CN103768114B - A kind of application of pharmaceutical composition in the medicine for treating or preventing cerebral apoplexy is prepared - Google Patents

A kind of application of pharmaceutical composition in the medicine for treating or preventing cerebral apoplexy is prepared Download PDF

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CN103768114B
CN103768114B CN201210405870.8A CN201210405870A CN103768114B CN 103768114 B CN103768114 B CN 103768114B CN 201210405870 A CN201210405870 A CN 201210405870A CN 103768114 B CN103768114 B CN 103768114B
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pharmaceutical composition
medicine
wilsonii
herba hyperici
cerebral apoplexy
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CN103768114A (en
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柯潇
董庆
高小平
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Sichuan Jishengtang Pharmaceutical Co.,Ltd.
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CHENGDU KANGHONG PHARMACEUTICALS GROUP Co Ltd
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Abstract

The invention provides a kind of application of pharmaceutical composition in the medicine for treating or preventing cerebral apoplexy is prepared, wherein pharmaceutical composition is made up of Herba Hyperici Monogyni and wilsonii, various formulations can be made with pharmaceutically acceptable carrier or excipient.Pharmacological research shows that the pharmaceutical composition is obviously improved to the animal survival time after global cerebral ischemia, significantly reduces the ischemic areas of post-stroke, has protective effect to nervous function, has the function that to prevent or treat cerebral apoplexy.

Description

A kind of application of pharmaceutical composition in the medicine for treating or preventing cerebral apoplexy is prepared
Technical field
The invention belongs to field of medicaments, and in particular to a kind of pharmaceutical composition treats or prevents the medicine of cerebral apoplexy preparing In application.
Background technology
Cerebral apoplexy be acute generation blood vessel or blood flow anomalies caused by brain blood circulation disorder and cause neurologic impairment Syndrome, there is the characteristics of high incidence, high disability rate, high relapse rate and high fatal rate, be to be only second to cardiovascular disease and cancer The third-largest " killer ", have become the principal disease for threatening human health and life.Also, as the whole world is to aging society Into the continuous quickening of paces, the incidence of disease of cerebral apoplexy is still further riseing, in view of the significant damage of cerebral apoplexy, exploitation reduces Stroke Death rate, patient's functional rehabilitation, the medicine for the treatment cerebral apoplexy for improving patients ' life quality is promoted to have become the whole world One of study hotspot of medical personal.
Ischemic cerebral apoplexy refers to because brain blood supplies obstacle, the ischemic of limitation brain tissue caused by ischemic, anoxic Property necrosis or cerebromalacia, pathophysiological process it is extremely complex, affected by many factors, wherein energy metabolism impairment, excitability ammonia The mechanism such as base toxic effect of acid, inflammatory reaction, Penumbra zone depolarising and Apoptosis take part in its pathophysiological process jointly.Mesh The preceding treatment to cerebral arterial thrombosis, mainly angularly enter from neuroprotection, anti-freezing, thrombolysis, increase CBF and hypotensive OK, conventional cerebral apoplexy chemotherapeutic agent includes:1)Thrombolysis class medicine, 2)Antiplatelet drug, 3)Anticoagulant, 4)Nerve Cell-protecting medicines etc..But these medicine majorities can only all be directed to being extenuated and/or being treated in a certain respect for cerebral apoplexy, treat Act on single, effect is undesirable, and many adverse reactions be present.For example, conventional thromboembolism treatment drug entities fibrin Dissolved preferment activator(tPA)Although can rapid thrombus, can not improve due to neuron caused by ischemic by Damage, and destruction blood-CSF barrier, increase bleeding risk, aggravation excititoxic etc. be present seriously not in its continuous is reported Good reaction [yellow meaningful ripple etc., neuroprotection and cerebral arterial thrombosis treatment, translational medicine research(Electronic edition)2012,2(1):40- 53], above mentioned problem is also thrombolysis class medicine in Clinical practice the defects of generally existing.
In addition, Chinese medicine preparation also makes some progress in terms of cerebral apoplexy is treated, such as common having improves the heart The gingko leaf preparation of Cerebrovascular disorders effect, there is definite work for treatment acute ischemic cerebral apoplexy by many research reports With.But providing that the total flavonoids content of ginkgo biloba p.e must not be less than 24.0% in 2010 editions pharmacopeia, terpene lactone contains Must not measure less than 6.0%, ginkgo acid content must not exceed 10%, and total flavonoids content and terpene lactone in ginkgo leaf medicinal material Content is only respectively 0.4% and 0.25%.Therefore, in gingko leaf preparation the high standard of corresponding active component content necessarily to its former material Quality, quantity, the extraction process of material have higher requirements, so as to cause higher production cost, in addition, ginkgo biloba p.e exists Easily occurring a variety of adverse reactions such as bleeding, hypertension induced, allergy on Clinical practice, [Wang Yuhui etc., ginkgo biloba p.e is not Good reaction, 2001,3:184-186].In addition, also disclose that some are other in the Chinese patent such as CN1686299, CN10197242 The Traditional Chinese medicine composition of cerebral apoplexy is treated, but its prescription is complicated, and production cost is high, and Drug's control difficulty is big, is unfavorable for Industrialized production.Therefore, seek a kind of prescription is simple, curative for effect, security is good, beneficial to industrialized production treatment brain soldier In Chinese medicine tool be of great significance.
Herba Hyperici Monogyni, is called St. john's wort, Guttiferae Hypericum herbaceos perennial, be distributed in the world it is most wide Natural plants, the ground such as Hubei, Sichuan, Guizhou, Gansu, Shanxi, Jiangxi, Jiangsu, Shandong are distributed mainly in China.Pass through Ye Jin Silk peach clinical practice in addition to the effect of traditional calmness, anti-inflammatory, wound healing etc., be also reported available for depression, The treatment of the disease such as A type and hepatitis B, AIDS, tumour.2006 again studies have reported that hyperforine is for brain soldier In after neurotrosis there is protective effect [Kumar V, Mdzinarishvili A, Kiewert C, et al.NMDA receptor-antagonistic properties of hyperforin,a constituent of St.John's Wort.J Pharmacol Sci.2006,102(1):47-54].In addition, the larger scale clinical research hair of Herba Hyperici Monogyni preparation It is existing, although it is in use in the presence of some side effects, such as GI irritation (0.6%), allergic reaction (0.5%), fatigue (0.4%) etc., but these side reactions be it is slight, temporary transient, and relative harmless [Yang get Po etc., foreign countries are to the anti-suppression of hypericum perforatum The clinical verification of strongly fragrant curative effect, Journal of Chinese Integrative Medicine, 2004,2(3):231-234].
Wilsonii be Araliaceae root, rhizome and stem, also known as slender acanthopanax ginseng, sting bent stick, be mainly distributed on China northeast, North China, and the ground such as Korea, Japan and Russia.Wilsonii is widely used, is with a long history, and modern pharmacology research shows It has many effects such as neuro-protective, immunological regulation, anti-aging, is clinically widely used.The research that week is waited by the emperor himself Report and use Chi-Wu-Jia Injection in Treating cerebral arterial thrombosis, the results showed that Chi-Wu-Jia Injection in Treating group is suffered from for cerebral apoplexy The therapeutic effect of person is substantially better than control group [the Chi-Wu-Jia Injection in Treating ischemic brains of admiring in week without using Radix Et Caulis Acanthopanacis Senticosi injection 228 clinical analysis of palsy, Guangxi medical science, 2006,28 (9):1396-1397].And the long term toxicity research of Radix Et Caulis Acanthopanacis Senticosi injection Show its high and low dose group and physiological saline(Blank)Control group compares, during successive administration 28d, to organ coefficient, animal The indices such as hematological indices, biochemical indicator have no significant effect;Each group animal is in diet, activity, excretion, spirit after drug withdrawal State etc. is showed no notable difference;Without specifically sexually revising after drug withdrawal without slowness toxicity [Song Yan occurs for histopathologic slide Spring etc., research of the Radix Et Caulis Acanthopanacis Senticosi injection to rat chronic toxicity test, drug evaluation research, 2010,33 (1):1-4].
Herba Hyperici Monogyni is respectively provided with widely distributed, raw material with wilsonii and is easy to get, and action target spot is more, and it is excellent that toxic side effect is small etc. Point.Capsule for reliving liver and reliving upset is the Chinese medicine composition with Herba Hyperici Monogyni and wilsonii prescription, for treating light, moderate unipolar depression Disease, it is the Chinese patent drug for being used to treat depression of domestic first SFDA approvals, treatment depression works well, and correlative study shows it Adverse events incidence is small over the course for the treatment of, and without the generation of serious and severe adverse events, [Sun Xinyu etc., capsule for reliving liver and reliving upset is controlled Treat the randomized double-blind placebo-controlled study of light moderate depressive patients, Chinese Journal ofNew Drugs, 2009,18 (5):413-416].
Have no at present and Herba Hyperici Monogyni and wilsonii are applied to treatment cerebral apoplexy jointly, and obtain curative for effect, safety The report of the good medicine of property.
The content of the invention
It is an object of the invention to provide a kind of pharmaceutical composition containing Herba Hyperici Monogyni and wilsonii prepare treatment or The percentage by weight of application in preventing brain stroke medicine, Herba Hyperici Monogyni and wilsonii is:Herba Hyperici Monogyni 35-65%, thorn five Add 65-35%;Preferable percentage by weight is Herba Hyperici Monogyni 50-65%, wilsonii 50-35%;Preferred percentage by weight is Herba Hyperici Monogyni 54.5%, wilsonii 45.5%.
Described cerebral apoplexy is preferably cerebral arterial thrombosis.
Pharmaceutical preparation can be made with pharmaceutically acceptable carrier or excipient in pharmaceutical composition provided by the invention, the system Agent can be traditional oral preparation, such as capsule, tablet, granule etc..
The present invention investigates medicine using bilateral common carotid arteries and the acute cerebral ischemia mouse model of vagus nerve caused by ligature The effect of composition, described mouse model modeling method are:The 0.5h after mouse last time gastric infusion, with ether to it It is rapid to ligature bilateral common carotid arteries and vagus nerve after carrying out superficial anesthesia, observe the mouse survival time.The animal model is anxious Property cerebral hypoxia ischemia common model, and acute cerebral ischemia anoxic is exactly one of pathological effect of cerebral arterial thrombosis, therefore, should Time-to-live after animal model administration can tentatively reflect protective effect of the medicine to cerebral ischemia, anoxic, can be used as and lack The screening index of courageous and upright cerebral apoplexy medicine.Test result indicates that heretofore described pharmaceutical composition is to bilateral ligation Mouse is caused to lack time-to-live significantly extension compared with model group after acute cerebral ischemia, with wilsonii is used alone or passes through leaf spun gold It is obvious to illustrate that the pharmaceutical composition acts on for cerebral ischemia, hypoxia protection compared to being also obviously prolonged for peach group, and with significant Synergy.
Middle cerebral artery occlusion model is acknowledged as the focal cerebral infarction animal model of standard, is moved wherein in line brush brain Arteries and veins cerebral ischemic model is preferred modeling method [the line brush rats after transient focal cerebral ischemia model for studying ischemic brain damage animal model Improvement and evaluation, Central-South medical science magazine, 2012,40 (3):291-294].Therefore the present invention is using caused by line brush Rat brain stroke model further study by the prevention to pharmaceutical composition or the effect for the treatment of cerebral apoplexy and dosage, described line Bolt method modeling method is:The 1h after rat last time gastric infusion, fiber crops are injected intraperitoneally with 10% yellow Jackets (30mg/kg) It is liquor-saturated, fixation of lying on the back, neck median incision, separate and expose left common carotid and the inside and outside artery of neck, ligature arteria carotis communis and neck Outer artery proximal part, an osculum is opened in arteria carotis communis distal end(Outside neck, internal carotid crotch about 5mm), insert MACO Bolt 2.0 ± 0.2cm of line, stops when feeling to have light resistance, tightens and fixes plug wire, skin suture, after blocking blood flow 2h, pulls out line Reperfu- sion is realized, rat is put to death in cerebral ischemia re-pouring 48h, and neurological deficits score is carried out before putting to death;Taken after sacrificed by decapitation Brain section observes rat cerebral ischemia volume.Neuromotor function defect appraisal result after rat model administration shows the medicine group Each dosage group of compound can significantly improve the neuromotor function of cerebral arterial thrombosis rat, and its ischemic volume result of study is shown Each dosage group of the pharmaceutical composition can significantly reduce brain tissue death domain and volume caused by ischemia-reperfusion.
The extraction preparation method of pharmaceutical composition provided by the invention is:Herba Hyperici Monogyni medicinal material is added into 70% alcohol reflux Extraction 2 times, 1 hour every time, merge extract solution, filtration, ethanol is recovered under reduced pressure, is concentrated into the leaching of relative density about 1.10 (70 DEG C) Cream, dry extract is spray-dried to obtain, obtains extract of hypericum perforatum;By wilsonii pulverizing medicinal materials into fragment, 3 are added water to cook It is secondary, 2 hours every time, collecting decoction, filter, filtrate is concentrated into the medicinal extract of relative density about 1.18 (70 DEG C), and being spray-dried to do Extract powder, obtain siberian Ginseng P.E;Above two extract is taken, uniformly mixes and produces pharmaceutical composition.The extracting method institute Need equipment, reagent simple, easy to operate, production cost is relatively low.
The present invention compared with prior art, has advantages below:
1st, in pharmaceutical composition provided by the invention during cerebral apoplexy is treated or prevented, due to Herba Hyperici Monogyni and thorn The synergy of slender acanthopanax, the pharmaceutical composition is to the time-to-live after bilateral ligation cause mouse ischemic and exclusive use Wilsonii or Herba Hyperici Monogyni group, which are compared, has notable extension to act on;And the pharmaceutical composition is transported for the nerve of post-stroke Damage after dynamic function, ischemia-reperfusion and have significant therapeutic effect, therapeutic effect is definite.
2nd, chemicals toxic side effect of the prior art is larger, and the present invention pharmaceutical composition in wilsonii and pass through The xicity related research of leaf Hypericum Chinense shows the two small toxicity, and adverse reaction occurs less, safe.
3rd, there is extraction process or formulation ingredients complexity, production cost height, quality control in Chinese medicine preparation of the prior art The problems such as difficulty is big, and the pharmaceutical composition in the present invention is only made up of two taste medicines, prescription is simple, is easier to quality control, and Extracting method is simple, and production cost is lower, is adapted to large-scale production.
Brief description of the drawings
Fig. 1 is the rat whole brain slice map of each experimental group in embodiment two, wherein 1 is negative control group in embodiment two (Normal rat)Whole br ain slices, 2 be cerebral apoplexy blank control group in embodiment two(Rat model)Whole br ain slices, 3 be embodiment Two positives control groups(Cerebral apoplexy rat model is treated through Folium Ginkgo)Whole br ain slices, 4 be pharmaceutical composition in embodiment two Low dose group whole br ain slices, 5 be pharmaceutical composition high dose group whole br ain slices in embodiment two
Embodiment
Following examples are that the present invention is explained further, it is impossible to are limited the scope of the invention.
The pharmaceutical composition of embodiment 1 is to the mouse survival time after ligation bilateral common carotid arteries and vagus nerve cause cerebral ischemia Influence
1. experiment material
Experimental animal:Kunming mice(KM mouse), lot number SCXK(River)2004-15, provided by Sichuan Academy of Medical Sciences;
Experimental drug:Folium Ginkgo(Tanakan), specification 40mg/ pieces, product batch number C02191, manufacturer be Bo Fu- Yi Pusheng industrial groups(France);Extractum Acanthopanacis Senticosi powder, lot number 110302, Herba Hyperici Monogyni extract powder, lot number 110303 by Chengdu Kanghong Medicine Group Co.ltd provides;
Experiment reagent:Ether(Analyze pure, Tianjin Fu Yu Fine Chemical Co., Ltd)
Operating theater instruments:Operating scissors, haemostatic clamp, needle forceps.
2. experimental method
Experiment packet:
Kunming mice 108 is taken, male and female half and half, following 9 groups are divided into according to body weight and sex:
Negative control group:It is given only the distilled water that gained volume is calculated by 10ml/kg mouse weights.
Positive controls:Give Tanakan 20mg/kg.
Wilsonii group:Give siberian Ginseng P.E 480mg/kg.
Herba Hyperici Monogyni group:Give extract of hypericum perforatum 480mg/kg.
Pharmaceutical composition 1:Herba Hyperici Monogyni:Wilsonii=35:65(Percentage by weight)Pharmaceutical composition, by 480mg/ Kg is administered.
Pharmaceutical composition 2:Herba Hyperici Monogyni:Wilsonii=50:50(Percentage by weight)Pharmaceutical composition, by 480mg/ Kg is administered.
Pharmaceutical composition 3:Herba Hyperici Monogyni:Wilsonii=54.5:45.5(Percentage by weight)Pharmaceutical composition, press 480mg/kg is administered.
Pharmaceutical composition 4:Herba Hyperici Monogyni:Wilsonii=62:38(Percentage by weight)Pharmaceutical composition, by 480mg/ Kg is administered.
Pharmaceutical composition 5:Herba Hyperici Monogyni:Wilsonii=65:35(Percentage by weight)Pharmaceutical composition, by 480mg/ Kg is administered.
Drug solution is prepared:Medicine by more than in each experimental group or each component in pharmaceutical composition are according to weight proportion And after mouse weight calculates total dosage, solution is configured to by solvent of distilled water, solvent volume is that 10ml/kg is small Mouse body weight.
According to above-mentioned experiment packet and each group drug solution volume, gastric infusion is carried out to mouse, it is 2 times a day, continuous to fill Stomach is administered 7 times.The 0.5h after last gavage, mouse is anaesthetized with ether superficial, it is rapid to ligature bilateral common carotid arteries and be confused absent-minded Through observing and recording the mouse survival time of each group(s), the results are shown in Table 1.
3. experimental result
Shadow of the pharmaceutical composition of table 1 to the time-to-live after cerebral ischemia caused by ligation mouse bilateral common carotid arteries and vagus nerve Ring
Compared with model control group, * P < 0.05
Upper table result shows, compared with negative control group, pharmaceutical composition 1-5 can be obviously prolonged the survival of model mice Time, illustrate that the pharmaceutical composition has preferable protective effect for cerebral ischemia, anoxic.Pharmaceutical composition 1-5 is administered and thorn five Add or time-to-live that Herba Hyperici Monogyni is administered alone compared to model mice substantially increases, illustrate wilsonii in the pharmaceutical composition Obvious synergy between Herba Hyperici Monogyni be present.Comparative drug composition 1-5 is learnt to the time-to-live of model mice When the weight proportion in pharmaceutical composition is Herba Hyperici Monogyni:35-65%, wilsonii:During 65-35%, each composition can be effective Extend the mouse survival time;When weight proportion is Herba Hyperici Monogyni:50-65%, wilsonii:During 65-50%(Pharmaceutical composition 2- 5), the prolonged survival period of mouse is more notable;When weight proportion is Herba Hyperici Monogyni:54.55%, wilsonii:When 45.45% (Pharmaceutical composition 3), mouse survival time lengthening is the most notable, its time-to-live and negative control group, wilsonii group and passes through leaf Section Ascyreia is compared and is improved largely, and, the drug regimen proportioning under suitable with positive control medicine group action effect Thing is best to focal cerebral ischemia protective effect.
The pharmaceutical composition of embodiment 2 causes the neurologic score and ischemic volume of Focal Cerebral Ischemia-Reperfusion in Rats to line brush Influence
1. experiment material
Experimental animal:SD rats, lot number SCXK(River)2004-15, provided by Sichuan Academy of Medical Sciences;
Experimental drug:Folium Ginkgo(Tanakan), specification 40mg/ pieces, product batch number C02191, manufacturer be Bo Fu- Yi Pusheng industrial groups(France);Extractum Acanthopanacis Senticosi powder, lot number 110302, Herba Hyperici Monogyni extract powder, lot number 110303 by Chengdu Kanghong Medicine Group Co.ltd provides;
Experiment reagent:2,3, 5-Triphenyltertrazoliumchloride (TTC), lot number BCBH1872V, produce company Sigma;Penta bar Than appropriate sodium(25g/ bottles), lot number:061222, Beijing chemical reagents corporation;
Laboratory apparatus:Electro-heating standing-temperature cultivator, model:DNP-9082, the upper grand experimental facilities Co., Ltd of Nereid;Cold light hand Art shadowless lamp, model:KL04L, section insult doctor's electricity;Canon's camera, model:EOS1100;Rat cerebral ischemia(MCAO)Line bolt, model: 2636-100,2838-100, Shadong Biological Technology Co., Ltd., Beijing.
Operating theater instruments:Operating scissors, haemostatic clamp, needle forceps, artery clamp.
2. experimental method
Experiment packet:
Healthy male SD rat 80,180~220g of body weight is taken, is divided into following 5 groups by weight average:
Negative control group:Healthy male SD rat, it is given only the distillation that gained volume is calculated by 10ml/kg rat body weights Water.
Blank control group:Rat after line brush modeling, it is given only the distillation that gained volume is calculated by 10ml/kg rat body weights Water.
Positive controls:Rat after line brush modeling, give Tanakan 20mg/kg.
Pharmaceutical composition low dose group:Herba Hyperici Monogyni:Wilsonii=54.5:45.5(Percentage by weight)Drug regimen Thing, it is administered by 120mg/kg.
Pharmaceutical composition high dose group:Herba Hyperici Monogyni:Wilsonii=54.5:45.5(Percentage by weight)Drug regimen Thing, it is administered by 240mg/kg.
Drug solution is prepared:Medicine by more than in each experimental group or each component in pharmaceutical composition are according to ratio and greatly After mouse body weight calculates total dosage, solution is configured to by solvent of distilled water, solvent volume is 10ml/kg rat bodies Weight.
According to above-mentioned experiment packet and each group drug solution volume, gastric infusion is carried out to mouse, it is one time a day, continuous to fill Stomach is administered 30 days.The 1h after last gavage, by rat with 10% yellow Jackets (30mg/kg) intraperitoneal injection of anesthesia, lie on the back solid Fixed, neck median incision, is separated and exposure left common carotid and the inside and outside artery of neck, ligation arteria carotis communis and external carotid artery are near Heart end, an osculum is opened in arteria carotis communis distal end(Outside neck, internal carotid crotch about 5mm), insertion MACO bolts line 2.0 ± 0.2cm, stop when feeling to have light resistance, tighten and fixed plug wire, skin suture, after blocking blood flow 2h, pull out line and realize and fill again Note, put to death after 48h.
Neurological deficits score is carried out to rat before execution, specific standards of grading are with reference to the third edition《Pharmacological evaluation side The science of law》In standards of grading carry out:1. putting forward rat-tail observation forelimb flexing situation, such as double forelimbs symmetrically stretch to ground, are designated as 0 point, Offside forelimb such as operation occurs that wrist is bent, elbow flexing, shoulder inward turning or existing wrist elbow flexing have shoulder inward turning person again, be calculated as 1 respectively, 2, 3rd, 4 points.2. animal is placed in ground grading, both shoulders are pushed away respectively and are moved to bilateral, check resistance, such as bilateral resistance is reciprocity and has Power, is calculated as 0 point, drop in resistance person when such as being promoted to the offside of operation, according to decline degree difference be divided into it is light, in, weigh three degree, point 1,2,3 point is not calculated as.3. the double forelimbs of animal are put on a wire netting, the Muscle tensility of double forelimbs is observed.The Muscle tensility pair of double forelimbs Deng and strong person be calculated as 0 point, declining degree difference also according to operation offside limb tension force is calculated as 1,2,3 point.Do not stop 4. animal has To the side person of turn-taking, 1 point is calculated as.According to standards of grading, full marks are 11 points, and fraction is higher, and the neurological dysfunction of animal is tighter Weight.Each group neurological deficits score result is as shown in table 2.
The sacrificed by decapitation rat at the end of experiment, takes out rapidly brain, quick-frozen 15min or so in -20 DEG C of refrigerators, takes hat The thick whole br ain slices of 2mm are uniformly cut into shape face, are put into rapidly in 2%TTC solution, 15min are incubated in 37 DEG C of lucifuges, therebetween every 4 ~5min is stirred once, whole br ain slices is carried out stain incubation uniformly in contact with to dye liquor, and the whole br ain slices being incubated are taken out, Digital camera amplifies 1.5 times and taken pictures, and each group Part of photos taken is as shown in Figure 1.Photo is inputted into computer, using imageplus6.0 Software calculates its infarct size, each whole br ain slices Infarction volume(2mm is multiplied by equal to infarct size)Sum is total Infarction volume, Total Infarction volume and the ratio of brain cumulative volume are cerebral ischemia volume.Each experimental group cerebral ischemia volume result is as shown in table 3.3. Experimental result
The cerebral arterial thrombosis rat motor function scores result of table 2
Compared with model control group, * P < 0.05, * * P < 0.01
The result of table 2 shows, two pharmaceutical composition groups and model group(Blank control group)Compare, neuromotor function scoring Significantly reduce, show that the pharmaceutical composition is significantly improved to the neurological dysfunction of animal pattern.And low dosage medicine The appraisal result of compositions is suitable with the medicine Tanakan action effect that positive controls use, high dose medicament composition Appraisal result is lower than Tanakan, illustrates the pharmaceutical composition in the nerve fortune for improving neurological dysfunction, promoting post-stroke It is suitable with the tablets of Ginkgo biloba L effect that purity is higher or more preferably in terms of dynamic functional rehabilitation.
The cerebral arterial thrombosis rat cerebral ischemia volume result of table 3
Compared with model control group, * * P < 0.01
Fig. 1 is observed, it is apparent that normal rat whole br ain slices are in rose, and the rat whole brain for infarct occur is cut Piece portion of tissue shows white, and boundary line is more clearly demarcated, wherein normal rat whole br ain slices whole br ain slices(No. 1 in accompanying drawing 1) It is in rose, cerebral apoplexy rat model whole br ain slices(No. 2 in accompanying drawing 1)It is large area infarct that large area white, which is presented, And the brain sections after Tanakan, pharmaceutical composition high dose, low dose therapy(3,4, No. 5 in accompanying drawing 1)Rose Obvious increase, pale infarct region significantly reduces.
The cerebral ischemia volume result being calculated in table 3 shows, two pharmaceutical composition groups and model group(Blank control Group)Compare, can pole substantially reduce rat infarcted region volume, improve cerebral ischemia.The infarcted region of low dose pharmaceutical compositions Volume is suitable with the medicine Tanakan that positive controls use, and the infarcted region of high dose medicament composition is smaller than Tanakan, Illustrate the pharmaceutical composition improve post-stroke ischemic injuries in terms of it is suitable with the tablets of Ginkgo biloba L effect that purity is higher or Person is more preferable.
The preparation of the pharmaceutical composition of embodiment 3
Pharmaceutical composition 1:Herba Hyperici Monogyni 1800g wilsoniis 1500g
Pharmaceutical composition 2:Herba Hyperici Monogyni 1155g wilsoniis 2145g
Pharmaceutical composition 3:Herba Hyperici Monogyni 2145g wilsoniis 1155g
Pharmaceutical composition 4:Herba Hyperici Monogyni 1650g wilsoniis 1650g
Pharmaceutical composition 5:Herba Hyperici Monogyni 2046g wilsoniis 1254g
Each pharmaceutical composition preparation method:70% alcohol reflux is added to extract 2 times the Herba Hyperici Monogyni medicinal material of the dosage, 1 hour every time, merge extract solution, filtration, ethanol is recovered under reduced pressure, is concentrated into the medicinal extract of relative density about 1.10 (70 DEG C), spray Dry dry extract, obtains extract of hypericum perforatum;By the wilsonii pulverizing medicinal materials of the dosage into fragment, add water to cook 3 times, 2 hours every time, collecting decoction, filter, filtrate is concentrated into the medicinal extract of relative density about 1.18 (70 DEG C), and being spray-dried to do Extract powder, obtain siberian Ginseng P.E;Above two extract is taken, uniformly mixes and produces pharmaceutical composition.
The preparation of the medicament composition capsule agent of embodiment 4
After the pharmaceutical composition being prepared according to preparation method in embodiment 3 is crossed into 40 mesh sieves, pregelatinized starch is added Its weight is reached 340g, add talcum powder 18g, magnesium stearate 2g is well mixed, and is loaded capsule, is made 1000.
The preparation of the medicinal composition tablets of embodiment 5
After the pharmaceutical composition being prepared according to preparation method in embodiment 3 is crossed into 40 mesh sieves, adding lactose makes its heavy Amount reaches 408g, adds starch 50g, hydroxypropylcellulose 40g, is well mixed, and with 75% alcohol granulation, dries, whole grain, adds 2g magnesium stearates are well mixed, tabletting, are made 1000.
The preparation of the medicament composition granule agent of embodiment 6
After the pharmaceutical composition being prepared according to preparation method in embodiment 3 is crossed into 40 mesh sieves, adding lactose makes its heavy Amount reaches 630g, and mannitol 70g is well mixed, and with 75% alcohol granulation, dries, whole grain, is made 450 bags.

Claims (2)

  1. A kind of 1. work of purposes, wherein described pharmaceutical composition of pharmaceutical composition in prevention or treatment cerebral apoplexy medicine is prepared Property composition is prepared by Herba Hyperici Monogyni and wilsonii, and the percentage by weight of wherein Herba Hyperici Monogyni and wilsonii is:Pass through Leaf Hypericum Chinense 54.5%, wilsonii 45.5%.
  2. 2. purposes according to claim 1, it is characterised in that the cerebral apoplexy is cerebral arterial thrombosis.
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