KR101410180B1 - Composition comprising the extract of Asarum heterotropoides Fr. mandshuricum for preventing and treating depression - Google Patents

Abstract

The present invention relates to a composition for the prevention and treatment of depression, which comprises an extract of Cecin as an active ingredient. More particularly, the cecin extract of the present invention is used for the fores swimming test and the tail suspension test ), It has been confirmed that depression is suppressed more strongly than the conventional antidepressant drugs, and thus it can be used in pharmaceutical compositions and health functional foods useful for prevention and treatment of depression.

Description

[0002] The present invention relates to a composition for preventing and treating depression, comprising as an active ingredient an extract of Sicin. manshuricum for preventing and treating depression}

The present invention relates to a composition for preventing and treating depression, which comprises acnes extract as an active ingredient.

[Literature 1] Cho YJ, et al., Journal of Korean medical Science ., 26 (2), pp279-83, 2011

[Document 2] Arborelius L, et al., The Journal of endocrinology . , 160 (1), pp 1-12, 1999.

[Document 3] Brady LS. et al., T he Journal of clinical investigation . 87 (3), pp 831-7, 1991

[Literature 4] Butterweck V. et al., Molecular psychiatry ., 6 (5), pp547-64, 2001

[Literature 5] Graeff FG. et al., Pharmacology , biochemistry , and behavior ., 54 (1), 129-41, 1996

[Literature 6] Garakani A. et al., Journal of affective disorders . 2012.

[Literature 7] Rovin ML et al., Neuropeptides . 46 (2), pp81-91, 2012

[Literature 8] Falowski SM. et al., Neurosurgery . 69 (6), pp1281-90, 2011

[Literature 9] Paxinos G. et al., Journal of neuroscience methods . 13 (2), pp139-43, 1985

Depression is a type of psychiatric disorder that is lost in despair and loses motivation and becomes obsessed with incompetence, isolation, impatience, guilt, and suicidal impulse. It is accompanied by somatic symptoms such as dyspepsia, headache, insomnia, constipation, diarrhea and loss of libido.

Depression is highly prevalent worldwide, is accompanied by a variety of dysfunctions, and because sociocultural factors have a significant impact on the manifestation of depression and the health-seeking pattern, it is necessary to establish measures, including optimal mental health policies, For this, precise and reliable epidemiological data is essential rather than anything.

In addition, Korea is experiencing many changes such as nuclear family, personalization, rapid economic growth, rapid aging, and suicide rate is already the number one place in OEDC countries in 2010, and the importance of depression is emphasized more than ever.

Until now, the mechanism of depression has not been clearly elucidated, and the lack of serotonin, norepinephrine, and dopamine, which are monoamine neurotransmitters in central nervous system synapses, is considered as the most likely hypothesis. Thus, most antidepressants have a pharmacological action that increases the concentration of the monoamine ganglioside substance in the central nervous system synapse.

Representative depressive therapies currently in use include benxodiazepine, diazepam, oxazepam, lorazepam, alprazolam, helazepam, clonazepam, and the like. These drugs are also used as sedatives and sleep inducers.

Corticotrophin-releasing factor (CRF) plays a major role in the stress response. CRF regulates anxiety and depressive disorders, chronic pain, fatigue, insomnia, acute or chronic neurodegeneration, and allergic reactions and metabolic syndrome (1). CRF is a peptide that modulates autonomic nervous system behavioral responses as well as neuroendocrine regulation of stress, and is known to be hyper-secreted from the hypothalamus due to the HPA axis and activity in depressed patients (2). These and other activities of CRF were normalized after the successful antidepressant treatment and the activity of the HPA axis was reversed (2). In depressed animal models with antidepressant medication, CRF mRNA expression was reduced in the hypothalamus (3), and CRF mRNA increased by chronic restraint stress decreased after long-term administration of imipramine (4). In acute or chronic stress, emotional changes such as anxiety, anxiety, and anger are induced, which are due to changes in the neurotransmitter serotonin 5-HT (5). And the increase of corticosterone (CORT) according to stress increases neurotransmission of 5-HT. Previous animal studies have reported a decrease in CORT and a decrease in serum and CSF 5-HT when treated with the antidepressant prozac, etc. (6). The cause of depression is the loss of neurotransmitters of dopamine and epinephrine besides serotonin Depression is reported to occur. Serotonin regulates the excess secretion of aggressive norepinephrine, addictive endorphins and dopamine (7). Those who lack serotonin for a long time seem to be easily aggressive or prone to emotional excitement. Tyrosine hydroxylase (TH) is a rate-limiting enzyme of dopamine and norepinephrine used to indirectly detect the expression of dopamine and norepinephrine (8).

Seshin refers to the rooted outpost of Asarum heterotropoides Fr. mandshuricum, Asarum sieboldi Miq, or Asarum maculatum, a perennial herbaceous plant belonging to Aristolochiaceae, It is known that it contains substances such as methyl eugenol, pinene, eucarvone, etc., and is known to have fever, analgesia and swallowing action (see Information, pp. 146-747, 1998).

None of the above documents, however, discloses or discloses the efficacy of cedar leaf extract as an antidepressant.

Accordingly, the present inventors have searched for a variety of natural products in order to develop a new antidepressant drug from natural products. As a result, the present inventors have found that the extract of Seesin extract is useful for in vivo screening of antidepressant drugs, It was confirmed that the immobility duration was significantly reduced in a concentration-dependent manner in a tail suspension test, thereby completing the present invention.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of depression, comprising cedar leaf extract as an active ingredient.

The present invention also provides a health functional food for preventing and ameliorating depression, comprising cedar leaf extract as an active ingredient.

As defined herein, the cedar includes the rooted outposts of Asarum heterotropoides Fr. mandshuricum, Asarum sieboldi Miq, or Asarum maculatum, but not the roots of Asarum heterotropoides Fr. mandshuricum. It is preferable to use outpost.

The extracts as defined herein may be formulated with a solvent selected from the group consisting of hexane, chloroform, methylene chloride, ethyl acetate, acetone, water, C ₁ to C ₄ lower alcohols or mixed solvents thereof, water or mixed solvents thereof, preferably hexane, Methylene chloride, ethyl acetate, or a mixed solvent thereof, more preferably, an extract which is soluble in hexane or chloroform.

Hereinafter, the cedma extract of the present invention can be obtained by an extraction method customary in the art. Hereinafter, the method for obtaining the above extract is described in detail.

(V / w), preferably about 5 to 20 times (v / w), of hexane, chloroform, methylene chloride, ethyl acetate, acetone, water, C ₁ to ₄ lower alcohols or a mixed solvent thereof, water or a mixed solvent thereof, preferably hexane, chloroform, methylene chloride, ethyl acetate or a mixed solvent thereof, more preferably hexane or chloroform, Extraction with hot water, extraction with hot water, extraction with ultrasound, reflux cooling, extraction with heating, preferably cold extraction or extraction, for example, at room temperature to 110 占 폚, preferably at room temperature for 1 hour to 5 hours, preferably for 1 hour to 3 hours After extraction with an ultrasonic extraction method, the filtrate is filtered, and the filtrate is concentrated under reduced pressure and dried to obtain the extract of the present invention.

Accordingly, the invention is about 1 to 100 times the dry slender sample weight (v / w) of hexane, chloroform, methylene chloride, ethyl acetate, acetone, water, C ₁ to a lower alcohol or a mixed solvent of the C _4, Water or a mixed solvent thereof, preferably hexane, chloroform, methylene chloride, ethyl acetate or a mixed solvent thereof, more preferably hexane or chloroform, at 10 to 110 ° C, preferably at room temperature for 1 hour to 5 A first step of extracting by a cold extraction, a hot water extraction, an ultrasonic extraction, a reflux cooling extraction, a heating extraction, or the like, preferably by a cold extraction or an ultrasonic extraction method for a period of time, preferably 1 hour to 3 hours; And a second step of filtering the filtrate and concentrating the filtrate under reduced pressure and drying the extract.

The present invention provides a pharmaceutical composition and a health functional food for the prevention and treatment of depression, which comprises the extract of Cedar japonica as an active ingredient. As a result of the in vivo screening method for foraging test and tail suspension test of the anti-depressant drug of the present invention, it was found that the extract was immobilized in a concentration- (Immobility duration) was significantly reduced. Thus, it was confirmed that the compounds were useful for the prevention and treatment of depression.

The pharmaceutical composition containing the extract of the present invention contains 0.1 to 50% by weight of the extract, based on the total weight of the composition.

However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.

Since the extract of the present invention has little toxicity and side effects, it can be safely used for long-term use for preventive purposes.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions, Examples of carriers, excipients and diluents that can be included in the composition containing the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. 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 at least one excipient such as starch, calcium carbonate, sucrose ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of liquid formulations for oral use include suspensions, solutions, emulsions, and syrups. Various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. may be included in addition to water and liquid paraffin which are simple diluents used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of suppository bases include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like.

The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, 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. However, for the desired effect, the extract of the present invention is preferably administered at 0.5 g / kg to 5 g / kg per day, preferably 1 g / kg to 3 g / kg per day. The administration may be carried out once a day or divided into several doses. Accordingly, the dosage is not limited in any way to the scope of the present invention.

The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

The present invention also provides a health functional food for preventing and ameliorating depression, comprising cedar leaf extract as an active ingredient.

Accordingly, the present invention also provides a food and a food additive containing the cedar leaf extract as an active ingredient having the effect of preventing and improving depression.

The composition containing the extract of the present invention can be used variously for medicines, foods and beverages for prevention and improvement of depression. Examples of the foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, health supplements and the like, and they can be used as powders, granules, tablets, capsules or beverages have.

The extract of the present invention can be added to food or beverage for the purpose of preventing and improving depression. At this time, the amount of the extract in the food or beverage is generally from 1 to 5% by weight of the total food weight of the health food composition of the present invention, and the health beverage composition is preferably 0.02 to 10 g based on 100 ml, Can be added at a ratio of 0.3 to 1 g.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient in ordinary beverages, in addition to containing the above extract as an essential ingredient in the indicated ratio. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose and sucrose and polysaccharides such as dextrin and sludge dextrin Conventional sugars and sugar alcohols such as xylitol, sorbitol, and erythritol. As a flavor other than the above, a natural flavoring agent (tau martin, which is advantageously used as a vial extract (for example, horseridin containing rebaudioside A) and a non-flavoring agent (saccharin, aspartame, etc.) The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 mL of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

As a result of confirming the antidepressant effect by the forced swimming test and the tail suspension test of the mice of the present invention, depression was suppressed more strongly than the existing antidepressant drugs. As a result, Can be used in pharmaceutical compositions and health functional foods useful for the prevention and treatment of harmless depression.

FIG. 1 is a graph showing the results of observing the expression of 5-HT in the dorsal raphe nucleus after a forced swimming test,
FIG. 2 is a graph showing the results of observing the expression of CRF in the paraventricular nucleus after the forced swimming test,
FIG. 3 is a graph comparing the immobility time in the forced swimming method with that in the control and the positive control groups for the mice administered with the cecin extract of the present invention,
FIG. 4 is a graph comparing the dwell time with the control group and the positive control group in the tail suspension test for mice administered with the cedma extract of the present invention.

Hereinafter, the present invention will be described in detail by reference examples, examples and experimental examples.

However, the following Reference Examples, Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Reference Examples, Examples and Experimental Examples.

Example  1. Seisin Hexane 100 Preparation of% extract

1.2kg of Seikin of Korean Traditional Oriental Medical Center was added twice with 5L of 100% hexane and extracted for 24 hours at room temperature. Then, the mixture was filtered through Whatman (No. 1) filter paper and 5L of 100% Filtered through a filter paper, and the filtrate was combined and concentrated under reduced pressure at 40 ° C to obtain 95 g of a concentrate (hereinafter referred to as 5-HT)

Reference example  1. Preparation of experimental animals

In this experiment, 5-week-old male ICR mice (SPF / VAF CrljBgi: CD-1) were supplied from Orient Co., Ltd. (Kyonggi-do, Korea). Experimental animals were divided into the control group and the experimental group in which the three new stimuli were inhaled after 7 days of adaptation in the animal room of Daegu Medical College. The animals were housed in a polycarbonate mice cage at a temperature of 23 ± 3 ° C and a humidity of 50 ± 10% and maintained at a constant 12-hour cycle. The animals were housed in a cage (polycarbonate mice cage) received.

Reference example  2. Statistical processing

All experimental results were statistically processed using a one way analysis of variance (ANOVA) , using the Student-Newman-Keuls Method P <significance test was carried out at the 0.05 level of significance or less when this is admitted.

Experimental Example  One. Immunohistochemistry  ( Immunohistochemistry )

In order to analyze the immunohistochemical changes of rats after completion of the behavioral test of the cecin extract of the above example, the following immunohistochemical method was used to carry out the experiment as follows.

The rats were anesthetized with sodium pentobarbital (80 mg / kg, ip) and perfused through 800 ml of 0.9% saline followed by 800 ml of 4% formalin solution in phosphate buffer. Fixed rats were taken out of the brain and fixed in the same fixative for 2 hours, and stored at 4 ° C in phosphate buffered saline (PBS) containing 20% sucrose. The brain was rapidly frozen the next day, and brain tissue was cut into a size of 30 um. (1: 200), rabbit monoclonal antibody, Abcam, Cambridge, USA), TH (1: 2000), rabbit monoclonal antibody, santacruz, CA, USA) or corticotrophin releasing The primary antibodies were diluted in 2% bovine serum (Sigma, St. Louis, Mo.) in 0.3% triton-X100 (PBST). Brain tissue was incubated in primary antiserum at 4 ° C for 72 hours. The brain tissue was then washed with PBST and incubated for 2 h at room temperature in biotinylated goat anti-rabbit serum (Vector Laboratories, Burlingame, Calif.) Diluted 200-fold in PBST containing 2% bovine serum. After washing with PBST, brain tissues were immersed in Elite standard vectastain avidin biotin complex (ABC) reagent (Vector Laboratories, Burlingame, CA) for 1 h at room temperature. After rinsing several times with PBST, brain tissue was developed using 3'-diaminobenzidine tetrahydrochloride (DAB, Sigma, St. Louis, MO) as a coloring agent. Colored tissue was placed on a slide glass and dried at room temperature. The tissue was transparent with xylene and sealed with polymount. The degree of color development of each part of brain tissue was observed with an optical microscope (OLYMPUS BX51) and photographed. The name of each part of the brain was referenced to Paxinos and Wastson (9). In the developed photograph, the degree of dyeing was counted by using a lattice (200 X 200 μm) in response to a certain region in the same region.

1-1. 5- HT Immunohistochemistry

The results of observing the expression of 5-HT in the dorsal raphe nucleus after the forced swimming test are shown in FIG. In the control group, the expression of 5-HT was decreased by about 50% in the dorsal raphe nucleus (F 3, 23 = 16.7, p <0.001). However, the expression of 5-HT was significantly increased in the 1 mg group of Seixin compared to the control group.

1-2. CRF Immunohistochemistry

The results of observing the expression of CRF in the paraventricular nucleus after forced swimming test are shown in FIG. 2 (F 3, 23 = 60.2, p <0.001). In the control group, the expression of CRF in the paraventricular nucleus was increased by about 300% compared to the normal group. However, the expression of CRF was significantly decreased in 0.5 mg and 1 mg of cesin compared to the control group.

1-3. TH Immunohistochemistry

The expression of TH in the locus coeruleus (LC) after the forced swimming test was as follows (F 3, 23 = 15.6, p <0.001). In the control group, the expression of TH in the LC was increased by about 50% as compared with the normal group. However, the expression of TH in sesquist 1 mg group was significantly lower than that of the control group.

Experimental Example  2. Identification of antidepressant activity by forced swimming

In order to measure the antidepressant activity of the sesessin extract by the forced swimming method, the following method was used using the standardized test method FST (RD Porsolt, et al., Behavioral despair in mice: a primary screening test for antidepressants, Arch Int Pharmacodyn Ther, 229, pp. 327-36, 1977).

As animal models for human disease research have limitations, FST has been controversial, but it is known to be the most basic method of detecting antidepressant effects in drug development. The experimental procedure of FST was performed according to the method of Porsolt et al.

The self-produced FST is used to measure the antidepressant effect after drug inhalation has ended.

In this experiment, a transparent acrylic cylindrical water tank with a height of 25 cm and a diameter of 11 cm was prepared. The water was forced to the water height of 25 ± 1 ° C so that the tail of the mouse could not touch the floor, And the immobility duration was measured using the EthoVision program. During the first two minutes of the experiment, the mouse shows a strong resistance to get out of it, but as time goes by, the time to show an increasingly floating posture increases, and the end tends to keep the body almost immobile. A typical immobile state is that a mouse floats on the surface of the water, leaving only a part of its face exposed above the surface of the water and showing only slight movement in order to maintain the balance of the body. The mouse with the FST was wiped off the body and returned to the breeding cage. The water temperature was always kept constant at 25 ± 1 ℃. Ssein was dissolved in alcohol at 0.25, 0.5, 1 and 2 g / kg dose, and was inhaled 3 hours before the start of the experiment. In the control group, only alcohol was inhaled. Each group consisted of 5-7 animals.

In order to confirm the antidepressant effect of the three stimulants, the immobility time was measured using FST.

As shown in FIG. 3, immobility time was 182.61 ± 7.78 seconds in the control group, and immobility time was 119.05 ± 16.75 seconds in the 0.5 g / kg inhaled group of cesin, which was significantly lower than that of the control group ( P < 0.05).

Experimental Example  3. Tail Suspension Experiment  Confirming antidepressant activity by

(Steru et al., The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85, pp.367 -370, 1985).

The antidepressant activity by TST was measured by Steru et al. Tailed mice showed alternating activity and immobility. Anti-depressant drugs decreased the time to show a dose-dependent immobility status, so they measured this time to confirm antidepressant activity. The self-produced TST is used to measure the antidepressant effect after drug withdrawal. In this experiment, the anti-depressive effect was measured by measuring the immobility duration for 10 minutes after attaching a tape 1 cm from the tail tip of the mouse to the edge of the table having a height of 50 cm. Ssein was dissolved in alcohol at 0.25, 0.5, 1 and 2 g / kg dose, and was inhaled 3 hours before the start of the experiment. In the control group, only alcohol was inhaled. Each group consisted of 5-7 animals.

TST was used to confirm the antidepressant effect of the three new stimulants.

As shown in FIG. 4, the immobility time of the control group was 218.55 ± 13.61 seconds, and the immobility time was decreased in the dose-dependent manner in the three-generation inhalation group. Especially, it was significantly decreased in the 2 g / kg dose group compared with the control group (144.21 ± 11.29 sec) ( P <0.05).

Experimental Example  4. Acute toxicity test

An acute toxicity test was conducted by orally administering the sesquicin extract (5-HT) obtained in the above Example using the mouse of Reference Example 1. As a result of the acute toxicity test, no case of death was observed at 2 g / kg of the extract of Seesin extract, and no significant abnormality was found in weight gain, feed intake and the like. Therefore, it was found that the extract of Seesin extract is a safe drug.

Hereinafter, formulation examples of the composition containing the acacia var. Umbraculifera extract 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

5-HT ------------------------------------ 20 mg

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

5-HT ------------------------------------ 10 mg

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

5-HT ------------------------------------ 10 mg

Crystalline cellulose ------------------------ 3 mg

Lactose ------------------------------ 14.8 mg

Magnesium stearate 0.2 mg &lt; RTI ID = 0.0 &gt;

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

5-HT ------------------------------------ 10 mg

Mannitol --------------------------------- 180 mg

Sterile sterile distilled water for injection -------------------- 2974 mg

Na ₂ HPO ₄ , 12H ₂ O ---------------------------- 26 mg

(2 ml) per 1 ampoule according to the usual injection preparation method.

Formulation example  5. Liquid  Produce

5-HT ------------------------------------ 20 mg

Isolation Party --------------------------------- 10 g

Mannitol ------------------------------------ 5 g

Purified water ------------------------------------

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, 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 ml with purified water, And sterilized to prepare a liquid preparation.

Formulation example  6. Manufacture of health food

5-HT - 1000 mg

Vitamin mixture ------------------------------

Vitamin A Acetate ----------------------- 70 ㎍

Vitamin E --------------------------------- 1.0 mg

Vitamin B1 ------------------------------- 0.13 mg

Vitamin B2 ------------------------------- 0.15 mg

Vitamin B6 -------------------------------- 0.5 mg

Vitamin B12 ------------------------------- 0.2 g

Vitamin C ---------------------------------- 10 mg

Biotin ------------------------------------ 10 μg

Nicotinic acid amide 1.7 mg

Folic acid -------------------------------------- 50 g

Calcium pantothenate ---------------------------- 0.5 mg

Inorganic mixture ------------------------------

Ferrous sulfate ------------------------------- 1.75 mg

Zinc oxide -------------------------------- 0.82 mg

Magnesium carbonate ---------------------------- 25.3 mg

Potassium phosphate monohydrate 15 mg

Secondary calcium phosphate ------------------------------- 55 mg

Potassium citrate -------------------------------- 90 mg

Calcium carbonate --------------------------------- 100 mg

Magnesium chloride ---------------------------- 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

Formulation example  7. Manufacture of health drinks

5-HT - 1000 mg

Citric acid -------------------------------- 1000 mg

Oligosaccharides -------------------------------- 100 g

Plum concentrate -------------------------------- 2 g

Taurine ------------------------------------ 1 g

Add purified water - 900 ml total

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, &Lt; / RTI &gt;

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 (8)

A pharmaceutical composition for the prevention and treatment of depression comprising, as an active ingredient, an extract of Asarum heterotropoides Fr. mandshuricum which is soluble in hexane or chloroform of a rooted outpost. delete delete delete Asperum heterotropoides Fr. mandshuricum, an effective ingredient for the prevention and improvement of depression containing an extract of the rooted outpox found in hexane or chloroform as an active ingredient. delete delete delete

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