KR20140019967A - Pharmaceutical composition comprising mixed extracts of paeonia lactiflora pallas and dried rhizomes of zingiber officinale roscoe for preventing or treating of dementia and cognitive dysfunction - Google Patents

Abstract

The present invention relates to: a pharmaceutical composition containing mixed extracts of Paeonia lactiflora Pallas and dried ginger for preventing or treating dementia and cognitive dysfunction; or a functional food composition. [Reference numerals] (AA) Recognition index(%); (BB) Scopolamine(1mg/kg); (CC) Donepezil(1mg/kg); (DD) Peony; (EE) Health; (FF) Peony 3 + Health 1; (GG) Peony 1 + Health 1; (HH) Peony 1 + Health 3

Description

[0001] PHARMACEUTICAL COMPOSITION COMPRISING MIXED EXTRACTS OF PAEONIA LACTIFLORA PALLAS AND DRIED RHIZOMES OF ZINGIBER OFFICINAL ROSCOE FOR PREVENTING OR TREATING OF DEMENTIA AND COGNITIVE DYSFUNCTION,

The present invention relates to a pharmaceutical composition for the prevention or treatment of dementia and cognitive dysfunction, and more particularly to a pharmaceutical composition for preventing or treating dementia and cognitive dysfunction which comprises a mixed extract of health, And to a pharmaceutical composition and a functional health food effective for prevention or treatment.

The world is entering an aging society at a rapid pace, and humans are pursuing a high quality of life that can live long without a disease. As the elderly population increases due to the extension of the life span due to the development of science, the proportion of dementia patients, neurodegenerative diseases, is increasing rapidly.

Generally, senile dementia, including Alzheimer's Disease, is characterized by a gradual loss of cognitive function, which severely lowers the quality of life, both personally and socially, and makes people and the people around them unhappy, It is the fourth leading cause of death in the elderly following diseases and strokes.

Dementia is caused by various causes, but the most convincing scientific causes are as follows. First, it has been recognized that a decrease in the concentration of neurotransmitter acetylcholine in the hippocampus region of the brain is highly related to dementia. In patients with dementia, acetylcholine is hydrolyzed by acetylcholine esterase, which acts to hydrolyze acetylcholine into choline, thereby lowering the concentration of acetylcholine. Therefore, it has been reported that when acetylcholinesterase is inhibited, the concentration of acetylcholine in the brain increases and symptoms of dementia patients are improved. Drugs such as donepezil, galanthamine, rivastigmine, etc., which have been approved by the FDA for use as an acetylcholinesterase inhibitor and developed and used as a treatment for dementia include donepezil, galanthamine, and rivastigmine.

However, most of these acetylcholinesterase inhibiting drugs have cholinergic side effects of peripheral nerves, are too short in half-life, and have serious side effects such as liver toxicity (Br.J. Psychiatry, 138, 46, 1981).

Second, aggregation of amyloid beta (Aβ) plaques and entanglement of intracellular nerve fibers are known to be the main cause of Alzheimer's dementia, which is frequently found in the brain of patients with dementia. Amyloid beta (Aβ) is produced by cleavage of β-amyloid precursor protein (βAPP) by BACE1 (β-site APP-cleaving enzyme 1) and β-secretase activity . Overexpression of BACE1 increases amyloid beta by increasing the [beta] -secretase cleavage of APP. The resulting amyloid beta inhibits neuronal signaling and induces inflammation. Thus, inhibition of aggregation of amyloid beta has been reported to reduce cognitive impairment and improve cognitive function.

Cognitive impairment refers to decreased attention, decreased learning ability, decreased memory, and impaired perception. The memory impairment is a common symptom, and most of the past events are fully memorized, but the ability to memorize and learn new information becomes obstructed, resulting in difficulties in learning.

In recent years, studies have been actively conducted to prevent or treat dementia or cognitive dysfunction by using an herbal medicine extract that inhibits acetylcholinesterase or inhibits aggregation of amyloid beta, a dementia-inducing protein (Korean Patent Laid- -2005-0095819). Herbal medicine extracts have significantly fewer side effects than other drugs, but in some cases there are other side effects.

The present invention provides a method of inhibiting acetylcholinesterase inhibition, amyloid beta agglutination inhibition activity, and nerve growth factor (NGF) activity using 46 herbal medicines including health and peonies, (NORT), Passive Avoidance Test (PAT), and Y (Score) induce secretory induction of scopolamine in animal models of memory impairment. The present inventors completed the present invention by developing a mixed extract having an excellent effect of improving memory effect, learning enhancement and spatial perception ability close to that of a normal animal in the Y maze test and confirming the efficacy thereof.

It is an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of dementia and cognitive dysfunction comprising a therapeutically effective amount of a health, peanut mixed extract and a pharmaceutically acceptable carrier.

It is also an object of the present invention to provide a functional food composition for improving dementia and cognitive dysfunction, which comprises an active ingredient of a mixture of health and peony extracts.

To achieve these and other advantages and in accordance with the purpose of the present invention, the present invention provides a pharmaceutical composition for preventing or treating dementia and cognitive dysfunction, which comprises a therapeutically effective amount of a health, peanut mixed extract and a pharmaceutically acceptable carrier.

The present invention also provides a functional food composition for improving dementia and cognitive dysfunction, which comprises an active ingredient of a mixture of a health and peony extract.

The present invention provides a pharmaceutical composition comprising a health and peanut mixed extract according to the present invention as an active ingredient effective for preventing and / or treating dementia and cognitive dysfunction. The pharmaceutical composition and / or food composition containing the health and peanut mixed extract of the present invention as an active ingredient can prevent or treat dementia prevention and / or treatment, memory disorder, and improve learning or memory.

FIG. 1 is a graph showing induction of secretion of nerve growth factor (NGF) by a mixed gangrene extract of the present invention in rat glioma C6 cell line.
FIG. 2 is a graph showing the promotion of secretion and cytotoxicity of NGF according to the mixing ratio of the health and peony blend extract of the present invention in rat glioma C6 cell line. FIG.
FIG. 3 is a graph showing the inhibitory effect of LPS-induced NO secretion and cytotoxicity in BV-2 cells according to the mixing ratio of the health and peanut mixed extract of the present invention.
FIG. 4 is a graph showing the effect of improving memory performance in a novel object recognition test (NORT) for a new object according to the blending ratio of the health and peony blend extract according to the present invention in scopolamine-induced rats. The recognition index is the ratio of time taken to search for new objects.
FIG. 5 is a graph showing the effect of improving the memory performance in the Y-maze test of the health and peony blend extract according to the present invention in scopolamine-induced rats.
FIG. 6 is a graph showing the effect of improving passive avoidance test (PAT) on the memory effect of the health and peony blend extract according to the present invention in scopolamine-induced rats.

The present invention provides a pharmaceutical composition for the prevention or treatment of dementia and cognitive dysfunction comprising a therapeutically effective amount of a healthy, peanut mixed extract and a pharmaceutically acceptable carrier.

The dementia and cognitive dysfunction of the present invention may include Alzheimer's disease and vascular dementia, Parkinson's disease, mild cognitive impairment, senile dementia, anterior temporal dementia, and the like.

The health and peonies used in the present invention have heretofore been used for herbal medicine treatment and prevention with herbal medicine.

Health (dried rhizomes of Zingiber officinale roscoe ) is a dried perennial herb ginger root stem belonging to the ginger family, and ginger has been widely used as a tonic, gangjeong and anticancer food. Ginger or the like, which is a spicy ingredient of ginger or ginger, has an effect of inhibiting acetylcholine esterase or aggregation of amyloid beta, and thus it has been known to be effective in the treatment of Alzheimer's disease and the like (Kim DS et al., J Altern. Complement Med . 2007 Apr; 13 (3): 333-40).

Paeonia lactiflora Pallas is a perennial herbaceous plant belonging to the family Ranunculaceae. It has previously contained paeoniflorin and alkaloids such as paeonine, tannin, resin and benzoic acid as glycosides. Peanut is also known to have neuroprotective activity and antioxidant activity (Korean Patent Laid-Open No. 10-2006-0023885, etc.).

The present invention is characterized by comprising a mixed extract of health and peony as an active ingredient. By using a mixed extract of health and peony, the effect of the additive effect is increased as compared with the case where each of health and peony is used as a single extract do. In addition, when used at a specific blending ratio, the effect is further maximized.

Each herbal ingredient used in the present invention is based on the dried weight.

The health and peanut mixed extracts may be mixed extracts obtained by mixing health and peanuts at a ratio of 1: 10 to 10: 1. Preferably, the extracts of health and peanut are mixed at a ratio of 1: 5 to 5: 1 It is an extract. It has been found that the most effective and lowest toxicity is in the composition and content ratio range as described above, and it shows the best efficacy.

The health and peanut mixed extract may be prepared by extracting a healthy pea extract with an extraction solvent selected from the group consisting of C ₁ to C ₄ alcohols, n-hexane, ethyl acetate, n-butanol, chloroform, And the like. More preferably, the health and peanut mixed extract may be an ethanol extract obtained by extracting a healthy pea extract with ethanol.

The amount of the extraction solvent to be used is not limited, and may be used in a ratio of about 1 to 10 times by volume, preferably about 5 to 10 times by volume, based on 1 weight of the powdery sample of the health food. The extraction can be carried out by extraction methods such as cold extraction, hot water extraction, ultrasonic extraction, and reflux cooling extraction for about 1 to 24 hours, preferably about 1 to 5 hours. Preferably, the extraction can be carried out by a reflux cooling extraction method at 79 DEG C, and the extraction process can be performed once or several times, preferably about 3 times. The ginger extract can be obtained in the form of liquid or powder by concentrating under reduced pressure or drying under reduced pressure at a temperature of about 20 to 100 째 C, preferably about 30 to 70 째 C, if necessary in accordance with necessity.

The health and peanut mixed extracts can be obtained by performing an additional extraction process to increase the content of the active ingredient. That is, (a) extracting a health food with a C ₁ -C ₄ alcohol; And (b) extracting the extract obtained in step (a) with water and n-hexane, and separating the resulting n-nucleic acid layer, whereby a health, A peony blend extract can be obtained.

Also optionally, (a) extracting a healthy, peanut with a C ₁ to C ₄ alcohol; (b ') extracting the extract obtained in the step (a) with water and n-hexane, and separating the resulting aqueous layer; And (c) extracting ethyl acetate from the aqueous layer obtained in the step (b ') and separating the obtained ethyl acetate layer, and then performing an extraction step (and an additional chromatographic fractionation step, if necessary) , Or (a) extracting a health food with a C ₁ -C ₄ alcohol; (b ') extracting the extract obtained in the step (a) with water and n-hexane, and separating the resulting aqueous layer; (c ') adding ethyl acetate to the aqueous layer obtained in the step (b') and extracting, and separating the obtained aqueous layer; And (d) extracting n-butanol to the aqueous layer obtained in the step (c ') and separating the resultant n-butanol layer or aqueous layer, and further performing an extraction step (and, if necessary, further chromatographic fractionation step ), A health and peanut mixed extract having a high active ingredient content can be obtained.

As used herein, "therapeutically effective amount" means the amount necessary to alleviate symptoms of at least one disease, such as those described herein, which are generally prevented, reduced or treated.

The composition of the present invention contains 0.01 to 95% by weight of the extract, based on the total weight of the composition.

The composition comprising the extract according to the present invention may be administered in various forms including pharmaceutically acceptable carriers such as oral preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, And sterile injectable solutions. Particularly preferably, it can be formulated into an oral formulation.

The pharmaceutically acceptable carrier is 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, mineral oil and the like. Also included are diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and the like. Oral solid preparations include tablets, pills, powders, granules, capsules and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose or lactose. ), Gelatin, and the like, and may include a lubricant such as magnesium stearate, talc, and the like. Oral liquid preparations include suspensions, solutions, emulsions, syrups, and the like, and may contain diluents such as water and liquid paraffin, wetting agents, sweetening agents, fragrances, preservatives and the like. Examples of the non-aqueous solution include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations and suppositories. Non-aqueous solvents and suspensions include vegetable oils such as propylene glycol, polyethylene glycol and olive oil, ethyl And injectable esters such as oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycero gelatin and the like can be used.

The dosage of the pharmaceutical composition comprising the health, peanut mixed extract of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the drug form, the administration route and the period, but can be appropriately selected by those skilled in the art. For example, the dose may be 0.01 to 500 mg / kg, preferably 10 to 300 mg / kg per day, and the administration may be administered once a day or divided into several times.

The present invention also provides a food composition for improving or alleviating a learning disorder or memory disorder, which comprises a health, peanut mixed extract as an active ingredient.

In the above food composition, the health and peanut mixed extracts can be obtained as described above.

The food composition of the present invention can be used as a dietary supplement. The term "functional food" as used herein means a food prepared and processed using a raw material or ingredient having a useful function in the human body pursuant to Law No. 6727 on Health Functional Foods, and the term "functional" And function of the nutrient for the purpose of obtaining a beneficial effect in health use such as controlling the nutrient or physiological action.

The food composition of the present invention may contain conventional food additives. Unless otherwise specified, the suitability of the food additives for the above-mentioned "food additives" Of the present invention.

Examples of the substances found in the above-mentioned "food additives" include natural compounds such as ketones, chemical compounds such as glycine, potassium citrate, nicotinic acid and cinnamic acid, coloring pigments, licorice extracts, crystalline cellulose, high- L-glutamic acid sodium preparations, noodle-added alkalis, preservative preparations, tar pigment preparations and the like.

The food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, circles, etc. for the purpose of improving or alleviating learning disorders or memory disorders, or for the purpose of learning or memory enhancement.

The food composition of the present invention may contain 0.01 to 95% by weight, preferably 1 to 80% by weight, of the health and peanut mixed extracts based on the total weight of the composition.

For example, the health functional food in tablet form may be prepared by granulating a mixture of health, peanut mixed extract, excipient, binder, disintegrant, and other additives in a conventional manner, followed by compression molding with a lubricant, The mixture can be directly compression molded. The health functional food of the tablet form may contain a mating agent and the like if necessary, and may be sieved to a suitable skin care agent if necessary.

The hard capsule of the capsule type health functional food can be prepared by filling a normal hard capsule with a mixture with an additive such as health, peanut mixed extract and excipient, or a granular product thereof or a gelatinized granular product. The mixture can be prepared by filling a mixture of the peony blend extract with an additive such as an excipient into a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.

The ring-shaped health functional food can be prepared by molding an appropriate mixture of excipients, binders, disintegrants, etc. in a mixture of the health and peanut mixed extracts. If necessary, the preparation may be mixed with white sugar or another suitable skin care agent, It may also be an objectionable substance.

The granular health functional food may be prepared by granulating a mixture of the above-mentioned health, peanut mixed extract, excipient, binder, disintegrant and the like by a suitable method and, if necessary, a flavoring agent, a mating agent and the like.

The definitions of the above-mentioned excipients, binders, disintegrants, lubricants, mating agents, flavoring agents and the like of the present invention are described in documents known in the art and include the same or similar functions (see, for example, Korean Association of Pharmacy, 5th ed., Pp. 33-48, 1989).

Hereinafter, the present invention will be described in more detail through examples and test examples. However, these examples and test examples are for illustrating the present invention, and the scope of the present invention is not limited to these examples and test examples.

<Examples>

Example  1: Preparation of health, peony blend extract

0.5 kg of health, 1.5 kg of peanut were ground, and 20 liters of 95% ethanol was added. The mixture was refluxed for cooling at 79 ° C for 3 hours, filtered, and the filtrate was separated. The resulting filtrate was combined and concentrated under reduced pressure to remove the solvent. The water was completely removed through lyophilization to obtain about 340 g of a mixture of the health and peony extracts.

In addition, in order to confirm the optimum effect for each compounding ratio was extracted by the blending ratio as shown in Table 1 below to prepare an extract for each blending ratio.

division Peony 10:
Health 1 Peony 5:
River 1 Peony 3:
Health 1 Peony 1:
Health 1 Peony 1:
Health 3 Peony 1:
Health 5 Peony 1:
Health 10 Peony
(kg) 1.81 1.66 1.5 1.0 0.5 0.33 0.18 health
(kg) 0.18 0.33 0.5 1.0 1.5 1.66 1.81 Extraction quantity
(kg) 320 340 340 335 350 345 350

Test Example  1. Nerve growth factor ( NGF ) Secretion effect

A glioma C6 cell line of rat known to secrete nerve growth factor (NGF) was used. C6 cells were purchased from Korean Cell Line Bank (KCLB No. 10107). C6 cells were cultured in DMEM medium supplemented with 3.4 g / L sodium bicarbonate (NaHCO ₃ ), 10% fetal bovine serum and 1% penicillin-streptomycin antibiotic (10000 U / ml) BRL, USA).

PC12 cells for studying neural differentiation by NGF were supplemented with 2.0 g / L sodium hydrogencarbonate, 10% horse serum, 5% fetal calf serum and 1% penicillin-streptomycin antibiotic (10000 U / ml) Gt; RPMI1640 &lt; / RTI &gt; medium (Gibco BRL, USA). The fetal bovine serum and horse serum were inactivated at 55 ° C for 30 minutes before use and cultured in a cell incubator maintained at 70% humidity and 37 ° C and supplied with 5% carbon dioxide.

C6 cells adhered to a 100 mm culture container were treated with 0.25% trypsin-EDTA (Gibco BRL, USA), and 10 ml of fresh medium was added thereto to prepare a cell suspension. Cell suspensions were then used And the number of living cells was measured and calculated. Based on the calculated values, the cells were dispensed into a 100 mm culture dish containing 2 × 10 ⁶ cells. After 24 hours of incubation, the existing medium was removed and replaced with 10 ml of DMEM medium supplemented with 2% fetal bovine serum at concentrations of 10, 50 and 100 μg / ml, respectively, obtained in Example 1, After culturing for 24 hours, medium was obtained. The obtained medium was centrifuged at 1500 rpm for 10 minutes, and only the supernatant was collected again.

The measurement of nerve growth factor secreted from C6 cells was quantified by treating the medium with a nerve growth factor kit (DY556, R & D system, USA). In order to examine the effect of mixed extracts of health and peony on induction of nerve growth factor secretion, nerve growth factor was quantitatively analyzed in conditioned medium obtained after treatment with C6 cells. The results are shown in FIG.

To examine cytotoxicity, the supernatant collected in the above example was collected and the remaining cells were incubated with 3- [4,5-dimethylthiazol-2-yl] -2,5-diphenyl-tetrazolium bromide (3- (MTT, Sigma Cat # M5655) was treated for 1 hour, and then 200 μl of DMSO was added to dissolve the cells. Then, the cells were incubated with 570 nm wavelength Lt; RTI ID = 0.0 &gt; ELISA &lt; / RTI &gt; plate reader.

As a negative control group, the NGF secretion promoting effect was different according to the ratio of peony and health mixed extracts when calculated according to 100% of the untreated group. The MTT assay showed that the stimulating effect was within the range of not showing cytotoxicity Respectively. In each case, it was judged that the optimal mixing condition was the highest concentration of NGF secretion by mixing and extracting in Peony 3 at a ratio of Health 1.

Test Example  2: On nerve inflammation  Involved NO  Confirming the secretion inhibition effect

Mouse-derived pneumocytes, BV-2 cells, were cultured in DMEM medium containing 5% fetal bovine serum and 1% penicillin / streptomycin.

The BV-2 cells were dispensed into each well of a 96-well plate in the number of 3 > 10 ⁴ , and then cultured for 24 hours. After that, the health and peanut mixed extract prepared in Example 1 was treated by concentration, and after 30 minutes, lipopolysaccharide (LPS) was treated at a concentration of 100 ng / ml and cultured for 24 hours. After 24 hours, the supernatant was collected and diluted 1: 1 with Griess reagent (N- (1-naphtyl) ethylenediamine dihydrochloride (Sigma cat # N9125) + Sulfanilic acid in 5% phosphoric acid (Sigma cat # S9251) After incubation at room temperature for 10 minutes, the absorbance at 570 nm wavelength was measured with an ELISA plate reader. The supernatant was collected and the remaining cells were treated with 3- [4,5-dimethylthiazol-2-yl] -2,5-diphenyl-tetrazolium bromide (MTT, Sigma Cat # M5655) for 1 hour, The cells were lysed and then measured for cytotoxicity by measurement with an ELISA plate reader at a wavelength of 570 nm. Health, and peony blossom extracts. The results are shown in FIG. 3.

As a result, the inhibition of NO secretion was different according to the ratio of peony and healthy mixed extracts, and it was confirmed that inhibition of NO secretion within the range of not showing cytotoxicity The effect was confirmed by MTT test. In each case, the optimum mixing condition was judged to be the highest inhibitory effect of NO on the ratio of health 1 to peony 3 and that of healthy 1 mixed with peony 1.

Test Example  3: With scopolamine  Cognitive testing of new things in an induced animal model ( novel object recognition test ; NORT )

In order to confirm the cognitive ability and the memory enhancement effect of the health and peony blend extract in the scorollamin induced memory impairment animal model, the following procedure was carried out.

An ICR male mouse (30-35 g) at 7 weeks of age was purchased from Orient Bio and used in an animal breeding room of Kyunghee University College of Pharmacy for more than 1 week. Water and feed were allowed to be freely consumed, and temperature (22 ± 2 ° C), humidity (53 ± 3%) and light period (12 hours) were automatically controlled.

Rats were divided into 9 groups of 8 rats. After 1 week of adaptation, Group 1 (control) was orally administered 0.5% methyl cellulose once a day for 1 day with 5 mL per kg of body weight in mice, and group 2 (scopolamine alone group) (50 mg / kg of healthy extract, 50 mg / kg of phytotoxic extract), Group 6 (50 mg / kg of healthy three phytotoxic extracts, 1 mg / (50 mg / kg group), 7th group (50mg / kg group), and 8th group (50mg / kg group of healthy one peony 3 mixture) were added 0.5% methylcellulose Was orally administered once a day for 1 day.

After oral administration of the drug once, 30 minutes after the administration of the drug, scopolamine (1 mg / kg) was intraperitoneally administered and NORT was performed 30 minutes later. The animals were moved to a behavioral observation room for 5 minutes, and after 3 minutes of exposure, 2 sets of identical objects (1 set) were placed at intervals of 30 cm, and then the animals were examined for 3 minutes. In the day after withdrawal, one of the objects revealed in the same box and the newly replaced object were prepared and the time for the animal to search was measured. The result is shown in FIG. 4.

Test Example  4: With scopolamine  Y-maze test in induced animal models (Y maze test )

Rats were divided into 4 groups of 10 rats. After 1 week of adaptation, Group 1 (control) was orally administered 0.5% methyl cellulose once a day for 1 day with 5 mL per kg of body weight in mice, and group 2 (scopolamine alone group) Group 3 (50 mg / kg of peony and healthy mixed extract) and Group 4 (1 mg / kg of donepezil) were orally administered once daily for 1 day in 0.5% methyl cellulose.

After oral administration of the drug once, 60 minutes after the administration of the drug, scopolamine (1 mg / kg) was intraperitoneally administered and 30 minutes later, the Y maze was performed.

The Y maze device consists of the same three arms (8 cm by 30 cm by 14 cm in height), each of which is arranged at a constant angle of 120 ° with respect to each other. The mouse was placed at the end of one arm and allowed to freely move around the Y maze for 8 minutes. Spontaneous alteration (%) was assessed by measuring the number and order of incisions in each cancer. The alteration is defined as when three arms enter sequentially, ie ABC, BCA, CAB, and so on. The% alteration was calculated by the following equation (1).

[Equation 1]

% Change = [total number of changes] / [total number of arm entered -2] x 100

As a result of the above-mentioned Y-maze test, the control group without scopolamine showed a spontaneous alteration of 65%. In the case of mice administered with scopolamine alone peroxidase, the memory was impaired and the value decreased to 47% Respectively. On the other hand, in the case of mice administered orally at 50 mg / kg / day, the spontaneous alteration was significantly increased to 58% and the memory was improved. The result is shown in FIG.

Test Example  5: With scopolamine  Passive avoidance test in induced animal models ( passive avoidance test )

Mice were divided into groups of 10 mice per group. In the first group (control group), 0.5% methyl cellulose was orally administered at 5 mL per kg of body weight for 3 days. In the second group, 1 mg / kg donepezil dissolved in 0.5% methyl cellulose, Group 3 was orally administered with 50 mg / kg of mixed extract of health and peonies dissolved in 0.5% methylcellulose for 3 days. One day a day for 3 days orally and 1 hour after the last oral administration, the passive avoidance task was performed as follows.

The passive avoidance test is a test device in which the internal structure is divided into two identical spaces. In the middle of the first day, with the door open and one side lit up and the other side darkened, And an electric stimulus of 0.25 mA was applied to the sole when the test animal moved to the dark space. After 24 hours, passive avoidance test was carried out in the same way and the time to stay in the bright place was measured. The result is shown in Fig.

The control group was maintained at 150 ± 3.39 sec. The memory effect was maintained by electric shock. In the donepezil group, about 90 seconds, in the healthy and peanut mixed extract 50 mg / kg group 120 seconds and in the scopolamine group 40 seconds, (P <0.05) increased the residence time.

Claims (8)

A pharmaceutical composition for preventing or treating dementia and cognitive dysfunction, comprising a health, peony mixed extract and a pharmaceutically acceptable carrier. The method of claim 1,
The health, peony mixed extract is characterized in that the health and peony mixed extract in a ratio of 1:10 to 10: 1, dementia and cognitive dysfunction preventing or treating pharmaceutical composition. The method of claim 1,
The health and peanut mixed extract may be obtained by extracting a health, peanut mixture with an extraction solvent selected from the group consisting of C ₁ -C ₄ alcohol, n-hexane, ethyl acetate, n-butanol, chloroform, Or a pharmaceutically acceptable salt thereof. The pharmaceutical composition for the prevention or treatment of dementia and cognitive dysfunction. The method of claim 1,
The pharmaceutical composition for preventing or treating dementia and cognitive dysfunction according to claim 1, wherein the health and peanut mixed extract is obtained by extracting a health, peanut mixture with ethanol. The method of claim 1,
The health, peony mixed extract is characterized in that it comprises 0.01 to 95% by weight relative to the total weight of the composition, pharmaceutical composition for preventing or treating dementia and cognitive dysfunction. The method of claim 1,
Wherein the dosage form of the pharmaceutical composition is an oral dosage form selected from the group consisting of powders, granules, tablets, capsules, suspensions, emulsions and syrups, for the prevention or treatment of dementia and cognitive dysfunction Gt; A food composition comprising the pharmaceutical composition according to claim 1 and a food acceptable additive. The method of claim 7, wherein
The food composition is a food composition, characterized in that containing 0.01 to 95% by weight of the health, peony mixed extract based on the total weight of the composition.

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