KR101502667B1 - A composition for preventing or treating neuropsychiatric disorders, comprising extracts of Acanthopanax koreanum - Google Patents

Abstract

The present invention relates to a method for producing Acanthopanax koreanum extract as an active ingredient, and more particularly to a pharmaceutical composition for preventing or treating neuropsychiatric diseases including an extract of an extract from a plant, a food composition for preventing or ameliorating a neuropsychiatric disorder, , A method for producing the composition, and a pharmaceutical composition and a food composition for nerve regeneration, which comprise an extract of a scallop.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing or treating a neuropsychiatric disorder, which comprises an extract of Aspergillus oryzae as an active ingredient, and a composition for preventing or treating neuropsychiatric disorders, comprising extracts of Acanthopanax koreanum

The present invention relates to a method for producing Acanthopanax koreanum extract as an active ingredient, and more particularly to a pharmaceutical composition for preventing or treating neuropsychiatric diseases including an extract of an extract from a plant, a food composition for preventing or ameliorating a neuropsychiatric disorder, A process for preparing the composition; And to a pharmaceutical composition and a food composition for nerve regeneration, which comprise an extract of an islet extract.

Acanthopanax koreanum Nakai is an Eleutherococcus species belonging to the Araliaceae. It is a species of Jeju native that is native to Jeju Island below 1400m above sea level. It is also called Jeju Island mountain and Tamraukogi. The time of flowering of the island oak is May, and the time when the fruit ripens is from September. The islet has a habit that the thorns grow on the ground and the growth power is very strong. Root has a distinctive aroma and is divided into main, root and fine root (Han KJ et al., Growth of seeding and germination characteristics of Acanthopanax koreanum Nakai, J. Medicinal Crop Sci., 11, 46-52, (2) The growth characteristics and native vegetation of Jirisan (Ogallium) and Oleaceae (Ogalli) were investigated.

The major components of the root, stem and leaf of the islet are the glycosides, flavonoids and diterpenoids, and it is known that a large amount of acanthoic acid is contained in the roots (Lim, JH et al., Changes in major constituents by soaking of Acanthopanax koreanum with spirit solution, J. Korean Soc. Appl. Biol. Chem., 48, 166-172, 2005). The above-mentioned islet is used as a therapeutic agent to lighten the body traditionally using roots in Korea and has been reported to be used for the diseases such as obesity, rheumatism, diabetes and hepatitis (Yang, EJ et al., Acanthopanax koreanum fruit waste inhibited lipopolysaccharide-induced production of nitric oxide and prostaglandin E2 in RAW 264.7 macrophages. J. Biomed Biotechnol., 2010, 715-739, 2010).

The number of patients diagnosed and treated as psychiatric disorders such as depression and anxiety due to the exhausting, busy daily life and stress of modern life has increased rapidly in recent years and is expected to continue to increase in the future. Depression is a common disease. In the United States, more than 18 million people suffer from depression each year. In Korea, the lifetime prevalence of depression is estimated to be about 15% of the total population. However, many patients in Korea are suffering from lack of awareness or social prejudice They are reluctant to take antidepressants. Anxiety disorder is a psychiatric disorder mainly manifested by anxious emotions. It has various negative effects on daily life because of various emotions such as autonomic nervous system disorder, muscle stiffness, and movement disorder. In the meantime, the research and development of psychiatric drugs have focused on the GABA, serotonin, noradrenaline and neuropeptide systems, which have contributed to the improvement of anxiety disorder and depression , Its side effects, and so on.

Under these circumstances, the present inventors have made intensive efforts to find natural products having a nerve regeneration effect while preventing and treating various mental diseases such as depression and anxiety disorder. As a result, it has been found that, among the Ogaki plants, An anxiolytic activity, and completed the present invention.

One object of the present invention is to provide a method of treating acanthopanax The present invention also provides a pharmaceutical composition for preventing or treating a psychological disorder,

Another object of the present invention is to provide a method of treating acanthopanax koreanum ) extract as an active ingredient. The present invention also provides a food composition for preventing or ameliorating a neuropsychiatric disorder.

It is a further object of the present invention to provide a method for treating neuropsychiatric disorders, comprising administering the pharmaceutical composition to a suspected individual having neuropsychiatric disorders.

It is still another object of the present invention to provide a method for producing the composition.

Another object of the present invention is to provide a method for treating acanthopanax koreanum ) extract as an active ingredient. The present invention also provides a pharmaceutical composition for nerve regeneration.

Another object of the present invention is to provide a method for treating acanthopanax koreanum ) extract as an active ingredient.

As one embodiment for achieving the above object, the present invention relates to a method for producing acanthopanax koreanum ) extract as an active ingredient. The present invention also provides a pharmaceutical composition for preventing or treating neuropsychiatric disorders.

As used herein, the term "island Acanthopanax (Acanthopanax koreanum "means a tree belonging to Araliaceae, a species of Eleutherococcus, which can be used in combination with Tamara oregano, etc. The islet is divided into leaves, stem, root and fruit, In particular, the root is divided into a main muscle, a root muscle, and a fine muscle. Although the above-mentioned islet is known to enhance liver disease, anti-inflammatory and immunity, its efficacy in neuropsychiatric disorders is unknown and newly discovered by the present inventors The islet can be obtained from natural sources or commercially available, but is not limited thereto.

As used herein, the term "island Acanthopanax (Acanthopanax koreanum) extract "is island extracts Acanthopanax means and the resultant extract. The island Acanthopanax extract in the present invention preferably refers to an extract obtained by extracting the root and / or stem of the island Acanthopanax The island Acanthopanax extract Can be prepared by extracting the island oxide crushed material with water, an alcohol having 1 to 6 carbon atoms, preferably an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof, preferably 1 Extracting by hot water extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, ultra-high pressure extraction or heat extraction for 8 to 8 hours. However, if it is a method of extracting substances having therapeutic effect or nerve regeneration effect for neuropsychiatric diseases, The water that has undergone the above-mentioned extraction process is subjected to filtration, concentration under reduced pressure and drying step in order to obtain the extract But not limited to, extracts, diluted solutions or concentrates of the extracts, dried products obtained by drying the extracts, or their controlled products or refined products. , And can be extracted from various organs of variant plants. In one embodiment of the present invention, 70% ethanol was extracted from roots and stems of anthocyanins (Example 1).

The extract of the present invention is characterized by comprising at least one component selected from the group consisting of eleutheroside B, eleutheroside E and achanthoic acid.

In the present invention, the term " eleutheroside B "is phenylpropanoid glycoside, also referred to as syringin, having the structure of the following formula (1).

In the present invention, the term " eleutheroside E "is a glucoside compound named Acanthoside D and has a structure represented by the following formula (2). It is known that the ureteroside E has hepatic protection activity, detoxification action and the like.

The term "acanthoic acid" in the present invention is known as having a strong muscle contraction, anti-inflammatory activity and homeostasis of the immune system. I have.

Since the extract of the present invention comprising the above-mentioned Eleventoside B, Eleesteroside E and Accantoic acid has nerve regeneration, anxiolytic and antidepressant activity, it is useful for preventing or treating various neuropsychiatric disorders Can be usefully used.

In the present invention, the term "neuropsychiatric disorder" means a psychiatric disorder that may be caused by a decrease in development of nerve cells or the like. For the purposes of the present invention, the neuropsychiatric disorders include anxiety, depression or affective disorder that can be treated by the extract of the present invention. The anxiety disorder refers to a mental disorder causing disorder in daily life due to abnormal and pathological anxiety and fear. The depression is a major symptom of depression and desensitization. It causes various cognitive and psychosomatic symptoms, Of the disease. The affective disorder refers to a type of neuropsychiatric disorder in which the mood is too good or depressed as a main symptom.

As used herein, the term "prevention" means any action that inhibits or delays the onset of neuropsychiatric disorders by administration of the composition, and "treatment" It means all acts that benefitfully change.

The pharmaceutical composition comprising the extract of the present invention may further comprise an appropriate carrier, adduct or diluent conventionally used in the production of a pharmaceutical composition. At this time, the content of the extract or the fraction thereof in the composition is not particularly limited, but it may be 0.0001 to 99.99% by weight, preferably 0.001 to 50% by weight based on the total weight of the composition.

The pharmaceutical composition may be in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories May have one formulation, and may be various forms of oral or parenteral administration. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, 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 are also 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 include sterilized 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 composition of the present invention may be administered in a pharmaceutically effective amount.

The term "pharmaceutically effective amount" as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will vary depending on the species and severity, age, sex, The type of drug, the activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art. However, for the desired effect, the pharmaceutical composition of the present invention is preferably parenterally or orally administered at a daily dose of 0.001 to 100 μg / kg, more preferably 0.01 to 100 μg / kg. The administration can be carried out once a day or divided into several times. The dosage can be administered in various ways to various mammals such as rats, livestock, humans, and the like, and the administration method is a conventional method in the art Without limitation, and can be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine, or intracerebral injection.

In one embodiment of the present invention, a 70% ethanol extract was prepared from the roots and stems of the plant, and it was confirmed that the extract of the extract had a neurogenic effect on the stress-induced hippocampal region 2, Experimental Example 1). It was also confirmed that the extract of the present invention has anti-depressant activity through the mouse forced swimming method, and thus it was confirmed that the composition of the present invention can be effectively used for the treatment of depression, which is a kind of neuropsychiatric disorder (Fig. 3, Experimental Example 2). In addition, it was confirmed that the extract of the present invention increases the staying time in the open space in the crossmaze test, and thus it is found to be useful for the prevention and treatment of anxiety disorder (FIG. 4, Experiment 3).

In another aspect, the invention provides a method of treating a neuropsychiatric disorder, comprising the step of administering the composition to a subject suspected of having a neuropsychiatric disorder.

The above composition and neuropsychiatric diseases are as described above.

Specifically, the method of treatment of the present invention comprises administering the pharmaceutical composition in a pharmaceutically effective amount into a subject suspected of having neuropsychiatric disorders. The term refers to whole mammals including dogs, cows, horses, rabbits, mice, rats, chickens or humans, but the mammal of the present invention is not limited by these examples. The pharmaceutical compositions may be administered by non-oral, subcutaneous, intraperitoneal, intrapulmonary, and intranasal routes and may be administered by a suitable method, including localized administration, if necessary, for localized treatment. The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and body weight of the individual, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art.

In another aspect, the present invention provides a method of treating acanthopanax koreanum ) extract as an active ingredient.

The above-mentioned islets, extracts and neuropsychiatric diseases are as described above.

Specifically, the extract of the present invention can be added to a food composition for the purpose of preventing or improving neuropsychiatric disorders.

When the extract of the present invention is used as a food additive, the extract or the fraction thereof may be added as it is or may be used together with other foods or ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use.

There is no particular limitation on the kind of the food of the present invention. Examples of the food to which the extract is added include meat products, sausages, breads, chocolates, candies, snacks, confectionery, pizza, ramen noodles, other noodles, gums, dairy products including ice cream, Alcoholic beverages, and vitamin complexes, and may include foods in a conventional sense, and foods used as feeds for animals.

In addition to the above, the food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, , A carbonating agent used in a carbonated drink, and the like. It may also contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. The food may also be prepared in the form of tablets, granules, powders, capsules, solutions in liquid form, and the like according to known production methods. There are no particular restrictions on the other ingredients other than those containing the extract of the extract according to the present invention as an active ingredient, and various usual flavors or natural carbohydrates can be added as an additional ingredient.

In another embodiment, the present invention relates to the above-mentioned islet extract; And a method for producing a composition comprising the same.

The above-mentioned islet and scutellum extracts are as described above.

Specifically, the preparation method comprises the steps of: (a) adding 1 to 100 times (v / w) water, an alcohol having 1 to 6 carbon atoms or a mixed solvent thereof to the weight of dried island excipient sample at 25 ° C to 120 ° C for 1 hour to 8 hours; And (b) filtering the water extracted in the step (a), concentrating under reduced pressure, and drying.

The step (a) is a step of extracting the island oak crushed material with water, an alcohol having 1 to 6 carbon atoms, preferably an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof using an extraction solvent . The extraction can be preferably performed by cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, ultra-high pressure extraction or heat extraction at 25 ° C to 120 ° C for 1 hour to 8 hours, the present invention is not particularly limited to a method for producing an extract containing eleutheroside B, eleutheroside E and achanthoic acid.

In the step (b), the water extracted in the step (a) is filtered, concentrated under reduced pressure, and dried.

The extract of anthocyanin of the present invention through the process comprising the above step; And a composition containing the same.

In another aspect, the present invention provides a method of treating acanthopanax koreanum ) extract as an active ingredient.

The above-mentioned islet skin, islet extract and pharmaceutical composition are as described above.

The term "neurogenesis" in the present invention means a process in which neurons are generated or regenerated from neural stem cells or progenitor cells. Such nerve regeneration involves proteins such as DCX (Doublecortin), and the degree of nerve regeneration can be confirmed by the expression level of DCX (Doublecortin). In addition, various neuropsychiatric disorders such as depression are known to reduce hippocampal nerve regeneration. Therefore, the extract of the present invention, which enhances the expression level of DCX and brings about nerve regeneration, can be useful not only for nerve regeneration but also for treatment of neuropsychiatric disorders.

In one embodiment of the present invention, when the composition containing the extract of the present invention was administered to a mouse having a reduced degree of nerve regeneration, it was confirmed that the DCX positive level was higher than that of the control group, (FIG. 2, Experimental Example 1).

In another embodiment, Acanthopanax koreanum ) extract as an active ingredient.

The above-mentioned islet oil, islet extract, nerve regeneration and food composition are as described above.

Since the extract of the present invention has nerve regeneration activity, it can be usefully used as a food composition for nerve regeneration.

The extract of the present invention is derived from a natural product which has been used for a long time as a natural medicinal product and has no side effects and has therapeutic effect on neuropsychiatric disorders such as depression and anxiety disorder; And a nerve regeneration effect, the composition of the present invention comprising the extract of the extract of the present invention can be used for preventing or treating neuropsychiatric disorders; And in fields requiring nerve regeneration.

FIG. 1 is a flowchart showing a method for producing an extract of an islet extract according to an embodiment of the present invention.
FIG. 2 is a graph comparing neural regeneration of the brain of mice treated with the extract of the present invention to the control group.
FIG. 3 is a graph comparing the dwell time with the control group in the forced swimming test for mice administered with the extract of the present invention.
FIG. 4 is a graph comparing the time spent in the open space of the elevated crucifer for the mice administered with the extract of the present invention compared to the control group.

Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are illustrative of the present invention, and the content of the present invention is not limited by the following examples.

Example  One: Ishigaki  Extract preparation

10 to 20 times (v / w) of 70% aqueous ethanol solution was added to 20 kg of dried island stem and root purchased from Jeju, and the mixture was reflux-extracted at 70 캜 for 3 to 5 hours in an extracting apparatus. After the extraction was completed, the mixture was filtered through a housing filter, concentrated under reduced pressure and lyophilized to obtain 1 kg of an extract of the extract.

Example  2: Preparation of experimental animals

Six-week-old ICR mice (23-25 g) were supplied from Seoulm Korea and used in animal experiments with 10 to 12 mice per group. The animals were allowed to freely consume water and feed, and the temperature (23 ± 2 ° C), humidity (55 ± 10%) and darkness (12 hours) .

Experimental Example  1: Confirmation of neurogenesis by immunohistochemistry in the hippocampal region of the brain

Since various stress, depression, and anxiety disorders reduce neuronal regeneration of the brain, in order to examine the effect of the extract of the extract on the promotion of neuronal regeneration in the hippocampal region of the brain, long-term administration of the extract to the stress- , And the neurogenesis effect was confirmed by staining DCX (Doublecortin), which is a neurogenesis marker, through immunohistochemistry.

As shown in FIG. 2, the number of DCX positive cells was increased at a dose of 100 mg / kg as compared with the control group, as shown in FIG.

The above results indicate that the extract of the present invention has a nerve regeneration effect and furthermore, it can treat stress, depression and anxiety disorder because it has a nerve regeneration effect in nerve damage induced by stress, depression and anxiety disorder It is suggestive.

Experimental Example  2: Confirming antidepressant activity by forced swimming

The forced swimming experiment was an animal experiment to examine the degree of motor activity and depression of experimental animals. Water was injected into a transparent acrylic tube of about 30 cm in length and about 25 cm in water (about 24 ℃) Were used.

When the immobility time and climbing time of the experimental animals were increased, it was judged that the will to life was weak.

The extract obtained from Example 1 was orally administered to the animals. After about 1 hour, 10 mice per group were measured in a room where noises were blocked.

As a result, as shown in Fig. 3, it was confirmed that the floating time decreased in all capacities (25, 50, 100, and 200 mg / kg). The above results suggest that the administration of the extract of the present invention has antidepressant activity.

Experimental Example  3: Elevated  By cross-lab test Anxiety  Verify Active

The cross-lab test is an experimental method to measure the degree of anxiety of an animal using an elevated plus-maze made of black acrylic. The mouse is gently lowered toward the open space at the center of the labyrinth And then performed a free search of the maze. At this time, the behavior was observed for 5 minutes and the time spent in the open space of the mouse and the closed space, the number of times of access to the space, and the total travel distance were measured by the EthoVision program (Noldus Information Technology, Wageningen, The effect was confirmed. The extract of the extract obtained in Example 1 was orally administered to the animals, and after about 1 hour, 10 dogs per group were measured in a room where the noise was blocked.

As a result, it was confirmed that the retention time in the open space was significantly increased at the concentration of 100 and 200 mg / kg as compared with the stress group. These results suggest that the extract of the present invention can significantly improve anxiety due to stress.

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 (10)

A pharmaceutical composition for accelerating nerve regeneration in the hippocampal region, comprising an extract of Acanthopanax koreanum as an active ingredient.
The composition of claim 1, wherein said extract is extracted from the roots, stems, or both of said extracts.
3. The composition according to claim 1, wherein the extract is extracted with water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.
The composition of claim 1, wherein the extract is an extract of eleutheroside B, eleutheroside E and acanthoic acid.
delete A food composition for accelerating nerve regeneration in the hippocampus, comprising an extract of Acanthopanax koreanum as an active ingredient.
(a) extracting from 1 to 100 times (v / w) water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof at 25 to 120 DEG C for 1 to 8 hours by weight of the dry sample; And
(b) a step of filtrating, concentrating under reduced pressure, and drying the water extracted in the step (a).
delete 2. The composition of claim 1, wherein the composition increases expression of DCX (Doublecortin). delete

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