KR101247633B1 - Composition for treating stroke - Google Patents

Abstract

The present invention relates to a composition for preventing or treating stroke, and more specifically, to prevent or treat a stroke comprising a Chinese herbal extract consisting of sugar ear, red peony, five drops, saengbuja, joiner, safflower, cabbage, cinnamon and licorice as an active ingredient It relates to a composition for. Herbal extracts of the present invention, sugar extract, red medicine, oak, hyangbuja, joiner, safflower, cauliflower, cinnamon and licorice extract is effective in promoting stroke relaxation, causing blood pressure drop, reducing cerebral infarction and reducing stroke. Since the composition of the present invention comprising such an herbal extract as an active ingredient can be usefully used for the prevention or treatment of stroke.

Description

Composition for treating stroke

The present invention relates to a composition for the prevention or treatment of stroke comprising herbal extract as an active ingredient.

Stroke, commonly known as stroke, is a disease in which the brain is damaged due to blockage or bursting of blood vessels that supply blood to the brain. There are two types of strokes: cerebral infarction (80-85%) and hemorrhage (15-20%). Caused by factors.

In ischemic stroke, the main cause is thromboembolism of the cerebral artery due to vascular atherosclerosis, or cardiac embolism due to embolism and heart disease.In case of cerebral hemorrhage, primary cerebral hemorrhage due to hypertension and subarachnoid hemorrhage due to arteriovenous malformation or aneurysm are important. to be.

Cerebral infarction, which is caused by clogged cerebrovascular vessels, is divided into thrombosis and cerebral embolism, which causes arteriosclerosis due to hypertension, diabetes mellitus, and hyperlipidemia, resulting in thickening or stiffening of the walls of the arteries. The inner wall is susceptible to wounds, so it is not smooth, and the blood is entangled and eventually clogged. The supply of blood is significantly reduced or interrupted, resulting in a lack of oxygen and nutrient supply to brain cells, leading to disorders of the brain function. Brain embolism or heart atrial fibrillation Due to the disease of the blood flow in the heart is abnormal, part of the blood is partly stagnant in the heart and thus coagulates, resulting in blood debris, which fall off to block the cerebral blood vessels, causing cerebral infarction.

In the case of cerebral hemorrhage, the pressure in the cerebral blood vessels is increased due to high blood pressure, so that the walls of the small blood vessels cannot endure, the primary cerebral hemorrhage is weak. Subarachnoid hemorrhage and cerebral arteriovenous malformation caused by bursting are inherently present, and high arterial pressure is transferred directly to the vein, resulting in cerebral hemorrhage.

Such strokes are one of the leading causes of death worldwide, including in Korea, and are the three leading causes of adult death, along with heart disease and malignant tumors, as the average life expectancy increases.

In the treatment of stroke, brain tissue is not regenerated once damaged, so the most important thing in stroke treatment is prevention.

The purpose of the treatment of stroke is to reduce risk factors and to pre-treat existing lesions to prevent recurrence, to reduce brain edema when cerebral infarctions occur, and to reduce secondary brain damage by allowing the ischemic state to circulate properly. will be.

The mechanism of occurrence of stroke and the prevention and treatment thereof according to the present are as follows.

Decreased cerebral blood supply, a representative sign of stroke, induces cerebral infarction, causing damage to the hippocampus associated with memory and learning cognitive function (H. Hodges et al., Neuroscience, 72 (4): 959-988, 1996 Ni JW et al., Brain Res. 673: 290-296, 1995), and are also closely associated with multiple necrosis of brain tissue (Nigel I. et al., J. cerebral Blood Flow and Metabolism, 17, 421-). 429, 1997). Therefore, anticoagulants, antiplatelets, or thrombolytic agents, which can prevent the occlusion of cerebrovascular vessels, are used as stroke treatments to restore cerebral blood flow.

On the other hand, since brain damage due to stroke is caused by damage to nerve cells, drugs that can inhibit the activity of glutamate, free radicals, and calcium channels, which are involved in damaging brain cells, are being developed as stroke treatments. . Glutamate, a particularly excitatory amino acid among the above toxic substances, is known to be closely related to brain cell damage in stroke disease, and the excitatory toxic inhibitors by glutamate have become a major stroke treatment.

However, these methods only improve the symptoms caused by stroke to some extent and have not yet been shown to be effective.

Meanwhile, herbal medicines have long been used to treat human diseases and protect the body, and are currently used as a preventive and therapeutic agent for various diseases. In particular, herbal medicine is a natural drug, which has a complex effect, has less side effects even in long-term use, and is more effective in multiple complex causes such as brain disease due to various physiological activities. As a result, interest is growing worldwide.

Therefore, the present inventors have tested the efficacy of the extracts by properly combining the nine kinds of Chinese herbal medicines through animal and cell experiments, significantly promote blood vessel relaxation, cause blood pressure drop, and reduce the site of cerebral infarction stroke treatment After confirming the effectiveness of the present invention was completed.

The present invention provides a composition for preventing or treating stroke, comprising a Chinese herbal extract consisting of Angelica, Red Peony, Ojak, Hyangbuja, Joiner, Safflower, Doin, Cinnamon and Licorice as an active ingredient.

Herbal extracts of the present invention, sugar extract, red medicine, oak, hyangbuja, joiner, safflower, cauliflower, cinnamon and licorice extract is effective in promoting stroke relaxation, causing blood pressure drop, reducing cerebral infarction and reducing stroke. Since the composition of the present invention comprising such an herbal extract as an active ingredient can be usefully used for the prevention or treatment of stroke.

1 is a measurement of the NO production ability in the cerebrovascular cells by the herbal medicine extract of the present invention.
Figure 2 is a graph showing the vascular relaxation response by the herbal medicine extract of the present invention.
Figure 3 shows the effect of the herbal medicine extract of the present invention on systemic blood pressure.
Figure 4 shows that the Hankukjae extract of the present invention has a protective effect on cerebral infarction, Figure 4A shows the cerebral infarction site by TTC staining, Figure 4B is the measurement of the infarct volume, Figure 4C Comparing the width of the cerebral infarction by slices at 2 mm intervals, we measured the reduction of the brain injury in the posterior part.
Figure 5 is an electrophoresis picture showing the increase in the amount of phospho-eNOS expression in the brain following oral administration of the herbal extract of the present invention.

The present invention relates to a composition for preventing or treating stroke, comprising a Chinese herbal extract consisting of Angelica, red peony, five drops, hyangbuja, joiner, safflower, cabbage, cinnamon and licorice as an active ingredient.

Hereinafter, the herbal medicine extract consisting of Angelica, red peony, five drops, hyangbuja, joiner, safflower, cabbage, cinnamon and licorice are simply called 'herbal extract'.

First, the herbal medicines constituting the herbal extracts, Angelica, Red Peony, five pills, Hyangbuja, joiner, safflower, cabbage, cinnamon and licorice will be described in detail.

Angelica ( Angelica gigas ) 'is a 2-3 year-old herb that uses roots and has the effects of blood, gut, landscaping, and menstruation in oriental medicine. , Decursin, decursinol, nodakenin, alpha-pinene, limonen, elemol and the like. Rice has a relatively active action of blood-squeezed ((), jeonsangyi (귀) has a relatively strong action of blood donation (補血 和 血), but the present invention is to use the desirable.

'Peonia lactiflora ' is a plant of the genus Butaria, 50-80㎝ tall, and perennial. It is reported that red pepper is dried and used as a medicinal herb. It is reported to contain various components such as essential oils, fatty oils, resinous substances, benzoic acid, tannins, peonyflorin, and peonine. Pharmacological action is known to have the effects of analgesic, fever, jingyeong, diuresis, hematopoiesis.

'Lindera strychnifolia' is a medicinal name of the root of the Yak tree, which is an evergreen shrub or small tree of the dianthus cultivar of the genus Lianaaceae, which grows in southern China and Taiwan, is also wild in southern Japan, and imported from Korea. The leaves of the hibiscus are alternate, wide oval, with flat edges, and have three large veins. Flowers are single, yellowish green, cut in 6, 9 stamens in male flowers, 1 pistil and degenerate stamens in female flowers. Fruits are nucleus, oval, mature from green to black. It is called Cheontae Yak because it is mainly made of Cheontae Mountain. It has a warm and spicy taste. It is known to have analgesic, sedative, healthy, warm, and acidic effects on parenteral, menopause, nerve and bladder.

'Cyperus rotundus' is a perennial herbaceous grass native to Korea, China, and Japan. The leaves are gathered from the roots, the flowers bloom in July-August, and the stems are 20-30㎝ long. 2-3 bracts run and branches spread in mountain. The roots are mainly used. Unlike the roots, tubers contain essential oils and fatty oils. In oriental medicine, they are used for headache, abdominal pain and menstrual irregularities.

Joiner ( Caesapinia sappan L) 'is a deciduous arborescent or shrub belonging to the legume, dried heartwood, which is collected throughout the year to remove the bark and sapwood, and reconstructed by taking only the central part. It is also called firefighting suit, firefighting, red-eye, and red porcelain. It is distributed in southern China and eastern India and grows in the tropics. The neck of the joiner contains about 2% of brazilin, a colorless primary pigment, as well as sappanine, L-phellandrene and ocimene. Essential oils and tannins are included. Pharmacological action is known to have an antimicrobial effect of inhibiting the growth of diphtheria bacteria, pneumococcal pneumoniae, yellow staphylococcus aureus.

Safflower ( Carthamus tinctorius L. ) 'is called red ram, flower bud, safflower and safflower. When it gets wet with early dew, dried flowers are called safflower and dried flowers are used as herbal medicine. It has the effect of activating the symptomatic blood circulation and beating pain, and it is applied to the diseases caused by various fish blood cells. It becomes a commercial drug.

Prunus persica ) 'is used as a medicinal herb to dry mature seeds. It has the efficacy of live bloodfish and yunjangtung stool, which can be applied to the symptoms caused by fish blood cells. .

Cinnamon is the bark of the camphor tree of the camphor tree and is divided into true cinnamon from Sri Lanka and cashier cinnamon from China, Japan and Korea. Remove cinnamon's crust or dry it, usually cinnamon or broiler. Extracts of cinnamon include ingredients such as cinnamic aldehyde, canpen, cineol, cinnamic acid, linalul, eugenol, fat, phosphorus, iron, vitamin A, and vitamin B group. The pharmacological action of cinnamon has been reported to improve the bacteriostatic action, white bacteriophage suppression action, psoriasis action, saliva and gastric juice secretion action.

' Glycyrrhiza uralenisis Fisch ) 'is a medicinal plant that is distributed in northeastern China, Siberia and Mongolia. The root is sweet and is used as a sweetener and herbal medicine.

Herbal extracts contained in the compositions of the present invention may be prepared according to conventional methods known in the art.

For example, sugar ear, red peony, oak, saengbuja, joiner, safflower, cauliflower, cinnamon and licorice may be added to the primary distilled water and extracted by applying heat, and then the extract is filtered under reduced pressure, and then the filtrate may be concentrated.

Meanwhile, the herbal extract included in the composition of the present invention may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze drying or spray drying.

According to a preferred embodiment of the present invention, the content of the herbal extract is 0.001 to 10% by weight based on the total weight of the composition. When the content of the herbal extracts of the present invention is less than 0.001% by weight can not expect a clear stroke prevention or treatment effect.

The composition for preventing or treating stroke according to the present invention may be a pharmaceutical composition or a food composition.

The pharmaceutical composition for preventing or treating stroke may be prepared using a pharmaceutically acceptable and physiologically acceptable adjuvant in addition to the herbal extract, and the adjuvant may include an excipient, a disintegrant, a sweetener, a binder, a coating agent, and an expanding agent. , Lubricants, lubricants or flavoring agents can be used.

The pharmaceutical composition may be preferably formulated into a pharmaceutical composition including one or more pharmaceutically acceptable carriers in addition to the herbal extract for administration.

Formulation forms of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a mixture. Suitable binders include but are not limited to natural and synthetic gums such as starch, gelatin, glucose or beta-lactose, corn sweeteners, acacia, trackercance or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like. Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile water and sterile water suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.

The dosage of the pharmaceutical composition of the present invention is not particularly limited, but in adults, it is preferable to administer the pharmaceutical composition of the present invention at a dose of 1 to 250 mg / kg once to several times daily. It is preferable that this dosage is appropriately increased or decreased depending on the age, condition, and symptoms of the patient. The daily dose may be administered once or in two or three times a day at appropriate intervals or may be administered intermittently at intervals of several days. However, since the dosage of the pharmaceutical composition of the present invention is determined in view of various related factors such as the route of administration, the age, sex, weight of the patient, the severity of the patient and the like, the dosage may limit the scope of the present invention in any aspect. It should not be understood as. The pharmaceutical compositions of the present invention may be administered in a conventional manner via the oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, sternum, transdermal, topical, intraocular or intradermal routes.

The food composition for preventing or treating stroke of the present invention may be formulated in the same manner as the pharmaceutical composition, used as a functional food, or added to various foods.

Foods to which the composition for preventing or treating stroke may be added include, for example, beverages, meat, chocolate, foods, confectionary, pizza, ramen, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes. , Dietary supplements and dairy products.

At this time, the amount of the herbal extracts added to the food is preferably 0.01 to 10 parts by weight based on the total food weight. In particular, when the food is a beverage, it may be added in a ratio of 0.001 to 1g, preferably 0.1 to 1g based on 100ml of the total beverage composition. If the amount added is less than 0.001g can not expect a clear stroke prevention or treatment effect, if the amount is added more than 1g the bitter taste of the herbal medicine will interfere with the taste of the food itself.

The food composition of the present invention may contain a conventional supplement as an additional ingredient in addition to the herbal extract. The adjuvant includes nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protection Sex colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks.

The present invention also provides a food for the prevention or treatment of stroke, which comprises a Chinese herbal extract consisting of Angelica, Red Peony, Yakja, Hyangbuja, Joiner, Safflower, Doin, Cinnamon and Licorice as an active ingredient.

The foods include, for example, beverages, meat, chocolate, foods, confectionery, pizza, ramen, other noodles, gums, candy, ice creams, alcoholic beverages, vitamin complexes, dietary supplements and dairy products.

The present invention also

(a) preparing a mixed medicinal herb by mixing Angelica delicacies, red peony, five drops, hyangbuja, joiner, safflower, cabbage, cinnamon and licorice;

(b) adding first distilled water to the mixed medicine and then heating and extracting it;

(c) concentrating the extract under reduced pressure; And

(d) drying the concentrate provides a herbal extract preparation method comprising the step of obtaining a dry extract.

In the step (a), the mixed medicinal herbs are mixed with sugar ear, red peony, five drops, saengbuja, joiner, safflower, cabbage, cinnamon and licorice in a weight ratio of 3: 2: 2: 2: 2: 2: 1.6: 1.4: 1.2: 1. It is preferable. When mixed in the above ratio, the effect of preventing or treating stroke of the herbal medicine extract of the present invention is increased.

In the step (b), it is preferable to perform the hot water for 120 minutes to 150 minutes at a temperature of 80 to 95 ℃ with an electric bath.

In the step (d), it is preferable to freeze-dry using a freeze dryer.

Advantages and features of the present invention and methods of achieving them will become apparent with reference to the embodiments described in detail below. However, the present invention is not limited to the embodiments disclosed below, but will be implemented in various forms, and only the embodiments are intended to complete the disclosure of the present invention, and the general knowledge in the technical field to which the present invention pertains. It is provided to fully convey the scope of the invention to those skilled in the art, and the present invention is defined only by the scope of the claims.

Example  1: Preparation of Extract

Sugar per capita 5.625g, red pepper 3.750g, oak 3.750g, hyangbuja 3.750g, sapling 3.750g, safflower 3.000g, sauerkraut 2.655g, cinnamon 2.250g, licorice 1.875g Tea was added to 1 liter of distilled water for 2 hours using a Daewoong medicinal water bath. After concentrating in a vacuum concentrator and then using a freeze dryer to obtain a dry extract of 10 grams (total yield 15%).

Example  2: in cerebrovascular cells Nitrik Oxide ( Nitric Oxide ) Generation efficiency measurement

Herbal Medicine Extract of Example 1 in Human Brain Microvascular Endothelial Cells (HBMEC) using 4-amino-5-methylamino-2,7-difluorofluorescein diacetate (DAF-FM), an NO fluorescence indicator that crosses the membrane well NO production was measured and the results are shown in FIG. 1.

As shown in Figure 1, it can be observed that the production of NO increases as the concentration of the herbal extract of Example 1 increases.

Example  3: Vascular Relaxation  Efficacy Measurement

The aorta of the C57BL / 6J mouse was extracted and connected to the organ chamber to measure the vasorelaxant efficacy of the extract of Example 1 through tension measurement. The aorta was cut to a length of 1.5 to 2 mm to form a ring shape and connected to the chamber to stabilize the basal tension to be 1.3 ± 0.6 g, and then phenylephrine (10 μmol / L) was administered to constrict the blood vessel. When the proper basal tension was obtained, the relaxation response was observed while administering 10, 30, 100 and 300 µg / ml of the herbal extract. Pretreatment of L-NAME (100μmol / L) with inhibitor of nitric oxide synthase and observation of vascular relaxation of the herbal extracts confirmed NO-dependent or non-dependent vascular reactions. 2 is shown.

As shown in Figure 2, when the aorta of the isolated C57BL / 6J mice were treated with the herbal extract of Example 1 by 10, 30, 100, 300 ㎍ / ml, respectively, the blood vessels relaxed as the concentration increased. (Control). On the other hand, pretreatment with L-NAME (100μmol / L), a nitric oxide synthase inhibitor, and extract treatment, significantly reduced vascular relaxation. As a result, it was confirmed that the vasorelaxation reaction by the extract of the present invention was a NO-dependent vasculature.

Example  4: verification of blood pressure lowering efficacy

C57BL / 6J mice (20-25 g) were anesthetized with isoflurane (70% N ₂ O and 30% O ₂ ), and then the herbal medicine extract of Example 1 was injected into the femoral vein using an infusion pump. While injecting, blood pressure was measured through a carotid artery to verify the blood pressure drop efficacy of the herbal extract. The body temperature was kept constant while measuring the rectal temperature with a thermostat (Homothermic Blanket Control Unit) while measuring the blood pressure, the results are shown in Figure 3 below.

As shown in Figure 3, while measuring the systemic blood pressure through the carotid artery while injecting the extract through the femoral vein of C57BL / 6J mouse (20-25g) using an injection pump, the concentration of the extract of the present invention is As the blood pressure increased, blood pressure was significantly lowered.

Example  5: verification of protective effect of ischemic cerebrovascular disease (stroke)

C57BL / 6J mice (20-25 g) fed the herbal extract of Example 1 (15 mg / kg / day) for 3 days orally were anesthetized with isoflurane (70% N 2 O and 30% O 2), followed by filament middle. The cerebral ischemia model was established by the cerebral artery occlusion method. After blocking the blood flow for 90 minutes and reperfusion for 24 hours, the brain was extracted and the cerebral infarction site was measured by TTC staining, and the results are shown in FIG. 4.

As shown in Figure 4, animals fed the herbal medicine extract (15 mg / kg / day) of the present invention for 3 days in the oral cavity, the cerebral infarction area was reduced (4A), compared to the animals that do not, the infarct volume (infarct) volume), the extract of the present invention significantly reduced the area of brain injury (4B). In addition, comparing the width of cerebral infarction by slices at 2mm intervals, it could be observed that the extract of the present invention reduced the brain injury of the posterior part, in particular (4C).

Example  6: Medicinal Herb Extracts in Ischemic Brain Tissues eNOS  Expression measurement

There are three enzymes that produce NO: endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and inducible NOS (iNOS). Among these, eNOS is mainly expressed in endothelial cells, and this enzyme produces NO. The NO thus formed is known to relax blood vessels mainly to increase blood flow, and to inhibit thrombosis and apoptosis. Therefore, in this Example, the effect of the herbal extract of the present invention on the activation of eNOS was evaluated.

To this end, cerebral ischemia was induced in C57BL / 6J mice (20-25 g) fed the extract of Example 1 (15 mg / kg / day) for 3 days orally, and the brain was extracted to measure eNOS expression. Since phosphorylation of eNOS is important for eNOS activation, the expression of phospho-eNOS was also measured.

As a result, as shown in Figure 5, the expression of eNOS in the oral brain (ipsilateral) where the ischemia of the animals fed the extract of the present invention (15 mg / kg / day) for 3 days in the oral cavity was not Although unchanged, the expression of phospho-eNOS was increased, showing a similar tendency in the contralateral non-ischemic brain. This herbal extract was found to increase eNOS activity by increasing the phosphorylation of eNOS.

Claims (5)

A pharmaceutical composition for preventing or treating stroke, comprising a Chinese herbal extract consisting of Angelica, Red Peony, Ojak, Hyangbuja, Joiner, Safflower, Doin, Cinnamon and Licorice as an active ingredient.
The method of claim 1,
The herbal extract is a pharmaceutical composition for preventing or treating stroke, characterized in that it comprises 0.001 to 10% by weight based on the total weight of the composition.
delete A food composition for preventing or improving stroke comprising a Chinese herbal medicine extract consisting of Angelica, Red Peony, Yakja, Hyangbuja, Joiner, Safflower, Doin, Cinnamon and Licorice as an active ingredient.
5. The method of claim 4,
The food is characterized in that one kind selected from the group consisting of beverages, meat, chocolate, food, confectionery, pizza, ramen, other noodles, gum, candy, ice cream, alcoholic beverages, vitamin complexes, dietary supplements and dairy products, Food composition for preventing or improving stroke.

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