WO2014084460A1 - Composition comprising acanthopanax koreanum extract as active ingredient for preventing or treating neuropsychiatric disorders - Google Patents

Abstract

The present invention relates to a composition comprising an Acanthopanax koreanum extract as an active ingredient. More particularly, the present invention relates a pharmaceutical composition comprising the Acanthopanax koreanum extract for preventing or treating neuropsychiatric disorders, to a food composition comprising the Acanthopanax koreanum extract for preventing or alleviating neuropsychiatric disorders, to a method for preparing the composition, and to a pharmaceutical composition and food composition comprising the Acanthopanax koreanum extract for neuranagenesis.

Description

A composition for the prevention or treatment of neuropsychiatric diseases comprising the extract of sesame stem as an active ingredient

The present invention relates to a composition comprising an extract of Acanthopanax koreanum as an active ingredient, specifically, a pharmaceutical composition for the prevention or treatment of neuropsychiatric diseases including the extract of S. a. Food composition for the prevention or improvement of the method of preparing the composition; It relates to a pharmaceutical composition and a food composition for neuronal regeneration comprising an extract of the island stem.

Acanthopanax koreanum Nakai is an Eleutherococcus species and belongs to the family Araliaceae. It is a special species of Jeju that grows at 1400m above sea level of Jeju Island in Korea. It is also called Tamraukogi. The flowering period of the island is in May, and the ripening season begins in September. The islands have strong thorns and have a habit of stalks hanging on the ground, and growth is very vigorous. The roots have a distinctive fragrance and are divided into main root, root and root (Han KJ et al., Growth of seeding and germination characteristics of Acanthopanax koreanum Nakai.Korean J. Medicinal Crop Sci. 11, 46-52, 2003, Byung-Sun Lim And 2 others, Growth Characteristics and Botanical Vegetation Survey of Ogalpi Jiri and Island Ogalpi, Journal of the Plant Resources Society of Korea, 12, 125-132, 1999).

The main components of the roots, stems and leaves of the isogapi include glycosides, flavonoids, diterpenoids, and the like, and in particular, it is known that the root contains acanthoic acid (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 island ogapi is traditionally used as a therapeutic agent to lighten the body, mainly by using roots, and has been reported to be used for diseases such as obesity, rheumatism, diabetes and hepatitis (Yang, EJ et al. Acanthopanax koreanum fruit waste). inhibits 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 for mental illnesses such as depression and anxiety disorders has increased rapidly in recent years due to the exhausting and busy daily life and stress of modern life. Depression is a common disease, and in the United States, more than 18 million people suffer from depression every year, and the lifetime prevalence of depression in Korea is known to be about 15% of the population, but many patients in Korea are suffering from lack of awareness or social prejudice against mental illness. Hesitant to take antidepressants. Anxiety disorder is a psychological disorder mainly manifested by anxiety emotions, and has a lot of negative effects on daily life due to tension emotions that continuously show various symptoms such as autonomic nervous system disorders, muscle stiffness, and motor disorders. In the past, research and development of psychiatric diseases have been focused on GABA nervous system, serotonin nervous system, noradrenaline nervous system and neuropeptide system. Due to its side effects, there are many restrictions.

Against this backdrop, the present inventors have made diligent efforts to find natural products having a neurological regeneration effect while preventing and treating various mental disorders such as depression and anxiety disorder. It was confirmed that the anti-anxiety activity, and completed the present invention.

One object of the present invention to provide a pharmaceutical composition for the prevention or treatment of neuropsychiatric disorders, including Acanthopanax koreanum extract as an active ingredient.

It is another object of the present invention to provide a food composition for preventing or improving neuropsychiatric diseases, comprising an extract of Acanthopanax koreanum as an active ingredient.

Still another object of the present invention is to provide a method of treating neuropsychiatric disorders, comprising administering the pharmaceutical composition to an individual suspected of neuropsychiatric disorders.

Still another object of the present invention is to provide a method for preparing the composition.

Still another object of the present invention is to provide a pharmaceutical composition for nerve regeneration, comprising an extract of Acanthopanax koreanum as an active ingredient.

Still another object of the present invention is to provide a neurological regeneration food composition comprising an extract of Acanthopanax koreanum as an active ingredient.

Seogagapi extract of the present invention is derived from a natural product that has been used as a natural medicine for a long time without the side effects, but also a therapeutic effect against neuropsychiatric diseases such as depression, anxiety disorders; And because it has a nerve regeneration effect, the composition of the present invention comprising isogapi extract is used for the prevention or treatment of neuropsychiatric diseases; And neural regeneration.

1 is a flow chart illustrating a method for preparing sesame stem extract according to an embodiment of the present invention.

Figure 2 is a graph comparing the neuronal regeneration of the brain in the mice administered the extract of the island of the present invention compared with the control.

Figure 3 is a graph comparing the immobility time with the control group in the forced swimming test for the mice administered the isogapi extract of the present invention.

Figure 4 is a graph comparing the time spent in the open space in the raised cruciform with the control mice for the mice administered the isogapi extract of the present invention.

As one aspect for achieving the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of neuropsychiatric diseases, including Acanthopanax koreanum extract as an active ingredient.

In the present invention, the term " Acanthopanax koreanum " refers to a tree belonging to the family Araliaceae as an Eleutherococcus species, and the island canopy can be used interchangeably with tamra orgapi. Seogagapi is divided into leaves, stems, roots, and fruits, and the roots are divided into main roots, roots, and roots. The isogapi is known to enhance liver disease, anti-inflammatory and immunity, but the efficacy on neuropsychiatric diseases is not known, it was newly identified by the present inventors. The islands can be used in nature or purchased commercially available, but is not limited thereto.

As used herein, the term " acanthopanax koreanum extract" refers to an extract obtained by extracting isopipi. In the present invention, the island extract is preferably an extract obtained by extracting the root or / and stem of the island. The sesame stem extract may be prepared by extracting the sesame stem pulverized product using water, an alcohol having 1 to 6 carbon atoms, preferably an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof. Extracted by cold needle extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, ultra-high pressure extraction or heat extraction for 1 to 8 hours at 120 ℃, but extracts a substance having a therapeutic effect or neuroregeneration effect for neuropsychiatric diseases If the method is not particularly limited to the kind. Water after the extraction process may be prepared as an extract of the present invention through filtration, concentrated under reduced pressure and drying in sequence, without being particularly limited thereto, extracts, dilutions or concentrates of extracts, dried products obtained by drying the extracts, or All these modifiers or purified products are included. In addition, the sesame stem extract can be extracted from various organs of natural, hybrid, varieties of plants. In one embodiment of the present invention was extracted using 70% ethanol from the roots and stems of the island stem (Example 1).

Seogagapi extract of the present invention is characterized in that it comprises at least one component selected from the group consisting of eleutheroside B (eleutheroside B), eleutheroside E (eleutheroside E) and achanthoic acid.

As used herein, the term "eleutheroside B" refers to a phenyl propanoid glycoside, also named syringin, and has a structure represented by the following Chemical Formula 1.

Formula 1

As used herein, the term "eleutheroside E" refers to a glucoside compound named Acanthoside D and has a structure represented by the following Chemical Formula 2. The eleuteroside E is known to have hepatoprotective activity, detoxification effect and the like.

Formula 2

As used herein, the term "acanthoic acid" is known to have potent analgesic components, such as potent analgesic suppression, anti-inflammatory activity, and maintenance of the homeostasis of the immune system. Have

Formula 3

Since the isogapi extract of the present invention comprising the above eleuteroside B, eleuteroside E and acantosan has neuronal regeneration, anti-anxiety and antidepressant activity, in the prevention or treatment of various neuropsychiatric diseases It can be usefully used.

As used herein, the term "neuropsychiatric disorder" means a mental disorder that may be caused by the development of neurons, and the like. For the purposes of the present invention, the neuropsychiatric disorders include anxiety, depression or affective disorders that can be treated by the extract of sesame stem of the present invention. The anxiety disorder refers to a mental illness that causes disorders in daily life due to abnormal and pathological anxiety and fear, and the depression is a disorder in which motivation and depression are the main symptoms, causing various cognitive and mental and physical symptoms, thereby causing daily functions. Means a disease that brings down the. The affective disorder refers to a type of neuropsychiatric disorder whose main symptom is moody or depressed mood.

As used herein, the term "prevention" refers to any action that inhibits or delays the onset of neuropsychiatric disorders by the administration of the composition, and "treatment" means that symptoms caused by neuropsychiatric disorders are improved by administration of the composition. It means any action that is beneficially changed.

The pharmaceutical composition comprising the sesame stem extract of the present invention may further comprise a suitable carrier, excipient or diluent commonly used in the preparation of the pharmaceutical composition. At this time, the content of the extract or fractions thereof included in the composition is not particularly limited, but 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 is any one selected from the group consisting of tablets, pills, powders, granules, capsules, suspensions, liquid solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories. It can have one formulation and can be a variety of oral or parenteral formulations. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The composition of the present invention may be administered in a pharmaceutically effective amount.

As used herein, the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level is determined by the type and severity, age, sex, disease of the individual. It may be determined according to the type, activity of the drug, sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical field. The compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. And single or multiple administrations. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, 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 administered parenterally or orally in the range of 0.001 to 100 µg / kg, more preferably in the range of 0.01 to 100 µg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the present invention in any aspect. The composition may be administered to various mammals such as rats, livestock, humans, etc. by various routes, and the mode of administration may be any conventional method in the art. Without limitation, it may be administered by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections.

In one embodiment of the present invention was prepared from the root and stem of the sesame stem using 70% ethanol extract was confirmed that the sesame stem extract has a neuronal regeneration effect in the hippocampal region in the stress-induced brain (Fig. 2, Experimental Example 1). In addition, it was confirmed that the sesame stem extract of the present invention has antidepressant activity through the forced swimming method of the mouse, and thus the composition of the present invention can be usefully used for the treatment of depression, which is a kind of neuropsychiatric disease (FIG. 3, Experimental Example 2). In addition, it was confirmed that the sesame stem extract of the present invention increases the time to stay in the open space in the cross maze test, it is useful for the prevention and treatment of anxiety disorder (Fig. 4, Experimental Example 3).

In another aspect, the present invention provides a method of treating neuropsychiatric disorders comprising administering the composition to a subject suspected of neuropsychiatric disorders.

The 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 in a subject suspected of neuropsychiatric disease. The subject means an entire mammal including a dog, cow, horse, rabbit, mouse, rat, chicken or human, but the mammal of the present invention is not limited to the above examples. The pharmaceutical composition may be administered orally, subcutaneously, intraperitoneally, pulmonary and intranasally, and may be administered by a suitable method including topical administration if necessary for local treatment. Preferred dosages of the pharmaceutical compositions of the present invention vary depending on the condition and weight of the individual, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.

In another aspect, the present invention provides a food composition for the prevention or improvement of neuropsychiatric diseases, including Acanthopanax koreanum extract as an active ingredient.

The islands, extracts and neuropsychiatric diseases are as described above.

Specifically, the extract of the present invention may be added to the food composition for the purpose of preventing or ameliorating neuropsychiatric diseases.

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

In addition, there is no particular limitation on the type of food of the present invention. Examples of foods to which the island extract may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, drinks, tea, Drinks, alcoholic beverages and vitamin complexes, and the like, may include all foods in the conventional sense, and includes foods used as feed for animals.

In addition to the above, the food composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonic acid used in carbonated beverages. Others may contain pulp for the production of natural fruit juices, fruit juice drinks and vegetable drinks. In addition, the food may also be prepared in the form of tablets, granules, powders, capsules, liquid solutions and pills according to known production methods. There is no particular limitation on other components except that the sesame stem extract according to the present invention is included as an active ingredient, and various conventional flavoring agents or natural carbohydrates may be included as additional ingredients.

In another embodiment, the present invention is an extract of the island of the snails; And it provides a method for producing a composition comprising the same.

The island and the island extract is as described above.

Specifically, the preparation method is (a) 1 to 100 times (v / w) of the dry sesame stem sample weight, water of 1 to 6 carbon atoms or a mixed solvent thereof is added to 25 to 120 ℃ for 1 hour to Extracting for 8 hours; And (b) filtration, concentration under reduced pressure, and drying the water extracted in step (a).

The step (a) is the step of extracting from the islands using the extraction solvent, the islands of the pulverized pulpy extract using water, alcohol having 1 to 6 carbon atoms, preferably alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof Extraction step. The extraction is preferably extracted by cold needle extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, ultra-high pressure extraction or heat extraction for 1 to 8 hours at 25 ℃ to 120 ℃, the eleuteroside B of the present invention (eleutheroside B), eleutheroside E (eleutheroside E) and akanho (achanthoic acid) is a method for producing an extract containing an acid (achanthoic acid) is not particularly limited to those kinds.

Step (b) is a step of filtration, concentration under reduced pressure and drying the water extracted in step (a).

Isao gapi extract of the present invention through a manufacturing method comprising the above step; And it can be prepared a composition comprising the same.

In another aspect, the present invention provides a pharmaceutical composition for neuronal regeneration comprising an extract of Acanthopanax koreanum as an active ingredient.

The sesame stem, sesame stem extract and the pharmaceutical composition are as described above.

As used herein, the term "neurogenesis" refers to a process in which neurons are produced or regenerated from neural stem cells or progenitor cells. Such nerve regeneration is involved in a protein such as DCX (Doublecortin), the degree of nerve regeneration can be confirmed through the level of DCX (Doublecortin) expression. In addition, various neuropsychiatric diseases such as depression are known to reduce nerve regeneration in the hippocampus. Therefore, the extract of the island of the present invention which increases the expression level of DCX and brings nerve regeneration can be usefully used not only for nerve regeneration but also for the treatment of neuropsychiatric diseases.

In one embodiment of the present invention, when administering the composition containing the extract of the island of the present invention to a mouse having a reduced degree of nerve regeneration, it was confirmed that the DCX positive level is higher than the control group, the composition of the present invention for nerve regeneration It was confirmed that it can be used (Fig. 2, Experimental Example 1).

In another aspect, it provides a food composition for nerve regeneration comprising an extract of Acanthopanax koreanum as an active ingredient.

The sumo gapi, iso gapi extract, nerve regeneration and the food composition is as described above.

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

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

Example 1 Preparation of Seogagapi Extract

10 to 20-fold (v / w) of 70% ethanol aqueous solution was added to 20 kg of dried island stems and roots purchased from Jeju, and refluxed at 70 ° C. for 3 to 5 hours in an extractor. After the extraction was completed, filtered through a housing filter, concentrated under reduced pressure and lyophilized to obtain 1 kg of sesame stem extract, which was used as a sample of the following experimental example.

Example 2: Experimental Animal Preparation

Six-week-old ICR mice (23-25 g) were supplied from Orient Co., Ltd. (Seoulm Korea) and used in animal experiments with 10-12 animals per group. The experimental animals were used in a clean cage for about 5 days, and the water and feed were freely consumed. The temperature (23 ± 2 ℃), humidity (55 ± 10%) and contrast cycle (12 hours) It was adjusted automatically.

Experimental Example 1: Confirmation of neuronal regeneration by hippocampal immunostaining

Various stresses, depressions and anxiety disorders reduce the neuronal regeneration in the brain, so long-term administration of the extracts of the islands to stress-induced animals to determine the effect of the extracts on the promotion of neuronal regeneration in the hippocampus , The neuronal regeneration effect was confirmed by staining DCX (Doublecortin), a neurogenesis marker through immunostaining.

As a result of confirming the neuronal regeneration after long-term administration of isogapi extract to stress-induced animals, it was confirmed that the number of DCX positive cells increased at a dose of 100 mg / kg when compared to the control group as shown in FIG.

The results as described above is that the sessipapi extract of the present invention has a neuronal regeneration effect, and furthermore, because it brings a neuronal regeneration effect in the nerve damage induced by stress, depression and anxiety disorders can be treated for stress, depression and anxiety disorders. It is suggestive.

Experimental Example 2: Confirmation of antidepressant activity by forced swimming method

The forced swimming test is one of the animal test methods to check the exercise activity and depression of the animals. The EthoVision program fills a 30cm long transparent acrylic tube with about 25cm of water (about 24 ℃) and displays the animal's behavior for 6 minutes. Observation was carried out by using.

When the immobility time and the climbing time of the test animals were increased, the determination of life was weak, and as it decreased, the determination of life was very strong.

About 1 hour after orally administering the isogapi extract obtained in Example 1 to the animals, 10 animals were measured for each group in a room where noise was blocked.

As a result, as shown in Figure 3, it was confirmed that the dead time is reduced at all doses (25, 50, 100, and 200 mg / kg). The above results suggest that the administration of the sesame stem extract of the present invention has antidepressant activity.

Experimental Example 3: Confirmation of anti-anxiety activity by elevated cross maze test

Cruciform maze test is an experimental method to measure the degree of anxiety of an experimental animal by using an elevated plus-maze made of black acrylic. The mouse is gently lowered toward the open space from the center of the maze. Placed and then freely navigated through the maze. At this time, the behavior is observed for 5 minutes, and the time of staying in the open and closed spaces of the mouse, the number of entrances and the total moving distance of each space are measured by the EthoVision program (Noldus Information Technology, Wageningen, Netherlands). The effect was confirmed. After administering orally to the isogapi extract obtained in Example 1 was measured for 10 animals in each group in a room where the noise is blocked after about 1 hour.

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

From the above description, those skilled in the art will appreciate that the present invention can be implemented in other specific forms without changing the technical spirit or essential features. In this regard, the embodiments described above are to be understood in all respects as illustrative and not restrictive. The scope of the present invention should be construed that all changes or modifications derived from the meaning and scope of the following claims and equivalent concepts rather than the detailed description are included in the scope of the present invention.

Claims (11)

1. Acanthopanax koreanum ( Acanthopanax koreanum ) comprising an extract as an active ingredient, a pharmaceutical composition for the prevention or treatment of neuropsychiatric diseases.
2. The composition of claim 1, wherein the sesame stem extract is extracted from the roots, stems, or both of the sesame stem.
3. The composition of claim 1, wherein the island extract is extracted with water, alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof.
4. The composition of claim 1, wherein the isogapi extract comprises eleutheroside B, eleutheroside E, and acanthoic acid.
5. The composition of claim 1, wherein the neuropsychiatric disorder is anxiety, depression or affective disorder.
6. A canthopanax koreanum ( Acanthopanax koreanum ) comprising the extract as an active ingredient, a food composition for preventing or improving neuropsychiatric diseases.
7. (a) adding 1 to 100 times (v / w) of water, alcohol having 1 to 6 carbon atoms or a mixed solvent thereof, and extracting for 1 to 8 hours at 25 ° C to 120 ° C; And

   (b) filtration, concentration under reduced pressure and drying the water extracted in the step (a), the method for producing a composition of any one of claims 1 to 5.
8. Acanthopanax koreanum ( Acanthopanax koreanum ) comprising a extract as an active ingredient, a pharmaceutical composition for neuronal regeneration.
9. The composition of claim 8, wherein the composition increases expression of Doublecortin (DCX).
10. Acanthopanax koreanum extract containing the extract as an active ingredient, a neurological regeneration food composition.
11. A method for treating neuropsychiatric disorders comprising administering Acanthopanax koreanum extracts to a suspicious neuropsychiatric subject.

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