CN1239197C

CN1239197C - Oral preparation for cerebral embolism and its preparing method

Info

Publication number: CN1239197C
Application number: CN 03140491
Authority: CN
Inventors: 王永炎; 袁锐光; 龙超峰
Original assignee: HUANAN PHARMACEUTICAL FACTORY GUANGDONG PROV
Current assignee: GUANGDONG HUANAN PHARMACEUTICAL GROUP CO Ltd; Huanan Pharmaceutical Co ltd Guangdong
Priority date: 2003-09-12
Filing date: 2003-09-12
Publication date: 2006-02-01
Anticipated expiration: 2023-09-12
Also published as: CN1491705A

Abstract

The present invention discloses a new oral preparation for cerebral embolism, which is prepared from Chinese herbal medicines of plants as raw materials, and also relates to a preparing method thereof. The new oral preparation for cerebral embolism is prepared form cattail pollen, red peony root, curcuma root, gastrodia tuber and uniflower swisscentaury root as the raw materials. According to different characteristics of all traditional Chinese medicines, extractum can be made by reflux extraction, extracting solution filtration and concentration respectively according to the extraction technology of pharmacy, and can be prepared into medicines for cerebral embolism according to the following different production methods that dripping pills can be prepared by adding a proper matrix, heating, dissolving, dripping and cooling; granules can be obtained by adding proper medicinal auxiliary materials and granulating; tablets can be obtained adding a right amount of the medicinal auxiliary materials, granulating and tabletting; hard capsules can be obtained by adding a right amount of the medicinal auxiliary materials, granulating and encapsulizing; soft capsules can be obtained by adding proper auxiliary materials, heating and blending through a pressing method or a dripping method; powder can be obtained by drying the extractum and pulverizing the dried extractum and a right amount of auxiliary materials into fine powder; oral liquids can be obtained by adding purified water, compounding, packing and sterilizing the liquids. The present invention has unique formulation and preparing method and obvious curative effect, and is suitable for patients with cerebrovascular diseases, such as cerebral thrombosis and cerebral hemorrhage, namely apoplexy in the syndrome differentiation of Chinese medicine.

Description

Medicine of treatment apoplexy and preparation method thereof

Technical field

The present invention relates to a kind of medicine for the treatment of apoplexy, is the oral formulations of the treatment apoplexy of feedstock production with the Chinese herbal medicine specifically, the invention still further relates to the preparation method of this medicine.

Background technology

Apoplexy is commonly encountered diseases, the frequently-occurring disease of middle-aged and elderly people, because of its sickness rate, case fatality rate, disability rate and relapse rate higher, and old man's life and health and life quality in having a strong impact on.

Domestic 1988 Epidemiological study result shows that China's town and country apoplexy sickness rate is 109.74/10 ten thousand, with being 115.61/10 ten thousand after the world standard population composition markization; Prevalence is 245.58/10 ten thousand, turns to 259.93/10 ten thousand with world standard population composition mark; Mortality rate is 77.16/10 ten thousand, with being 81.33/10 ten thousand after the world standard population composition markization, has become second of all kinds of causes of the death of urban and rural residents, about 3/4 DB that has in various degree among the survivor, and wherein the severe disabled person accounts for more than 40%.According to measuring and calculating, the total value of delay work loss (comprising family members) and medical expense that China every year causes because of apoplexy is up to 11,200,000,000 yuan, and over nearly 10 years, the age of onset of apoplexy still has in advance and the trend of rejuvenation, therefore, to effective control of apoplexy, key subjects of medical research in the world wide have been become.

Summary of the invention

The object of the present invention is to provide a kind of promoting blood circulation to remove obstruction in the collateral that has, eliminating the phlegm relieves dizziness, high fever, infantile convulsions, epilepsy, etc., and safe and effective treatment apoplex involving the channels and collaterals belongs to wind-phlegm blood stasis numbness resistance venation person's Apoplexy treating medicine preparation.

Another object of the present invention provides the preparation technology of this medicine.

Solution of the present invention is based on the understanding and the Therapeutic Principle of motherland's medical science centering blower fan reason, achieve with reference to modern pharmacological research, obtain at clinical preliminary test to filter out on the basis of better treatment and have the treatment cerebral infarction, blood fat reducing, atherosclerosis, resisting hypertension, the natural plant of many-sided pharmacological action optimum medicine efficacy combination such as cerebral blood flow increasing amount and antithrombotic formation, skim the cream off milk, and under Chinese medical theory instructs prescription, evident in efficacy, and require to design comparatively reasonably preparation technology with reference to modern study data and clinical application.

The pure compound Chinese medicinal preparation that the capsule of this medicine is made up of five tastes medical materials such as Pollen Tyjphae, Radix Paeoniae Rubra, Radix Curcumae, Rhizoma Gastrodiae and Radix Rhapontici.Pollen Typhae is the key medicine of removing stasis to stop bleeding; it gives birth to the effect of then invigorating blood circulation outstanding; studies show that; Pollen Tyjphae has that antiplatelet gathers, blood vessel dilating and microcirculation improvement effect; can improve the anti-hypobaric hypoxia ability of cardiac muscle and brain; the heart, cerebral anoxia are had protective effect, and Pollen Tyjphae also has blood fat reducing and study of anti-atherogenic effect simultaneously.Stagnating has the effect of removing heat from blood, blood stasis dispelling, pain relieving in the Radix Paeoniae Rubra benefaction blood, studies show that Radix Paeoniae Rubra preparation and Radix Paeoniae Rubra glucoside thereof have anticoagulant, blood vessel dilating, increase regional blood flow, improves and organizes oxygen supply and increase body to effects such as anoxybiotic tolerances.Radix Curcumae is longer than the circulation of qi promoting of vegetables liver, promoting blood circulation and stopping pain, also is present a kind of blood-activating and stasis-removing commonly used and important, and modern pharmacological research shows that Radix Curcumae has antioxidation and antiatherogenic effect.More than three medicines, traditional tcm clinical practice is used for diseases such as all diseases of trusted subordinate more.According to its pharmacological research progress, the clinical diseases such as coronary heart disease, atherosclerosis and hypertension that are used for the treatment of of modern Chinese medicine scholar more, obtained curative effect preferably, further be applied at present the treatment of ischemic cerebrovascular again, widened the clinical application range of Pollen Typhae, Radix Paeoniae Rubra and Radix Curcumae, Rhizoma Gastrodiae has the effect of suppressing the hyperactive liver to relieve the wind syndrome, can control dizziness and headache, numb limbs and tense tendons, half body by diseases such as not smoothgoing puckery, the infantile convulsion tics of, speech.Pharmacological research shows that Rhizoma Gastrodiae has calmness, convulsion and analgesic activity to the central nervous system, can reduce cerebral vascular resistance, cerebral blood flow increasing amount, the animal dead rate when being reduced in hypobaric hypoxia, the effect of antioxidation and delaying sanility.Clinically, the Rhizoma Gastrodiae action range, it is sick long-standing to be used for the treatment of apoplexy, and has become the common drug for the treatment of cerebrovascular disease clinically.Radix Rhapontici has heat-clearing and toxic substances removing, detumescence and apocenosis, effects such as logical muscle arteries and veins, and pharmacological research discloses, and Radix Rhapontici has blood fat reducing, antioxidation, antithrombotic formation and effects such as atherosclerosis and protection blood vessel endothelium.More than all medicines share, QI and blood is two transfers, the expectorant stasis of blood two disappears, mainly be applicable in the wind-phlegm of apoplexy apoplex involving the channels and collaterals contain, the treatment of blood stasis numbness resistance disease.

Medicine of the present invention is to make (consumption is a weight portion) by following component

Pollen Typhae 28.2～53.2 Radix Paeoniae Rubra 18.7～26.7 Radix Curcumaes 14.1～24.1 Rhizoma Gastrodiaes 4.6～14.6

Radix Rhapontici 9.4～17.4

Formula optimization weight (part) ratio range of preparation medicine of the present invention is:

Pollen Typhae 30.2～38.5 Radix Paeoniae Rubra 20.7～26.7 Radix Curcumaes 16.1～22.1 Rhizoma Gastrodiaes 6.6～12.6

Radix Rhapontici 11.4～17.4

The optimum weight of medicine of the present invention (part) proportioning is:

Pollen Typhae 33.3 Radix Paeoniae Rubra 23.8 Radix Curcumaes 19.1 Rhizoma Gastrodiaes 9.6 Radix Rhapontici 14.2

First kind of production method above-mentioned each component being made medicine of the present invention is:

[1] earlier with Radix Paeoniae Rubra with 70% alcohol reflux 2 times, each 1 hour, alcohol adding amount was 7 times (or 5 times), merge extractive liquid, filters, filtrate recycling ethanol is condensed into thick paste, 85 ℃ of oven dry, dried cream are standby; Radix Curcumae 80% soak with ethanol 12 hours, reflux, extract, 2 times, each 1 hour, alcohol adding amount was 7 times (or 5 times), merge extractive liquid, filters, filtrate for later use; Medicinal residues are collected in addition;

[2] Pollen Typhae (dress cloth bag), Rhizoma Gastrodiae, Radix Rhapontici, Radix Curcumae medicinal residues, decoct 2 times after 2 hours with 80 ℃ of warm water soaking, each 1 hour, amount of water is 10 times (or 8 times), it is 1.04 (40 ℃) that merge extractive liquid,, filtration, filtrate are concentrated into relative density, adds ethanol and makes and contain alcohol amount and reach 70%, stir evenly cold preservation 48 hours;

[3] medicinal liquid filters, and the alcohol extract of filtrate and Radix Curcumae merges, and reclaims ethanol, is concentrated into thick paste, and 85 ℃ of dryings merge, pulverize, sieve, add appropriate amount of starch with the dried cream of Radix Paeoniae Rubra, mixing, alcohol granulation, oven dry;

[4] add 0.5% magnesium stearate, cross 18-20 mesh sieve granulate, filled capsules, packing, packing gets final product.

Second kind of production method above-mentioned each component being made medicine of the present invention is:

[1] earlier with Radix Paeoniae Rubra with 70% alcohol reflux 2 times, each 1 hour, alcohol adding amount was 7 times (or 5 times), merge extractive liquid, filters, filtrate recycling ethanol is condensed into extractum; Radix Curcumae 80% soak with ethanol 12 hours, reflux, extract, 2 times, each 1 hour, alcohol adding amount was 7 times (or 5 times), merge extractive liquid, filters, filtrate for later use; Medicinal residues are collected in addition;

[3] medicinal liquid filters, and the alcohol extract of filtrate and Radix Curcumae merges, and reclaims ethanol, is concentrated into extractum;

[4] extractum adds Polyethylene Glycol, and its extractum: Polyethylene Glycol is 1: 0.8～6.0;

Drop pill when [5] heating for dissolving is to 60 ℃～90 ℃ of fluid temperature, coolant are with dimethicone or vegetable oil or liquid Paraffin, and coolant temperature is controlled at 2～20 ℃, uses the dropping-pill machine ball, and ball weighs 25～100mg/ grain, makes drop pill.

The third production method of above-mentioned each component being made medicine of the present invention is:

[1] earlier with Radix Paeoniae Rubra with 70% alcohol reflux 2 times, each 1 hour, alcohol adding amount was 7 times, 5 times, merge extractive liquid, filters, filtrate recycling ethanol is condensed into extractum; Radix Curcumae 80% soak with ethanol 12 hours, reflux, extract, 2 times, each 1 hour, alcohol adding amount was 7 times (or 5 times), merge extractive liquid, filters, filtrate for later use; Medicinal residues are collected in addition;

[2] Pollen Typhae (dress cloth bag), Rhizoma Gastrodiae, Radix Rhapontici, Radix Curcumae medicinal residues, decoct 2 times after 2 hours with 80 ℃ of warm water soaking, each 1 hour, amount of water is 10 times, 8 times, it is 1.04 (40 ℃) that merge extractive liquid,, filtration, filtrate are concentrated into relative density, adds ethanol and makes and contain alcohol amount and reach 70%, stir evenly cold preservation 48 hours;

[4] extractum adds sucrose or other solubility pharmaceutic adjuvant, mix homogeneously, and pelletize is sieved, and oven dry is sieved, and granule is made in packing.

The 4th kind of production method above-mentioned each component being made medicine of the present invention is:

[4] extractum adds an amount of pharmaceutic adjuvant, mixing granulation, and oven dry, tabletting is made tablet.

The 5th kind of production method above-mentioned each component being made medicine of the present invention is:

[4] extractum adds suitable adjuvant, and the heating mix homogeneously is made soft capsule with pressing or dropping preparation method.

The 6th kind of production method above-mentioned each component being made medicine of the present invention is:

[4] extract dry and appropriate amount of auxiliary materials are ground into fine powder, make powder.

The 7th kind of production method above-mentioned each component being made medicine of the present invention is:

[4] extractum adds purified water, stirs, and filters, and mixture (oral liquid) is made in filtrate bottling sterilization.

Medicine of the present invention can adopt the conventional method of Chinese medicine preparation to be prepared into any conventional oral formulations, preferred capsule.

For improving concentration medicine, be prerequisite to reduce dosage, the optimum extraction condition of following medicine is investigated:

1 Radix Paeoniae Rubra: reflux, extract,, extraction conditions individual event factor is investigated, and to used concentration of alcohol, alcohol adding amount, extraction time, extraction time, relatively gets the cream amount respectively, and paeoniflorin must be measured, and therefrom selects out optimum extraction condition.

Table 1: the investigation test and the result of concentration of alcohol

The dried cream amount of feed ethanol concentration alcohol adding amount time number of times the rate of extract content of paeoniflorin paeoniflorin must be measured

(g) (doubly) (%) (g) (%) (%) (%) of (h) (inferior)

20 60 7,5 1 2 6 30 9.88 0.593

20 70 7,5 1 2 5 25 11.30 0.565

20 80 7,5 1 2 4 20 12.29 0.491

Above result shows, takes all factors into consideration and adopts 70% ethanol extraction more suitable.

Table 2: alcohol adding amount is investigated test and result

(g) (doubly) (%) (g) (%) (%) (%) of (h) (inferior)

20 70 7 1 2 4.5 22.5 12.42 0.559

20 70 5 1 2 4.0 20.0 11.08 0.443

20 70 3 1 2 3.0 15.0 13.80 0.414

Above result shows, alcohol adding amount be 7 times more suitable, because of the second no longer imbibition of material of boiling medicine, get final product so alcohol adding amount is 5 times.

Table 3: extraction time is investigated test and result

(g) (doubly) (%) (g) (%) (%) (%) of (h) (inferior)

20 70 7.5 0.5 2 4.5 20 9.55 0.382

20 70 7.5 1.0 2 5.0 25 10.04 0.502

20 70 7.5 1.5 2 5.0 25 10.52 0.526

Above result shows, extracts to get final product in 1 hour.

Table 4: extraction time is investigated test and result

(g) (doubly) (%) (g) (%) (%) (%) of (h) (inferior)

20 70 7.5 1 1 4.0 20.0 10.04 0.416

20 70 7.5 1 2 4.5 22.5 11.11 0.500

20 70 7.5 1 3 5.0 25.0 10.88 0.544

Above result shows, extracts to get final product for 2 times.

Demonstration test after four single factors investigations, is verified with the optimum condition in each single factor, the results are shown in Table 5:

Table 5: demonstration test and result

(g) (doubly) (%) (g) (%) (%) (%) of (h) (inferior)

200 70 7.5 1 2 51.48 25.74 9.89 5.09

200 70 7.5 1 2 53.10 26.55 9.85 5.23

200 70 7.5 1 2 51.84 25.92 9.92 5.14

Above result shows that the extraction conditions of Radix Paeoniae Rubra is stablized feasible.

2. water is proposed the investigation of medicine condition

Water is carried Pollen Typhae, Radix Curcumae, Rhizoma Gastrodiae, Radix Rhapontici in the medicine, wherein Pollen Typhae is a monarch drug, its dose accounts for 1/3rd of full recipe quantity, but do not have standard substance and contain the survey index, though and Rhizoma Gastrodiae has standard substance, it is measured seldom, therefore select behind the Pollen Typhae chromatography yellow fluorescence speckle at wavelength 285nm place, scan, the size of the integrated value of fluorescence speckle is determined the quality of extraction conditions under the more different extraction conditions, to select out optimum extraction condition.The results are shown in Table 6,7,8,9.

Table 6: the investigation test and the result of alcohol precipitation concentration

The dried cream amount of raw material amount of water time number of times volume alcohol precipitation concentration the rate of extract wavelength 285nm place speckle

(g) (doubly) (h) (inferior) (ml) (%) (%) (%) dot product score value

32 10,8 1 1 50 60 5.0 15.6 1885.93

32 10,8 1 1 50 70 3.5 10.9 2186.26

32 10,8 1 1 50 80 1.6 5.0 1945.72

The looking down upon greatly of dried cream yield and speckle integrated value from table 6, alcohol precipitation concentration transfers to 70% and is advisable.

Table 7: the investigation test and the result of amount of water

(g) (doubly) (h) (inferior) (ml) (%) (%) (%) dot product score value

32 10 1 2 50 70 5 15.63 9839.23

32 8 1 2 50 70 3 9.38 8043.93

32 6 1 2 50 70 2 6.25 7554.23

Above result shows that amount of water is advisable for 10 times, because of the second no longer imbibition of material of boiling medicine, adds 8 times of amounts and gets final product

Table 8: the investigation test and the result that boil the time of carrying

(g) (doubly) (h) (inferior) (ml) (%) (%) (%) dot product score value

32 10,8 0.5 2 50 70 2 6.25 3586.52

32 10,8 1.0 2 50 70 3 9.38 5262.64

32 10,8 1.5 2 50 70 3 9.38 5590.65

See that from table 8 to extract 1 hour identical with 1.5 hours the rate of extract, the speckle integrated value is also similar, when saving, energy-conservation consideration boils and carry 1 hour and get final product.

Table 9: boil and put forward number of times investigation test and result

(g) (doubly) (h) (inferior) (ml) (%) (%) (%) dot product score value

32 10 1 1 50 70 3.2 10.00 3875.43

10 1 2 50 70 1.2 3.75 1049.12

10 1 3 50 70 0.4 1.25 428.59

Above result shows, boils to carry 2 times and get final product.

Table 10: demonstration test result

Raw material amount of water time number of times relative density of medicine liquid alcohol precipitation concentration cold preservation the rate of extract wavelength 285nm place speckle

(g) (doubly) (h) (inferior) (40 ℃) (%) (h) (%) account for integrated value

320 10,8 1 2 1.04 70 48 6.85 5375.28

320 10,8 1 2 1.04 70 48 7.23 5518.47

320 10,8 1 2 1.04 70 48 7.08 5403.62

Above result shows that institute's process conditions of selecting are rationally feasible, and average the rate of extract is 7.05%.

By above method for making, 3 batches of lab scales, 3 batches of pilot scales are operated in Workshop Production equipment, and the result is as follows:

Table 11: 3 batches of trial results of lab scale

The dried cream amount of inventory the rate of extract should be adorned the real dress of capsule capsule yield

Lot number

(g) (g) (%) (grain) (grain) (%)

950214 5340 624 11.69 2000 1930 96.5

950306 5340 643 12.04 2000 1946 97.3

950328 5340 635 11.89 2000 1956 97.8

Table 12: 3 batches of trial results of pilot scale

Lot number

(g) (g) (%) (grain) (grain) (%)

951010 53400 6530 12.23 2000 19500 97.5

951108 53400 6450 12.08 2000 19680 98.4

951204 53400 6570 12.30 2000 19560 97.8

Table 13: the rate of extract

The average the rate of extract (%) of lot number the rate of extract (%)

950214 11.69

950306 12.04

950328 11.89 12.04

951010 12.23

951108 12.08

951204 12.30

According to three batches of lab scales, the rate of extract of three batches of pilot scales, prescribed product the rate of extract is not less than 10.5%.

Above result shows that three batches of lab scales and three batches of pilot scale the rate of extract are more stable, feasible process.Sample is by " 95 years versions of Chinese pharmacopoeia, a general rule capsule prescription is checked.The results are shown in Table 14.

Table 14: manufacture experimently capsular quality examination result

Lot number content of paeoniflorin moisture content uniformity disintegration

(mg/ grain) be (min) (%)

951,010 12.73 5.3 22 is qualified

951,108 14.08 4.5 20 is qualified

951,204 13.52 4.1 19 is qualified

Three batch sample health examinations the results are shown in Table 15

Table 15: trial product health examination result

Lot number total number of bacteria total number of molds escherichia coli demodicid mite alive

(individual/g) (individual/g) (individual/g)

951,010 100＜10 do not detect

951,108 100＜10 do not detect

951,204 80 80 do not detect

This shows this feasible process.

Clinical drug of the present invention uses the result to show that following advantage is arranged:

1. the curative effect of Drug therapy apoplexy of the present invention is better than XIAOSHUAN TONGLUO PIAN.

2. the effect that has remarkable blood pressure lowering and triglyceride reducing, cholesterol.

3. cerebral hemorrhage patient hemorrhagic focus is obviously absorbed, and peripheral edema obviously alleviates.

4. safety testing shows, this product finds no anomalous effects to vitals such as liver, kidney, the hearts.

For showing the therapeutic effect of medicine of the present invention to apoplexy, the present invention is through the clinical trial of 401 routine systems, be divided into A group (logical No. 1 of brain bolt) 100 examples and B group (logical No. 1 of brain bolt) 100 examples and B group (logical No. 2 of brain bolt) 100 examples and C group (the logical open group of brain bolt) 201 examples at random, clinical application around the course of treatment is observed, demonstrating A group total effective rate is 93.00%, obvious effective rate is 69.00%, B group total effective rate is 85.00%, obvious effective rate is 51.00%, A group curative effect is better than the B group, there were significant differences to learn processing by statistics, and C group total effective rate is 92.54%, and obvious effective rate is 56.22%.Observe through head CT, each group all can promote the absorption of cephalophyma and alleviate cephalophyma or block cerebral edema on every side that safety is not seen tangible toxicity during observing and showing medication, thereby proof brain bolt extensively treating treatment apoplexy has certain curative effect, take safety, do not see obvious adverse reaction.

Take in the case ordinary circumstance and see Table 16～18

Table 16 is taken in case sex data relatively

The A group B group C group (X of A～B) ²Value (A～B) be worth

Case sum 100 100 201

The male 69 71 116 0.09＞0.75

The women 31 29 85

Table 17 is taken in case age data relatively

The A group B group C group (Tx of A～B) ²(the p value of A～B)

Mean age 63.75 ± 5.63 64.05 ± 7.76 63.58 ± 6.75 0.210＞0.5

≤ 50 years old 11 9 18

51～60 years old 23 22 51 0.29＞0.5

61～70 years old 66 69 132

Table 18 is taken in case feelings data relatively

A group B group C group (the t value of A～B) (the p value of A～B)

Average course of disease (my god) 3.56 ± 2.64 3.92 ± 2.98 3.86 ± 3.69 0.286＞0.5

Initial card marquis marks 11.30 ± 3.39 10.86 ± 5.07 11.58 ± 6.01 0.463＞0.5

Initial clinical score 10.08 ± 4.65 9.95 ± 2.89 10.53 ± 4.34 0.964＞0.5

Upper limb muscular strength 3.86 ± 1.22 3.54 ± 1.49 3.25 ± 1.86 0.21＞0.5

Lower-limb muscular strength 3.87 ± 1.19 3.68 ± 1.46 3.88 ± 1.35 0.54＞0.5

Systolic pressure 20.45 ± 2.99 20.75 ± 2.92 20.33 ± 2.65 0.699＞0.5

Diastolic pressure 12.56 ± 2.38 12.82 ± 1.62 12.21 ± 2.02 0.254＞0.5

A, two groups of data of B are through t check and X 2 test, and no significant difference has comparability.

The case survey data of being received contrasts, and sees Table 19.

Table 19 is received blood fat data before the case treatment

Group example number triglyceride cholesterol high density lipoprotein

(mmol/l) (mmol/l) (mmol/l)

A organizes 100 1.65 ± 1.24 4.75 ± 1.33 1.11 ± 0.46

B organizes 100 1.56 ± 0.96 4.62 ± 0.98 1.16 ± 0.48

C organizes 201 1.63 ± 0.92 5.23 ± 1.89 1.36 ± 1.04

T value (A～B ratio) 0.256 0.108 0.740

P value (A～B ratio)＞0.5＞0.5＞0.2

A, two groups of data of B are checked through t, and there was no significant difference has comparability.

The case head CT data of being received contrast sees Table 20.

Table 20 is received case head CT data

The group example number cerebral infarction cerebral hemorrhage surrounding tissue edema center line hemorrhage volume (cm that is shifted ³)

A organizes 100 84 16 50 21 12.82 ± 15.97

B organizes 100 77 23 43 18 11.36 ± 9.84

C organizes 201 134 67 123 46 15.46 ± 11.25

X ²T value (A～B ratio) 1.56 0.98 0.29 0.874

P value＞0.5＞0.5＞0.5＞0.2

A, two groups of data of B are through t check and X 2 test, and there was no significant difference has comparability.

The apoplexy clinical efficacy sees Table 21.

Table 21 apoplexy clinical efficacy

Group example number is cured produce effects enabledisable total effective rate (%) obvious effective rate (%)

A organizes 100 14 55 24 7 93.00 69.00

B organizes 100 6 45 34 15 85.00 51.00

C organizes 201 23 90 73 15 92.54 56.22

P value (A～B ratio)＜0.01＜0.01

Analyze through Ridit, u=2.7509, p＜0.01 explanation A, there were significant differences for two groups of curative effects of B, and two groups of obvious effective rates are compared in X 2 test, p＜0.01, thus the curative effect of proof A group is better than the B value.

The relation of table 22 curative effect and the course of treatment

Cure produce effects enabledisable total effective rate % obvious effective rate % X the course of treatment ²Value P value

3 days 006 94 6.00 0.00

7 days 1 10 40 49 51.00 11.00 16.89＜0.005

14 days 3 29 36 32 68.00 32.00

28 days 14 55 24 7 93.00 69.00

3 days 004 96 4.00 0.00

7 days 07 36 57 43.00 7.00 14.91＜0.005

14 days 1 24 28 42 53.00 25.00

28 days 6 45 34 15 85.00 51.00

3 days 00 12 189 5.97 0.00

7 days 2 21 79 99 50.74 11.44 16.89＜0.005

14 days 7 60 71 63 68.66 33.33

28 days 23 90 73 15 92.54 56.22

By table 22 as seen, curative effect and positive correlation was arranged between the course of treatment, the course of treatment is long more, and curative effect is good more, and marked difference is arranged.

The clinical integration therapeutic effect of apoplexy sees Table 23

The clinical integration of apoplexy relatively before and after table 23 treatment

After controlling

Before controlling

3 days 7 days 14 days 21 days 28 days

10.08±4.65 9.66±4.76 7.99±4.69 6.47±4.65 5.04±3.89 3.93±3.62

9.95±2.89 8.94±5.98 7.23±5.61 6.21±5.53 5.19±5.42 5.21±5.08

10.53±4.34 9.85±4.55 8.01±4.69 6.55±3.98 5.01±4.02 3.99±3.25

P value (A～B ratio) 0.048

Through the t check, all promptly to have an effect in the 7th day for three groups from treating, the clinical integration of apoplexy lowers (p＜0.05), but A group curative effect is better than the B group, and there were significant differences for statistical test.

Syndrome in TCM marquis's integration relatively sees Table 24

Table 24 tcm syndrome integration relatively

After controlling

Before the example number is controlled

3 days 7 days 14 days 21 days 28 days

100 11.30±3.39 9.92±3.51 8.43±3.32 6.47±3.96 5.85±3.14 4.35±2.77

100 10.68±5.07 9.45±2.86 7.35±2.98 5.96±2.69 5.47±2.96 5.30±2.78

201 11.58±6.01 10.01±3.20 8.99±3.65 7.11±3.85 6.24±3.03 4.98±3.04

P value (A～B ratio) 0.041

To the comparison of tcm syndrome integration, through the t check, treat i.e. generation effect in the 3rd day, Syndrome in TCM marquis's integration lowers (p＜0.01), but A, the therapeutic effect that B is two groups has significant difference, and the A group is better than the B group.

The logical influence to the limbs muscular strength of brain bolt saw Table for 25 (muscular strength represents that with level being 0 grade is 0, and one-level is one, and secondary is 2)

The variation of upper limb muscular strength before and after table 25 treatment

Control back (level)

Organize routine number and control preceding (level)

7 days 14 days 21 days 28 days

A organizes 100 4.41 ± 1.27 3.86 ± 1.22 3.92 ± 1.26 4.21 ± 1.29 4.38 ± 1.13

B organizes 100 4.08 ± 1.42 3.54 ± 1.49 3.58 ± 1.47 3.84 ± 1.33 3.98 ± 1.41

C organizes 201 4.34 ± 1.25 3.25 ± 1.86 3.45 ± 1.30 3.68 ± 1.29 4.26 ± 1.06

Each group all can be improved muscular strength, and through t check, one week of medication can obviously be improved (p＜0.001), but A, and two groups of B do not have significant difference (p=1.00) to upper limb muscular strength improvement effect.

The variation of lower-limb muscular strength sees Table 26 before and after the treatment

The variation of lower-limb muscular strength before and after table 26 treatment

Control back (level)

Before group example number is controlled (level)

7 days 14 days 21 days 28 days

A organizes 100 4.58 ± 0.82 3.87 ± 1.19 4.08 ± 1.26 4.33 ± 0.95 4.43 ± 0.86

B organizes 100 4.49 ± 1.27 3.68 ± 1.46 4.06 ± 1.38 4.36 ± 1.24 4.38 ± 1.19

C organizes 201 4.50 ± 0.98 3.88 ± 1.35 3.96 ± 1.22 4.29 ± 1.02 4.42 ± 1.25

Through the t check, each is organized and can improve lower-limb muscular strength (p＜0.001) in one week of medication, but A, two groups of effects of B similar (p=0.52).

The logical influence to blood pressure of brain bolt sees Table 27

Table 27 liang group medicine is to the influence of blood pressure

Control back (level)

Before group example number project is controlled (level)

7 days 14 days 21 days 28 days

A organizes 100 systolic pressures 20.45 ± 2.99 19.35 ± 2.23 19.29 ± 1.87 18.79 ± 1.79 18.34 ± 1.92

Diastolic pressure 12.56 ± 2.38 11.13 ± 1.07 11.18 ± 1.12 10.78 ± 1.15 10.58 ± 1.07

B organizes 100 systolic pressures 20.75 ± 2.92 19.43 ± 2.28 18.78 ± 1.57 18.68 ± 1.44 18.38 ± 1.38

Diastolic pressure 12.82 ± 1.62 11.46 ± 1.26 11.21 ± 1.06 10.81 ± 0.89 10.76 ± 0.88

C organizes 201 systolic pressures 20.33 ± 2.65 20.13 ± 2.36 19.88 ± 1.79 18.99 ± 1.68 18.87 ± 1.89

Diastolic pressure 12.21 ± 2.02 11.97 ± 1.92 11.23 ± 1.09 10.87 ± 1.12 10.85 ± 1.08

Through the t check, each organizes medication three all after-contraction pressures and diastolic pressure all has obvious decline (p＜0.0001), but A, two groups of effects of B do not have significant difference (systolic pressure relatively p=0.92 diastolic pressure compares p=0.55)

The logical influence to blood fat of brain bolt sees Table 28

Table 28 brain bolt extensively treating is treated the influence to blood fat

Triglyceride (mmol/l) cholesterol (mmol/l) high density lipoprotein

Group example number

After controlling before controlling after controlling before controlling after controlling before controlling

A organizes 100 1.65 ± 1.24 1.27 ± 0.76 4.75 ± 1.33 4.05 ± 0.99 1.11 ± 0.46 1.15 ± 0.49

B organizes 100 1.56 ± 0.96 1.53 ± 0.94 4.62 ± 0.98 4.34 ± 0.98 1.16 ± 0 48 1.12 ± 0.44

C organizes 201 1.67 ± 0.92 1.23 ± 0.97 5.23 ± 1.89 4.98 ± 1.05 1.36 ± 1.04 1.38 ± 0.52

Through the t check, A group and C group have the effect of triglyceride reducing and cholesterol, (p=0.0136,0.025; 0.0142,0.021), but the not obvious (p=0.10 of the effect of high density lipoprotein increasing; 0.135), and the B group does not all have this effect (p=0.734,0.788,0.259), and A, the B group sees that comparison p is all＜0.001.

The brain bolt is logical to see Table 29 to hemorheological influence

Table 29 brain bolt is logical to hemorheological influence

Organize than the p value than p value A～B before and after controlling the back treatment before group is controlled

A group 4.88 ± 1.07 4.43 ± 0.99 0.0021

The whole blood height

B group 4.91 ± 0.92 4.42 ± 0.85 0.0018 0.149

Cut viscosity

C group 4.91 ± 1.53 3.66 ± 1.54 0.001

A group 9.96 ± 2.94 8.12 ± 2.89＜0.001

Whole blood is low

B group 9.95 ± 2.79 8.87 ± 2.32 0.022 0.929

Cut viscosity

C group 8.25 ± 1.64 7.15 ± 1.62 0.001

A group 7.99 ± 1.41 7.34 ± 1.52 0.016

Reduction is high

B group 8.36 ± 1.92 7.83 ± 1.65 0.083 0.124

Cut viscosity

C group 10.62 ± 2.01 8.99 ± 2.21 0.015

A group 18.09 ± 3.65 17.28 ± 4.52 0.223

Reduce low

B group 18.37 ± 4.98 17.42 ± 4.45 0.283 0.876

Cut viscosity

C group 21.36 ± 3.59 19.11 ± 3.37 0.058

A group 1.79 ± 0.39 1.79 ± 0.41 0.909

Plasma viscosity B group 1.82 ± 0.33 1.71 ± 0.44 0.109 0.335

C group 1.88 ± 0.84 1.71 ± 0.64 0,81

A group 45.96 ± 7.92 44.43 ± 8.19 0.614

Hematocrit B group 47.82 ± 9.49 44.08 ± 7.44 0.014 0.821

C group 42.09 ± 3.89 41.78 ± 2.69 0.15

A group 1.98 ± 0.23 2,02 ± 0.47 0.515

Erythrocyte

B group 1.99 ± 031 1.98 ± 0.28 0.689 0.579

Gather index

The C group

A group 3.69 ± 1.19 3.37 ± 1.33 0.887

Erythrocyte

B group 3.81 ± 1.28 3.71 ± 1.52 0.648 0.232

Rigidity index

The C group

Find out that by table 29 the brain bolt is logical little to the hemorheology influence, only to slightly improvement effect of whole blood viscosity, and A, B does not have significant difference for two groups.

Brain bolt extensively treating is treated the variation of apoplexy head CT

A organizes 73 examples, and B organizes 68 examples, and C organizes 184 examples and treats cross-reference through head CT, A organizes 16 routine cerebral hemorrhages, B organizes 23 routine cerebral hemorrhages, and C organizes 67 routine cerebral hemorrhages, and hemorrhagic focus all obviously absorbs, peripheral edema also is clearly better, the occupy-place effect is several to disappear, and for cerebral infarction, infarct size is not seen obviously and dwindled before and after the treatment, but the peripheral edema band all obviously alleviates, and sees Table 30

Head CT changed (peripheral edema band) when table 30 brain bolt extensively treating was treated apoplexy

Treatment back edema band example number improvement rate before the treatment

Group

Edema band example number disappears and alleviates no change (%)

A organizes 50 37 13 0 100

B organizes 43 31 12 0 100

C organizes 123 82 41 0 100

Each organizes the peripheral edema band all tangible improvement, through X 2 test p＞0.05, and no marked difference.

Safety is observed:

All carry out routine blood test before and after two groups of patient treatments, routine urinalysis, stool routine examination, liver function, renal function and Electrocardioscopy are not seen any unusual.See table 31 for details

Table 31. security inspection

A group B group C group

After preceding treatment is treated in the treatment back before treating after the treatment before the treatment

Classification

Just different just different just different just different just different just different

Usually

Routine blood test 96 4 100 0 86 14 97 3 196 5 201 0

Routine urinalysis 92 8 93 7 88 12 92 8 193 8 198 3

Stool routine 100 0 100 0 99 1 100 0 201 0 201 0

Liver function 96 4 97 3 95 5 96 4 199 2 199 2

Renal function 94 6 98 2 93 7 96 4 194 7 200 1

Electrocardio Figure 72 28 75 15 71 29 77 23 171 30 179 22

The variation mmol/L of table 32 (1) serum total cholesterol content (X ± SD)

2 months treatment backs of the high fat of dosage descend

Group

(n) (g/kg) the preceding high fat of experiment was treated 1 month % in 1 month

Model group (8) 1.71 ± 0.44 22.96 ± 0.28 20.82 ± 0.44 9.30 ± 2.10

(8) 7.0 1.28±0.40 23.03±0.36 20.43±0.10* 11.13±1.62

The logical group of brain bolt

(8) 17.5 1.86±0.67 23.06±0.11 20.47±0.11* 11.20±0.55

XIAOSHUAN TONGLUO PIAN group (8) 14.4 1.59 ± 054 23.03 ± 0.11 20.43 ± 0.13* 11.61 ± 0.61

With model group than * P＜0.05

The variation mmol/L of table 32 (2) serum height fat egg cholesterol level (X ± SD)

2 months treatment backs of the high fat of dosage descend

Group

(g/kg) 1 month (n) % of (n) high fat (n) treatment in 1 month before the experiment

Model group 0.48 ± 0.12 (11) 0.97 ± 0.75 (8) 0.67 ± 0.22 (8)

7.0 0.49±0.23(11) 0.62±0.23(11) 1.10±0.19 ^★★★▲ (9)＜0.01

The logical group of brain bolt

17.5 0.50±0.19(9) 0.41±0.14(10) 0.92±0.29 (8)＜0.01

XIAOSHUAN TONGLUO PIAN group 14.4 0.52 ± 0.17 (10) 0.75 ± 0.75 (6) 0.75 ± 0.32 (10)

With model group than * * * P＜0.001 and XIAOSHUAN TONGLUO PIAN ratio ▲ P＜0.005

Brain bolt open capsule is to the influence of serum triglycerides content:

Test forward and backwardly and forward and backward with shaking, the serum glyceride content is organized equal no significant difference at each, and standard deviation is all very big, does not demonstrate drug effect, and table slightly.

Experimental result:

The comparison of (1) atherosclerosis of aorta pathological changes:

Moving atherosclerotic lesion takes place in the experiment all animals, and incidence rate is 100%, illustrates that model moulds successfully.It is different that each organizes arteriopathy mark performance, and account at its area aspect the percent of the gross area: model group 55.9 ± 14.5, the large and small dosage group of brain bolt open capsule is respectively 28.5 ± 9.4 and 23.3 ± 6..3, all less than model group, the difference highly significant (P (0.001), the XIAOSHUAN TONGLUO PIAN group is 34.1 ± 16.1, though significantly less than model group (P＜0.01), greater than the large and small dosage group of brain bolt open capsule, with small dose group than difference remarkable (P＜0.05).Compare from the O.D value of pathological changes thickness, the model group maximum, the XIAOSHUAN TONGLUO PIAN group is taken second place.The logical equal highly significant of large and small dosage group of brain bolt is less than model group (P＜0.01), and XIAOSHUAN TONGLUO PIAN group O.D value nitre is less than model group, but do not have significant difference.Microscopically is observed: model group lesion nature 57.1% belongs to the progress type that enlivens, XIAOSHUAN TONGLUO PIAN is close with it to be 55.6%, and the large and small dosage group of brain bolt open capsule is enlivened the progress type, and XIAOSHUAN TONGLUO PIAN is close with it to be 55.6%, and the large and small dosage group of brain bolt open capsule is enlivened the type pathological changes and only accounted for 12.5％。Brain bolt open capsule treatment can be described based on the above results 30 days, can make that the fast area of atherosis speckle obviously dwindles, degree alleviates, and obviously suppress the development of pathological changes.The results are shown in Table 33.

The anti-rabbit atherosclerosis of table 33 brain bolt open capsule---the comparison of aortic disease

Lesion nature (%)

Group

(n) dosage (g/kg) pathological changes incidence rate (%) pathological changes area (%) pathological changes thickness (O.D) is generally active

Model group (9) 100 22.96 ± 0.28 20.82 ± 0.44 42.9 57.1

(10) 7.0 100 23.03±0.36 20.43±0.10* 87.5 12.5

The logical group of brain bolt

(10) 17.5 100 23.06±0.11 20.47±0.11* 87.5 12.5

XIAOSHUAN TONGLUO PIAN group (10) 14.5 100 23.03 ± 0.11 20.43 ± 0.13* 44.4 55.6

With model group than ★ ★ P＜0.01 ★ ★ ★ P＜0.001

With positive drug XIAOSHUAN TONGLUO PIAN group ratio ▲ P＜0.05

Annotate: this experiment aortopathy variable area, thickness are image analyzer detection by quantitative result, and lesion nature is the om observation result.

(2) arteries and veins histological observation

Each group of administration, its pathological changes thickness is all thinner than the model group, and through the significant difference (P＜0.01) of the heavy dose of group of brain bolt open capsule, and its lesion nature all belongs to generality, and the pathological changes of model group all is to enliven the progress type.Though XIAOSHUAN TONGLUO PIAN group pathological changes thickness reduces than model group, have 66.7% to belong to and enliven type, and its pathological changes incidence rate is 100%, apparently higher than other group, show that its therapeutic effect is not as brain bolt open capsule, with consistent in the aorta finding.The results are shown in Table 34

Table 34 brain bolt open capsule resists all sclerosis of tame rabbit arterial medicated porridge-pulmonary artery pathological changes relatively

Lesion nature (%)

Group

(n) dosage (g/kg) pathological changes incidence rate (%) pathological changes thickness (O.D) is generally active

Model group (9) 78.8 287.9 ± 93.3 0 100

(9) 7.0 77.8 171.4±84.2 ^★ 42.9 57.1

The logical group of brain bolt

(9) 17.5 88.9 144.4±40.6 ^★★ 100 0

XIAOSHUAN TONGLUO PIAN group (9) 14.5 100 106.2 ± 80.9 ^★33.3 66.7

With model group than ★ P＜0.05 ★ ★ P＜0.01

(3) brain bolt open capsule is to the influence of kidney type hypertensive rat blood pressure

Can find out that from table 35 the large and small dosage of brain bolt open capsule all has the reduction effect to type hypertension, and from the blood pressure drops percentage rate, the reduction effect of heavy dose of group is better than the positive drug group, simultaneously, the hypotensive effect of small dose group also has the trend that is better than the positive drug group.

Table 35 brain bolt open capsule is to kidney type hypertensive rat blood pressure influence (X ± SD)

Compare blood pressure drops before and after the dosage blood pressure (mmHg)

Group

(n) the preceding medication of (g/kg) medication (water) (water) back P value percentage rate (%)

Normal group 110.4 ± 2.89 108.7 ± 4.04

Model group (10) 131.1 ± 8.54 131.4 ± 10.3

(10) 7.0 139.0±11.36 112.7±5.20 ＜0.001 18.6

The logical group of brain bolt

(10) 17.5 137.6±8.97 109.0±5.86 ＜0.001 21.00±6.07

XIAOSHUAN TONGLUO PIAN group (10) 14.4 146.2 ± 10.6 125.8 ± 10.3＜0.001 13.88 ± 7.11

Annotate: and the percentage comparisons of XIAOSHUAN TONGLUO PIAN group blood pressure drops ▲ ▲ P＜0.01

(4) the network Yiganning capsule is to the influence of castration type hypertensive rat blood pressure

From table 36, also can find out the blood pressure of this medicine, the effect of reduction is also arranged castration type rat.

Table 36 brain bolt open capsule is to the influence of castration type rat blood pressure (X ± SD)

Compare blood pressure drops before and after the dosage blood pressure (mmHg)

Group

Normal group (10) 109.3 ± 3.53 105.98 ± 4.55

Model group (10) 130.6 ± 9.73 129.4 ± 8.89

(10) 7.0 137.1±10.07 117.9±8.5 ＜0.001 10.8±6.41

The logical group of brain bolt

(10) 17.5 135.0±12.6 112.7±6.18 ＜0.001 16.0±5.33

XIAOSHUAN TONGLUO PIAN group (10) 14.4 136.9 ± 8.94 117.3 ± 5.1＜0.001 14.8 ± 7.11

Table 37 brain bolt open capsule is to influence (the low shear rate 20s of rat blood viscosity ¹) (X ± SD)

Group (n) dosage (g/kg) whole blood viscosity whole blood reduced viscosity plasma viscosity

Normal group (12) 6.36 ± 0.69 12.62 ± 1.50 1.82 ± 0.07

Model group (12) 9.20 ± 0.49 ^{△ △ △}10.34 ± 1.08 ^{△ △ △}2.11 ± 0.09 ^{△ △ △}

(12) 7.0 7.09±0.47 ^★★★ 13,57±1.32 ^★★★ 1.86±0.05 ^★★★▲

The logical group of brain bolt

(11) 17.5 6.77±0.47 ^★★★ 13.32±1.61 ^★★★ 1.92±0.09 ^★★★

XIAOSHUAN TONGLUO PIAN group (12) 14.4 6.80 ± 0.44 ^{★ ★ ★}14.03 ± 1.19 ^{★ ★ ★}1.93 ± 0.10 ^{★ ★ ★}

Compare ★ ★ ★ P＜0.001 with model group

With removing obstruction from collaterals pill group comparison ▲ P＜0.05

Table 38 brain bolt open capsule is to the influence of rat erythrocyte sedimentation rate and packed cell volume (X ± SD)

Group (n) dosage (g/kg) erythrocyte sedimentation rate (mm) packed cell volume (%)

Normal group (12) 30.50 ± 2.72 42.75 ± 3.88

Model group (12) 44.42 ± 1.89 ^{△ △ △}44.75 ± 1.69

(12) 7.0 45.08±3.04 41.83±0.99 ^★★★

The logical group of brain bolt

(11) 17.5 44.91±1.93 42.36±2.22 ^★★★

XIAOSHUAN TONGLUO PIAN group (12) 14.4 46.42 ± 3.23 41.50 ± 1.44 ^{★ ★ ★}

Compare △ △ △ P＜0.001 with normal group

Compare * * P＜0.01 * * * P＜0.001 with model group

Experimental result sees Table 39

Table 39 brain bolt open capsule is to the influence of platelet aggregation in the mice body (X ± SD)

Group (n) dosage (g/kg) reactivate the time (branch)

Normal group (10) 6.57 ± 0.75

(10) 7.0 2.26±0.45 ^{△△△▲▲▲}

The logical group of brain bolt

(10) 17.5 1.47±0.14 ^△△△

XIAOSHUAN TONGLUO PIAN group (10) 14.4 1.58 ± 0.29 ^{△ △ △}

Compare △ △ △ P＜0.001 with normal group

Compare with the XIAOSHUAN TONGLUO PIAN group ▲ ▲ ▲ P＜0.001

After the brain bolt open capsule two weeks, can obviously suppress the inductive platelet aggregation of ADP, heavy dose of effect is better than small dose group.The effect of XIAOSHUAN TONGLUO PIAN group is better than small dose group, but not as heavy dose of group.

Experimental result sees Table 40

Table 40 brain bolt open capsule is induced the influence (X ± SD) of rat platelet concentration to ADP

Group (n) dosage (g/kg) gathers rate (%) suppression ratio (%)

Normal group (10) 48.00 ± 3.57

(10) 7.0 32.50±7.20 ^△△△ 32.20

The logical group of brain bolt

(10) 17.5 24.80±8.06 ^△△△▲ 48.33

XIAOSHUAN TONGLUO PIAN group (10) 14.4 31.40 ± 5.80 ^{△ △ △}34.58

Compare △ △ △ P＜0.001 with normal group

With XIAOSHUAN TONGLUO PIAN group comparison ▲ P＜0.05

Brain bolt open capsule gathers the inductive rat platelet of ADP the obvious suppression effect, and the inhibitory action of the heavy dose of group of brain bolt open capsule is more remarkable.All obviously be better than small dose group and XIAOSHUAN TONGLUO PIAN group (P＜0.05).

In addition, also observed arachidonic acid-induction platelet aggregation experiment, the inhibitory action of brain bolt open capsule with induce experimental result close to ADP.

Experimental result sees Table 41

Table 41 brain bolt open capsule is to the influence of rat suppository formation time (X ± SD)

Group (n) dosage (g/kg) thrombus formation time (branch)

Normal group (10) 18.14 ± 1.49

(10) 7.0 26.12±2.81 ^{△△△▲▲▲}

The logical group of brain bolt

(10) 17.5 37.77±2.83 ^{△△△▲▲▲}

XIAOSHUAN TONGLUO PIAN group (10) 14.4 45.26 ± 3.94 ^{△ △ △}

Compare △ △ △ P＜0.001 with normal group

Compare with the XIAOSHUAN TONGLUO PIAN group ▲ ▲ ▲ P＜0.001

The big low dose of brain bolt open capsule all obviously prolongs thrombus formation time, the thrombotic effect of inhibition is promptly arranged. compare brain bolt open capsule small dose group with normal group and prolong 1.44 times of thrombus formation time, the heavy dose of group of brain bolt open capsule prolongs 2.08 times, the XIAOSHUAN TONGLUO PIAN group prolongs 2.5 times of thrombus formation time, obviously is better than brain bolt open capsule group (p＜0.01).

The blood flow variation sees Table 42.

The logical influence to the rats with cerebral ischemia blood flow of table 42 brain bolt (X ± SD)

After the dosage ligation before the ligation with the model group ratio

Group (n)

(g/kg) cerebral blood flow (%) P value

Sham operated rats (15) 101.93 ± 13.61 0.001

Model group (15) 52.03 ± 7.96

(15) 7.0 87.36±10.07 ^▲▲ 0.001

The logical group of brain bolt

(15) 17.5 89.38±33.72 ^▲▲ 0.01

XIAOSHUAN TONGLUO PIAN group (15) 14.4 147.96 ± 53.48 0.001

Compare with positive drug XIAOSHUAN TONGLUO PIAN group ▲ ▲ P＜0.01

Model group rat brain blood flow is significantly less than sham operated rats (P＜0.001).The low dose of treatment group of brain bolt open capsule and heavy dose of treatment group be also all obviously greater than model group (P＜0.001 and P＜0.01), the blood flow of brain when two dosage of prompting brain bolt open capsule all can obviously improve rat cerebral ischemia. do not see obviously (P＜0.05) between the two dosage groups.The XIAOSHUAN TONGLUO PIAN group also obviously greater than model group (P＜0.001), points out this medicine also can obviously improve cerebral blood flow.

(5) vascular permeability changes

See Table 43.Model group obviously increases than the cerebrovascular permeability of sham operated rats, and showing as the interior EB content of unit organization obviously increases (P＜0.001).The low dose of treatment of brain bolt open capsule and heavy dose of treatment all obviously reduce (P＜0.001) than model group, the variation of cerebrovascular permeability when the big low dose of prompting brain bolt open capsule all can reduce ischemia.Do not see notable difference (P) 0.05 between the two dosage groups), they do not see notable difference (P) 0.05 with the sham operated rats ratio yet), the XIAOSHUAN TONGLUO PIAN group also has notable difference (P＜0.001) with the model group ratio

Table 43 brain bolt open capsule is to the influence of rats with cerebral ischemia cerebrovascular permeability

(X ± SD) (ug/g) and model group are than the P value for group (n) dosage cerebral tissue EB content

Sham operated rats (12) 4.62 ± 0.90 0＜0.001

Normal group (12) 7.34 ± 0.53

(12) 7.0 4.88±0.37 ^* ＜0.001

The logical group of brain bolt

(12) 17.5 4.85±0.86 ＜0.001

XIAOSHUAN TONGLUO PIAN thin (12) 14.4 4.15 ± 0.68＜0.001

With positive drug XIAOSHUAN TONGLUO PIAN group than * P＜0.05

Experimental result:

1. the brain bolt is logical to the unusual influence of ischemic brain infarction rat behavior.

Observe rat behavior as stated above, the result is false except that any unusual (0 grade) is not seen in the behavior of operation group, all the other each groups all have dystropy in various degree, see Table 44 through X 2 test, five groups of results have significant difference, wherein observe P＜0.01 between the big young waiter in a wineshop or an inn of a medicine dosage group and model group, P between positive drug group and the model group＜0.05, all difference is remarkable.Between the logical large and small dosage group of brain bolt and and positive drug between all do not have significant difference P＞0.05.

The logical influence (unit: only) of table 44 brain bolt to lacking property cerebral infarction rat behavior

2. the brain bolt leads to the protective effect to the cerebral tissue that lacks boots cerebral infarction rat.

To testing group rat half (10 every group) totally 50, get brain in back two hours broken ends of operation and do crown section, get the section of the preceding 2mm of optic chiasma and make TTC dyeing gross examination of skeletal muscle, the results are shown in Table 45.Get the section behind the optic chiasma, make the microscope histological observation.

The logical control of table 45 brain bolt is to the influence of ischemic brain infarction area (X ± S)

Group (n) area % (g/kg) and model group than t p and positive drug than t p

Model group (10) 7.03 ± 1.99

Brain bolt logical (10) 2.72 ± 1.09 7.027＜0.001

3.117＜0.01

Heavy dose of group

Brain bolt logical (10) 3.91 ± 1.37 4.144＜0.001

1.386＞0.005

Small dose group

Positive control drug group (10) 4.95 ± 1.99

2.33＜0.05

Sham operated rats (10) 0

By table as seen, the brain bolt is logical heavy dose of organizes and percent value that the small dose group infarct size accounts for the coronal section brain gross area is significantly less than the cerebral infarction model group, difference highly significant (P＜0.001).Positive drug XIAOSHUAN TONGLUO PIAN group infarct size percentage ratio is also less than model group, and significant difference (P＜0.05) is organized but lead to heavy dose greater than the brain bolt, and significant differences (P＜0.01) is arranged.Sham operated rats does not see that cerebral infarction forms.

3. the logical influence that ischemic brain infarction tissue metabolism is changed of brain bolt

To testing half (10 every group) totally 50 of an animal, get brain in back 2 hours broken ends of operation, cut the cerebral tissue between each 2mm of optic chiasma front and back, measure lactic acid content after the homogenate.Mensuration sees Table 46.

The logical control of table 46 brain bolt is to lacking the influence of boots cerebral infarction cerebral tissue lactic acid content

Lactic acid Mm/g and model group ratio

Group (n)

Cerebral tissue P value and positive drug ratio

Model group (10) 22.93 ± 3.55

Brain bolt (10) 22.22 ± 2.80＜0.02＜0.05

Heavy dose of group

Brain bolt logical (10) 25.28 ± 1.63＞0.05＞0.05

Small dose group

Positive control drug group (10) 29.26 ± 8.32＜0.05

Sham operated rats (10) 18.71 ± 4.08＜0.001

Blank group (5) 16.38 ± 2.28＜0.001

Lactic acid content is 18.71 ± 4.08mm/g in the visible sham operated rats rat cerebral tissue of table 46, blank group normal value 16.38 ± 2.28 is close, model group brain lactic acid content 25.93 ± 3.55 is significantly higher than sham operated rats P＜0.001, the logical heavy dose of group of brain bolt is 22.22 ± 2.80, content is starkly lower than model group, significant difference P＜0.02; Also obviously greater than positive drug group P＜0.05.The positive drug group is then apparently higher than model group, and P＜0.05 also is higher than the logical small dose group P of brain bolt＜0.05.

Lipid peroxide contents is measured and is seen Table 47.

The logical ischemic brain infarction of table 47 brain bolt is organized the influence of MDA content

MDA mM/g and model group ratio and positive drug ratio

Group (n)

Cerebral tissue P value P value

Model group (10) 0.655 ± 0.073

Brain bolt logical (10) 0.624 ± 0.139＞0.05＞0.05

Heavy dose of group

Brain bolt logical (10) 0.661 ± 0.116＞0.05＞0.05

Small dose group

Positive control drug group (10) 0.758 ± 0.137＞0.05

Sham operated rats (10) 0.470 ± 0.068＜0.001

Blank group (5) 0.413 ± 0.061＜0.001

By table 47 as seen, sham operated rats MDA content and blank are normally close, model group apparently higher than sham operated rats, and the content of 3 medication groups is all close with model group, no significant difference, 3 medication groups are followed successively by logical heavy dose of, low dose of, the positive drug of brain bolt, and the trend of increasing progressively is arranged.

The instructions of taking of medicine of the present invention is: 3/time, and day clothes 3 times.1 month is a course of treatment.

The specific embodiment

Take by weighing raw material (gram) by following proportioning

Pollen Typhae 890 Radix Paeoniae Rubra 635 Radix Curcumaes 510 Rhizoma Gastrodiaes 255 Radix Rhapontici 380

[1] earlier with Radix Paeoniae Rubra with 70% alcohol reflux 2 times, each 1 hour, alcohol adding amount was 7 times, 5 times, merge extractive liquid, filters, filtrate recycling ethanol is condensed into thick paste, 85 ℃ of oven dry, dried cream are standby; Radix Curcumae 80% soak with ethanol 12 hours, reflux, extract, 2 times, each 1 hour, alcohol adding amount was 7 times, 5 times, merge extractive liquid, filters, filtrate for later use; Medicinal residues are collected in addition;

[4] add 0.5% magnesium stearate, cross 18--20 mesh sieve granulate, filled capsules is made brain bolt open capsule.The every capsules loading amount of this product is 0.4g, is chosen to be capsulae vacuus No. 1 according to capsulae vacuus number and approx. volume.Homogeneous granules is filled in the capsulae vacuus seals, every capsules is equivalent to crude drug in whole 2.67 grams, packing, and packing gets final product.

[1] earlier with Radix Paeoniae Rubra with 70% alcohol reflux 2 times, each 1 hour, alcohol adding amount was 7 times, 5 times, merge extractive liquid, filters, filtrate recycling ethanol is condensed into extractum; Radix Curcumae 80% soak with ethanol 12 hours, reflux, extract, 2 times, each 1 hour, alcohol adding amount was 7 times, 5 times, merge extractive liquid, filters, filtrate for later use; Medicinal residues are collected in addition;

[4] extractum adds Polyethylene Glycol, and its extractum: Polyethylene Glycol is 1: 0.8～6.0.

Drop pill when [5] heating for dissolving is to 60 ℃～90 ℃ of fluid temperature, coolant are with dimethicone or vegetable oil or liquid Paraffin, and coolant temperature is controlled at 2～20 ℃, uses the dropping-pill machine ball, and ball weighs 25～100mg/ grain, makes the agent of brain bolt dripping pills for dredging.

[4] extractum adds sucrose or other solubility pharmaceutic adjuvant, mix homogeneously, and pelletize is sieved, and oven dry is sieved, and the logical granule of brain bolt is made in packing.

[4] extractum adds an amount of pharmaceutic adjuvant, mixing granulation, and oven dry, tabletting is made the logical tablet of brain bolt.

[3] medicinal liquid filters, and the alcohol extract of filtrate and Radix Curcumae merges, and reclaims ethanol, is concentrated into extractum:

[4] extractum adds suitable adjuvant, heating mix homogeneously, the brain bolt clearing soft capsule agent made from pressing or dropping preparation method.

[4] extract dry and appropriate amount of auxiliary materials are ground into fine powder, make the logical powder of brain bolt;

[4] extractum adds purified water, stirs, and filters, and the logical mixture (oral liquid) of brain bolt is made in filtrate bottling sterilization.

Claims

1. a medicine for the treatment of apoplexy is characterized in that it is the medicine of being made by the following weight proportion raw material

Radix Rhapontici 9.4～17.4.

2. the medicine of treatment apoplexy according to claim 1, wherein the weight proportion of each raw material is

Radix Rhapontici 11.4～17.4.

3. the medicine of treatment apoplexy according to claim 1, wherein the weight proportion of each raw material is

Pollen Typhae 33.3 Radix Paeoniae Rubra 23.8 Radix Curcumaes 19.1 Rhizoma Gastrodiaes 9.6 Radix Rhapontici 14.2.

4. the medicine of treatment apoplexy according to claim 1 is characterized in that it is a peroral dosage form.

5. the preparation method of treatment apoplexy medicine according to claim 1 is characterized in that:

[1] earlier with Radix Paeoniae Rubra with 70% alcohol reflux 2 times, each 1 hour, alcohol adding amount was 7 times or 5 times, merge extractive liquid, filters, filtrate recycling ethanol is condensed into thick paste, 85 ℃ of oven dry, dried cream are standby; Radix Curcumae 80% soak with ethanol 12 hours, reflux, extract, 2 times, each 1 hour, alcohol adding amount was 7 times or 5 times, merge extractive liquid, filters, filtrate for later use; Medicinal residues are collected in addition;

[2] Pollen Typhae, Rhizoma Gastrodiae, Radix Rhapontici, the Radix Curcumae medicinal residues of dress cloth bag, decoct 2 times after 2 hours with 80 ℃ of warm water soaking, each 1 hour, amount of water is 10 times or 8 times, merge extractive liquid,, filtration, and it is 1.04 that filtrate is concentrated into relative density, temperature is 40 ℃, add ethanol and make and contain alcohol amount and reach 70%, stir evenly cold preservation 48 hours;

6. the preparation method of treatment apoplexy medicine according to claim 1 is characterized in that:

[1] earlier with Radix Paeoniae Rubra with 70% alcohol reflux 2 times, each 1 hour, alcohol adding amount was 7 times or 5 times, merge extractive liquid, filters, filtrate recycling ethanol is condensed into extractum; Radix Curcumae 80% soak with ethanol 12 hours, reflux, extract, 2 times, each 1 hour, alcohol adding amount was 7 times or 5 times, merge extractive liquid, filters, filtrate for later use; Medicinal residues are collected in addition;

Drop pill when [5] heating for dissolving is to 60 ℃～90 ℃ of fluid temperature, coolant are with dimethicone or vegetable oil or liquid Paraffin, and coolant temperature is controlled at 2～20 ℃, uses the dropping-pill machine ball, and ball weighs 25～100mg/ grain, makes the drop pill of treatment apoplexy.

7. the preparation method of treatment apoplectic agent according to claim 1 is characterized in that:

[1] earlier with Radix Paeoniae Rubra with 70% alcohol reflux 2 times, each 1 hour, alcohol adding amount was 7 times, 5 times, merge extractive liquid, filters, filtrate recycling ethanol is condensed into extractum; Radix Curcumae 80% soak with ethanol 12 hours, reflux, extract, 2 times, each 1 hour, alcohol adding amount was 7 times or 5 times, merge extractive liquid, filters, filtrate for later use; Medicinal residues are collected in addition;

[2] Pollen Typhae, Rhizoma Gastrodiae, Radix Rhapontici, the Radix Curcumae medicinal residues of dress cloth bag, decoct 2 times after 2 hours with 80 ℃ of warm water soaking, each 1 hour, amount of water is 10 times, 8 times, merge extractive liquid,, filtration, and it is 1.04 that filtrate is concentrated into relative density, temperature is 40 ℃, add ethanol and make and contain alcohol amount and reach 70%, stir evenly cold preservation 48 hours;

[4] extractum adds sucrose or other solubility pharmaceutic adjuvant, mix homogeneously, and pelletize is sieved, and oven dry is sieved, and the granule for the treatment of apoplexy is made in packing.

8. the preparation method of treatment apoplexy medicine according to claim 1 is characterized in that:

[4] extractum adds an amount of pharmaceutic adjuvant, mixing granulation, and oven dry, tabletting is made the tablet for the treatment of apoplexy.

9. the preparation method of treatment apoplexy medicine according to claim 1 is characterized in that:

[1] earlier with Radix Paeoniae Rubra with 70% alcohol reflux 2 times, each 1 hour, alcohol adding amount was 7 times, 5 times, merge extractive liquid, filters, filtrate recycling ethanol is condensed into extractum; Radix Curcumae 80% soak with ethanol 12 hours, reflux, extract, 2 times, each 1 hour, alcohol adding amount was 7 times or 5 times, merge extractive liquid, filters, filtrate for later use, medicinal residues are collected in addition;

[4] extractum adds suitable adjuvant, and the heating mix homogeneously is made the soft capsule for the treatment of apoplexy with pressing or dropping preparation method.

10. the preparation method of treatment apoplexy medicine according to claim 1 is characterized in that:

11. the preparation method of treatment apoplexy medicine according to claim 1 is characterized in that:

[4] extractum adds purified water, stirs, and filters, and the mixture for the treatment of apoplexy is made in filtrate bottling sterilization.