KR20110075496A - Composition comprising the extract of prunella vulgaris l for preventing and treating schizophrenia and amnesia - Google Patents

Abstract

PURPOSE: A composition containing Prunella vulgaris L extract for preventing and treating paleophrenia and amnesia is provided to suppress prepulse in a model animal with paleophrenia and to improve learning and space perception. CONSTITUTION: A pharmaceutical composition for preventing and treating metal diseases and amnesia contains Prunella vulgaris L extract as an active ingredient. The extract is isolated from flowers, roots, and whole plant of Prunella vulgaris L using water including purified water, low alcohol of C1-C4, or mixture solvent. A health food for preventing and treating metal diseases and amnesia contains Prunella vulgaris L extract as an active ingredient. The food is various foods, beverage, gum, tea, or vitamin complex.

Description

Composition comprising the extract of Prunella vulgaris L for preventing and treating schizophrenia and amnesia}

The present invention relates to a composition for the prevention and treatment of psychotic disorders and forgetfulness containing the extract of Hagocho as an active ingredient.

Kay et al., 1987 Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 13 (1987) pp. 261-276.

Lieberman et al., 2005. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 353 (2005) pp. 1209-1223.

Molteni et al., 2009. Molteni R, Calabrese F, Racagni G, Fumagalli F, Riva MA. Antipsychotic drug actions on gene modulation and signaling mechanisms. Pharmacol Ther. 124 (2009) pp. 74-85.

[4] Howes and Kapur, 2009. Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version III--the final common pathway. Schizophr Bull. 35 (2009) pp. 549-562.

[5] Terry and Buccafusco, 2003. Terry AV Jr, Buccafusco JJ. The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 306 (2003) pp. 821-827.

6, Kar et al., 2004. Kar S, Slowikowski SP, Westaway D, Mount HT. Interactions between beta-amyloid and central cholinergic neurons: implications for Alzheimer's disease. J Psychiatry Neurosci. 29 (2004) pp. 427-441.

Akhondzadeh et al., 2008. Akhondzadeh S, Gerami M, Noroozian M, Karamghadiri N, Ghoreishi A, Abbasi SH, Rezazadeh SA. A 12-week, double-blind, placebo-controlled trial of donepezil adjunctive treatment to risperidone in chronic and stable schizophrenia. Neuropsychopharmacol Biol Psychiatry. 32 (2008) pp. 1810-1815.

Cummings et al., 2008. Cummings, J.L., Mackell, J., Kaufer, D. Behavioral effects of current Alzheimer's disease treatments: a descriptive review. Alzheimers Dement. 4 (2008) pp. 49-60.

Voss et al., 2008. Voss B, Thienel R, Leucht S, Kircher T. Therapy of cognitive deficits in schizophrenia with acetylcholinesterase inhibitors. A systematic overview. Nervenarzt. 79 (2008) pp. 47-8, 50-2, 54-9.

Psotovet al., 2003 Psotov J, KolM, Sousek J, Svagera Z, Vicar J, Ulrichov J. Biological activities of Prunella vulgaris extract. Phytother Res. 17 (2003) pp. 1082-1087.

Ryu et al., 2000. Ryu, SY, Oak, MH, Yoon, SK, Cho, DI, Yoo, GS, Kim, TS, and Kim, KM. Anti-allergic and anti-inflammatory triterpenes from the herb of Prunella vulgaris . PlantaMed. 66 (2000) 358-360.

12. Kim et al., 2006. Kim, DH, Hung, TM, Bae, KH, Jung, JW, Lee, S., Yoon, BH, Cheong, JH, Ko, KH, Ryu, JH. improves scopolamine-induced memory impairment in mice. Eur. J. Pharmacol. 7 (2006) pp. 129-135.

13 Ong et al., 2005. Ong JC, Brody SA, Large CH, Geyer MA. An investigation of the efficacy of mood stabilizers in rodent models of prepulse inhibition. J Pharmacol Exp Ther. 315 (2005) pp. 1163-71.

Noda et al., 2001. Noda, A., Noda, Y., Kamei, H., Ichihara, K., Mamiya, T., Nagai, T., Sugiura, S., Furukawa, H. , Nabeshima, T. Phencyclidine impairs latent learning in mice: interaction between glutamatergic systems and signa1 receptors. Neuropsychopharmacology 24 (2001) 451-460.

15 Barr et al., 2006. Barr, A.M., Powell, S.B., Markou, A., Geyer, M.A. Iloperidone reduces sensorimotor gating deficits in pharmacological models, but not a developmental model, of disrupted prepulse inhibition in rats. Neuropharmacology 51 (2006) 457-65.

Schizophrenia is a psychiatric disorder that affects less than 1% of the general population, and is a wide range of endogenous disorders that involves changes in the thinking, perception, and behavior of people with illness. Symptoms of schizophrenia are classified as negative symptoms characterized by lack of spontaneous behavior, severe maladjustment, monotonous feelings, lack of interpersonal relationships and abnormal thoughts, and positive and cognitive disorders such as psychomotor excitement, delusions, hallucinations and hallucinations. . The cause of schizophrenia is related to the imbalance of dopamine, a neurotransmitter in the brain, and damage to the frontal lobe, and is known to be the result of genetic causes, prenatal environmental, social causes, or drug abuse. The treatment of schizophrenia is based on neurostables, apart from psychological therapy, and conventional antipsychotics have focused on treating positive symptoms such as hallucinations, delusions and confusion. These drugs are known to be useful as dopamine antagonists, and most of them are indispensable for long-term administration over a year. Specifically, haloperidol, chlorpromazine and fluphenazine are used. It is used. However, these drugs not only have many side effects such as dyskinesia, involuntary muscle spasms, slowing emotions, fatigue, lack of driving force and weight gain, but also have limitations in that they cannot treat negative symptoms and cognitive impairment. Recent atypical antipsychotics target the cerebral limbic system to block dopamine D2 receptors, which have fewer side effects and treat both positive and negative symptoms compared to conventional antipsychotics. Examples of such atypical antipsychotics include clopazine, risperidone, asenapine, olanzapine and iloperidone (Kay et al., 1987; Lieberman). et al., 2005; Molteni et al., 2009; Howes and Kapur, 2009).

The causes of dementia, characterized by learning and memory impairments, are largely divided into Alzheimer's dementia and vascular dementia. Alzheimer's dementia, first discovered in 1906 by a German doctor named Alois Alzheimer's, is a form of dementia commonly observed in the West, characterized by extensive accumulation of beta amyloid in certain areas of the brain, especially in the destruction of cholinergic neurons. It is a disease that appears. Vascular dementia is a dementia that occurs due to various diseases such as heart disease, arteriosclerosis, hypertension, stroke, and hyperlipidemia due to abnormal blood vessels going to the brain, resulting in the death of nerves such as the hippocampus and the limbic system. There is less research. Although these two types of dementia have different causes, they have the same mechanism in that they cause damage to memory by reducing the action of the neurotransmitter cholinergic nervous system. In patients with dementia, the concentration of the neurotransmitter acetylcholine is lowered, and acetylcholinesterase inhibitors have been reported to improve the acetylcholine levels in the brain to improve symptoms of dementia patients. There are four drugs that are developed and used as a treatment for dementia by FDA approval, including tacrine, donepezil, galanthamine, and rivastigmine, all of which are acetylcholinesterase inhibitors. On the other hand, there have been reports that donepezil and galanthamine improve cognitive impairment in schizophrenia, but the effect is not clear (Terry and Buccafusco, 2003; Kar et al., 2004; Akhondzadeh et al., 2008; Cummings et al., 2008; Voss et al., 2008).

Prunella vulgaris L. is a perennial herbaceous plant ( Prunella ) belonging to Lamiaceae. vulgaris var. lilacina) and P. vulgaris L. It has long been used as a folk medicine in oriental medicine circles in China, Japan, Korea, and Europe, in the East, for cirrhosis and hypertension, and in Europe since 17th century, it has been used to reduce throat inflammation, fever and promote wound healing ( Psotovet al., 2003). Recent studies on physiological activity of hachoricho have reported the effects of anti-allergic, anti-inflammatory (Ryu et al, 2000), antioxidant, antimicrobial, antiviral (Psotov et al., 2003).

However, there is no suggestion or disclosure at all regarding the treatment and improvement of schizophrenia and forgetfulness, etc.

Accordingly, the present inventors searched hundreds of natural products to develop new schizophrenia and forgetfulness medicines from natural products, and the vinegar extract was induced into apomorphine through in vivo experiments with animals. In the schizophrenic animal model, prepulse is suppressed, and scopolamine-induced memory deprivation animals have been found to improve learning and spatial perception ability than conventional drugs to complete the present invention. It became.

In order to carry out the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of psychotic disorders and forgetfulness, which contains the hagocho extract as an active ingredient.

In addition, the present invention provides a health functional food for the prevention and improvement of psychotic disorders and forgetfulness containing the edible extract as an active ingredient.

The hagocho as defined herein includes flower water, flowers, roots and starches, but it is preferred to use a flower water part.

The extract as defined herein includes water, including purified water, C ₁ to C ₄ lower alcohols or mixed solvents thereof, preferably water, ethanol or a mixed solvent thereof, more preferably water or a water and ethanol mixed solvent, Even more preferably water or extracts soluble in 60-95% ethanol.

As defined herein, “psychiatric disorders” include more specifically schizophrenia, schizophrenic disorders, schizophrenia disorders, delusional disorders, short term psychotic disorders, shared psychotic disorders, social isolation, preferably schizophrenia.

Hereinafter, the extract of the present invention can be obtained by a conventional extraction method in the art, the following describes the method of obtaining the extract in detail.

For example, about 1 to 100 times (v / w), preferably about 5 to 20 times (v / w) water, C ₁ to C ₄ lower alcohols, or mixed solvents thereof, of the dry vinegar sample weight. , Preferably water, ethanol or mixed solvents thereof, more preferably water and ethanol mixed solvents, even more preferably 60 to 95% ethanol, and then 30 to 110 ° C, preferably 50 to 100 ° C for 1 hour. Extraction method such as cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, heating extraction for 5 hours, preferably 1 hour to 3 hours, preferably extracted by ultrasonic extraction or reflux cooling extraction, and then the filtrate Filtration, concentration under reduced pressure and drying can yield the extract of the present invention.

Accordingly, the present invention is added for 1 to 5 hours at 30 to 110 ℃ by adding about 1 to 100 times (v / w) of water, C ₁ to C ₄ lower alcohol, or a mixed solvent thereof, of the dry vinegar sample weight, A first step of extracting by cold sediment extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, or heat extraction; It provides a method for producing a vinegar extract comprising a second step of filtering the filtrate, and concentrated under reduced pressure and dried.

The present invention provides a pharmaceutical composition and health functional food for the prevention and treatment of psychotic disorders and forgetfulness, which contain the extract of Hagocho as obtained as an active ingredient.

The present invention has the effect of restoring the dysregulation of prepulse inhibition in the schizophrenic animal model induced by agar morphophore (apomorphine), and the animal which induced the dysregulation of prestimulation inhibition by social isolation Experimental results showed excellent recovery effect, memory loss induced by scopolamine, improved the learning and spatial perception ability of animals to a high level, and confirmed the excellent effect of improving the learning ability in normal animals. At the same time, it was confirmed that it has an excellent activity in the treatment of forgetfulness and the treatment of dementia, so it is useful for the treatment of psychotic disorders, Alzheimer's dementia and the forgetfulness.

The pharmaceutical composition containing the extract of the present invention comprises 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.

The extract itself of the present invention is a drug that can be used with confidence even when taken for a long time for the purpose of prevention because there is little toxicity and side effects.

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

The compositions of the present invention can be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups, and may include various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. As the non-aqueous solvent and suspending agent, 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 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, 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 can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

Accordingly, the present invention also provides a food and food additive containing the above edible extract as an active ingredient having an effect of preventing and improving psychotic disorders and forgetfulness.

The composition comprising the extract of the present invention can be used in various ways, such as drugs, foods and drinks for the prevention and improvement of psychotic disorders and forgetfulness. Foods to which the extract of the present invention may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and may be used in the form of powders, granules, tablets, capsules, or beverages. have.

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

In addition to containing the extract as an essential ingredient in the indicated proportions, the health beverage composition of the present invention is not particularly limited in the liquid component and may contain various flavors or natural carbohydrates as additional ingredients in ordinary beverages. Examples of the above-mentioned natural carbohydrates are monosaccharides such as disaccharides such as glucose and fructose, for example polysaccharides such as maltose and sucrose, and conventional sugars such as dextrin, cyclodextrin and the like. And sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 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 beverages. These components can 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.

Hachocho extract of the present invention was confirmed that the improvement of learning and spatial perception ability of scopolamine-induced amnesia animal group is superior to tacrine and also effective effect in schizophrenic group induced by apomorphine It has been shown to be effective in animal models induced by social isolation, and can be used in pharmaceutical compositions and health foods useful for the prevention and treatment of psychotic disorders and forgetfulness.

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  One. Hagocho  Preparation of Extract

1-1. Hagocho  Preparation of 70% Ethanol Extract

The dried vinegar was purchased at Gyeongdong Market (Seoul, Korea) and separated only from Hwasu, which was then powdered using a home mixer. 10% (v / v) of 70% ethanol was added to the powder, and extracted twice at 60 ° C. with an ultrasonic extractor (POWERSONIC 420, Hwasin Tech) for 2 hours. The extract was filtered through cotton wool, concentrated under reduced pressure with a vacuum condenser (N-1000, EYELA), lyophilized with a lyophilizer (FDU-2000, EYELA) to obtain a powder. The freeze-dried powder was stored in a -70 ° C. freezer and used by dissolving in distilled water during the experiment. (Hereinafter referred to as “PV70E”, yield: 70% ethanol-16.85%).

1-2. Hagocho  Preparation of Water Extract

At the Gyeongdong market (Seoul, Korea), dried dried vinegar was purchased and separated only from Hwasu, which was cut to a suitable size. 10 times the amount of distilled water was added at the same time, and the mixture was extracted under reflux at about 100 ° C. for 2 hours in a warmer (MS-E104, TOPS). The extract obtained above was filtered under reduced pressure with a vacuum condenser (N-1000, EYELA), and then lyophilized with a freeze dryer (FDU-2000, EYELA) to obtain a powder. The freeze-dried powder was stored in a -70 ° C. freezer and used by dissolving in distilled water during the experiment. (Hereinafter referred to as “PVW”, yield: distilled water-22.03%).

1-3. Hagocho  Extract Solvent fraction  Produce

Take 70% ethanol ultrasonic extract of edible fruit, dissolve in 1000 mL, add 1 L each of hexane, chloroform, and BuOH, and then perform solvent fractionation.The obtained fractions were obtained (yield: hexane fraction (PVH)-8.29%, ethyl acetate fraction ( PVE)-25.03%, butanol fraction (PVB)-15.53%, water fraction (PVFW)-51.15%) were obtained, and each of the obtained fractions was filtered under reduced pressure with a vacuum condenser (N-1000, EYELA), and then freeze-dried (FDU). -2000, EYELA) to freeze-dried to obtain a powder. The freeze-dried powder was stored in a -70 ° C. freezer and used by dissolving in distilled water during the experiment. In addition, the separation of each fraction was confirmed well using TLC.

Reference Example  1. Drugs and reagents

Scopolamine (S2500), tacrine (A3773), and apomorphine (A4393) were purchased from Sigma-Aldrich Chemistry Co., and the reagents were commercially available. .

Reference Example  2. Preparation of experimental animals

Six-week-old ICR mice (26-28 g) were supplied from Orient Co., Ltd. (Seoul, Korea) and used for 5 days in a clean cage at Kyung Hee University College of Pharmacy. Temperature (23 ± 2 ° C.), humidity (55 ± 10%) and contrast period (12 hours) were automatically adjusted.

Reference Example  3. Preparation of Socially Isolated Animal Models

Three-week-old ICR mice were supplied by Orient Co., Ltd., and were bred one per clean cage in the animal room of the College of Pharmacy, Kyung Hee University. The mice were subjected to more than 10 weeks of social isolation. The test was carried out.

Reference Example  4. Statistical Processing

All experimental results were statistically analyzed using ANOVA (one way analysis of variance), and the significance test was performed at P <0.05 level using Student-Newman-Keuls Test when significance was recognized.

Experimental Example  1. Observation of memory change by manual evasion experiment

In order to confirm the memory through the manual avoidance test for the scopolamine-induced forgetfulness animal model of the extracts of the present invention obtained in the above example was tested as follows (Kim et al., 2006).

1-1. Pretreatment

First, the herbal extract prepared in Example 1 was dissolved in 0.9% saline (Biopure, SOD001) and then orally administered at various doses (12.5, 25, 50, 100 mg / kg). The positive control group received tacrine 10 mg / kg and the control group received 0.9% physiological saline. Passive avoidance tests were performed on the scopolamine-induced forgetful animal model for the haejucho extract prepared in 1-1, 1-2, 1-3 of Example 1, and each group was subjected to 10 mice. Used.

1-2. Learning experiment

30 minutes after drug administration, scopolamine dissolved in distilled water was intraperitoneally administered at a dose of 1 mg / kg, and 30 minutes after scopolamine administration, the rat was placed in a brightly lit compartment with a 10-second exploration time. ) Can be opened into the dark compartment. Mice that did not enter the dark side within 60 seconds after the guillotine door were opened were excluded from the experiment. After the guillotine door was opened, the time until the rat entered the dark side was measured. Once the mouse enters the dark side, the guillotine door closes, and a 0.5 mA electric shock flows through the bottom of the grid for three seconds and the mouse remembers this electrical action.

1-3. Passive evasion experiment

The experiment was conducted 24 hours after the study test. After 10 seconds of searching time, the time required for the guillotine door to open and the 4 foots to enter the dark side (latency time) was measured up to 300 seconds. The longer the time taken, the better the learning and memory of passive avoidance.

1-4. Experiment result

As a result of this experiment, the manual evacuation test on the scopolamine-induced forgetful animal model was performed on the haegocho extract prepared in 1-1, 1-2, 1-3 of Example 1, and in all experiments. Compared with the control group, the retention time of the scopolamine-only group was significantly reduced, indicating that a memory loss model was produced. In the efficacy test of the 70% ethanol extract (PV70E) of FIG. 1, the retention time of the scopolamine-only group was 31.76 ± 7.18 seconds, whereas 110.25 ± 22.15 (p <0.01) in the 25 and 50 mg / kg administration groups, respectively. 120.75 ± 20.39 (p <0.05) showed a significant increase. In addition, as a result of the efficacy test of the water extract (PVW) of FIG. 2, the retention time of the scopolamine-only group was 23.50 ± 5.96 seconds, while the significant increase was 141.42 ± 37.21 (p <0.05) seconds in the 50 mg / kg administration group. Showed. As shown in FIG. 3, the retention time of the butanol fraction 2.5 and 10 mg / kg administration groups was 159.77 ± 32.96, while the retention time of the scopolamine-only group was 44.830 ± 7.12 seconds in the solvent fraction (PVB) comparison experiment of butanol. (p <0.05) and 168.55 ± 30.49 (p <0.05) seconds showed a significant increase. (mean ± S.E.M.)

Experimental Example  2. Observation of memory change by Morris underwater maze experiment

In order to confirm the memory through the underwater maze test of the extracts of the present invention obtained in the above examples, the experiments described in the literature were applied as follows (Kim et al., 2006).

The four rounds of stars, squares, triangles, and circles are equally spaced on a circular grass 90 cm in diameter and 45 cm high, and a 29 cm high platform is placed below the star. Fill the water up to 0.5 cm above the platform (water temperature 21 ± 1 ℃), and use a pigment (Borak Co., Ltd., 200902001) to dim the water so that the platform is not visible from the water surface. Carefully lower the mouse into a section of the pool and measure the time it takes to reach the platform for 60 seconds. After 30 seconds, put the mouse in the same position again and measure the time to reach the platform for 60 seconds. Repeat the above four times, changing the position of laying down for a total of four days. On the fifth day, remove the platform and place it where you left your mouse on the first day, and measure the time spent in the compartment where the platform resided for 60 seconds.

As a result of the experiment, Morris water maze experiment was performed on the scopolamine-induced forgetfulness animal model of the Hagocho extract prepared in Example 1-1. Each group used 10 mice. In all experiments, the time to platform of the scopolamine-only group was significantly increased compared to the control group, indicating that the memory loss model was produced. As shown in Figure 4, the time taken to the platform of the scopolamine-only group in the training experiment was 52.75 ± 2.12 seconds, 46.50 ± 2.52 seconds on the 3rd and 4th day, respectively, and 25 mg / kg administration of 70% ethanol extract The group showed a significant decrease of 29.27 ± 3.24 (p <0.05) and 22.77 ± 3.28 (p <0.05) seconds, respectively. In addition, as shown in FIG. 4-2, the retention time ratio of the quadrant with the platform was 24.22 ± 1.29% in the group administered with scopolamine only in the 5 days probe experiment, whereas in the group administered with 25 mg / kg of 70% ethanol extract 33.25 ± 1.77 (p <0.05)% showed a significant increase. (mean ± S.E.M.)

Experimental Example  3. Measurement of schizophrenia changes by pre-stimulation test

The schizophrenic animal model experiments of the extracts of the present invention obtained in the above examples were tested as follows by applying the method disclosed in the literature to identify schizophrenic changes (Ong et al., 2005).

This test is a neurophysiological and behavioral measure of sensorimotor association. In schizophrenic animal models, administration of NMDA inhibitors, such as MK-801, or dopamine agonists, such as apomorphine, has not been shown to inhibit prepulse (Noda et al., 2001; Howes and Kapur, 2009). ). It has also been reported that pre-stimulation inhibition does not occur when mice are subjected to social isolation for 10 weeks or more (Barr et al., 2006).

Based on this fact, the rats are stimulated with a few dB of powerful sound in a start box and the response is measured to determine whether the drug is effective for schizophrenic animal models. Surprise box is a box that can lightly detain rats, a system capable of consistently producing sound stimuli from 5 to 130 dB, equipment for measuring animal movements, programs for digitizing measured stimuli, and sounds. It consists of a source and a speaker that can be provided. The rats are allowed to acclimate for 5 minutes in a detention box for each test. Put white noise (70dB) in the background. Since animals may overreact to stimuli, adapt the animal to several 120 dB, 40 ms sound stimuli. Then give an 80 ~ 120 dB sound stimulus to measure the animal's response to each stimulus. Each response is then randomly given four situations: only 120 dB (SS), only prepulse (PP), no stimulus, 120 dB after 40 ms after pre-stimulation. Measure After measuring the animal's surprise response to each stimulus, the response rate between the 120 stimulus and 120 dB stimulation after pre-stimulation is measured and calculated by the following equation 1 to analyze the data.

As a result of this experiment, the prestimulus inhibition test was performed on the schizophrenic animal model induced by apomorphine on the hachocho extract prepared in Example 1-1. Each group used 10 mice. In all experiments, the pre-stimulation inhibition rate of the apomorphine-only group was significantly decreased compared to the control group. As shown in FIG. 5, the pre-stimulation inhibition rate of the apomorphine-only group was 24.64 ± 6.60 and 50.86 ± 4.86% in PP6 and PP12, respectively, whereas in the high dose 70% ethanol extract (PV70E) 25 mg / kg group The significant increase was 44.82 ± 5.99 and 67.80 ± 8.17 (p <0.05)%, respectively. In addition, as shown in FIG. 6, the pre-stimulation inhibition rate of the group that induced social isolation was 11.23 ± 7.70, 38.18 ± 6.18, 50.21 ± 7.54% in PP6, PP12, and PP16, respectively, and 70% ethanol extract (PV70E) ) The 25 mg / kg group increased to 19.99 ± 8.13, 55.90 ± 8.71, and 61.70 ± 8.14%, respectively. (mean ± S.E.M.)

Hereinafter, the preparation examples of the composition comprising the extract of Hagocho of the present invention, but the present invention is not intended to limit it, it is intended to explain in detail only.

Formulation example  One. Powder  Produce

20 ml of Hagocho extract

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation example  2. Preparation of Tablets

Higocho extract (PV70E) 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation example  3. Manufacture of capsule

Higocho extract 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation example  4. Preparation of injections

PV70E 10 mg

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO ₄ , 12H ₂ O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation example  5. Liquid  Produce

PV70E 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method of preparing a liquid solution, each component is added to the purified water to dissolve it, the lemon flavor is appropriately added, the above components are mixed, purified water is added, the whole is adjusted to 100 ml by the addition of purified water, and then filled in a brown bottle. The solution is prepared by sterilization.

Formulation example  6. Manufacture of health food

PV70E 1000 mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 [mu] g vitamin B12

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients may be mixed according to a conventional health food manufacturing method. Next, the granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation example  7. Manufacture of health drinks

PV70E 1000 mg

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to a total of 900 ml

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.

1 is a diagram showing the effect of haejucho ethanol extract on passive avoidance test of schizophrenic model animals;

FIG. 2 is a diagram showing the effect of Prunella hydrothermal extract on passive avoidance test of schizophrenic model animals; FIG.

3 is a diagram showing the effect of butanol fraction of ethanol ethanol extract on passive avoidance test of schizophrenic model animals;

4 is a diagram showing the effect of ethanol ethanol extract on the Morris water maze test of schizophrenic model animals;

FIG. 5 is a diagram showing the effect of Algae ethanol extract on pre-stimulation inhibition test of apomorphine-induced schizophrenic model animals;

Figure 6 is a diagram showing the effect of the ethanol extract of Hachocho ethanol on the pre-stimulation inhibition test in model animals induced by social isolation.

Claims (7)

A pharmaceutical composition for the prevention and treatment of psychotic disorders and forgetfulness containing the extract of Hagocho as an active ingredient. The pharmaceutical composition of claim 1, wherein the edible vinegar comprises flower water, flowers, roots and starches. The pharmaceutical composition of claim 1, wherein the extract is water including purified water, C ₁ to C ₄ lower alcohols, or a mixed solvent thereof. The pharmaceutical composition of claim 1, wherein the psychotic disorder is schizophrenia, schizophrenic disorder, schizophrenia disorder, delusional disorder, short term psychotic disorder, social isolation, or shared psychotic disorder. Health functional food for the prevention and improvement of psychotic disorders and forgetfulness which contains the extract of Hagocho as an active ingredient. Food or food additives containing the above-mentioned Hachicho extract as an active ingredient having an effect of preventing and improving psychotic disorders and forgetfulness. The food according to claim 6, which is a variety of foods, beverages, gums, teas, vitamin complexes, or dietary supplements.

Images