CN104324250B - A kind of cerebral arterial thrombosis Chinese medicine composition and preparation method thereof - Google Patents

Abstract

The invention discloses a traditional Chinese medicine composition for ischemic stroke and a preparation method thereof. The traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials in parts by weight: 100-150 parts of Panax notoginseng, 170-250 parts of leech, 30-50 parts of astragalus, 5-10 parts of borneol, 15-25 parts of lotus seed heart, 15-25g of dendrobium, 35 parts of Gastrodia elata ‑50 parts, 3‑5 parts of scorpion, 15‑25 parts of ground beetle. The preparation method is as follows: respectively pulverize notoginseng, leech, astragalus, lotus seed heart, dendrobium, gastrodia elata, scorpion and ground beetle into fine powder, sieve, weigh and mix according to the weight ratio to form a mixed medicinal powder; then borneol Add it to ethanol and mix it evenly, spray it evenly into the mixed medicine powder, seal it for 24 hours, and you get it. The traditional Chinese medicine composition of the present invention can be made into common oral pharmaceutical dosage forms together with pharmaceutically acceptable carriers and excipients, such as capsules, tablets, granules, pills and the like. The medicinal composition of the present invention has remarkable therapeutic effect on ischemic stroke.

Description

A kind of traditional Chinese medicine composition for ischemic stroke and preparation method thereof

technical field

The invention belongs to a traditional Chinese medicine composition, and specifically discloses a traditional Chinese medicine composition for ischemic stroke and a preparation method thereof.

Background technique

Ischemic stroke, also known as apoplexy, is a common intractable disease that seriously endangers human health and life safety. The motherland's medical science lists it as the first of the four difficult diseases of "wind, tuberculosis, phlegm, and diaphragm". There are obvious Three highs (high morbidity, high disability, high mortality) phenomenon. According to statistics, there are 2 million patients with ischemic stroke in China every year, and the incidence rate is as high as 1.20/100,000; 1.2 million patients died due to ischemic stroke, and there are 7 million surviving patients, of which 4.5 million patients have lost to varying degrees. The labor force and daily life cannot take care of themselves, and the disability rate is as high as 75%. Ischemic stroke poses a great threat to human health and life, not only brings great pain to patients, but also brings great economic burden to patients' families. Therefore, it is imperative to fully understand its severity, improve its treatment and prevention, and reduce its morbidity, disability and mortality.

At present, there are many western medicines for the treatment of ischemic stroke, including vasodilators, blood volume expansion drugs, thrombolytic drugs, anticoagulant drugs, calcium ion antagonists, etc. These drugs are widely used, but they may cause intracerebral steal syndrome, Risk of adverse reactions such as bleeding.

Contents of the invention

Aiming at the problems existing in the prior art, the object of the present invention is to provide a traditional Chinese medicine composition for ischemic stroke and a preparation method thereof. The pharmaceutical composition of the present invention has mild drug effect, simple formula, clear mechanism, less toxic and side effects, and has the effects of nourishing qi and activating blood circulation, dredging meridian and activating collaterals, dispelling blood stasis and promoting regeneration, refreshing the brain and resuscitating the brain, and is used for treating ischemic stroke. significantly.

In order to achieve the above object, the present invention adopts the following technical solutions.

A traditional Chinese medicine composition for ischemic stroke, characterized in that it comprises the following traditional Chinese medicine components in parts by weight: 100-150 parts of Panax notoginseng, 170-250 parts of leeches, 30-50 parts of astragalus, 5-10 parts of borneol, lotus seeds Heart 15-25 parts, Dendrobium 15-25g, Gastrodia elata 35-50 parts, Scorpio 3-5 parts, Wood beetle 15-25 parts.

Preferably, the dosage of the traditional Chinese medicine components is: 130-138 parts of panax notoginseng, 188-230 parts of leech, 37-45 parts of astragalus, 7-9 parts of borneol, 19-23 parts of lotus seed heart, 19-23 g of dendrobium, 37 parts of Gastrodia elata -45 parts, 3-5 parts of scorpion, 19-23 parts of ground beetle.

Preferably, the optimal dosage of the traditional Chinese medicine components is: 125 parts of panax notoginseng, 208 parts of leech, 41.2 parts of astragalus, 8.3 parts of borneol, 20.8 parts of lotus seed heart, 20.8 parts of dendrobium, 41.2 parts of Gastrodia elata, 4.2 parts of scorpion, 4.2 parts of ground beetle 20.8 servings.

The preparation method of the above-mentioned traditional Chinese medicine composition for ischemic stroke is characterized in that it comprises the following steps: respectively pulverizing Panax notoginseng, leech, astragalus, lotus seed heart, dendrobium, gastrodia elata, scorpion and ground beetle into fine powder, and passing 100 Mesh sieve, weigh and mix into mixed medicinal powder according to the weight ratio; add borneol to 8-10 parts of ethanol, mix evenly, evenly spray into the mixed medicinal powder, seal and stuff for 24 hours, to obtain.

The above-mentioned traditional Chinese medicine composition for ischemic stroke together with pharmaceutically acceptable carriers and excipients can be further made into common oral pharmaceutical dosage forms known in the art, such as capsules, tablets, granules, pills or oral liquids.

Compared with the prior art, the present invention has the following advantages and beneficial effects.

The etiology and pathogenesis of apoplexy are mostly lack of righteousness, stagnation of qi due to cold condensation, blood stasis and arterial obstruction. In the process of its formation and development, most of them are empty first and then empty, and there are also those who are empty first and then full. .

The traditional Chinese medicine composition of the present invention selects notoginseng, leech, astragalus, borneol, lotus seed heart, dendrobium, gastrodia elata, scorpion and ground beetle for combination. This composition uses Radix Astragali to invigorate vital energy, arouse righteousness, and promote blood circulation as the main drug; "Nihuazi Materia Medica" believes that Astragalus can help Qi strengthen muscles and bones, grow flesh and nourish blood. Leech, scorpion, ground beetle, Panax notoginseng break blood, remove blood stasis, dredge collaterals, and relieve pain, supplemented by the treatment of stasis blockage; ... Leeches are most fond of eating human blood, and use its strength to attack long-standing cures." "Kaibao Materia Medica" records that the whole worm can "cure all kinds of rheumatic rashes, strokes, hemiplegia, crooked mouth and eyes, astringent speech, and twitching of hands and feet." , "Wang Qiu Yaojie" thinks that Panax notoginseng can "harmonize the blood to stop bleeding, dredge the channels and promote blood stasis, stop blood stasis and astringe new blood". Gastrodia elata and borneol are matched, calming the liver, quenching wind, calming convulsions, and resuscitating as adjuvant medicine; Without saying a word, you can get through all the apertures." Dendrobium and Lianzixin are cold in nature, so it is used to treat the above-mentioned medicines that are too warm. Above-mentioned medicines are used in combination to benefit qi and activate blood, dredge meridian and activate collaterals, remove blood stasis and generate new energy, refresh the brain and have one's ideas straightened out.

Modern pharmacological studies have confirmed that astragalus has the effect of directly expanding blood vessels to quickly reduce blood pressure, and has anti-hypoxia effect, which can improve the resistance of heart and brain tissue to hypoxia when cerebral infarction and myocardial infarction occur; Scorpion can dilate blood vessels, hinder blood coagulation, and prevent embolism; Panax notoginseng can dilate coronary arteries and lower blood pressure; Gastrodia elata can increase myocardial nutritional blood flow, improve myocardial circulation, increase myocardial oxygen supply, and protect myocardial hypoxia effect. These traditional Chinese medicine combinations make the efficacy of each medicine produce a synergistic effect, thereby being able to effectively treat ischemic stroke.

The traditional Chinese medicine composition of the present invention has mild drug effect, simple formula, clear mechanism, less toxic and side effects, has the effects of nourishing qi and activating blood circulation, dredging meridian and activating collaterals, removing blood stasis and promoting regeneration, refreshing the brain and resuscitating the brain, and is effective for treating ischemic stroke significantly.

Detailed ways

Five typical specific examples of the present invention are given below, but the present invention is not limited to these examples.

Example 1:

It is a Chinese medicine composition for ischemic stroke of the present invention, the dosage form is capsule, and its specific Chinese medicine components and preparation method are as follows:

(1) Weighing raw materials: 102g Panax notoginseng, 175g leech, 33g astragalus, 7g borneol, 15g lotus seed heart, 15g dendrobium, 35g Gastrodia elata, 3g scorpion, 15g ground beetle.

(2) Grind notoginseng, leech, astragalus, lotus seed heart, dendrobium, gastrodia elata, scorpion and ground beetle into fine powder respectively, pass through a 100-mesh sieve, weigh and mix into a mixed powder by weight; add borneol to Mix evenly in 8mL of ethanol, evenly spray into the mixed medicinal powder, seal for 24 hours, pack into capsules to obtain the capsule of the present invention.

Example 2:

It is a traditional Chinese medicine composition for ischemic stroke of the present invention, the dosage form is a tablet, and its specific Chinese medicine components and preparation method are as follows:

(1) Weighing raw materials respectively: 125g notoginseng, 208g leech, 41.2g astragalus, 8.3g borneol, 20.8g lotus seed heart, 20.8g dendrobium, 41.2g Gastrodia elata, 4.2g scorpion, 20.8g ground beetle.

(2) Grind notoginseng, leech, astragalus, lotus seed heart, dendrobium, gastrodia elata, scorpion and ground beetle into fine powder respectively, pass through a 100-mesh sieve, weigh and mix into a mixed powder by weight; add borneol to Mix in 9mL ethanol, spray evenly into the mixed medicinal powder, seal it for 24 hours, use 80% ethanol as a wetting agent to granulate, granulate, dry, pass through a 20-mesh sieve, granulate, and add magnesium stearate for granulation Blending, tableting and film coating to obtain the tablet of the present invention.

Example 3:

It is a traditional Chinese medicine composition for ischemic stroke of the present invention, the dosage form is granules, and its specific Chinese medicine components and preparation method are as follows:

(1) Take raw material drug respectively: 148g Panax notoginseng, 250g leeches, 50g Radix Astragali, 9g Borneol, 25g lotus seed heart, 25g dendrobium, 50g Gastrodia elata, 5g scorpion, 25g ground beetle;

(2) Grind notoginseng, leech, astragalus, lotus seed heart, dendrobium, gastrodia elata, scorpion and ground beetle into fine powder respectively, pass through a 100-mesh sieve, weigh and mix into a mixed powder by weight; add borneol to Mix in 10mL ethanol, spray evenly into the mixed medicinal powder, seal it for 24 hours, use 80% ethanol as a wetting agent to granulate, granulate, dry, pass through a 20-mesh sieve, granulate, and add medicinal starch excipient Prepare the granules of the present invention.

Example 4:

It is a Chinese medicine composition for ischemic stroke of the present invention, the dosage form is capsule, and its specific Chinese medicine components and preparation method are as follows:

(1) Weighing raw materials: 138g Panax notoginseng, 230g leech, 45g astragalus, 9g borneol, 23g lotus seed heart, 23g dendrobium, 45g Gastrodia elata, 5g scorpion, 23g ground beetle.

(2) Grind notoginseng, leech, astragalus, lotus seed heart, dendrobium, gastrodia elata, scorpion and ground beetle into fine powder respectively, pass through a 100-mesh sieve, weigh and mix into a mixed powder by weight; add borneol to Mix evenly in 10mL of ethanol, evenly spray into the mixed medicinal powder, seal for 24 hours, pack into capsules to obtain the capsule of the present invention.

Example 5:

It is a Chinese medicine composition for ischemic stroke of the present invention, the dosage form is capsule, and its specific Chinese medicine components and preparation method are as follows:

(1) Weighing raw materials: 130g Panax notoginseng, 188g leech, 37g Astragalus membranaceus, 7g Borneol, 19g lotus seed heart, 19g dendrobium, 37g Gastrodia elata, 3g scorpion, 19g ground beetle.

(2) Grind notoginseng, leech, astragalus, lotus seed heart, dendrobium, gastrodia elata, scorpion and ground beetle into fine powder respectively, pass through a 100-mesh sieve, weigh and mix into a mixed powder by weight; add borneol to Mix evenly in 8mL of ethanol, evenly spray into the mixed medicinal powder, seal for 24 hours, pack into capsules to obtain the capsule of the present invention.

The beneficial effect of medicine of the present invention is further set forth below by test example.

Test example: the therapeutic effect of Chinese medicine composition of the present invention on rat ischemic cerebrovascular disease

(1) MCAO modeling

Take 60 healthy Wistar rats, both male and female, weighing 180-220 g (provided by the Experimental Animal Center of Fourth Military Medical University, production certificate number: scxk (Jun) Zi No. 2008-005). Raised in separate cages in the laboratory for 1 week, and randomly divided into 6 groups, 10 in each group. All experimental animals were intraperitoneally injected with penicillin 100,000 U per animal 3 days before the operation, twice a day. Before the operation, the rats were fasted and watered for 12 hours, and the rat model of middle cerebral artery occlusion (MCAO) was made by suture method. Intraperitoneal anesthesia was performed with 1% pentobarbital sodium at 30 mg/kg body weight, the supine position was fixed on a sterile ultra-clean workbench, the skin was prepared, and local disinfection was performed with strong iodine. A midline incision was made in the neck with a length of about 2.5 cm. The tissues were separated layer by layer to expose the right common carotid artery, and the internal and external carotid arteries were freed to the head. The external carotid artery was ligated at the bifurcation of the internal carotid artery and the external carotid artery, the common carotid artery was ligated at the proximal end, and a ligature was preset at the distal end. Clamp the distal end of the internal carotid artery with an arterial clip, and puncture the wall of the common carotid artery with a No. 5 needle at a point 3 mm from the bifurcation of the internal carotid and external carotid arteries, and insert it with a known length and a diameter of 0.20 mm. One end is heated into a microspherical nylon thread; while relaxing the arterial clamp, gently push the nylon thread to enter the cranium through the internal carotid artery to the middle cerebral artery (MCA). The length of the thread is about 17-20mm. The common carotid artery was ligated together with nylon thread, the arterial clamp was removed, and the incision was sutured layer by layer. After the operation, penicillin 100,000 U/cause was injected intraperitoneally, twice a day for 3 consecutive days to prevent infection. Postoperative room temperature was controlled at 26-30°C.

Evaluation criteria for MCAO modeling: the left forelimb is flexed and cannot be fully extended; when the tail is raised, the grasping force of the left forelimb is weakened; when the tail is raised, turn to the left; when free movement, there is no directionality, turn to the left or fall; Unable to walk spontaneously, loss of consciousness.

If the rats after modeling have one of the above symptoms, the modeling is successful, otherwise it is a failure and will not be included in the experimental group.

Determination of neurological deficit score. The model animals were scored 24 hours after the operation for neurological function. The scoring method was based on Bederson's right middle cerebral artery infarction model 5-point scoring standard: 0 points, no symptoms of neurological deficit; 1 point, the left forelimb cannot be fully extended; 2 points, circular motion to the left, mild focal neurological deficit; 3 points, dumping to the left, moderate focal neurological deficit; 4 points, unable to walk naturally, suppressed level of consciousness, severe neurological deficit.

(2) Test method

2-1 group administration

After carefully feeding the successfully modeled rats for 15 days, the surviving rats were randomly divided into a model group, a control group, a high-dose treatment group, a middle-dose treatment group, and a low-dose treatment group, with 10 rats in each group, and a normal group at the same time. 10 only. Those who died during the medication were not included in the statistics.

The Chinese medicine composition of the present invention is prepared according to the following formula: 125g Panax notoginseng, 208g leech, 41.2g astragalus, 8.3g borneol, 20.8g lotus seed heart, 20.8g dendrobium, 41.2g Gastrodia elata, 4.2g scorpion, 20.8g ground beetle. Prepare solutions with different concentrations for later use, and administer them to each group according to the design in Table 1, and the control group is injected intraperitoneally once a day. The administration time is 30 days. The brain function of the rats was evaluated 24 hours after ischemia and 30 days after administration. The grouping and medication information are shown in Table 1.

Table 1 Grouping and Medication

2-2 Material collection

After 30 days of medication, the rats in each group were anesthetized with 1% pentobarbital sodium at 30 mg/kg body weight. The anesthetized rats were fixed supine on the operating table, the chest was opened, the aorta was intubated, and the right atrium was cut open. First, 50 mL of sterilized normal saline was perfused from the aorta, and then 250 mL of neutral 4% paraformaldehyde was perfused for internal fixation. After perfusion was maintained for 20 minutes, the brain was quickly removed and placed in 4% paraformaldehyde fixative for 36 hours, and then external fixation was performed.

2-3 Routine paraffin embedding and sectioning

The fixed brain tissue was cut coronally at the optic chiasm, and small pieces of brain tissue of 5 mm were cut coronally at the front and back; dehydrated step by step with volume fractions of 70%, 80%, 95%×2, and 100%×2 ethanol ; Transparent twice in xylene; brain tissue was taken for paraffin embedding; continuous coronal section was cut into 6 μm thick slices;

2-4 Immunohistochemical staining procedure

Use 3-aminopropyl-3-methoxysilane (APES) to glue the glass slides, and after the brain tissue slices are adhered, bake the slices on a baking machine at 60-62°C for 30-60 minutes to make the slices adhere tightly; Wax to water; distilled water was freshly prepared with 3% H2O2, and the slices were placed at room temperature for 5-10 minutes to inactivate endogenous enzymes. Wash the slices with distilled water for 3 times; add compound digestive solution dropwise, place at room temperature for 5-10 minutes, and wash with distilled water for 3 times; add normal serum blocking solution dropwise, keep at room temperature for 20 minutes, shake off excess liquid without washing; add appropriately diluted primary antibody dropwise, Overnight at 4°C, wash with 0.01mPBS (phosphate buffer) for 2min×3 times; add biotinylated goat anti-mouse/rabbit IgG dropwise, at 20～37°C, 20min, wash with 0.01mPBS for 2min×3 times; dropwise add reagent SABC ( Streptavidin complex), 20～37℃, 20min, 0.01mPBS wash 10min×4 times; DAB (3,3N-diaminobenzidine) color development: use DAB color development kit, add 1mL distilled water, add The ratio of 1 drop of A, B, and C reagents in the kit is mixed evenly and then dropped onto the slices. The color is developed at room temperature, and the reaction time is controlled under the microscope. Wash with distilled water; counterstain lightly with hematoxylin, dehydrate, clear, and mount the slides.

(3) Test results

3-1 Neurofunctional score

The results of neurological function score at different time after cerebral ischemia in each group are shown in Table 2.

Table 2 Neurofunctional scores of rats in each group at different times after cerebral ischemia

(n=10, )

Note: Compared with the model control group, ^## P＜0.01

24 hours after rat ischemia, the comparison between each group was P>0.05, and there was no significant difference, indicating that the degree of neurological deficit of the modeled animals in each group was consistent; The defect is obviously alleviated, and there is a statistical difference with the model group, while the effect of the control group and the 40 mg/kg body weight of the drug of the present invention is more significant.

3-2 Optical microscope observation

The expression of bFGF and VEGF in the brain tissue around the infarct was mainly observed. The reaction intensity was judged as follows: most of the cell membrane and cytoplasm stained in brown were strongly positive (+++); the staining intensity of the cell membrane and cytoplasm was weakened, showing Those with light brownish yellow color are weak positive expression (+); those with coloring intensity between the two are positive expression (++); those with little or no coloration are negative expression (-). The detection results of bFGF expression are shown in Table 3, and the detection results of VEGF expression are shown in Table 4.

Table 3b FGF expression detection results

(n=10, )

Note: Compared with the model control group, ^## P＜0.01

According to Ridit analysis, compared with the normal group, the high and middle dose groups of the treatment group, P<0.01, there is a very significant difference; compared with the normal group, the low dose treatment group, P<0.05, there is a significant difference; Compared with the model group, P<0.01, there was a very significant difference; compared with the model group, P<0.01, there was a very significant difference; compared with the control group, P<0.01, there was a significant difference. Very significant difference.

Table 4 VEGF expression detection results

According to Ridit analysis, compared with the normal group, the high and middle dose groups of the treatment group, P<0.01, there is a very significant difference; compared with the normal group, the low dose treatment group, P<0.05, there is a significant difference; Compared with the model group, P<0.01, there was a very significant difference; compared with the model group, P<0.01, there was a very significant difference; compared with the control group, P<0.01, there was a significant difference. Very significant difference.

The experimental results show that, compared with the normal group, the model group and the control group, the administration group has a significant therapeutic effect on ischemic cerebrovascular disease in rats.

Claims (4)

1. A Chinese medicine composition for ischemic stroke, characterized in that, it is made of the following Chinese medicine components in parts by weight: 130-138 parts of Panax notoginseng, 188-230 parts of leech, 37-45 parts of Radix Astragali, 7-7 parts of Borneol 9 parts, lotus seed heart 19-23 parts, dendrobium 19-23 parts, Gastrodia elata 37-45 parts, scorpion 3-5 parts, ground beetle 19-23 parts. 2. The traditional Chinese medicine composition for ischemic stroke according to claim 1, wherein the dosage of said Chinese medicine is: 125 parts of Panax notoginseng, 208 parts of leech, 41.2 parts of astragalus, 8.3 parts of borneol, 20.8 parts of lotus seed heart 20.8 parts of dendrobium, 41.2 parts of Gastrodia elata, 4.2 parts of scorpion, 20.8 parts of ground beetle. 3. The preparation method of the Chinese medicine composition for ischemic stroke according to claim 1, is characterized in that, comprises the following steps: firstly combine Panax notoginseng, leech, astragalus, lotus seed heart, dendrobium, gastrodia elata, scorpion and ground turtle The worms were respectively crushed into fine powder, passed through a 100-mesh sieve, weighed in proportion by weight and mixed into a mixed powder; then borneol was added to 8-10 parts of ethanol, mixed evenly, evenly sprayed into the mixed powder, and sealed for 24 hours. 4. The preparation method of the Chinese medicine composition for ischemic stroke according to claim 3, characterized in that, capsules, tablets, granules, and pills are further made into capsules, tablets, granules, and pills together with pharmaceutically acceptable carriers and excipients or oral solution.