Traditional Chinese medicine composition and application thereof

Abstract

The invention provides a traditional Chinese medicine composition and application thereof, the traditional Chinese medicine composition contains total salvianolic acid and total triterpenic acid of hawthorn, and the traditional Chinese medicine composition has an excellent treatment effect on prevention or treatment of cerebrovascular diseases, especially ischemic cerebrovascular diseases.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, a traditional Chinese medicine composition and its use, and in particular to a traditional Chinese medicine composition containing total phenolic acids from salvia miltiorrhiza and total triterpenic acids from hawthorn and its use in preparing a medicine for preventing or treating cerebrovascular diseases. Background Art

[0002] Stroke, commonly known as stroke, is a clinically common cerebrovascular disease with a high mortality rate and poor prognosis, which places a great burden on the patient's own life, family and social medical care. Stroke is divided into ischemic stroke and hemorrhagic stroke. It is a disease caused by damage to cerebral blood vessels due to various reasons, resulting in focal or overall brain tissue damage. Among them, ischemic stroke is the most common type of stroke in my country, accounting for 75% to 90% of all strokes. Stroke is characterized by high morbidity, disability rate, recurrence rate and mortality rate. With the acceleration of the aging process of the population, the incidence of stroke has increased year by year, and stroke has become one of the most serious diseases affecting human health.

[0003] Currently, surgical treatment is a major clinical treatment strategy for ischemic cerebrovascular disease. However, due to the narrow treatment time window and the risk of hemorrhagic transformation, as well as the low rate of vascular recanalization, only a few patients can benefit from this treatment method. In addition, the recanalization of blood flow will induce a series of secondary pathological injuries, thereby aggravating the tissue damage of ischemic cerebrovascular disease. Therefore, the active development of safe and effective therapeutic drugs is of great significance for the prevention and treatment of ischemic cerebrovascular disease.

[0004] Patent CN 02112488.4 discloses a pharmaceutical composition containing total phenolic acids from salvia miltiorrhiza and total triterpenic acids from hawthorn, which is used to prevent or treat hyperlipidemia. Currently, there is no report that a pharmaceutical composition containing total phenolic acids from salvia miltiorrhiza and total triterpenic acids from hawthorn can be used to treat cerebrovascular diseases. Summary of the invention

[0005] A first aspect of the present invention provides a traditional Chinese medicine composition, which contains total phenolic acids from Salvia miltiorrhiza and total triterpenic acids from Crataegus pinnatifida, and is used for preventing or treating cerebrovascular diseases.

[0006] In the Chinese medicine composition, the content of total phenolic acids of Salvia miltiorrhiza accounts for 80-20% of the total weight of the Chinese medicine composition, and the content of total triterpene acids of Crataegus pinnatifida accounts for 20-80% of the total weight of the Chinese medicine composition.

[0007] The cerebrovascular diseases described in the present invention include ischemic cerebrovascular diseases and hemorrhagic cerebrovascular diseases, preferably ischemic cerebrovascular diseases; the cerebrovascular diseases include acute cerebrovascular diseases and chronic cerebrovascular diseases, preferably acute cerebrovascular diseases; more preferably, the cerebrovascular diseases are acute ischemic cerebrovascular diseases.

[0008] The ischemic cerebrovascular disease described in the present invention specifically includes ischemic stroke (also known as cerebral infarction), cerebral thrombosis, cerebral embolism, cerebral artery steal syndrome, cerebral ischemia-reperfusion injury, etc.; preferably, the ischemic cerebrovascular disease is selected from ischemic stroke or cerebral ischemia-reperfusion injury; more preferably, the ischemic cerebrovascular disease is selected from ischemic stroke.

[0009] The ischemic stroke described in the present invention is preferably acute ischemic stroke.

[0010] The ischemic stroke described in the present invention is caused by cerebral ischemia-reperfusion injury.

[0011] As a preferred embodiment of the present invention, a traditional Chinese medicine composition is provided, wherein the traditional Chinese medicine composition contains total phenolic acids from salvianolic acid and total triterpenic acids from hawthorn, and the traditional Chinese medicine composition is used for preventing or treating ischemic cerebrovascular diseases.

[0012] As a preferred embodiment of the present invention, a traditional Chinese medicine composition is provided, which contains total phenolic acids from salvianolic acid and total triterpenic acids from hawthorn, and is used for preventing or treating ischemic stroke or cerebral ischemia-reperfusion injury.

[0013] As a preferred embodiment of the present invention, a Chinese medicine composition is provided, which contains 80-20% of total phenolic acids from Salvia miltiorrhiza and 20-80% of total triterpenic acids from Crataegus pinnatifida in terms of the total weight of the Chinese medicine composition, and is used for preventing or treating ischemic cerebrovascular disease.

[0014] As a preferred embodiment of the present invention, a Chinese medicine composition is provided, which contains 80-20% of total phenolic acids from Salvia miltiorrhiza and 20-80% of total triterpenic acids from Crataegus pinnatifida, accounting for 80% to 20% of the total weight of the Chinese medicine composition. The Chinese medicine composition is used to prevent or treat ischemic stroke or cerebral ischemia-reperfusion injury.

[0015] The Chinese medicine composition of the present invention further contains one or more pharmaceutically acceptable excipients.

[0016] Preferably, the pharmaceutically acceptable excipients include one or more of a diluent, an antioxidant, a preservative, a solubilizer, a disintegrant, a lubricant, a pH regulator, a colorant, a dispersant, an osmotic pressure regulator or a surfactant.

[0017] Preferably, the diluent is selected from one or more of sucrose, lactose, galactose, glucose, starch, dextrin, gelatin, microcrystalline cellulose, carboxymethyl cellulose, ethyl cellulose and the like.

[0018] Preferably, the antioxidant is selected from one or more of ascorbic acid or butylated hydroxytoluene (BHT).

[0019] Preferably, the preservative is selected from one or more of benzoic acid, sodium benzoate, p-hydroxybenzoate, sorbic acid or glycerin.

[0020] Preferably, the lubricant is selected from one or more of magnesium stearate, calcium stearate or talc.

[0021] The Chinese medicine composition of the present invention is selected from capsules, tablets, granules, pills, powders, dispersants, solutions, emulsions or suspensions, etc.; preferably, the Chinese medicine composition is selected from capsules or tablets.

[0022] The dosage of the Chinese medicine composition of the present invention is 0.1-1000 mg / kg / day, preferably 1-500 mg / kg / day, and more preferably 1-100 mg / kg / day.

[0023] The dosage of the traditional Chinese medicine composition of the present invention is 250-5000 mg / day, preferably 500-3750 mg / day, and more preferably 750-2500 mg / day.

[0024] In a second aspect, the present invention provides a use of a Chinese medicine composition in preparing a drug for preventing or treating cerebrovascular diseases, wherein the Chinese medicine composition contains total phenolic acids from Salvia miltiorrhiza and total triterpene acids from Crataegus pinnatifida.

[0025] As a preferred embodiment of the present invention, there is provided a use of a Chinese medicine composition in preparing a medicament for preventing or treating ischemic cerebrovascular disease, wherein the Chinese medicine composition contains total phenolic acids from salvianolic acid and total triterpenic acids from hawthorn.

[0026] As a preferred embodiment of the present invention, there is provided a use of a Chinese medicine composition in preparing a medicament for preventing or treating ischemic stroke or cerebral ischemia-reperfusion injury, wherein the Chinese medicine composition contains total phenolic acids from salvianolic acid and total triterpenic acids from hawthorn.

[0027] In the Chinese medicine composition, the content of total phenolic acids of Salvia miltiorrhiza accounts for 80-20% of the total weight of the Chinese medicine composition, and the content of total triterpene acids of Crataegus pinnatifida accounts for 20-80% of the total weight of the Chinese medicine composition.

[0028] As a preferred embodiment of the present invention, there is provided a use of a Chinese medicine composition in the preparation of a medicament for preventing or treating ischemic cerebrovascular disease, wherein the Chinese medicine composition contains 80-20% of total phenolic acids of Salvia miltiorrhiza and 20-80% of total triterpenic acids of Crataegus pinnatifida of the total weight of the Chinese medicine composition.

[0029] As a preferred embodiment of the present invention, there is provided a use of a Chinese medicine composition in the preparation of a medicament for preventing or treating ischemic stroke or cerebral ischemia-reperfusion injury, wherein the Chinese medicine composition contains 80-20% of total phenolic acids of Salvia miltiorrhiza and 20-80% of total triterpenic acids of Crataegus pinnatifida of the total weight of the Chinese medicine composition.

[0030] The Chinese medicine composition of the present invention has excellent preventive or therapeutic effects on cerebrovascular diseases, especially ischemic cerebrovascular diseases, especially ischemic stroke or cerebral ischemia-reperfusion injury. Specifically, the Chinese medicine composition of the present invention can improve behavioral disorders and brain tissue damage in ischemic stroke and inhibit the area of ​​cerebral infarction. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 . Effect of XYJZ on the cerebral infarction area of ​​tMCAO model mice (TTC staining of brain slices shows the brain tissue damage of mice in each treatment group, red is the TTC-positive area, which is healthy brain tissue, and white is the infarction area). DETAILED DESCRIPTION

[0032] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0033] In the following examples, unless otherwise specified, the reagents and consumables used were purchased from conventional reagent manufacturers in the field; unless otherwise specified, the experimental methods and technical means used were conventional methods and means in the field.

[0034] Example 1 Pharmacodynamic study of the Chinese medicine composition (XYJZ) in treating ischemic stroke in mice

[0035] Preparation of Chinese medicine composition: prepared according to patent CN 02112488.4, the Chinese medicine composition is hereinafter referred to as XYJZ.

[0036] Animal model: The mouse middle cerebral artery occlusion-reperfusion model (tMCAO).

[0037] Modeling method: C57BL / 6J mice, 8-10 weeks old, were selected. Mice were anesthetized by inhalation of 1.5% isoflurane, and the body temperature was monitored by rectal temperature monitoring system. The common carotid artery (CCA), internal carotid artery (ICA) and external carotid artery (ECA) were separated, exposed and freed to avoid damaging the vagus nerve. The external carotid artery and its branch, the superior thyroid artery, were freed, and the superior thyroid artery was melted with electrocoagulation forceps. Two 6-0 silk threads were placed under the ECA, and the distal end was ligated, while the proximal end was not ligated temporarily to keep the fixed thread plug. The artery clamps were used to clamp the CCA and ICA, blocking the blood flow of the CCA and the blood flow reflux of the ICA. A "V"-shaped incision was made on the ECA with microscissors. The incision was selected between the two ligatures of the ECA, as close to the distal end of the ECA as possible. The appropriate thread plug was selected according to the weight of the mouse, inserted into the ECA to the bifurcation of the CCA, cut the ECA, adjusted the direction of the thread plug, inserted the thread plug from the ECA into the ICA, loosened the hemostatic clamp on the ICA, and continued to push the thread plug along the ICA to avoid entering the pterygomandibular artery. When slight resistance was felt, the thread plug was stopped. At this time, the insertion depth of the thread plug was about 10mm. The thread plug was fixed and the surface of the incision was covered with a cotton ball of physiological saline. The anal temperature was monitored and maintained at 37°C during the entire ischemic period. Reperfusion: After 60 minutes of ischemia, the thread plug was pulled out, and the artery clamp on the CCA was loosened after the carotid stump was ligated. After the wound was cleaned with physiological saline, the skin was sutured in place, and 1 mL of physiological saline was injected subcutaneously for fluid replacement. After surgery, the mice were placed in a quiet environment and the ambient temperature was maintained at about 25°C.

[0038] Grouping and administration: The mice were divided into model group, XYJZ group, and edaravone and dextromethorphan positive control group (hereinafter referred to as Eda group), with 10 mice in each group. The mice were administered drugs once a day 30 minutes, 1 day, 2 days, and 3 days after tMCAO. The XYJZ group was intragastrically administered with XYJZ (300 mg / kg), the Eda group was intraperitoneally administered with edaravone and dextromethorphan (15 mg / kg), and the model group was intragastrically administered with an equal volume of normal saline.

[0039] Detection indicators:

[0040] 1) mNSS score at 24h of reperfusion;

[0041] 2) Longa mNSS score at 72 h after reperfusion;

[0042] 3) After 72 hours of reperfusion, brain slices were collected and stained with TTC to evaluate the brain death area ratio.

[0043] Data processing: The data were expressed as mean ± standard deviation, and one-way ANOVA test was used to perform statistical difference analysis among the XYJZ group, Eda group and model group.

[0044] Experimental results:

[0045] (1) Behavioral disorder manifestations

[0046] The mNSS and Longa scores of mice in each experimental group 24h and 72h after surgery are shown in Table 1-1 below:

[0047] Table 1-1 mNSS and Longa scores of each group 24h and 72h after surgery

[0048]

[0049] Compared with the model group, *p<0.05, **p<0.01, ***p<0.001.

[0050] At the 24h postoperative monitoring point, the mNSS score results showed that compared with the model group, both the XYJZ group and the Eda group had the ability or trend to reduce the mNSS score, showing statistical differences, and the effects of the two groups were comparable.

[0051] At the monitoring point of 72h after surgery, the mNSS evaluation results showed that compared with the model group, both the XYJZ group and the Eda group had the effect or trend of reducing the mNSS score, among which the XYJZ group reached a statistically significant difference; the effect of XYJZ was better than that of the Eda group.

[0052] At the 72h postoperative monitoring point, the Longa score results showed that compared with the model group, both the XYJZ group and the Eda group had the effect or trend of reducing the Longa score, reaching a statistically significant difference, and the XYJZ group was superior to the Eda group.

[0053] (2) Evaluation of drug efficacy in brain tissue damage

[0054] After completing behavioral testing 72 hours after surgery, the experiment was terminated, and brain tissue sections of mice were taken for TTC staining to evaluate brain tissue damage in each group of mice. The results of cerebral infarction area in each group of mice are shown in Table 1-2 below. Compared with the model group, both the XYJZ group and the Eda group significantly inhibited the proportion of cerebral ischemic infarction area in mice 72 hours after tMCAO surgery, and the results of One-way ANOVA analysis showed significant differences. The XYJZ group was equivalent to the Eda group.

[0055] Table 1-2 Results of cerebral infarction area in each group

[0056]

[0057] Compared with the model group, *p<0.05, **p<0.01, ***p<0.001.

[0058] XYJZ can improve brain tissue damage, inhibit cerebral infarction area, and alleviate behavioral disorders caused by cerebral ischemia-reperfusion in mice with ischemic stroke.

[0059] Example 2 Study on the efficacy of a Chinese medicine composition (XYJZ) in preventing ischemic stroke in mice

[0060] Preparation of Chinese medicine composition: prepared according to patent CN 02112488.4, the Chinese medicine composition is hereinafter referred to as XYJZ.

[0061] Animal model: mouse middle cerebral artery occlusion reperfusion (tMCAO) model. Refer to the modeling method in Example 1.

[0062] Grouping and administration: The mice were divided into a model solvent group and an XYJZ group, with 8 mice in each group. The mice were administered XYJZ (1 g / kg, intragastric administration) once a day for 5 consecutive days before tMCAO and 6 hours after surgery. The XYJZ group was administered XYJZ (1 g / kg, intragastric administration), and the model solvent group was administered an equal volume of normal saline (intergastric administration).

[0063] Detection indicators: 24 hours after reperfusion, the behavioral disorders of mice were evaluated by mNSS scoring method, and the proportion of cerebral infarction (white infarct area / total brain area) was evaluated by brain section / TTC staining.

[0064] Data processing: The data were expressed as mean ± standard deviation, and the Student-t test was used for two-tailed analysis of the statistical differences between the XYJZ group and the model solvent group.

[0065] Experimental results:

[0066] (1) Behavioral manifestations

[0067] The mNSS scores of mice in each experimental group after 24 hours of reperfusion are shown in Table 2-1 below:

[0068] Table 2-1 mNSS scores of each group after 24 hours of reperfusion

[0069]

[0070] Compared with the model solvent group, *p<0.05, **p<0.01, ***p<0.001.

[0071] Compared with the model solvent group, XYJZ at a dose of 1g / kg has the effect of alleviating the behavioral disorders caused by ischemia-reperfusion, which is specifically manifested by significantly alleviating the mNSS score.

[0072] (2) Evaluation of drug efficacy in brain tissue damage

[0073] Figure 1The TTC staining results of the brain sections of mice in each group are shown. After statistical analysis, the results of the cerebral infarction area of ​​mice in each experimental group are shown in the following Table 2-2:

[0074] Table 2-2 Results of cerebral infarction area in each group

[0075]

[0076] Compared with the model group, *p<0.05, **p<0.01, ***p<0.001.

[0077] The results of TTC staining of brain sections of mice in each group showed that XYJZ at a dose of 1g / kg could reduce the cerebral infarction area of ​​ischemic stroke mice, which was significantly different from the model solvent group.

[0078] The applicant declares that the present invention illustrates the technical solution of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

[0079] The preferred embodiments of the present invention are described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, a variety of simple modifications can be made to the technical solution of the present invention, and these simple modifications all belong to the protection scope of the present invention.

[0080] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any suitable manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

Claims

1. A Chinese medicine composition, comprising total phenolic acids from Salvia miltiorrhiza and total triterpenic acids from Crataegus pinnatifida, and is used for preventing or treating cerebrovascular diseases.

2. The Chinese medicine composition according to claim 1, wherein the content of total phenolic acids of Salvia miltiorrhiza accounts for 80-20% of the total weight of the Chinese medicine composition, and the content of total triterpenic acids of Crataegus pinnatifida accounts for 20-80% of the total weight of the Chinese medicine composition.

3. The Chinese medicine composition according to claim 1, wherein the cerebrovascular disease is ischemic cerebrovascular disease.

4. The Chinese medicine composition according to claim 3, wherein the ischemic cerebrovascular disease is selected from ischemic stroke, cerebral thrombosis, cerebral embolism, cerebral artery steal syndrome, and cerebral ischemia-reperfusion injury; preferably ischemic stroke or cerebral ischemia-reperfusion injury; more preferably ischemic stroke.

5. The Chinese medicine composition according to claim 4, wherein the ischemic stroke is caused by cerebral ischemia-reperfusion injury.

6. The Chinese medicine composition according to claim 1, further comprising one or more pharmaceutically acceptable excipients.

7. The Chinese medicine composition according to claim 1, wherein the Chinese medicine composition is selected from capsules, tablets, granules, pills, powders, dispersants, solutions, emulsions or suspensions; preferably capsules or tablets.

8. The Chinese medicine composition according to claim 1, wherein the dosage of the Chinese medicine composition is 0.1-1000 mg / kg / day, preferably 1-500 mg / kg / day, and more preferably 1-100 mg / kg / day.

9. The Chinese medicine composition according to claim 1, wherein the dosage of the Chinese medicine composition is 250-5000 mg / day, preferably 500-3750 mg / day, and more preferably 750-2500 mg / day.

10. Use of the traditional Chinese medicine composition according to any one of claims 1 to 9 in the preparation of a medicament for preventing or treating cerebrovascular diseases.

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