KR101690175B1 - Pharmaceutical composition for preventing or treating insomnia comprising Angelica tenuissima extract - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating insomnia comprising Angelica tenuissima extract as an active ingredient, and a health functional food for prevention or improvement. The composition comprising the extract of Ganoderma extract of the present invention has an efficacy to prevent, treat or ameliorate insomnia and does not cause side effects to the human body. Therefore, the pharmaceutical or health care for preventing, treating or improving various cognitive disorders and depression including insomnia It can be applied to functional foods.

Description

[0001] The present invention relates to a pharmaceutical composition for preventing or treating insomnia,

The present invention relates to a pharmaceutical composition for preventing or treating insomnia comprising Angelica tenuissima extract as an active ingredient, and a health functional food for prevention or improvement.

In modern society, many people suffer from sleep disturbance due to stress, anxiety and irritability. However, when the period is short and weak, medication is not necessary, but medication is necessary if it interferes with the work. According to the statistics, about 15% of adults are known to need medication due to insomnia due to anxiety symptoms.

Insomnia can be caused by stress, excessive anxiety, tension, or fear. Primary insomnia is not caused by other primary sleep disorders, psychiatric problems, medical or neurological problems, It is insomnia. It is also presumed that hyperarousal to ascending reticular formation system activity is caused not only by arousal but also by excessive sleep.

There are a variety of medicines used for the treatment of insomnia. Early types of insomnia are drugs known as classical benzodiazepines. These benzodiazepines exhibit pharmacological actions by interacting with the benzodiazepine binding site associated with the GABA _A receptor. Significant allosteric modulation effects of drugs acting at the benzodiazepine site were initially recognized and the distribution of activity in the different receptor subtypes was in the intensive pharmacological discovery area. However, some classical benzodiazepines considered to be a complete agonist at the GABA _A receptor benzodiazepine site are generally considered effective for induction and maintenance of sleep, which is believed to be due to their relatively long half-life in the range of 10 to 40 hours, Resulting in undesirable residual effects. A particular problem with classical benzodiazepines is recoil insomnia, caused by agitation and sleepiness, which occurs during drug withdrawal. In addition, the quality of sleep induced by these compounds is not physiological. Classic benzodiazepines are typically SWS. Reduces rapid eye movement sleep (REM), and generally has a deleterious effect on the sleep surface. One of the causes for these undesirable side effects was considered to be related to the relatively long half-life of the classical benzodiazepines mentioned above.

To overcome these problems, drugs with shorter half-lives have been studied. Examples of such agents include so-called non-benzodiazepines, such as zolpidem and zaleprone, which also act as complete agonists at the GABA _A receptor benzodiazepine site. However, these new drugs are generally effective for a reduction in time to sleep initiation (i. E., A reduction in sleep latency), but have been found to be less effective in the treatment of late insomnia as well as improvement in sleep maintenance.

Under these circumstances, the present inventors have made efforts to find natural products harmless to the human body with few side effects while showing the effect of preventing or treating insomnia. As a result, the inventors of the present invention have found that the extract of guinea pigs shortens the sleep induction time induced by pentobarbital, And that the present invention can be applied to a medicament for preventing or improving insomnia or a health functional food, thereby completing the present invention.

[Patent Document 1] Korean Registration No. 10-1106110 [Patent Document 2] Korean Registration No. 10-1468551 [Patent Document 3] Korean Registration No. 10-1315888 [Patent Document 4] International Publication No. WO 2012/027882

It is an object of the present invention to provide a pharmaceutical composition for preventing or treating insomnia comprising Angelica tenuissima extract as an active ingredient.

Another object of the present invention is to provide a health functional food for preventing or ameliorating insomnia, which comprises ganoderma extract as an active ingredient.

In one aspect of the present invention, the present invention provides a pharmaceutical composition for preventing or treating insomnia comprising Angelica tenuissima extract as an active ingredient.

The term " Angelica tenuissima " used in the present invention is a perennial plant belonging to the mountain type family, and is a plant native to the deep mountain range of the whole country. It is also called Jinsin, Ulleung, It is a herb that grows up to 40 to 80 cm in length and is fragrant. The gobbled leaves are finely divided by root leaves and four feather leaves, flowers bloom in white from August to September, and seeds are born in October. It is used in headache, fever, seawater, sputum and runny nose caused by external sensation because of strong spicy taste and hot and spicy taste. It also has the effect of stopping two sore head aches, which contains a volatile essential oil, which is calm, analgesic, antipyretic, anti-inflammatory It shows for addition one of the uterine smooth muscle and inhibit the secretary shows a strong inhibitory action on baekseongyun, neurogenic dermatitis, itching, and medicinal plants having a loss of the oscillation of the skin effect.

Particularly, roots of the above-mentioned vertebrae are used as medicinal herbs, and about 0.5% of essential oil, 3-butylidenephthalide senkyunolide, cnidilide, ligustilide and the like are known as root constituents and β-sitosterol and prangolarin are known as seeds.

In addition, various effects such as antioxidant and antiinflammatory effects have been studied in relation to the gonads. There are no reports of effects on insomnia related diseases. Accordingly, the inventors of the present invention have confirmed that the extract of Ganoderma lucidum according to the present invention has an effect on insomnia using an animal model.

The term "extract" used in the present invention means a preparation which is obtained by squeezing a herbal medicine with an appropriate leaching solution and concentrating by evaporating the leaching solution. The diluent or concentrate or extract of the extract obtained by the extraction treatment, Dried products obtained by these methods, their controlled products or purified products.

The extract of the present invention can be prepared by extracting with an extraction solvent or extracting with an extraction solvent and fractionating the extract with a fraction solvent. The organic solvent may be a lower alcohol having 1 to 4 carbon atoms, a polar solvent such as ethyl acetate or acetone, a solvent such as hexane or dichloro Methane, or a mixed solvent thereof may be used. Further, water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof may be preferably used. More preferably ethanol, methanol or butanol. Also, in one embodiment of the present invention, an extract using a mixed solvent of water and ethanol as the solvent was prepared.

The extract may be prepared by a general extraction method, separation and purification methods known in the art. Specifically, extraction methods include, but are not limited to, hot water extraction, hot water extraction, cold extraction, Extraction, reflux cooling extraction, ultrasonic extraction, or the like. Preferably, the extraction method may be repeated 2 to 5 times, and more preferably, it may be repeated twice. In one embodiment of the present invention, the dry solid and 70% ethanol were mixed and immersed at a weight ratio of 1: 4, and then the mixture was heated and extracted twice.

After extracting or fractionating the extract, it may be subjected to a vacuum filtration process or further concentrated and / or lyophilized to concentrate or remove the solvent. The extract of the extract of the present invention is stored in a rapid freezing refrigerator . In addition, the filtration, sterilization, concentration and drying in the production of the ganoderma lucidum extract can be applied by adopting a method generally accepted in the art, and the present invention is not limited by these choices.

In one embodiment of the present invention, the extract was filtered, the filtrate was concentrated under reduced pressure, and then lyophilized to obtain a powder of a ganoderma extract.

As used herein, the term "sleep" is an important physiological function of brain-developed animals and refers to indispensable behavior for survival. Also, if you do not take good sleep, you will have a fatal impact on higher animals with a cerebral brain that has an adverse effect on the brain's ability to process information. Thus, the brain can exert its ability to process high-dimensional information only if there is good sleep.

As used herein, the term "Insomnia" refers to a disorder of sleep, also known as sleep disturbance, which is not sufficient to awaken and is reported to affect about 15% of all adults in Korea throughout the year. The insomnia is also widely used as meaning any and all sleep loss types and grades.

The insomnia may include any type of sleep disorder known in the art, including, but not limited to, primary insomnia.

As used herein, the term "primary insomnia" refers to a sleep disorder that affects the onset of sleep or difficulty in maintaining sleep, or sleep that is not restored, and other primary sleep disorders, psychiatric problems, It is not caused by neurological problems, drug use or discontinuation of use, but insomnia. In addition, the cause of primary insomnia may be hyperarousal to ascending reticular formation system activity not only at arousal but also at the time of sleep. The types of primary insomnia symptoms include psycho-physiologic insomnia, sleep statemisperception, inadequate sleephygiene and idiopathic insomnia, among which psychophysiological insomnia, Insomnia is known as the most common primary insomnia.

As used herein, the term " psycho-physiologic insomnia "is a symptom in which negative sleep experiences are repeated and learned and related to internal mental activity or external stimuli. The conditional association to the external stimulus is caused by the frequent association of sleep-related situations or behaviors with sleeplessness, resulting in conditioned hyperactivity just prior to sleep. Such repeated awakening can cause excessive awakening, even when lying awake in bed, and the actions associated with bedtime, such as cleaning the teeth, preparing bedding, or turning off a fire, can also cause excessive awakening do. Because of this excessive anxiety, I can not sleep, I can not sleep, I try to sleep more, I become more awake, and I get a symptom that causes a vicious circle that can not sleep more and more. The psychiatric insomnia is found in 1 to 2% of the total population and is diagnosed in about 12 to 15% of the insomnia patients who have been referred to the sleep center, and is more common in women than men, usually between 20 and 40 years of age It is insomnia.

As used herein, the term " sleep statemisperception "refers to insomnia subjectively, but it is insomnia without any problem in starting or maintaining sleep in an objective sleep test result. The prevalence of the sleeping cognitive impairment is not known but is estimated to be less than 5% of insomnia patients visiting the outpatient clinic. There is no theory that accurately describes the difference between subjective and objective results, but most are insomnia characterized by patients experiencing objective problems unknown to standard sleep polyvalence.

As used herein, the term " inadequate sleephygiene "refers to insomnia caused by habits and daily activities that prevent sleeping well at night and keep you awake during the day. In addition, the specific prevalence of such inadequate sleep hygiene is unknown, but it is estimated that 1 to 2% of the total population will show this abnormality, and insomnia diagnosed in about 5 to 10% of people visiting the sleeping center.

As used herein, the term "idiopathic insomnia" is a very rare case of insomnia that fails to take adequate sleep during a lifetime. It may also start at birth or at the earliest puberty and may have a family history. Although the prevalence of idiopathic insomnia is not known, the prevalence of idiopathic insomnia is estimated to be 0.7% in puberty and 1% in early adulthood.

In the present invention, the extract of guinea pigs of the present invention was injected into an animal model in which pentobarbital was administered to a fasted mouse, and the effect of the extract on the induction time of sleep and sleeping time was confirmed.

As a result, it was found that when the extract of the present invention was administered to an animal model in which pentobarbital was administered to a fasted mouse, the induction time of the sleep was slightly lower than that of the control group administered with distilled water (Fig. 1) (Fig. 2). ≪ tb > < TABLE > These results show that the extract of Ganoderma lucidum shortens the sleep induction time and significantly increases the sleeping time.

Thus, by confirming that the sleeping disorder induced by fasting can be shortened by shortening the sleep inducing time and prolonging the sleeping time by the extract of the present invention, it can be confirmed that the extract of Ganoderma lucidum has improvement and treatment effect on insomnia.

As used herein, the term "prevention" means any action that inhibits or delays the onset of insomnia by the administration of the pharmaceutical composition according to the present invention, and "treatment" means suspicion of insomnia and / Means any action that alters or alleviates symptoms of an onset individual.

The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier. The term " pharmaceutically acceptable "as used herein means that the composition is free of toxicity to cells or humans exposed to the composition. Compositions comprising a pharmaceutically acceptable carrier can be of various oral or parenteral formulations. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used. The carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, But may be at least one selected from the group consisting of polyvinylpyrrolidone, physiological saline, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol and liquid paraffin, But are not limited to, ordinary carriers, excipients or diluents. The components may be added independently or in combination to the active ingredient extract of the alimentary tract.

Solid formulations for oral administration may include tablet pills, powders, granules, capsules and the like, which may contain one or more excipients, such as starch, calcium carbonate, sucrose or lactose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The pharmaceutical composition of the present invention may also be in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, Or a pharmaceutically acceptable salt thereof.

The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. There is no particular restriction on the dosage, and it may vary depending on the body's absorption, body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, severity of disease and the like.

The pharmaceutical composition of the present invention is prepared in consideration of an effective dose range, and the unit dosage formulations thus formulated are classified according to the judgment of the expert who monitors or observes the administration of the drug, if necessary, Or may be administered several times at a predetermined time interval. Preferably, the pharmaceutical composition of the present invention may be administered at a dose of 0.5 to 5000 mg / kg, preferably 50 to 500 mg / kg, more preferably 50 mg / kg, based on the amount of the goat extract , And the administration may be carried out once a day or several times.

In another aspect, the present invention can provide a method for treating insomnia, comprising the step of administering to a subject a pharmaceutical composition comprising the extract of Ganoderma luciferase as an active ingredient.

As used herein, the term "administering " means introducing a predetermined substance into a subject by an appropriate method, and the administration route of the composition can be administered through any conventional route so long as it can reach the target tissue. But are not limited to, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, oral, topical, intranasal, intrathecal, rectal.

In addition, the term "individual " refers to all animals, including humans, that have developed or may have developed dementia.

In another aspect, the present invention provides a health functional food for preventing or ameliorating insomnia comprising an extract of Ganoderma luciferase as an active ingredient.

When the composition of the present invention is used as a food additive, the extract of the present guinea pig may be directly added or used together with other food or food ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (preventive, health or therapeutic treatment), and the composition of the present invention is environmentally friendly and has no problem in terms of stability.

The term "health functional food" in the present invention refers to a food prepared by processing a specific ingredient as a raw material for the purpose of health assisting or by extracting, concentrating, refining, mixing or the like a specific ingredient contained in a food raw material, Refers to foods that are designed and processed so that the body control function such as bio-defense, regulation of bodily rhythm, prevention and recovery of disease, etc. can sufficiently be exerted on the living body. The composition for health foods is used for prevention of diseases, Can perform related functions. The health functional food may include food-acceptable food supplementary additives, and may further include suitable carriers, excipients and diluents conventionally used in the production of health functional foods.

The health functional food of the present invention is a concept that can cover all kinds of foods as long as it can achieve the prevention or amelioration effect of insomnia including the extract of ganoderma. Foods that can be applied to the present invention include, for example, special nutritional foods such as crude oil, milk, and baby food, meat products, fish products, tofu, mushrooms, noodles such as ramen and noodles, Foods such as soy sauce, soybean paste, kochujang, mixed potatoes, sauces, confectionery such as snacks, dairy products such as fermented milk and cheese, other processed foods, kimchi, pickled foods (various kinds of kimchi, May include all foods such as beverages (e.g., fruit, vegetable beverages, beverages, fermented beverages, etc.), natural seasonings (e.g., ramen soup, etc.)

In addition, when the health functional food composition of the present invention is used in the form of a drink, it may contain various sweetening agents, flavoring agents, or natural carbohydrates as additional components such as ordinary beverages. In addition to the above, the health functional food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, , Alcohols, carbonating agents used in carbonated drinks, and the like. It may also contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks.

In addition, in the health functional food for the purpose of preventing or ameliorating insomnia, there is no limitation on the content of the active ingredient ganoderma extract, but the amount of the ganoderma extract may be 0.01 to 15% by weight of the total food, The beverage composition may be contained at a ratio of 0.02 to 5 g, preferably 0.3 to 1 g, based on 100 ml.

The composition comprising the extract of Angelica tenuissima according to the present invention has an efficacy to prevent, treat or ameliorate insomnia and does not cause side effects to the human body. Therefore, it is possible to prevent, treat or ameliorate various cognitive disorders and depressions including insomnia Or to a health functional food.

FIG. 1 is a graph showing the effect of guinea pig extract on sleep induction time in an animal model induced by pentobarbital.
FIG. 2 is a graph showing the effects on the sleeping time in pentobarbital-induced animal models after fasting extracts.

Hereinafter, the constitution and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited by these examples.

Example 1: Preparation of gooseberry extract

The extracts were prepared by hot water extraction method using a water - alcohol mixed solvent from the ginsengs purchased from Kyungdong market and dried. 200 g of dried ghobone was mixed with 1 L of 70% ethanol (1: 4 wt%) and then heated at 40 to 80 DEG C for 3 hours under heating. Thereafter, the extract was filtered to separate the filtrate, and the extract was concentrated under reduced pressure at 90 to 95 ° C, and then lyophilized to obtain 35.3 g of a gibbon extract powder.

Example 2: Measurement of sleep induction time and sleep time of pentobarbital-induced animal model

In order to confirm the effect of the extract of the present invention on insomnia, the sleep induction time and the sleeping time of the pentobarbital-induced animal model mouse were measured as an animal test for confirming the effect on insomnia in general.

Specifically, male C57BL / 6 mice with an average body weight of 20 g purchased from Orient were fasted for 24 hours, and pentobarbital (45 mg / kg) was intraperitoneally administered.

The water level was set as the point at which the cliff reflexes disappeared. The animals that did not take their sleep within 15 minutes were excluded from the test and the breaking time was defined as the time the animal returned to the cloak.

The oral administration of the extract of the extract of Example 1 showed the effect on sleep induction time and sleeping time in the pentobarbital-induced mice after the fasting (Table 1).

group Sleep induction time (seconds) Sleep time (seconds) Control D.D.W. 158.75 ± 28.0903 2843.75 ± 256.9641 Ganoderma extract ( Angelica tenuissima Nakai) 156.00 ± 14.4742 4406.75 ± 330.8588

As shown in Table 1, the sleep induction time of the mice administered with the extract of Pentobarbital after administration of pentobarbital to the mice for 24 hours was 156.00 ± 14.4742 seconds, and the induction time of the mice of distilled water was 158.75 It was confirmed that it decreased slightly compared to ± 28.0903 (sec) (FIG. 1).

In addition, it was confirmed that the sleeping time of the mouse administered with the extract of the present invention to the animal model was 4406.75 ± 30.8588 (sec), which was significantly increased compared to the sleeping time of 2843.75 ± 256.9641 (sec) in mice injected with distilled water 2).

These results show that the extract of Ganoderma lucidum has the effect of shortening the sleep induction time, especially the sleeping time.

These results indicate that the extract of Ganoderma lucidum can improve the sleeping time and prolong the sleeping time by the extract of Ganoderma lucidum against the sleeping induced by the fasting.

From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the above-described embodiments are to be considered in all respects as illustrative and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.

Claims (5)

A pharmaceutical composition for preventing or treating insomnia comprising, as an active ingredient, water of Angelica tenuissima, a C ₁ to C ₂ lower alcohol or a mixed solvent extract thereof.
delete The composition of claim 1, wherein the alcohol is ethanol.
2. The composition of claim 1, wherein the insomnia is primary insomnia.
A health functional food for preventing or ameliorating insomnia comprising, as an active ingredient, water of Angelica tenuissima, a lower alcohol of C ₁ to C ₂ or a mixed solvent extract thereof.

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