KR100830353B1 - Agent for prophylaxis or treatment of cerebrovascular diseases containing ethanol extract of Aralia cordata - Google Patents

Abstract

The present invention relates to a cerebrovascular disease prevention or treatment containing ethanol, especially 60% ethanol, extract of Aralia cordata as an active ingredient, the cerebrovascular disease prevention or treatment of the present invention is cerebral infarction, cerebral ischemia, stroke and / Or vascular dementia can be effectively prevented or treated without side effects.

Description

Agent for prophylaxis or treatment of cerebrovascular diseases containing ethanol extract of Aralia cordata}

1 is a graph showing the effect of inhibiting neuronal cell death by beta amyloid of the venom extract (AC);

Figure 2 is a graph showing the effect of inhibiting apoptosis of neurons by beta amyloid of poison extract (AC);

3 is a graph showing the effect of inhibiting the increase in intracellular calcium concentration by beta amyloid of the venom extract (AC);

Figure 4 is a graph showing the inhibitory effect of free radical production by beta amyloid of the poison extract (AC);

5a and 5b are photographs and graphs showing the effect of inhibiting cerebral infarction of the venom extract (AC).

The present invention relates to an agent for preventing or treating cerebrovascular diseases, and more particularly, to an agent for preventing or treating cerebrovascular diseases such as cerebral infarction, cerebral ischemia, stroke, and vascular dementia, containing an ethanol extract of poison as an active ingredient.

Cerebral apoplexy, or cerebral infarction, is the main cause of thromboembolism of the cerebral arteries due to vascular atherosclerosis or from cardiac embolism due to embolism and heart disease. Cerebral infarction, which is caused by clogged cerebrovascular vessels, is divided into cerebrothrombosis and embolism. Cerebral thrombosis is caused by arteriosclerosis due to hypertension, diabetes, hyperlipidemia, etc., and the walls of the arteries become thick or hard. As a result, blood vessels are narrowed and the inner walls of the blood vessels are not smooth, so blood is entangled and eventually clogged, and blood supply is significantly reduced or stopped, resulting in insufficient oxygen and nutrient supply to brain cells, leading to impaired brain function. Cerebroembolism causes abnormal blood flow in the heart due to diseases such as heart valve disease or atrial fibrillation, causing some of the blood to become stagnant in the heart, thus clotting and causing blood clots, which fall off and block the cerebral blood vessels. This will occur.

In addition, dementia refers to a case in which a normal person loses intellectual ability due to various diseases of the brain. The most common cause of dementia is Alzheimer's disease (AD), a type of degenerative brain disease, accounting for about 50-60%, followed by Vascular dementia (VaD). The remaining 10-30% is dementia due to other causes. Alzheimer's disease is the first common degenerative brain disease reported by German psychiatrist Alois Alzheimer in 1907, the most common cause of dementia. This disease is a disease in which the neuronal cells gradually disappear as the toxic substance called beta amyloid (Aβ; Amyloid β) accumulates in the brain. Microscopic examination of the brain of a deceased Alzheimer's disease reveals characteristic senile plaques and neurofibrillary tangles with Aβ deposition. The next most common cause of Alzheimer's disease is vascular dementia caused by clogging or narrowing of blood vessels (for example, cerebral infarction). Until the 1990s, vascular dementia was thought to be caused by multiple cerebral infarction, but now it has been expanded to include all vascular dementia, and due to vascular disease, brain changes, degenerative diseases, host factors and cognitive function. It is described as a complex interaction. Vascular dementia begins suddenly and suddenly worsens, which is clinically different from Alzheimer's disease. However, not all vascular dementia shows this typical course, and when microvascular vessels are repeatedly or gradually blocked, there may be a gradual progression that is difficult to distinguish from Alzheimer's disease. Brain imaging tests such as CT or MRI show signs of cerebrovascular diseases such as cerebral infarction or cerebral hemorrhage in patients with vascular dementia. Vascular dementia is more prevalent than Alzheimer's dementia in Asia, including Japan and China, and the rate of vascular dementia in Korea is higher than that of Alzheimer's dementia.However, unlike Alzheimer's dementia, it is known that prevention and treatment are possible. There is an urgent need to develop effective drugs with fewer side effects.

On the other hand, Aralia cordata (Aralia cordata Thunb.) Is a perennial grass belonging to Araliaceae (Araliaceae), exaction, hogang lion, howang dead, poisonous yocho, Malmo Araliaceae, metdureup, todanggwi, Guan Aralia cordata, udo herbs, ttatdureup, pool Araliaceae, It is called ginseng bark. This plant is called poisonous because its stem grows straight and does not shake well in the wind. Coarse stem with a few short hairs and smells good. The height is about 1.5m, the leaves are alternate, and the pinnate leaves are twice. The flower is a male and female, and grows in a large cone inflorescence at the end of the branch and the main stem or the upper axil of the upper part in July-August, and hangs in the shape of a round mountain inflorescence at the end of the freshly split shoot. Petals are light green with 5 diameters of 3 mm, 5 stamens and 5 pistils respectively. Fruits ripen in September-October with rounded axillas. It is distributed in Korea, Japan, and China. Poisonous vigor has the effects of swelling, bleeding, sweating, pain and pain, and is used in Korean medicine to treat headaches, rheumatism and neuralgia. 10 ml of root is added to 700 ml of water and the decoction solution is taken in half in the morning and evening. Wash the affected area with decoction for external use. Currently, toxin has been known to have several pharmacological activities such as COX2-dependent PGE2 inhibition, analgesic, hypothermic effect, and pentobarbital induced anesthesia, but there are not many studies on the central nervous system. Did.

Korean Patent Publication No. 10-2006-0072642 (published on June 28, 2006) discloses that one or two or more herbal extracts or fractions selected from venom bowels, headwort, haedongpi, sokdan, dew, and gastric ulcer may be used to inhibit beta amyloid production and It has been shown to be effective in improving deteriorated cognitive function, and can be used for the prevention and treatment of mild cognitive impairment (MCI) or dementia. However, the published patent only confirms the effects on Alzheimer's dementia, and does not disclose or even suggest the effects on vascular dementia or cerebral infarction. For reference, Aricept® from Eisai Co., Ltd., a representative treatment for dementia, was approved by the US FDA for Alzheimer's dementia, but not for vascular dementia. High mortality rates have been reported. As described above, Alzheimer's dementia and vascular dementia are diseases in which the etiology is different from each other. Furthermore, the published patent uses a 50% ethanol extract and butanol fraction therefrom, and reports that the butanol fraction is superior to the ethanol extract.

The present inventors have noticed the possibility of inhibiting brain injury caused by cerebral ischemia, due to the fact that ethanol extract of poisonous activity, especially toxical aerial part, has strong antioxidant activity and COX inhibitory activity, and cultured neurons at the in vitro level Was used to cause cell damage by Aβ, a known cause of Alzheimer's disease, and to examine the protective effect of ethanol extract of venom. In addition, cerebral ischemia caused by cerebral ischemia in animal models was tested, and the effect of ethanol extract of venom on brain infarction was tested. As a result, it was confirmed that the ethanol extract of venom alone can be used as a prophylactic or therapeutic agent for cerebral infarction, cerebral ischemia, stroke and / or dementia, especially vascular dementia, by having an excellent protective effect against Aβ cell damage and cerebral infarction, The present invention has been completed.

Accordingly, an object of the present invention is to provide an agent for the prevention or treatment of cerebrovascular diseases such as cerebral infarction, cerebral ischemia, stroke, and vascular dementia containing ethanol extract of venom as an active ingredient.

The present invention relates to a prophylactic or therapeutic agent for at least one cerebrovascular disease, selected from the group consisting of cerebral infarction, cerebral ischemia, stroke and vascular dementia, containing an ethanol extract of venom as an active ingredient. The ethanol extract is 60% ethanol extract, it is preferable that the venom is the upper part of the venom.

The prophylactic or therapeutic agent for cerebrovascular disease according to the present invention may further contain a pharmaceutically acceptable carrier.

Hereinafter, the present invention will be described in detail.

We isolated and cultured cerebral cortical neurons from the fetuses of rats and induced toxicity by adding Aβ (25-35) to the neurons, and then examined how the ethanol extract of toxin (AC) inhibits toxicity. . As a result, Aβ (10 μM) caused apoptotic cell death, which was inhibited by a dose of active extract (1-10 μg / ml). Toxicity inhibited the increase of intracellular Ca ²⁺ concentration and the production of free radicals (ROS) by Aβ. Therefore, the present invention inhibits the death of neurons by Aβ, which is known to be a causative agent of dementia, and its mechanism is caused by the death of apoptosis by Aβ, increase of intracellular Ca ²⁺ concentration and intracellular free radicals. It was first identified that it is inhibition of production of ROS). In addition, as a stroke model, rats induced infarction by ischemia, and it was confirmed that ethanol extract (50 mg / kg) of venom effectively inhibited it. Therefore, the venom extract according to the present invention can be effectively used as a prophylactic or therapeutic agent for cerebrovascular diseases such as cerebral infarction, cerebral ischemia, stroke, and vascular dementia.

When preparing the cerebrovascular disease prevention or treatment of the present invention in the form of a pharmaceutical preparation, the active ingredient is combined with a conventionally acceptable pharmaceutically acceptable carrier, depending on the purpose of administration, tablets, hard or soft capsules, chewing tablets, It may be formulated in the form of preparations for oral administration such as powders, solutions or suspensions or preparations for parenteral administration such as injectable solutions, suspensions, nasal washes and the like.

When the active ingredient of the present invention is formulated into tablets, capsules, chewing tablets, powders, solutions, suspensions and the like for the purpose of oral administration, a binder such as gum arabic, corn starch, microcrystalline cellulose or gelatin, Excipients such as dicalcium phosphate or lactose, disintegrants such as alginic acid, corn starch or potato starch, glidants such as magnesium stearate, sweeteners such as sucrose or saccharin and flavoring agents such as peppermint, methyl salicylate or fruit flavor Can be. When the unit dosage form is a capsule, a liquid carrier such as polyethylene glycol or fatty oil may be included in addition to the above components.

In addition, injections in the form of solutions or suspensions for parenteral administration can be administered parenterally, eg, subcutaneously, intravenously, intramuscularly or intraperitoneally. Generally, an injectable solution or suspension is an effective amount in a pharmaceutically acceptable liquid carrier such as water, saline, aqueous dextrose and related sugar solutions, nonvolatile oils, glycols such as ethanol, glycerin, polyethylene glycol, propylene glycol, and the like. It can be prepared by mixing the active ingredient homogeneously. In addition, if necessary, auxiliary agents such as solubilizers, antibacterial agents, chelating agents, buffers, and preservatives may be included.

As the pharmaceutically acceptable carrier, any adjuvant may be used that is pharmaceutically pure, substantially non-toxic, and which does not inhibit the action of the active ingredient.

The ethanol extract of poisonous activity according to the present invention is a natural extract, and as a result of animal experiments, it did not show any unusual symptoms at all doses, and it was shown to be toxic to the living body and do not cause any side effects. Therefore, the cerebrovascular disease prevention or treatment of the present invention, in addition to the pharmaceutical preparations described above, in addition to the conventional soft drinks, mineral water, alcoholic beverages such as beverage products or chewing gum or caramel products, candy, ice cream, confectionary, etc. It may be prepared in the form of a food or food supplement by incorporating it into a health supplement containing a mineral or the like or a food additive.

The daily dose of the cerebrovascular disease prevention or treatment agent according to the present invention may be changed depending on various factors such as the severity, complications, weight, age, sex, etc. of the target subject to be administered, but in general, toxin extract 1 to 1,000 mg / kg, preferably 10 to 500 mg / kg, more preferably 10 to 100 mg / kg may be orally administered 1 to 3 times a day.

Hereinafter, the present invention will be described in more detail with reference to Examples, but these are not intended to limit the scope of the present invention in any way.

Example 1: Preparation of Ethanol Extract of Toxic

Dokbok was cultivated at Chungnam National University Herbal Medicine and identified at the College of Pharmacy. The ground portions (4 kg) of the venom were extracted three times at room temperature in a reflux condenser with 60% ethanol for 3 days each. Combine this solution, Whatman No. Filtration through 1 paper, concentrated using a rotary vacuum evaporator to recover 300 g of the extract.

Example 2: Preparation of Hard Capsule

10 mg of 10-fold concentrate of the poisonous extract of Example 1

D-sorbitol 10 mg

Lactose 5 mg

Colloidal silicon dioxide 5 mg

Magnesium stearate 3mg

Total amount 33 mg

According to the conventional capsule preparation method, the above-mentioned ingredients were combined in a prescribed amount, and then filled into hard gelatine capsules of appropriate size so as to have a blend of 33 mg per capsule, thereby preparing a desired capsule.

Example 3: Preparation of Tablets

10 mg of 10-fold concentrate of the poisonous extract of Example 1

D-sorbitol 10 mg

Lactose 5 mg

Colloidal silicon dioxide 5 mg

Magnesium stearate 3mg

                           Total amount 33 mg

After mixing the components in the specified amounts, tablets were prepared according to the conventional method for preparing tablets.

Example 3: Preparation of Soft Capsule

10 mg of 10-fold concentrate of the poisonous extract of Example 1

Soybean oil 100 mg

Palm oil 76 mg

                           Total amount 186 mg

After blending the above components in the specified amount, a soft capsule was prepared according to a conventional soft capsule preparation method.

Example 4: Preparation of Injection

10 mg of 10-fold concentrate of the poisonous extract of Example 1

Tocopherol 172 mg

Selenium 30 mg

Suitable amount of distilled water for injection

PH adjuster

The above components were prepared according to a conventional injection method for injection of one vial (10 μs).

Experimental Example 1 Culture of Cerebral Cortical Neurons

Pregnant Sprague-Dawley (SD) rats (Daehan Biolink, South Korea, Chungbuk) are housed one by one, and the photoperiod is controlled in a 12 hour light / dark cycle and free to feed and water. It was kept in the air conditioning quarter (temperature 22 ± 2 ° C.) with access.

Rats at 15 days of gestation were removed from the fetus under ether anesthesia and only cerebral cortex was isolated under a microscope. This was added to Joklik-modified Eagle's medium (Sigma Chemical Co., USA, Mo., St. Lewis) containing trypsin (0.25 mg / ml) and 5 ml Mechanically dispersed by pipette. This was incubated at 37 ℃ for 10 minutes to perform enzymatic separation. The cell suspension was centrifuged at 1500 rpm for 5 minutes in a precipitate layer containing the cells sodium bicarbonate (44 mM), penicillin (40 U / mL), gentamycin (50 g / mL), KCl (5 mM) and 10 Nylon mesh (35 μm) was adjusted by adding DMEM (Sigma Chemical Co.) containing% Fetal Bovine Serum (FBS) (Gibco, USA, UT, Logan) to 2 × 10 ⁶ cells / ml. ). For measuring cell death, nerve cells were previously coated with poly-L-lysine in a culture vessel (Corning 3512, USA, NY), [Ca ²⁺ ] _c , coverslip for measuring free radicals and apoptosis. (Fisher Scientific 12CIR, USA, PA, Pittsburgh). After incubation for 2 days, the medium was replaced with fresh growth medium with changes in fetal calf serum and KCl concentrations of 5% and 15 mM, respectively. Cultures were maintained in a CO ₂ incubator at 37 ° C., 5% CO ₂ /95% air, with medium change twice weekly.

Experimental Example 2: Determination of the neuronal cell death inhibitory effect of the poisonous extract-MTT colorimetric assay

The MTT colorimetric assay of this experiment is a very sensitive and stable method for quantitatively measuring the survival and proliferation of cells. The yellow water-soluble substrate MTT (3- [4,5-dimethylthiazole-2) in living cells -Yl] -2,5-diphenyl-tetrazolium bromide) is based on the activity of the mitochondria to convert the dark blue formazan. Therefore, the amount of formazan produced is proportional to the number of living cells, and the higher the absorbance, the more the number of living cells.

Culture medium was removed from the cerebral cortical neurons cultured in Example 1 and replaced with serum-free growth medium. Neurons were incubated for 20 min in the medium and incubated for an additional 24 hours in the presence of 10 μM Aβ (25-35) (Bachem, Switzerland, Bubendorf) (Aβ only group). At this time, the ethanol extract of the venom active prepared in Example 1 was added 15 minutes before the Aβ treatment to be present in the medium during the incubation period with Aβ, which was used as a venom extract treatment group. After removing the medium, MTT (0.5 mg / ml, Sigma Chemical Co.) solution in serum-free growth medium was added and incubated at 37 ° C. for 4 hours. The MTT solution was then removed and 200 μl of acid-isopropanol (0.04 N HCl in isopropanol) was added to all wells to dissolve the dark blue formazan crystals formed, followed by a microelisa reader (Bio-Tech ( Absorbance was measured at a wavelength of 570 nm (reference wavelength 630 nm) by Bio-Tek), EL _× 808, USA, VT, Winosky). At this time, when the Aβ-treated cells were used as a control (control), the absorbance of the Aβ-only treatment group and the venom extract treatment group was expressed in%.

The results are shown in FIG. As shown in FIG. 1, in the group treated with Aβ (10 μM) alone, the absorbance was reduced to 71.1 ± 1.4% compared to the control (100%). This means that about 29% of the cells were killed by Aβ. On the other hand, in the venom extract treatment group, the absorbance was suppressed by 76.0% when treated with 1 μg / ml, 83.0% when treated with 5 μg / ml, and 84.4% when treated with 10 μg / ml, respectively. This effect corresponds to the effect of the butanol fraction (85.1 ± 6.3% at 10 μg / ml) of 50% ethanol extract (82.4 ± 5.6% at 20 μg / ml) of Korean Patent Publication No. 10-2006-0072642. .

Experimental Example 3: Determination of the Apoptosis Inhibitory Effect of Toxic Extracts on Neurons-Hoechst Staining

 In this experimental example, Hoechst 33342 staining was performed to demonstrate that apoptosis by Aβ is apoptosis.

Bisbenzimidazole dye, Hoechst 33342, stains DNA across the plasma membrane. Normal cells show rounded nuclei by this reagent, but apoptosis causes morphological changes in the nucleus shape. Using this, neurons on coverslips were exposed to 10 μM Aβ (25-35) or Aβ (25-35) and venom extracts in serum-free growth medium as described in Experimental Example 2, followed by 4% paraformaldehyde. After fixing for 20 minutes at room temperature, the solution was treated with Hoechst 33342 (1 μg / ml; Molecular Probes Inc., OR, Eugene, USA) for 15 minutes and fluorescence microscope (Olympus IX70-EL, Japan). , Tokyo) was observed the shape change of the cells. Total cell number and apoptosis-causing cells were counted to determine apoptosis.

The results are shown in FIG. As shown in FIG. 2, the control group caused killing of 9.5%, whereas the group treated with Aβ caused 33.6% of killing. In the case of the venom extract treatment group, killing by Aβ was 18.7% when treated with 1 μg / ml. , 10 ㎍ / ㎖ treatment was suppressed to 11.8%, it can be seen that the poisonous extract effectively inhibits the death due to Aβ at a concentration of 10 ㎍ / ㎖.

Experimental Example 4: Determination of Inhibitory Effect of Toxin Extract on Intracellular Calcium Concentration

In this experiment, the fluorescent dye, Fluo-4 AM (3 μM; Molecular Probes, Inc.), was added to cultured neurons, and when Aβ was added thereto, the intracellular Ca ²⁺ concentration increased. The measurement method using the property that the reagent is combined with Ca ²⁺ to increase the absorbance was used.

That is, neurons grown on coverslips were loaded with 3 μM fluor-4 AM (soluble in dimethylsulfoxide (DMSO) in serum-free growth medium for 45 minutes at 37 ° C. in a CO ₂ incubator. Coverslips containing fluorine-4 AM-labeled neurons were mounted on a perfusion chamber containing culture buffer and added to a laser scanning confocal microscope (Carl Zeiss LSM 510, Obercohen, Germany) to 488. Scanning was performed every 3 seconds using a nm excitation argon laser and a 515 nm long pass radiation filter. After baseline of [Ca ²⁺ ] _c was observed for 50 seconds, to measure the change in [Ca ²⁺ ] _c 10 μΜ Aβ (25-35) was added to the perfusion chamber. To test the effect of toxin extract on Aβ (25-35) -induced [Ca ²⁺ ] _c changes, neurons were pretreated with toxin extract (10 μg / ml) 15 minutes before Aβ (25-35) treatment. It was.

The results are shown in FIG. As shown in FIG. 3, when Aβ was added to fluorine-4 AM-treated neurons, fluorescence intensity rapidly increased while intracellular calcium concentration ([Ca ²⁺ ] _c ) was increased. Compared to the default value of 100, the maximum fluorescence intensity increased to 220 when Aβ was applied. On the other hand, when pre-treatment of the venom extract (10 μg / ml), an increase in [Ca ²⁺ ] _c induced by Aβ was suppressed, showing only a slight increase.

Experimental Example 5: Determination of the inhibitory effect of free radical production of ROS extract

In this Experimental Example, the inhibitory effect of Aβ on the activation of free radicals was determined by 2'7'-dichlorofluorescin, a fluorescent product of H ₂ DCF-DA (Molecular Probes, Inc.) ( DCF) was used for the microfluorescence analysis. That is, neurons grown on coverslips were washed three times with phenol-free DMEM and incubated in the presence of 10 μM Aβ (25-35) at 37 ° C. for 24 hours. At this time, the poisonous extract was added 15 minutes before the Aβ treatment to be present in the medium during the incubation period with Aβ. Acquisition of H ₂ DCF-DA (final concentration, 5 μM) dissolved in DMSO was performed for the last 10 minutes of incubation with Aβ (25-35). After washing, the coverslip containing cortical neurons loaded with H ₂ DCF-DA was mounted on a confocal microscope stage, and the neurons were confocal scanning laser microscope using 488 nm excitation, a 510 nm radiation filter ( Observation by Bio-rad, MRC1021ES, Maylands, UK). Five to six images per cover slip were taken and the average fluorescence intensity measured in each cell of each field was expressed in relative units of DCF fluorescence. In this case, the higher the fluorescence intensity, the higher the generation of free radicals.

The results are shown in FIG. As shown in FIG. 4, the fluorescence intensity increased about 2.5-fold from 50.6 to 126.7 of control cells due to the generation of reactive oxygen by Aβ. In contrast, when the poison extract (1, 10 ㎍ / ㎖) treatment, the fluorescence intensity was reduced to 66.7 and 58.0, respectively.

Experimental Example 6: Measurement of Cerebral Infarction Inhibitory Effect of Toxin Extract

300 ± 5 g SD rats were inhaled with 1-2% isoflurane (N ₂ O: O ₂ = 4: 1) and then surgically exposed the right carotid artery. The groin artery branching from the external carotid artery to the central part and the thyroid gland branching from the external carotid artery to the internal carotid artery were ligated electrochemically. Arrange the area well until a Y-shaped branch is found above the internal carotid artery, and then the head of the external carotid artery is threaded to block blood flow and to prevent blood flow between the total carotid and internal carotid arteries. The bottom was clipped. After inserting a probe through a small hole in the carotid artery, the probe and the lower part of the external carotid artery were lightly tied to the thread just enough to prevent bleeding, and then the clip that blocked the blood flow was removed. After cutting between the hole where the probe was inserted and the tied portion of the external carotid artery, the probe inserted into the external carotid artery was carefully inserted into the internal carotid artery. The probe was inserted into the inner vessel of the blood vessel branching Y-shaped above the internal carotid artery. The probe was inserted only 20 mm from the total carotid artery branch. Immediately after surgery, the rectal body temperature was measured at 37.5 ° C. and maintained at 38 ± 0.5 ° C. for 6 hours. The probe was removed and reperfused after 3 hours of ligation. After 24 hours, the rats were dislocated and the brains were separated, cut into 2 mm thick using a brain substrate, stained with 2% TTC (2,3,5-triphenyltetrazolium chloride) solution for 30 minutes at 37 ° C, and then digitally photographed. The infarct volume was measured using an image analysis system.

Infarct volume = [(right normal tissue volume-left normal tissue volume) / right normal tissue volume] × 100

The results are shown in FIGS. 5A and 5B. According to Figure 5a, the left cerebral tissue induces cerebral ischemia in the state without processing anything, it can be seen that the cerebral infarction is white in the left hemisphere, compared with the brain of the right picture before the artery ligation When administered orally 30 minutes and 1 hour after ligation and 1 hour after ligation removal, cerebral infarction caused by cerebral ischemia caused by carotid artery ligation was significantly suppressed. In addition, as shown in FIG. 5B, the control group had an infarct volume of 50.6%, the venom extract 30 mg / kg administration group, 40.1%, and the venom extract 50 mg / kg administration group showed an infarct volume of about 60%. Sikkim was known.

According to the present invention, the ethanol extract of virulence significantly inhibited apoptosis induced by Aβ, increased intracellular calcium concentration, and free radical production, and significantly inhibited cerebral infarction due to cerebral ischemia. Therefore, the toxic ethanol extract of the present invention can effectively prevent or treat cerebral infarction, cerebral ischemia, stroke and / or dementia, especially vascular dementia, without side effects.

Claims (4)

A prophylactic or therapeutic agent for cerebral infarction, cerebral ischemia, stroke or vascular dementia, containing an ethanol extract of Aralia cordata as an active ingredient. The prophylactic or therapeutic agent according to claim 1, wherein the ethanol is 60% ethanol. The prophylactic or therapeutic agent according to claim 1, wherein the venom is a venom vigor. The prophylactic or therapeutic agent according to any one of claims 1 to 3, further comprising a pharmaceutically acceptable carrier.

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