutical composition of the present invention can be administered orally or parenterally. In the case of parenteral administration, the composition can be administered by intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration, etc., .

The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient, Usually, a skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.001-10 g / kg.

The pharmaceutical composition of the present invention can be prepared in unit dose form by formulating it with a pharmaceutically acceptable carrier and / or excipient or can be manufactured by inserting it into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.

In addition, the present invention provides a food composition for improving, preventing or treating an unknown disease containing mixed extracts such as Mulberry, Baekbokryeong, Taxa,

The food composition according to the present invention can be formulated in the same manner as the above pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, confectioneries, diet bars, dairy products, meat, chocolates, pizza, ram noodles, other noodles, gums, ice cream, .

The food composition of the present invention may contain, as an effective ingredient, not only mixed extracts such as Mokpo, Baekbokryeong, Taxa, and Haji, but also components that are ordinarily added during the manufacture of food. Examples thereof include proteins, carbohydrates, Seasoning and flavoring agents. Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings. For example, when the food composition of the present invention is prepared from a drink and a beverage, it may be mixed with citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, And the like.

The present invention provides a health functional food comprising a food composition for improving, preventing or treating insomnia comprising, as an active ingredient, a mixed extract of Mulberry, Baekbokryeong, Taxa, and a night school. The health functional food is a food prepared by adding a mixed extract such as Momonji, Baekbokryeong, Taejak, and a nightclub to a food material such as beverage, tea, spice, gum or confection, or encapsulated, powdered or suspended, However, unlike general medicines, it has the advantage that there are no side effects that may occur when a drug is taken for a long time using the food as a raw material. The health functional food of the present invention thus obtained is very useful because it can be ingested routinely. The amount of the mixed extract such as Momonji, Baekbokryeong, Taejiae, and Hagoromo is not uniformly determined depending on the kind of the health functional food to be used in such a health functional food. However, the addition amount of the mixed extract is not limited so long as the original taste of the food is not impaired And is usually in the range of 0.01 to 50% by weight, preferably 0.1 to 20% by weight based on the target food. In the case of health functional foods in the form of pills, granules, tablets or capsules, they may be added usually in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.

In addition, the present invention provides the use of mixed extracts such as Korean herbal medicine, Baekbokryeong, pharmacology, and horseradish for the preparation of medicines or foods for improving, preventing or treating insomnia. As described above, the mixed extracts such as Mulberry, Baekbokryeong, Taxa, and Haji can be used for the improvement, prevention or treatment of insomnia.

The present invention also provides a method for the amelioration, prevention or treatment of insomnia comprising administering to a mammal an effective amount of a mixed extract, such as Mulberry, Bacillus subtilis, Taxa, and a night school.

The term "mammal " as used herein refers to a mammal that is the subject of treatment, observation or experimentation, preferably a human.

As used herein, the term "effective amount" refers to the amount of active ingredient or pharmaceutical composition that elicits a biological or medical response in a tissue system, animal, or human, as contemplated by a researcher, veterinarian, physician or other clinician, ≪ / RTI > inducing a reduction of the symptoms of the disease or disorder. The effective amount and the administration frequency for the active ingredient of the present invention can be changed according to the desired effect. Thus, the optimal dosage to be administered can be readily determined by those skilled in the art and will vary with the nature of the disease, the severity of the disease, the amount of active and other ingredients contained in the composition, the type of formulation, and the age, The age, body weight, sex, diet, time of administration, route of administration and fraction of the composition, duration of treatment, concurrent medication, and the like. In the prevention, treatment, or improvement method of the present invention, in the case of an adult, administration is carried out at a dose of 0.001 g / kg to 10 g / kg, once or several times a day, with mixed extracts such as Mulberry, .

In the treatment method of the present invention, the composition comprising the mixed extract of Mulberry, Baek Bok-Yeong, Taxa, and a schoolyard as an active ingredient can be administered orally, rectally, intravenously, intraarterially, intraperitoneally, intramuscularly, intrasternally, transdermally, Or via the intradermal route in a conventional manner.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit or scope of the present invention. Such variations and modifications are intended to be within the scope of the appended claims.

Control 1

The mixture was mixed at a weight ratio of 1:10, and water was extracted from the mixture at 90 ° C for 3 hours to obtain an extract of Momordica sativa L. (Momordica sativa L.).

Control 2

Control 1 was prepared in the same manner as in Control 1, except that Baekbokryeong was used instead of Mulberry.

Control 3. Tax alone

Control 1 was prepared in the same manner as in Control 1 except that the extract of Baekbokryeong was obtained by using Taxa instead of Mulberry.

Control 4.

Control 1 was prepared in the same manner as in Control 1, except that an extract of Baekbokryeong was obtained by using a whiskey or the like instead of a strawberry.

Example 1: Weight ratio of 1: 1: 1: 1: 2

1: 1: 2 weight ratio, which was purchased from Korean Kook Shin Yak Pharmaceutical Co., Ltd., Nonsan, Korea, was mixed at a weight ratio of 1: 1: 1: : 10, and the mixture was subjected to hot water extraction at 90 占 폚 for 3 hours to obtain a mixed extract such as Mulberry, Baekbokryeong, Taxa,

Example 2: Weight ratio of 1: 1: 1: 2: 1 of rhizome: Baekbokryeong:

The mixture was mixed in a weight ratio of 1: 1: 2: 1 to obtain a mixed extract.

Example 3: The weight ratio of 1: 2: 1: 1 of rhizome: Baekbokryeong:

The mixture was mixed in the same manner as in Example 1, except that the mixture was mixed at a weight ratio of 1: 2: 1: 1, such as Mulberry, Baekbokryeong,

Comparative Example 1: Weight ratio of 1: 10: 10: 13: rhizome: Baekbokryeong:

The mixture was mixed in a weight ratio of 1:10:10:13 to obtain a mixed extract.

Comparative Example 2: Weight ratio of 1: 0.5: 0.5: 1 in rhizome: Baekbokryeong:

The mixture was mixed in a weight ratio of 1: 0.5: 0.5: 1 to obtain a mixed extract.

Comparative Example 3: Weight ratio of wood: Phosphorus: Phat = 1: 1: 1

The mixture was mixed in the same manner as in Example 1, except that the mixture was mixed at a weight ratio of 1: 1: 1.

COMPARATIVE EXAMPLE 4 Boron Phosphate: Baek Bok-ryeong: Phytase: Phosphorus ratio = 1: 1: 1: 2

The mixture was mixed in a weight ratio of 1: 1: 1: 2 to obtain a mixed extract.

Comparative Example 5: Weight ratio of 1: 1: 1: 1: 2 of rhizome: Baekbokryeong:

The mixture was mixed at a weight ratio of 1: 1: 1: 2 to obtain a mixed extract.

Comparative Example 6: Weight ratio of 1: 1: 1: 1: 2

The mixture was mixed in a weight ratio of 1: 1: 1: 2 to obtain a mixed extract.

Comparative Example  7. Mouthpiece: Baekbokryung  : Tarsa  : Sukiyonghwang: Ma: Sansui = 1: 1: 1: 2.6: 1.3: 1.3 weight ratio

The mixture was mixed in the same manner as in Example 1 except that the mixture was mixed at a weight ratio of 1: 1: 1: 2.6: 1.3: 1.3 in the ratio of 1: 1 to 1: 1.

< Test Example >

Test Example  1. Antagonistic effect measurement

Serotonin (5-HT) 2 receptors play an important role in sleep and are divided into three subtypes, 5-HT2a, 5-HT2b and 5-HT2c receptors. It is important to regulate the 5-HT2c receptor in the slow wave sleep rather than in other subtypes. Since the 5-HT2c receptor plays an important role in the regulation of REM sleep (rapid eye movement sleep) and NREM sleep (non rapid eye movement sleep), the following experiment was conducted to select an antagonistic effect to the 5-HT2c receptor do.

(50 mM Tris-HCl, 10 mM MgCl 2) at 5 μg / ml in 5-HT2c receptor (Serotonin 5-HT2c membrane preparation in HEK293 cells, Product # 6110548400UA, Perkin- , 1 mM EDTA, 0.1% BSA pH 7.4) and fixed at 4 ° C for 16 hours on a protein chip (ProteinChip, Proteogen and Innopharmascreen Inc.). The dried 5-HT2c receptor chip was reacted with 3% BSA blocking buffer for 1 hour at room temperature, washed with Washing Buffer (0.05% PBST) for 10 minutes, dried using N2 gas, 0.05% PBST), and reacted with Cy5-Tryptamine (500 uM, using 30% glycerol in PBS as buffer, Peptron) for 1 hour. The protein chip on which the reaction was performed was washed with PBST and DW, dried with N2 gas, and then fluorescence values of each spot were measured using a fluorescent scanner (GenePix pro A4100) to determine 5-HT2c receptor binding ability using GenePix pro 6.0 Instruments, CA, USA).

FIG. 1 is a graph showing the binding potency of 5-HT2c receptor for each concentration of Cy5-Tryptamine and 5-HT2c receptor immobilized on a protein chip for a binding assay system based on a protein chip.

As shown in FIG. 1, optimal concentrations of Cy5-Tryptamine and 5-HT2c receptors for binding assay systems based on protein chips were 500 uM and 50 μg / ml, respectively.

The binding assay system based on the protein chip is used for screening medicinal herbs.

The 5-HT2c receptor was immobilized on the surface of the protein chip at a concentration of 50 μg / ml in the same manner as described above, washed and dried. The dried 5-HT2cR chip was reacted with 3% BSA blocking buffer for 1 hour at room temperature After washing, 0.5 mg / ml of the extract prepared in the control, Examples and Comparative Examples was added to the 5-HT2cR chip and allowed to react at 37 ° C for 1 hour. Then, 500 μM Cy5-Tryptamine (500 μg / ml) was added and reacted for 1 hour. The 5-HT2cR chip was washed and dried, and fluorescence values of each spot were measured using a fluorescence scanner.

division Control 1 Control 2 Control 3 Control 4 Example 1 Example 2 Example 3 Fluorescence value 38200 35400 38000 35100 25100 27300 28400 division Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 Comparative Example 5 Comparative Example 6 Comparative Example 7 Fluorescence value 36900 35400 35500 30900 32400 31100 31800

As shown in Table 1, the extracts prepared according to Examples 1 to 3 of the present invention were found to have lower fluorescence values than the extracts prepared according to Controls 1 to 4 and Comparative Examples 1 to 7.

Since the low fluorescence value means the most effective antagonist, it was confirmed that the extracts of Examples 1 to 3 were superior antagonists to the 5-HT2c receptor as compared with the extracts of other groups.

Among the extracts of Examples 1 to 3, the extract of Example 1 is the most excellent antagonist for the 5-HT2c receptor. Therefore, the experiment is performed using the extract of Example 1 in the following.

The 5-HT2c receptor was immobilized on the surface of the protein chip at a concentration of 50 μg / ml in the same manner as described above, washed and dried. The dried 5-HT2cR chip was reacted with 3% BSA blocking buffer for 1 hour at room temperature After washing, the extract prepared in Example 1 was added to the 5-HT2cR chip for each concentration, and reacted at 37 ° C for 1 hour. Then, 500 μM of Cy5-Tryptamine was added to react for 1 hour. The 5-HT2cR chip was washed and dried, and the fluorescence value of each spot was measured using a fluorescence scanner.

FIG. 2 is a graph showing the antagonistic effect on the 5-HT 2c receptor according to the concentration of the extract prepared according to Example 1 using a protein chip-based binding assay system.

As shown in FIG. 2, when the concentration of the 5-HT 2c receptor was 50 μg / ml, the IC ₅₀ of the extract of Example 1 against Cy5-Tryptamine was found to be 167.81 mg / ml. These data indicate that the extract of Example 1 blocks the interaction between the 5-HT2c receptor and Cy5-Tryptamine, so that the extract of Example 1 is a useful substance for controlling the sleep surface structure.

Animal experiment

250-300 g of Wistar rats (SAMTAKO, Korea, male) were used for behavioral studies. The animals were housed in an acrylic cage (45 x 60 x 25 cm ³ ), fed with sufficient feed and water, and adjusted for 12 hours of daytime and night with appropriate artificial illumination (from 8:00 am). It maintained a constant temperature (20 ~ 24 ℃) and humidity (45 ~ 65%). We observed for a week to adjust to the changed environment, maintained the sleep cycle, and confirmed abnormal behavior.

All experiments using animals were performed in compliance with the MFDS's National Institute of Toxicological Research for the care and use of laboratory animals (KHUASP (SE) -14-051) .

Experimental animals were divided into a normal group in which physiological saline was administered by randomly selecting healthy animals with constant weight change, control groups 1 to 4 in which extracts of Controls 1 to 4 were respectively administered, and a control group in which a sample administered with the extract of Example 1 And 8 mice were used per experimental group.

Test Example  2. Measurement of sleep structure

1) EEG injection

Transmitters (Data Sciences TA11CTA-F40) for EEG measurements should be implanted in each rat. The transmitter is implanted under the skin and placed in the center of the scapula. Two wires are inserted into the frontal cortex, and two wires are inserted into the muscles of the occipital area to measure EEG and EMG, respectively, with four strands of wire. The upper part of the ribs of the rat is divided into the scalp between the scalpel and the surgical scalpel to allow the frontal cortex to be seen on the frontal cortex. Thin muscles of the occiput are penetrated thinly with sterile syringe needles, and then inserted into the muscles through wires between the needles. The inserted wire is bundled using a surgical thread so that it does not shake. To insert the wire into the Cortex, clean the tissue above the frontal bone using a scalpel blade or blade. Bleed blood is wiped off with sterile cotton. To insert a transmitter wire into the frontal cortex, a small hole is drilled on the left and right sides of the frontal bone using a medical drill, and a stripped wire is inserted through the hole into the frontal cortex of the brain. After surgery, the hole was sealed with a dental cement to prevent wire from escaping and to prevent further contamination. When the dental cement is completely hardened, the skin is tightly sutured and the rats are restored by administering antibiotics for one week after surgery.

2) Administration of extract

Seven days after surgery, the extracts of Controls 1 to 4 and the extract of Example 1 (50 mg / kg each) were orally administered 3 hours before the measurement of EEG.

3) Data collection and analysis

For the EEG signal, the transmitter is -0.5 / + 0.5 volts per units X 2 and the original signal measured at the transmitter is 0.5-20.0 Hz, and the signal is processed by the Data Sciences analog converter.

The EEG recordings were started at 9:00 am and measured for 12 hours in all rats, and EEG signals were recorded via SleepSign Ver.3 software (Kissei Comtec, Nagano, Japan). The sleep state is SleepSign Ver. 3 software (Kissei Comtec, Nagano, Japan) automatically distinguishes between awake, REM sleep and NREM sleep.

The EEG power spectrum is calculated and averaged at 0.5 Hz intervals and is divided into delta wave activity with a frequency range of 0.65 to 4 Hz, a seta activity of 6 to 10 Hz and an alpha wave activity of 12 to 14 Hz. The EEG power density of the NREM sleep surface is calculated from the ratio of each section from the total EEG power (0-20 Hz) of each rat.

Among three sleep states, awakening has low amplitude EEG and high voltage EMG activity, NREM sleep has high amplitude, spindle EEG and low voltage EMG activity, and REM sleep has low amplitude EEG and low voltage EMG activity.

4) Statistical analysis

All statistical analyzes were performed using SigmaStat software (IBM ^® SPSS ^® Statistics Ver. 21). Tukey test was performed after ANOVA.

The REM sleep takes about 20-25% of the total sleep, resulting in about 90-120 minutes in total and occurs over 4-5 times. The REM sleep has various theories such as putting the vitality of the body, playing a role in growth, and playing a mental role in firmly fixing certain memories.

The NREM sleep consists of four stages. As the stage progresses, deep sleep subsides, which leads to relief of fatigue and enhancement of the immune system. Therefore, NREM sleep is related to sleep quality.

division Total time (%) Normal group Control 1 Control group 2 Control group 3 Control group 4 Example 1 Awakening 81.1 80.5 80.1 80.8 79.4 72.5 REM sleep 6.5 6.7 7.0 6.6 7.2 10.1 NREM sleep 12.4 12.8 12.9 12.6 13.4 17.4

As shown in Table 2, the rats administered with the extract prepared according to Example 1 of the present invention showed a decrease in awakening time and an increase in REM sleep and NREM sleep time compared to the normal group and the control groups 1 to 4. In particular, the rats administered with the extract prepared according to Example 1 showed that the NREM sleep time increased more than the REM sleep time.

Hereinafter, formulation examples of the composition containing the powder of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.

Formulation example  One. Sanje  Produce

500 mg of the extract powder obtained in Example 1

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

Formulation example  2. Preparation of tablets

300 mg of the extract powder obtained in Example 1

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Formulation example  3. Preparation of capsules

200 mg of the extract powder obtained in Example 1

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation example  4. Preparation of injections

600 mg of the extract powder obtained in Example 1

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO _{4 ,} 12H ₂ O 26 mg

It is prepared by the above-mentioned component content per ampoule according to the usual injection preparation method.

Formulation example  5. Liquid  Produce

4 g of the extract powder obtained in Example 1

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 g with purified water, To prepare a liquid agent.

Formulation example  6. Preparation of granules

1,000 mg of the extract powder obtained in Example 1

Vitamin mixture quantity

70 ug of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

Vitamin B12 0.2 ug

Vitamin C 10 mg

Biotin 10 ug

Nicotinic acid amide 1.7 mg

Folic acid 50 ug

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

The composition ratio of the above-mentioned vitamins and minerals is comparatively comparatively mixed with the granules according to the preferred embodiment. However, the blending ratio may be arbitrarily changed, and the above components are mixed according to the ordinary granule preparation method, Can be prepared and used in the manufacture of a health functional food composition according to a conventional method.

Formulation example  7. Manufacture of functional beverages

 1,000 mg of the extract powder obtained in Example 1

Citric acid 1,000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to the flask to obtain a total of 900 mL

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The solution thus prepared was filtered and sterilized in a sterilized 2 L container, It is used in the production of the functional beverage composition of the invention.

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (6)

Paeonia suffruticosa , Poria cocos , Alisma orientale , and the like ( Polygonum The composition according to any one of claims 1 to 3, wherein the composition comprises at least one compound selected from the group consisting of multiflorum , The method according to claim 1, wherein the Paeonia suffruticosa , Poria cocos , Alisma orientale , and Polygonum multiflorum are mixed at a weight ratio of 1: 1-8: 1-8: 1-12 Or a pharmaceutically acceptable salt thereof. The method according to claim 1, wherein the Paeonia suffruticosa , Poria cocos , Alisma orientale , and Polygonum multiflorum are mixed at a weight ratio of 1: 1-5: 1-5: 1-8 Or a pharmaceutically acceptable salt thereof. The pharmaceutical composition for preventing or treating insomnia according to claim 1, wherein the mixed extract is extracted with water, a lower alcohol having 1 to 4 carbon atoms, ethylene glycol, ethyl ether or a mixed solvent thereof. A composition for preventing or improving insomnia characterized by containing as an active ingredient a mixed extract comprising Paeonia suffruticosa , Poria cocos , Alisma orientale and Polygonum multiflorum . The method of claim 5, wherein the mokdanpi (Paeonia suffruticosa), baekbokryeong (Poria cocos), Alismataceae (Alisma orientale) and (Polygonum multiflorum), etc. yagyo is 1: 1-5: 1-10: food for preventing or improving insomnia characterized in that the mixture in a weight ratio of 1-8 Composition.

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