阅读说明：本技术 一种药物组合物、制备方法及其在缺血性脑卒治疗中的应用 (pharmaceutical composition, preparation method and application thereof in treating cerebral arterial thrombosis ) 是由 屈晶 朱海波 普盼盼 渠凯 程妍 杨柳 于 2018-07-18 设计创作，主要内容包括：本发明涉及一种药物组合物,及其在制备治疗脑卒中药物中的应用。此药物组合物由三七总皂苷、川芎提取物、红花提取物、葛根提取物、和山楂提取物制成,其重量配比是,三七总皂苷1～5份,红花10～30份的提取物,葛根15～60份的提取物,川芎10～40份的提取物,山楂20～45份的提取物。红花、葛根、川芎、山楂分别经提取分离纯化得到相应的提取物,与三七总皂苷混合均匀即得。本发明涉及的组合物具有优异的溶解性及成药性,易于吸收和快速起效。(The invention relates to pharmaceutical compositions and an application thereof in preparing a medicine for treating cerebral apoplexy, wherein the pharmaceutical composition is prepared from 1-5 parts of panax notoginseng saponins, 10-30 parts of safflower, 15-60 parts of kudzu vine root, 10-40 parts of ligusticum wallichii and 20-45 parts of hawthorn, and the safflower, the kudzu vine root, the ligusticum wallichii and the hawthorn are respectively extracted, separated and purified to obtain corresponding extracts which are uniformly mixed with the panax notoginseng saponins.)

1, pharmaceutical composition, wherein the composition comprises safflower extract, kudzu root extract, chuanxiong rhizome extract, hawthorn fruit extract and panax notoginseng saponins.

2. The pharmaceutical composition according to claim 1, characterized by comprising the following raw materials:

1-5 parts of panax notoginseng saponins, 10-30 parts of safflower extract, 15-60 parts of kudzu root extract, 10-40 parts of ligusticum wallichii extract and 20-45 parts of hawthorn extract.

3. The pharmaceutical composition according to claim 1, characterized by comprising the following raw materials:

1 part of panax notoginseng saponins, 20 parts of safflower extract, 57 parts of kudzu root extract, 17 parts of ligusticum wallichii extract and 34 parts of hawthorn fruit extract.

4. The pharmaceutical composition according to claim 1, characterized in that:

the preparation method of the safflower extract comprises weighing quantitative safflower, extracting with 8-15 times of water or ethanol water solution for 2-3 times, each for 1-3 hr, mixing extractive solutions, concentrating to about 10 times of crude drug amount, passing through macroporous adsorbent resin column, eluting with water to remove impurities, eluting with 50% ethanol water solution, concentrating eluate, drying, and pulverizing.

5. The pharmaceutical composition according to claim 1, characterized in that:

the preparation method of the radix puerariae extract comprises the steps of weighing quantitative radix puerariae, extracting with 6-10 times of 50-95% ethanol water for 2-3 times, 1-3 hours each time, combining extracting solutions, carrying out reduced pressure distillation to recover ethanol, adding water to about 1-2 times of crude drug amount, passing through a macroporous adsorption resin column, eluting with water to remove impurities, eluting with 70% ethanol water, concentrating eluent, drying and crushing to obtain the radix puerariae extract.

6. The pharmaceutical composition according to claim 1, characterized in that:

the preparation method of the rhizoma Ligustici Chuanxiong extract comprises weighing quantitative rhizoma Ligustici Chuanxiong, extracting with 6-10 times of water or ethanol water solution for 2-3 times, each for 1-3 hr, mixing extractive solutions, concentrating to 4 times of crude drug amount, passing through macroporous adsorbent resin column, eluting with water to remove impurities, eluting with 50% ethanol water solution, concentrating the eluate, drying, and pulverizing.

7. The pharmaceutical composition according to claim 1, characterized in that:

the preparation method of the hawthorn extract comprises weighing quantitative hawthorn, extracting with 6-10 times of 40-70% ethanol water solution for 2-3 times, each time for 1-3 hours, mixing the extractive solutions, distilling under reduced pressure to recover ethanol, adding water to about 2.5 times of crude drug amount, passing through macroporous adsorbent resin column, eluting with water to remove impurities, eluting with 40-75% ethanol water solution, concentrating the eluate, drying, and pulverizing.

8. The pharmaceutical composition of any one of of claims 4-7, wherein the macroporous adsorbent resin column has an adsorption rate of 1-3BV/h, a water washing removal rate of 1-3BV/h, and a desorption rate of 1-3 BV/h.

9. The pharmaceutical composition according to claim 1, wherein the saponin content of the panax notoginseng saponins is 75% or more.

10, A preparation containing the pharmaceutical composition of any one of claims 1-9- , wherein the preparation is prepared from a therapeutically effective amount of the pharmaceutical composition of any one of claims 1-9- and a pharmaceutically acceptable excipient.

11. The preparation according to claim 10, wherein the preparation is kinds selected from tablet, capsule, granule and oral liquid.

12. Use of the pharmaceutical composition of any one of claims 1-9 and and the formulation of any one of claims 10-11 and in the preparation of a medicament for preventing or treating cerebral arterial thrombosis.

Technical Field

The invention relates to a formula of pharmaceutical compositions and a preparation method thereof, and also relates to application of the pharmaceutical compositions in preparing medicines for treating cerebral arterial thrombosis.

Background

Chinese stroke prevention and treatment reports (2017) show that more than 1760 people die of cardiovascular and cerebrovascular diseases in 2016 globally, the stroke incidence rate in China is continuously rising and younger, the morbidity rate is increased to 1.23% in almost two decades, the recurrence rate in reaches 17%, the cumulative recurrence rate in 5 years is more than 30%, the stroke becomes the leading cause of the disease death of residents in China, the number of dead people is 4-5 times higher than in Europe and America, and the ischemic stroke death rate of stroke types accounts for more than 60% -80% and is increased by 28.8%.

The pathogenesis and pathophysiology mechanism of ischemic stroke injury are very complex, and the networked molecular disorder of a plurality of target areas in a plurality of links is involved, and the current strategies and medicines for treating ischemic stroke clinically mainly comprise:

1. thrombolysis

The recovery of cerebral blood flow after cerebral ischemia is the key to the treatment of cerebral ischemia. The thrombolytic therapy is the most important blood flow recovery measure at present, the recombinant tissue plasminogen activator (rt-PA) and Urokinase (UK) are the main thrombolytic drugs used in China at present, and the effective treatment time window is within 3 hours, 4.5 hours or 6 hours after the onset of disease.

However, UK causes a thrombolytic state of the whole body, has a long action time and is easy to bleed, and is not suitable for treating acute cerebral infarction. rt-PA can selectively act on plasminogen in local thrombus to convert the plasminogen into plasmin to play a role in thrombolysis, but also has bleeding risk, and reports show that the rt-PA can significantly increase lethal intracranial bleeding rate; in addition, the appearance of vasogenic edema has been reported to cause obstruction of the airway. And the thrombolytic drug must be used by intravenous injection, and is not effective when being taken orally.

2. Antiplatelet agent

Although the clinical treatment of acute cerebral ischemia by thrombolytic drugs has a good effect, the risk of high bleeding rate is not solved. Because of the lack of therapeutic drugs, preventive drugs such as aspirin and the like are currently used for secondary prevention. Aspirin can obviously reduce the death rate or disability rate at the end of a follow-up period, reduce relapse, only slightly increase the risk of symptomatic intracranial hemorrhage, and is the most commonly used platelet aggregation resisting medicine at present.

Gastrointestinal symptoms are well-known adverse reactions of aspirin, oral aspirin can directly stimulate gastric mucosa to cause epigastric discomfort, nausea and vomiting, and the oral aspirin is easy to cause gastric mucosa injury to cause gastric ulcer and gastrorrhagia after long-term use. For long-term use, blood images, stool occult blood tests and necessary gastroscopy should be monitored frequently.

In addition, for patients who cannot tolerate aspirin, antiplatelet drugs such as phosphodiesterase inhibitors (dipyridamole), adenosine receptor antagonists (ticlopidine or clopidogrel) and the like can be considered.

3. Anticoagulation

Anticoagulant drugs mainly include oral anticoagulants (warfarin) and non-oral anticoagulants (heparins). Reports have shown that anticoagulant treatment cannot reduce end-of-visit mortality; the disability rate at the end of the follow-up period is not obviously reduced; anticoagulant therapy can reduce the recurrence rate of ischemic stroke, reduce the incidence of pulmonary embolism and deep vein thrombosis, but is offset by the increase of symptomatic intracranial hemorrhage, with higher risk of cerebral hemorrhage.

4. Neuroprotection

Theoretically, drugs (neuroprotective agents) directed against acute ischemia or post-reperfusion cell injury can protect brain cells and improve tolerance to ischemia and hypoxia. Currently, the clinically used neuroprotective agents mainly include:

calcium antagonist (nimodipine) can relieve ischemic brain injury and directly protect neurons;

free radical scavengers (superoxide dismutase, dexamethasone, mannitol, VE, VC, aminosteroid, etc.);

butylphthalide can improve mitochondrial function and brain microcirculation, reduce Glu release, and improve neurological deficit.

The cerebral ischemic injury is a multi-factor participation process in the initial and delayed injury processes, the single use of the medicines only solves aspects in the complex process in the treatment, and an ideal effect cannot be obtained, the simultaneous blocking of a plurality of links in the cerebral ischemic pathological process is very important in the treatment, different medicines or a plurality of medicines are used for matching treatment in different disease onset periods, the acute-stage treatment needs strict adaptation and strict monitoring, the treatment needs to be carried out by adopting the nerve recovery promoting medicines in the recovery period, the rehabilitation treatment needs to be carried out, and the better effect can be obtained by comprehensively considering the transition of the medicines in the acute and recovery periods, the adjustment of the dosage, the interaction among the medicines, the reduction of side reactions and the like.

The traditional Chinese medicine has the characteristics of multiple components, multiple ways, multiple targets, integral action and high safety, can fully play the characteristics of chronic onset, acute attack and after-disease recuperation in the treatment of complex diseases, particularly the treatment of cerebrovascular diseases with multiple links and multiple factor changes, and has obvious advantages and characteristics.

The pseudo-ginseng has the effects of removing blood stasis, stopping bleeding, relieving swelling and relieving pain; the main component of the panax notoginseng saponins can promote blood circulation, remove blood stasis, dilate blood vessels and improve blood circulation. The safflower has the functions of promoting blood circulation, stimulating the menstrual flow, removing blood stasis and relieving pain; the safflower yellow can promote blood circulation to remove blood stasis, promote blood circulation and relieve pain. Radix Puerariae has effects of relieving muscles and fever, promoting fluid production to quench thirst, promoting eruption, invigorating yang and relieving diarrhea, dredging meridian passage, and relieving alcoholism; the radix Puerariae total flavone has effects of promoting blood circulation and removing blood stasis, and can be used for treating blood stasis and obstruction of channels and collaterals in meridian recovering period of ischemic apoplexy. The fructus crataegi has effects of resolving food stagnation, invigorating stomach, activating qi-flowing, removing blood stasis, eliminating turbid pathogen, and reducing blood lipid.

Modern pharmacological studies show that the panax notoginseng is rich in panax notoginseng saponins, and has pharmacological effects of expanding blood vessels, reducing oxygen consumption of cardiac muscle, inhibiting platelet aggregation, prolonging blood coagulation time, reducing blood fat, removing free radicals, resisting inflammation and resisting oxidation and the like; chalcone components such as safflower yellow in safflower have good activity in the aspects of increasing coronary flow, resisting ischemia, resisting blood coagulation and thrombus and the like; the radix Puerariae total flavone has effects of improving immunity, enhancing myocardial contraction force, protecting myocardial cell, lowering blood pressure, and resisting platelet aggregation; the rhizoma ligustici wallichii and the hawthorn can dilate coronary arteries and increase coronary flow; the rhizoma Ligustici Chuanxiong and fructus crataegi contain high content of ferulic acid, and have strong antioxidant and free radical scavenging activities.

The five traditional Chinese medicines are reasonably compatible, so that the traditional Chinese medicine composition can effectively expand blood vessels, increase the blood flow of heart and brain, improve microcirculation, has the effects of resisting platelet aggregation, resisting arteriosclerosis, reducing blood pressure and blood fat, reducing lipid peroxidation, removing free radicals, protecting nerves and the like, can simultaneously act on a plurality of pathological links of ischemic stroke, realizes multi-component, multi-path and integral effects, is used for treating the acute stage and the recovery stage of cerebral ischemia, can accelerate the recovery process, and has obvious advantages and characteristics.

However, most of the traditional Chinese medicine preparation methods are to mix and decoct the medicinal materials, and the effective components are not clear; mostly, the process control is carried out, and the quality controllability is poor; the medicine has poor solubility, poor preparation performance, large dosage for patients and poor compliance.

Disclosure of Invention

The invention provides pharmaceutical compositions for treating ischemic stroke with good solubility, good stability and high curative effect and a preparation method thereof.

The present invention features that the notoginseng total saponin as the effective component of notoginseng is extracted from safflower, kudzu vine root, Chuanxiong rhizome and haw separately through alcohol-water extraction process and adsorption resin technology to enrich the effective components of the Chinese medicinal materials, and the composition is prepared in proportion.

The medicine composition of the present invention is total arasaponin and effective parts of safflower, kudzu vine root, Chuanxiong rhizome and haw in the weight proportion: 1-5 parts of panax notoginseng saponins, 10-30 parts of safflower extract, 15-60 parts of kudzu root extract, 10-40 parts of ligusticum wallichii extract and 20-45 parts of hawthorn extract

The invention adopts the following technical scheme:

1. pulverizing Carthami flos, radix Puerariae, rhizoma Ligustici Chuanxiong, and fructus crataegi;

2. weighing quantitative flos Carthami, extracting with 8-15 times of water or ethanol water solution for 2-3 times, each for 1-3 hr, mixing extractive solutions, concentrating to about 10 times of crude drug amount, passing through macroporous adsorbent resin column, removing impurities with water, eluting with 50% ethanol water solution, concentrating eluate, drying, and pulverizing.

3. Weighing quantitative radix Puerariae, extracting with 6-10 times of 50-95% ethanol water solution for 2-3 times for 1-3 hr, mixing extractive solutions, distilling under reduced pressure to recover ethanol, adding water to 2-3 times of crude drug amount, passing through macroporous adsorbent resin column, removing impurities with water, eluting with 70% ethanol water solution, concentrating eluate, drying, and pulverizing.

4. Weighing quantitative rhizoma Ligustici Chuanxiong, extracting with 6-10 times of water or ethanol water solution for 2-3 times, each for 1-3 hr, mixing extractive solutions, concentrating to 4 times of crude drug amount, passing through macroporous adsorbent resin column, removing impurities with water, eluting with 50% ethanol water solution, concentrating eluate, drying, and pulverizing.

5. Weighing quantitative fructus crataegi, extracting with 6-10 times of 40-70% ethanol water solution for 2-3 times, each for 1-3 hr, mixing extractive solutions, distilling under reduced pressure to recover ethanol, adding water to about 2.5 times of crude drug amount, passing through macroporous adsorbent resin column, removing impurities with water, eluting with 40-75% ethanol water solution, concentrating eluate, drying, and pulverizing.

6. Mixing the above Carthami flos extract, radix Puerariae extract, rhizoma Ligustici Chuanxiong extract, fructus crataegi extract and Notoginseng radix total saponin, and mixing to obtain pharmaceutical composition.

The invention relates to pharmaceutical compositions, which comprise extracts prepared by the method of the invention and pharmaceutically acceptable carriers.

The extract obtained by the method can be freeze-dried or vacuum-dried into dry powder, or the concentrated liquid can be directly spray-dried into dry powder and then made into various dosage forms.

The invention also relates to pharmaceutical compositions containing as active ingredient an extract according to the invention together with conventional pharmaceutical excipients or adjuvants. Generally, the extract accounts for 1-95% of the total weight of the pharmaceutical composition.

The invention also provides pharmaceutical compositions, which comprise a pharmaceutically effective dose of the extract of Xanthium strumarium as an active ingredient and a pharmaceutically acceptable carrier.

For this purpose, the extract of the invention can be combined with or more solid or liquid pharmaceutical excipients and/or adjuvants, if desired, to make suitable administration forms or dosage forms for pharmaceutical use.

The composition of the present invention or the pharmaceutical composition containing it can be administered in unit dosage form, and the administration route can be intestinal or parenteral, such as oral, muscle, subcutaneous, nasal, oral mucosa, eye, lung, skin, vagina, peritoneum, rectum, etc., preferably oral administration.

The dosage form for administration may be a liquid dosage form, a solid dosage form, or a semi-solid dosage form. The liquid dosage forms can be solution (including true solution and colloidal solution), emulsion (including oil-in-water type, water-in-oil type and multiple emulsion), suspension, injection (including water injection, powder injection and infusion), eye drop, nose drop, lotion and liniment; the solid dosage form can be tablet (including common tablet, enteric coated tablet, buccal tablet, dispersible tablet, chewable tablet, effervescent tablet, orally disintegrating tablet), capsule (including hard capsule, soft capsule, and enteric coated capsule), granule, powder, pellet, dripping pill, suppository, pellicle, patch, aerosol (powder), spray, etc.; semisolid dosage forms can be ointments, gels, pastes, and the like.

The extract can be prepared into common preparations, sustained release preparations, controlled release preparations, targeting preparations and various particle delivery systems.

For tableting the unit dosage form, may be used with a variety of excipients known in the art, including diluents, binders, wetting agents, disintegrants, lubricants, glidants, the diluents may be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc., the wetting agents may be water, ethanol, isopropanol, etc., the binders may be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, acacia slurry, gelatin slurry, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinyl pyrrolidone, polyethylene dipropyl alcohol, etc., the disintegrants may be dry starch, microcrystalline cellulose, low substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfonate, and the lubricants and glidants may be talc, silicon dioxide, stearate, tartaric acid, liquid paraffin, paraffin wax, etc.

The tablets may also be further processed at step to make coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or double-layer and multi-layer tablets.

For making the administration unit into a pill, can be used in a wide variety of carriers well known in the art, and examples of the carriers are, for example, diluents and absorbents such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, polyvinylpyrrolidone, macrogol laurate, kaolin, talc and the like, binders such as acacia, xanthan gum, gelatin, ethanol, honey, liquid sugar, rice paste or batter and the like, and disintegrating agents such as agar powder, dried starch, alginate, sodium dodecylsulfate, methyl cellulose, ethyl cellulose and the like.

For the purpose of making the administration unit into suppositories, various carriers well known in the art can be used .

For the encapsulation of the administration units, the active ingredient of the extract of the invention is mixed with the various carriers mentioned above and the mixture thus obtained is placed in hard gelatin capsules or soft capsules. The effective component of the extract can also be prepared into microcapsules, and the microcapsules are suspended in an aqueous medium to form a suspension, and can also be filled into hard capsules or prepared into injections for application.

For example, the extract of the present invention can be prepared into injectable preparations, such as solutions, suspensions, emulsions, lyophilized powders, which may be aqueous or non-aqueous, and may contain and/or more pharmaceutically acceptable carriers, diluents, binders, lubricants, preservatives, surfactants or dispersants, for example, the diluents may be selected from water, ethanol, polyethylene glycol, l, 3-propanediol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitol fatty acid esters, etc.

In addition, colorants, preservatives, flavors, flavorings, sweeteners or other materials may also be added to the pharmaceutical preparation, if desired.

For the purpose of administration, enhancing the therapeutic effect, the extract or pharmaceutical composition of the present invention can be administered by any known administration method.

The dosage of the pharmaceutical composition of the present invention may vary widely depending on many factors, such as the nature and severity of the disease to be prevented or treated, the sex, age, weight, character and individual response of the patient or animal, the route of administration, the number of times of administration, and the purpose of treatment, and thus the therapeutic dosage of the present invention may vary widely the dosage of the pharmaceutical composition of the present invention is generally known to those skilled in the art, and may be suitably adjusted to achieve the purpose of preventing or treating the present invention according to the actual amount of the drug contained in the final formulation of the extract composition of the present invention, and the dosage of the extract of the present invention may be suitably adjusted per day in such a manner that the pharmaceutical composition of the present invention is administered in a single dosage form or divided into several, e.g., two, three or four dosage forms, depending on the clinical experience of the administering physician and the dosage regimen including other therapeutic means, and the total dosage of the pharmaceutical composition may be adjusted 6335 or 3683 or combined with the dosage of the other drugs for each treatment.

The research on the effect of the pharmaceutical composition on a mouse and rat focal cerebral ischemia reperfusion model proves that the pharmaceutical composition has the effects of obviously reducing the cerebral ischemia area of a model animal and improving the nerve behavioral function deficiency.

The preferred technical scheme of the invention is as follows:

A pharmaceutical composition for treating cerebral ischemic stroke, which is characterized in that the composition comprises safflower extract, kudzu root extract, chuanxiong rhizome extract, hawthorn fruit extract and panax notoginseng saponins.

The preferable raw material ratio is as follows:

1-5 parts of panax notoginseng saponins, 10-30 parts of safflower extract, 15-60 parts of kudzu root extract, 10-40 parts of ligusticum wallichii extract and 20-45 parts of hawthorn extract.

The more preferable raw material ratio is as follows:

1 part of panax notoginseng saponins, 20 parts of safflower extract, 57 parts of kudzu root extract, 17 parts of ligusticum wallichii extract and 34 parts of hawthorn fruit extract.

In the pharmaceutical composition, the saponin content of the panax notoginseng saponins is more than 75%.

The preparation method of the pharmaceutical composition is characterized by comprising the following steps:

the preparation method of the safflower extract comprises the steps of weighing quantitative safflower, extracting for 2-3 times by using 8-15 times of water or ethanol water solution, extracting for 1-3 hours each time, combining extracting solutions, concentrating to about 10 times of crude drug amount, passing through a macroporous adsorption resin column, eluting by using water to remove impurities, eluting by using 50% ethanol water solution, concentrating eluent, drying and crushing to obtain the safflower extract.

The preparation method of the radix puerariae extract comprises the steps of weighing quantitative radix puerariae, extracting with 6-10 times of 50-95% ethanol water for 2-3 times, 1-3 hours each time, combining extracting solutions, carrying out reduced pressure distillation to recover ethanol, adding water to about 1-2 times of crude drug amount, passing through a macroporous adsorption resin column, eluting with water to remove impurities, eluting with 70% ethanol water, concentrating eluent, drying and crushing to obtain the radix puerariae extract.

The rhizoma Ligustici Chuanxiong extract is prepared by weighing quantitative rhizoma Ligustici Chuanxiong, extracting with 6-10 times of water or ethanol water solution for 2-3 times, each for 1-3 hr, mixing extractive solutions, concentrating to 4 times of crude drug amount, passing through macroporous adsorbent resin column, eluting with water to remove impurities, eluting with 50% ethanol water solution, concentrating eluate, drying, and pulverizing.

The preparation method of the hawthorn extract comprises the steps of weighing quantitative hawthorn, extracting with 6-10 times of 40-70% ethanol water for 2-3 times, each time for 1-3 hours, combining extracting solutions, carrying out reduced pressure distillation to recover ethanol, adding water to about 2.5 times of crude drug amount, passing through a macroporous adsorption resin column, eluting with water to remove impurities, eluting with 40-75% ethanol water, concentrating eluent, drying, and crushing to obtain the hawthorn extract.

In the preparation method, the adsorption speed of the macroporous adsorption resin column is 1-3BV/h, the flow rate of water washing impurity removal is 1-3BV/h, and the desorption speed is 1-3 BV/h.

The technical scheme of the invention also provides preparations containing the pharmaceutical composition, which are characterized in that the preparations are prepared from therapeutically effective dose of the pharmaceutical composition and pharmaceutically acceptable excipients, and the preparations are kinds of tablets, capsules, granules and oral liquid.

The technical scheme of the invention also provides the application of the pharmaceutical composition and the preparation in preparing the medicine for preventing or treating cerebral arterial thrombosis.

The invention has the technical advantages that:

1. the medicinal material resources are rich and easy to obtain, the preparation process is simple, and the method is suitable for large-scale industrial production.

2. Has obvious functions of reducing cerebral ischemia area and improving nerve behavior function deficiency.

3. The basis and the mechanism of action of the acting substance are clear, stable and controllable, and the use is safe.

4. The application range is particularly , and application is easy to push.

Drawings

FIG. 1 shows the improvement effect of the pharmaceutical composition (PP6) on the cerebral ischemic area of ICR mouse MCAO/R model

FIG. 2 shows the improvement effect of the pharmaceutical composition (PP6) on the cerebral ischemic area of the MCAO/R model of SD rats

Note: # p <0.001 compared to sham group; compared to the model group, p <0.05, p <0.01, p < 0.001.

FIG. 3 Single-treatment of SD rat MCAO/R model with pharmaceutical composition (PP6) Longa method neurobehavioral function score

Note: in comparison to sham group, # # p < 0.01; p <0.05, p <0.01 compared to model group.

FIG. 4. effect of prophylactic administration of pharmaceutical composition (PP6) on cerebral ischemic area in MCAO/R model in SD rat

Note: # p <0.001 compared to sham group; p <0.05 compared to model group.

FIG. 5 shows that pharmaceutical composition (PP6) was administered to SD rats in MCAO/R model for prevention of neurobehavioral scores by Longa method

Note: in comparison to sham group, # # p < 0.01; p <0.05, p <0.01 compared to model group.

FIG. 6 different groups of SD rat MCAO/R model magnetic resonance imaging T2WI scanning image (4h,24h)

FIG. 7. effect of prophylactic administration of pharmaceutical composition (PP6) on the area of cerebral ischemia in SD rat MCAO/R model at different times (4h,24h)

Note: # p <0.001 compared to sham group; compared to the model group, p <0.05, p <0.01, p < 0.001.

FIG. 8 prophylactic administration of pharmaceutical composition (PP6) to SD rat MCAO/R model Longa's neurobehavioral function scores at various times (4h,24h)

Note: # p <0.001 compared to sham group; compared to the model group, p <0.05, p <0.01, p < 0.001.

FIG. 9 preventive administration of pharmaceutical composition (PP6) to SD rat MCAO/R model 3D-TOFMRA vascular Structure at different times (4h,24h)

FIG. 10. Effect of prophylactic administration of pharmaceutical composition (PP6) on the levels of major brain metabolites at different times in the MCAO/R model in SD rats (4h,24h)

FIG. 11. Effect of pharmaceutical composition (PP6) on the expression of tPA and PAI-1, ischemic lateral brain tissue proteins, in MCAO/R model in SD rat, on 7 days after prophylactic administration

(n-4-6, mean + -SEM; compare with sham, # # p < 0.01; compare with model, # # p <0.01)

FIG. 12. Effect of the pharmaceutical composition (PP6) on the expression of tPA and PAI-1, ischemic lateral brain tissue proteins in MCAO/R model of SD rat for 7 days

(n ═ 6, mean ± SEM; compare with sham group, # p < 0.01; compare with model group, # p <0.001, # p <0.01, # p <0.05)

Detailed Description

The following examples and pharmacological activity experiments are further to illustrate the present invention, but are not intended to limit the present invention in any way.