CN105596788B

CN105596788B - A kind of preparation method preventing and treating cerebrovascular disease medicament preparation

Info

Publication number: CN105596788B
Application number: CN201010592530.1A
Authority: CN
Inventors: 张乐陵; 张海; 饶永平; 周强; 罗阳洋; 皮海燕
Original assignee: Guizhou Three Power Pharmacy Stock Co Ltd
Current assignee: Guizhou Three Power Pharmacy Stock Co Ltd
Priority date: 2010-12-17
Filing date: 2010-12-17
Publication date: 2019-06-11
Anticipated expiration: 2030-12-17
Also published as: CN105596788A

Abstract

The present invention is a kind of pharmaceutical preparation and preparation method thereof for preventing and treating cranial vascular disease, it after Rhizoma Gastrodiae, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, Radix Angelicae Pubescentis, rhizoma ligustici, radix scrophulariae, Radix Angelicae Sinensis, glutinous rehmannia, radix cyathulae, mistletoe, the extracted purification of Rhizoma Et Radix Notopterygii by adding appropriate amount of auxiliary materials to be prepared；Drug of the invention has suppressing hyperactive liver for calming endogenous wind, cold dispelling of invigorating blood circulation, relaxing muscles and tendons analgesic efficacy, it is mainly used for ischemic cerebrovascular disease caused by liver yang causing wind, Cold-dampness and sees that tendon and vessel takes along pain, extremity numbness, inconvenient walking, waist and leg ache, headache and dizziness are looked dull, the treatment of the diseases such as dysphonia.Compared with prior art, the present invention is to extract effective parts formulation, and purity is high, taking dose is small, and bioavilability is high, and quality is stablized, and curative effect is more excellent, and toxicity is low, and safety is more preferable.

Description

A kind of preparation method preventing and treating cerebrovascular disease medicament preparation

Technical field

The present invention relates to the preparation methods of anti-treatment cerebrovascular disease medicament preparation, belong to the technical field of drug.

Background technique

Cranial vascular disease refers to that the various causes of disease lead to cerebral tissue change caused by cerebrovascular insult.Acute onset is simultaneously rapid The cranial vascular disease for brain disorder occur is known as acute cerebrovascular disease, also referred to as cerebrovascular accident, headstroke or cerebral apoplexy, has Morbidity is high, and disability rate height and the high feature of recurrence rate, are middle-aged and the old's common frdquently encountered diseases.Cranial vascular disease, cardiovascular disease and Malignant tumour occupies the front three of mankind's natural death reason.The disease incidence of cranial vascular disease is because of different areas, nationality, life Habit etc. and it is different, in China cranial vascular disease disease incidence be 110~2,00/,100,000, illness rate 394~7,19/,100,000, the death rate 116~1,42/,100,000, in terms of gender, the ratio of men and women's disease incidence is 1.3~1.7: 1；In terms of the age, since the age is brain One kind of artery sclerosis can not intervention risk factor, therefore, with the growth at age, the risk that cranial vascular disease occurs is more Greatly, the age is bigger, and disease incidence is higher.It especially attracts people's attention, present 40 years old or so a middle-aged person suffers from the general of cranial vascular disease Rate is also being substantially increased, and middle-aged population body active prevention cranial vascular disease has become a very urgent problem.In recent years, Due to the raising for the treatment of level, the death rate of cranial vascular disease decreases, but disability rate is still high, about 80% survival Person still has different degrees of dysfunction, brings heavy burden to patient home and society.Therefore disability rate is reduced, is improved Rehabilitation speed and prevention are the task of top priority for treating this disease at present.

The technology of the present invention is progress technological improvement on the basis of original product strength gastrodia capsule, and prescription is by Rhizoma Gastrodiae, Du Secondary (salt system), wild aconite root, radix aconiti lateralis preparata, Radix Angelicae Pubescentis, rhizoma ligustici, radix scrophulariae, Radix Angelicae Sinensis, glutinous rehmannia, radix cyathulae, mistletoe, Rhizoma Et Radix Notopterygii composition, former dosage form Preparation method is to be mixed with after crushing Rhizoma Gastrodiae with the crude extract of other medicinal materials, and major function is that " relieve heat promoting blood circulation, relaxing muscles and tendons stop Bitterly.Pain, extremity numbness, inconvenient walking, waist and leg ache, headache and dizziness etc. are taken along for tendon and vessel caused by apoplexy ".Clinical application for many years Show that former dosage form clinical efficacy is good, but have the disadvantage that (1) former dosage form cures mainly and stated completely with TCM-related Terms, is not associated with west Doctor illustrates what disease treated, and brings certain limitation to the popularization of the drug, and clinical practice applies to treat in ischemic brain The pain of tendon and vessel caused by wind, cerebral thrombosis, cerebral arteriovenous malformation, cerebral insufficiency, hypertension etc., extremity numbness, inconvenient walking, waist-leg acid Bitterly, the diseases such as headache and dizziness；(2) former dosage form preparation process is coarse, and technology content is not high, is mainly reflected in: 1. Radix Angelicae Pubescentis in former preparation, Rhizoma ligustici, Radix Angelicae Sinensis contain a large amount of volatile materials in Rhizoma Et Radix Notopterygii four traditional Chinese medicine material, cannot protect volatilization completely using ordinary preparation technology Property substance and cause it largely to lose, not can guarantee drug quality and curative effect；2. former preparation is only slightly to mention being process, wherein containing There are a large amount of impurity, bring following problems to preparation: first is that keeping its amount of formulation big containing a large amount of impurity, making troubles to medication, second is that Some impurity water imbibitions are strong, are easy to keep its preparation moisture absorption rotten, not can guarantee drug quality and curative effect；3. by Rhizoma Gastrodiae in former preparation Preparation is made after directly crushing, brings following problems to preparation: first is that keeping its amount of formulation big containing a large amount of impurity, being brought not to medication Just, second is that the direct starch of medicinal material, active principle cannot fully absorb, keep its bioavilability low；Third is that medicinal material is directly raw Powder is used as medicine, and takes rear effective component and needs dissolution that process is absorbed and utilized, keeps its drug effect slow.Entire preparation process is made a general survey of, The quality and curative effect of preparation cannot be embodied very well.Now compared with prior art, have following excellent by technological innovation into process modification More property: taking dose is reduced, and bioavilability significantly improves, and drug effect is fast, and toxic side effect is low, and medication is safer, and clinic is treated Effect is more preferable, drug quality is more stable.

In order to reach above-mentioned technology, explores and study applicant carried out a large amount of.

Summary of the invention

It is an object of the invention to: it is to provide a kind of pharmaceutical preparation and preparation method thereof for preventing and treating cranial vascular disease, this The drug of invention has no toxic side effect, and therapeutic effect is good, and rapid-action, and bioavilability is high, and the quality of the pharmaceutical preparations is stablized, existing to solve Technology there are the problem of.

The present invention is implemented as follows: in parts by weight, it by Rhizoma Gastrodiae 2%~18%, Cortex Eucommiae processed 9.5%~ 11.5%, wild aconite root 0.5%~1.5%, radix aconiti lateralis preparata 0.5%~1.5%, Radix Angelicae Pubescentis 5%~7%, rhizoma ligustici 6.5%~7.5%, profound Join 6.5%~7.5%, Radix Angelicae Sinensis 11%~13%, glutinous rehmannia 18.5%~20.5%, radix cyathulae 6.5%~7.5%, mistletoe 6.5%~7.5%, the extracted processing of Rhizoma Et Radix Notopterygii 11%~13% is prepared.Exactly, it is calculated according to weight, it is by Rhizoma Gastrodiae 9.6%, Cortex Eucommiae 10.3% processed, wild aconite root 1.2%, radix aconiti lateralis preparata 1.2%, Radix Angelicae Pubescentis 6.0%, rhizoma ligustici 7.1%, radix scrophulariae 7.1%, Radix Angelicae Sinensis 12.0%, glutinous rehmannia 19.3%, radix cyathulae 7.1%, mistletoe 7.1%, the extracted processing of Rhizoma Et Radix Notopterygii 12.0% are prepared.

The pharmaceutical preparation that the present invention prevents and treats cranial vascular disease is prepared:

(1) Rhizoma Gastrodiae raw medicinal material is weighed, 30%~90% ethyl alcohol is added to extract, filtration, it is spare to obtain ethanol extract, remaining day Anaesthetic slag is spare；It weighs Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii to extract 4~10 hours, separation, It is spare to obtain volatile oil；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, radix cyathulae, mistletoe Merge, adds 6~12 times of amount water to extract 1~4 time, 1~4 hour every time, combined extract, filtration, filtrate was concentrated into dense containing crude drug The medical fluid that degree is 1: 1~3: 1 is let cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content up to 40%~80%, stands 8~48 hours, It takes supernatant liquid filtering to obtain ethanol, merges with Rhizoma Gastrodiae alcohol extract, recycling ethyl alcohol and being concentrated into relative density is 1.05~1.40 (60 DEG C) medicinal extract, merge volatile oil, adding auxiliary material, routinely different pharmaceutical preparations is made in preparation process.

Specifically: Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 2 times, 2 hours every time, merges, Filtration, obtains that ethanol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material of Rhizoma Et Radix Notopterygii is weighed to use Steam distillation extracts 6 hours, and it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, system are attached Son, radix scrophulariae, glutinous rehmannia, radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, 3 hours for the first time, second 2 hours, merge Extracting solution, filtration, filtrate are concentrated into the medical fluid that concentration containing crude drug is 1.0: 1, let cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content Up to 60%, 24 hours are stood, takes supernatant liquid filtering to obtain ethanol, merges with Rhizoma Gastrodiae alcohol extract, recycle ethyl alcohol and is concentrated into opposite Density is the medicinal extract of 1.05~1.40 (60 DEG C), merges volatile oil, adding auxiliary material, routinely different medicines is made in preparation process Object preparation.

(2) Rhizoma Gastrodiae raw medicinal material is weighed, 30%~90% ethyl alcohol is added to extract, filtration, it is spare to obtain ethanol extract, remaining day Anaesthetic slag is spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material supercritical CO of Rhizoma Et Radix Notopterygii₂It extracts, it is standby to obtain volatile oil for separation With；The remaining dregs of a decoction merge with the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, radix cyathulae, mistletoe, add 6~ 12 times of amount water extract 1~4 time, and 1~4 hour every time, combined extract, filtration, it was 1: 1~3 that filtrate, which is concentrated into concentration containing crude drug: 1 medical fluid lets cool to room temperature, is added on resin column, with 30%~90% ethanol elution, eluent is collected, with Rhizoma Gastrodiae alcohol extract Merge, recycling ethyl alcohol simultaneously be concentrated into relative density be 1.05~1.40 (60 DEG C) medicinal extract, merge volatile oil, add auxiliary material by Different pharmaceutical preparations is made in conventional formulation technique.

Specifically: Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 2 times, 2 hours every time, merges, Filtration, obtains that ethanol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material of Rhizoma Et Radix Notopterygii is weighed to use Supercritical CO₂It extracts, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae, radix aconiti agrestis, monkshood, radix scrophulariae, glutinous rehmannia, Radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, and 3 hours for the first time, second 2 hours, combined extract, filtration, Filtrate is concentrated into the medical fluid that concentration containing crude drug is 1.0: 1, lets cool to room temperature, is added on large pore resin absorption column, with 60% ethyl alcohol Elution is collected eluent, is merged with Rhizoma Gastrodiae alcohol extract, and recycling ethyl alcohol and being concentrated into relative density is 1.05~1.40 (60 DEG C) Medicinal extract merges volatile oil, and adding auxiliary material, routinely different pharmaceutical preparations is made in preparation process.

(3) Rhizoma Gastrodiae raw medicinal material is weighed, 30%~90% ethyl alcohol is added to extract, filtration, filtrate recycling ethanol is simultaneously concentrated into phase It is the medicinal extract of 1.05~1.40 (60 DEG C) to density, obtains that Rhizoma Gastrodiae alcohol-extracted extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, Rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material supercritical CO of Rhizoma Et Radix Notopterygii₂It extracts, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and day anaesthetic Slag, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, radix cyathulae, mistletoe merge, and 6~12 times of amount water is added to extract 1~4 time, 1~4 hour every time, combined extract filtered, and filtrate is filtered by UF membrane, collected filtered fluid, and filter is concentrated into relative density and is The medicinal extract of 1.05~1.40 (60 DEG C), merges with Rhizoma Gastrodiae alcohol-extracted extract, volatile oil, and adding auxiliary material, routinely preparation process is made Different pharmaceutical preparations.

Specifically: weighing Rhizoma Gastrodiae raw medicinal material, add 5 times of 50% alcohol refluxs of amount to extract 2 times, 2 hours every time, close And filter, filtrate recycling ethanol is simultaneously concentrated into the medicinal extract that relative density is 1.05~1.40 (60 DEG C), and it is standby to obtain Rhizoma Gastrodiae alcohol-extracted extract With the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material supercritical CO of Rhizoma Et Radix Notopterygii₂It extracts, separation, It is spare to obtain volatile oil；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, radix cyathulae, mistletoe Merge, 10 times of amount water is added to extract 2 times, 3 hours for the first time, second 2 hours, combined extract filtered, and filtrate passes through ceramic membrane Separating and filtering, collect filtered fluid, filter be concentrated into relative density be 1.05~1.40 (60 DEG C) medicinal extract, with Rhizoma Gastrodiae alcohol-extracted extract, Volatile oil merges, and adding auxiliary material, routinely different pharmaceutical preparations is made in preparation process.

In the preparation method of above-mentioned prevention and treatment cerebrovascular disease medicament preparation, the pharmaceutical preparation is oral preparation, including Granule, oral solution, pill, tablet, hard capsule, soft capsule and dripping pill etc..

Specifically, in the pharmaceutical preparation of above-mentioned prevention and treatment cranial vascular disease and preparation method, the pharmaceutical preparation is hard Capsule；It is described the preparation method comprises the following steps: taking polyethylene glycol -6000 and polyethylene glycol-4000 mix heating melting, volatilization is added Oil, medicinal extract, stir evenly, be transferred in pill dripping machine in 60 DEG C keep the temperature 10 minutes, dripping pelletization, de-oiling, low temperature drying, it is filling in In Capsules to get.

Pharmaceutical preparation side of the present invention solution: apoplexy is to generate wind, fire, phlegm, the stasis of blood since qi and blood is inverse disorderly, cause brain vessle-Bi symptom-complex hinder or Blood overflows except brain arteries and veins.Clinic using the no oblique, speech of unexpected confused servants, hemiplegia, dispute it is stuttering puckery or in silence, hemianesthesia is primary symptom. This disease is roughly equivalent to the ischemic and hemorrhagic cerebrovascular disease of doctor trained in Western medicine.Apoplexy mostly because product damage just declining, overstrain internal injury, diet not Section, emotional stress etc. lead to stagnation of blood stasis, accumulation phlegm-heat in the interior or liver yang causing wind, bleeding resulting from adverse flow of QI, and the resistance of brain vessle-Bi symptom-complex or blood is caused to be overflow It is sent out except brain arteries and veins.Its inducement is common: weather cataclysm, bothers excessively, feelings will Xiang Ji, falls to flutter and exerts wound etc..Apoplexy position in brain, with The heart, kidney,liver,spleen are closely related.Its interpretation of the cause, onset and process of an illness has void, fire, wind, phlegm, gas, six end of blood, and interacts under certain condition, each other Cause and effect.Characteristic of disease is mostly asthenia in origin and asthenia in superficiality, upper excess and lower deficiency, and it is few that this is the deficiency of liver-yin and kidney-yin, qi and blood declines, and is designated as febrile disease complicated by wind, phlegm wet stops up Sheng, the stasis of blood Blood retardance, qi and blood are inverse disorderly.And its basic pathogenesis is then that qi and blood is inverse disorderly, is above disturbed in brain.The treatment of apoplexy, acute stage, which is worked as with eliminating evil, is It is main, commonly use calming the liver to stop the wind, clearing heat and eliminating phlegm, the methods such as resolving sputum pain internal organs, promoting blood circulation and removing obstruction in channels, inducing resuscitation are had one's ideas straightened out.Card is closed to control with eliminating evil inducing resuscitation of having one's ideas straightened out, The exhaustion of vital energy at the critical stage of an illness is controlled with strengthening body resistance, rescues negative Hui Yang.Convalescence and sequela phase, control suitable strengthening vital QI to eliminate pathogenic factors, it is common educate yin relieve dizziness, high fever, infantile convulsions, epilepsy, etc., qi and activate blood circulation Etc. methods.With Rhizoma Gastrodiae, Cortex Eucommiae, radix cyathulae, mistletoe calming the liver west wind in side, remove obstruction in channels to relieve pain；Radix scrophulariae, glutinous rehmannia, Radix Angelicae Sinensis nourishing yin and nourishing blood, with Yin system sun；Monkshood, radix aconiti agrestis are warming channel and expelling cold, remove obstruction in channels to relieve pain；Rhizoma Et Radix Notopterygii, Radix Angelicae Pubescentis, rhizoma ligustici wind-dispelling, dehumidifying, cold dispelling are removed obstruction in channels to relieve pain.All medicines It shares, plays suppressing hyperactive liver for calming endogenous wind altogether, cold dispelling of invigorating blood circulation, the function of relaxing muscles and tendons analgesic.

It is of the invention major function: suppressing hyperactive liver for calming endogenous wind, cold dispelling of invigorating blood circulation, relaxing muscles and tendons analgesic.For caused by liver yang causing wind, Cold-dampness Ischemia apoplexy, cerebral thrombosis, cerebral arteriovenous malformation, cerebral embolism, cerebral infarction, cerebral insufficiency, hypertension, encephalatrophy, vascular The cranial vascular diseases such as dementia are shown in that tendon and vessel takes along pain, extremity numbness, and inconvenient walking, waist and leg ache, headache and dizziness looks dull, language It is unfavorable etc..

In order to verify drug of the present invention with good therapeutic effect, applicant carried out series of experimental research, specifically It is as follows:

One, craft screening and preliminary comparative efficacy test

(1) process route and sample preparation

1, former preparation process (raw medicine) and sample preparation: 12 taste medicinal material of prescription is taken, Rhizoma Gastrodiae is ground into fine powder, Radix Angelicae Pubescentis, ligusticumic Sheet, Radix Angelicae Sinensis, Rhizoma Et Radix Notopterygii extract volatile oil, and seven taste such as the dregs of a decoction and Cortex Eucommiae adds water to cook secondary, 3 hours first times, second 2 hours, Collecting decoction, filtration, filtrate are condensed into cream, and with above-mentioned powder, mixing be dry, pulverize, and is sieved, particle is made, dry, spray into Volatile oil mixes, and sealed package is up to former formulation samples.Inventory is 2.5 times of recipe quantities, and the amount of being made is 1800g.Sample is compiled Number: 20091018.

2, new process 1 and sample preparation: taking 12 taste medicinal material of prescription, and Rhizoma Gastrodiae is ground into coarse powder, and 5 times of 50% ethyl alcohol of amount is added to return Stream extracts 2 times, 2 hours every time, merges, filtration, and filtrate recycling ethanol is simultaneously concentrated into relative density as 1.25~1.40 (60 DEG C) Medicinal extract, it is spare to obtain Rhizoma Gastrodiae alcohol-extracted extract, and Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, Rhizoma Et Radix Notopterygii extract volatile oil, and seven taste such as the dregs of a decoction and Cortex Eucommiae adds water It decocts secondary, 3 hours first times, second 2 hours, collecting decoction, filtration, it is 1.25~1.40 that filtrate, which is concentrated into relative density, The medicinal extract of (60 DEG C), with above-mentioned Rhizoma Gastrodiae alcohol-extracted extract, mixing be dry, pulverize, and is sieved, particle is made, dry, spray into volatile oil, It mixes, sealed package to obtain the final product.Inventory is 2.5 times of recipe quantities, and the amount of being made is 1530g.Sample number into spectrum: QL0910-1.

3, new process 2 and sample preparation: taking 12 taste medicinal material of prescription, and Rhizoma Gastrodiae is ground into coarse powder, and 5 times of 50% ethyl alcohol of amount is added to return Stream extracts 2 times, 2 hours every time, merges, and filtration obtains that ethanol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Radix Angelicae Pubescentis, rhizoma ligustici, when Return, Rhizoma Et Radix Notopterygii extraction volatile oil, seven tastes such as the dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae Cortex Eucommiae add water to cook secondary, 3 hours first times, second Secondary 2 hours, collecting decoction filtered, and filtrate is concentrated into the medical fluid that concentration containing crude drug is 1.0: 1, lets cool to room temperature, was added to macropore suction On attached resin column, with 60% ethanol elution, eluent is collected, is merged with Rhizoma Gastrodiae alcohol extract, recycled ethyl alcohol and be concentrated into relatively close Degree is the medicinal extract of 1.25~1.40 (60 DEG C), be dry, pulverize, and is sieved, particle is made, dry, sprays into volatile oil, is mixed, sealing It packs to obtain the final product.Inventory is 2.5 times of recipe quantities, and the amount of being made is 330g.Sample number into spectrum: QL0910-2.

4, new process 3 and sample preparation: taking 12 taste medicinal material of prescription, and Rhizoma Gastrodiae is ground into coarse powder, and 5 times of 50% ethyl alcohol of amount is added to return Stream extract 2 times, 2 hours every time, merge, filtration, the dregs of a decoction are spare, filtrate recycling ethanol and be concentrated into relative density be 1.25~ The medicinal extract of 1.40 (60 DEG C), it is spare to obtain Rhizoma Gastrodiae alcohol-extracted extract, and Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, Rhizoma Et Radix Notopterygii extract volatile oil, the dregs of a decoction and Rhizoma Gastrodiae Seven taste such as the dregs of a decoction, Cortex Eucommiae adds water to cook secondary, 3 hours first times, second 2 hours, collecting decoction, combined extract, filter It crosses, filtrate is filtered by ceramic membrane separation, collects filtered fluid, and filter is concentrated into the leaching that relative density is 1.25~1.40 (60 DEG C) Cream, with above-mentioned Rhizoma Gastrodiae alcohol-extracted extract, mixing be dry, pulverize, and is sieved, particle is made, dry, is sprayed into volatile oil, is mixed, sealing It packs to obtain the final product.Inventory is 2.5 times of recipe quantities, and the amount of being made is 1450g.Sample number into spectrum: QL0910-3.

5, new process 4 and sample preparation: taking 12 taste medicinal material of prescription, and Rhizoma Gastrodiae is ground into coarse powder, and 5 times of 50% ethyl alcohol of amount is added to return Stream extracts 2 times, 2 hours every time, merges, and filtration, it is spare to obtain ethanol extract, and Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, Rhizoma Et Radix Notopterygii extract volatile oil, Seven taste such as the dregs of a decoction and Cortex Eucommiae, adds water to cook secondary, 3 hours first times, second 2 hours, combined extract, filtration, and filtrate is dense It is reduced to the medical fluid that concentration containing crude drug is 1.0: 1, is let cool to room temperature, ethyl alcohol, which is added, makes solution alcohol content up to 60%, 24 hours are stood, It takes supernatant liquid filtering to obtain ethanol, merges with Rhizoma Gastrodiae alcohol extract, recycling ethyl alcohol and being concentrated into relative density is 1.25~1.40 (60 DEG C) medicinal extract, dry, pulverize, be sieved, particle is made, it is dry, spray into volatile oil, mix, sealed package to obtain the final product.Inventory is 2.5 times of recipe quantities, the amount of being made are 360g.Sample number into spectrum: QL0910-4.

6, new process 5 and sample preparation: taking 12 taste medicinal material of prescription, and Rhizoma Gastrodiae is ground into coarse powder, and 5 times of 50% ethyl alcohol of amount is added to return Stream extracts 2 times, 2 hours every time, merges, and filtration obtains that ethanol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare, Radix Angelicae Pubescentis, rhizoma ligustici, when Return, Rhizoma Et Radix Notopterygii extraction volatile oil, seven taste such as the dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae adds water to cook secondary, 3 hours first times, second 2 Hour, combined extract filters, and filtrate is concentrated into the medical fluid that concentration containing crude drug is 1.0: 1, lets cool to room temperature, and ethyl alcohol, which is added, to be made Solution alcohol content stands 24 hours, takes supernatant liquid filtering to obtain ethanol, merge with Rhizoma Gastrodiae alcohol extract up to 60%, and recycling ethyl alcohol is simultaneously It is concentrated into the medicinal extract that relative density is 1.25~1.40 (60 DEG C), dry, pulverize, is sieved, particle is made, it is dry, spray into volatilization Oil mixes, and sealed package to obtain the final product.Inventory is 2.5 times of recipe quantities, and the amount of being made is 450g.Sample number into spectrum: QL0910-5.

(2) pharmacodynamics comparative experiments experiment purpose: known strength gastrodia elata-cortex capsule raw medicine has inhibition to platelet aggregation Effect, this experiment observe 5 kinds of strength gastrodia elata-cortex capsule test medicine (tests using gastrodia elata-cortex capsule raw medicine as positive control drug Medicine 1,2,3,4,5) ADP external to normal rat and thrombin induction maximum platelet aggregation rate influence.

1, experimental material

1.1 experimental animal Sprague-Dawley (SD) rats, male, weight 280-320g, cleaning grade, by University Of Suzhou Laboratory animal center of medical college offer (production licence XCYK (Soviet Union): No2002-0008, it uses licensing SYXK (Soviet Union): No2002-0037).Feeding conditions are as follows: six cages, and 22 DEG C of room temperature, humidity 50-60%, well-ventilated, manually round the clock (12h/12h), water of freely ingesting.Before experiment, animal is adapted to 1 week in feeding environment.

1.2 laboratory apparatus TYXN-96 multifunctional intellectual blood pool instrument, Shanghai GM mechanical & electrical technology research；80-2 is desk-top Low speed centrifuge, surgical instrument factory, Shanghai Medical instrument Co., Ltd.

1.3 drugs and reagent strength gastrodia elata-cortex capsule raw medicine (20091018) and 5 kinds of strength gastrodia elata-cortex capsules are tested Medicine [test medicine 2 (QL0910-2), test medicine 3 (QL0910-3), test medicine 4 (QL0910-4), survey by test medicine 1 (QL0910-1) Reagent 5 (QL0910-5)], sample is provided by seminar, is made into suspension with distilled water；Biphosphate receives (Dihydrogen Phosphate Chinese medicines group product batch number F20090624)；Disodium hydrogen phosphate (Disodium Phosphate Chinese medicines group production Product batch number 20090915)；Chinese holly edge acid sodium (Sodium Citrate Shanghai Reagent One Plant produces product batch number 96-02-03)； ADP (Solarbio production, product batch number A8290)；Fibrin ferment (Thrombin) (Sigma) production, product batch number 9002-04- 4)。

2, experimental method

2.1 experimental design health male SD rats 70, weight 280-320g are randomly divided into 7 groups, every group 10, distinguish For Normal group, strength gastrodia elata-cortex capsule raw medicine group (raw medicine group, 350mg/kg are equivalent to a day dosing 4.2g) and strength day Numb eucommia bark capsules test medicine 1 (300mg/kg is equivalent to a day dosing 3.6kg), 2 (67mg/kg is equivalent to a day dosing 0.8), and 3 (283mg/kg is equivalent to a day dosing 3.4g), 4 (70mg/kg is equivalent to a day dosing 0.84g), 5 (89mg/kg is equivalent to and takes daily Measure 1.07g) group.Administration group rat oral gavage strength gastrodia elata-cortex capsule raw medicine respectively tests medicine, and Normal group presses 0.2ml/ 100g stomach-filling distilled water, 1 time a day, continuous 4 weeks.Abdominal aortic blood measurement ADP and fibrin ferment after rat last dose 2 hours The maximum platelet aggregation rate of induction (see attached drawing 1)

The measurement rat last dose of 2.2 platelet aggregations anaesthetizes abdominal aortic blood measurement blood platelet most after 2 hours Big aggregation rate.It follows these steps to operate:

(1) anti-coagulants is sour using 3.28% Chinese holly edge, and the ratio of blood drawing amount and anti-coagulants should be 9: 1, falls to mix 2~3 immediately It is secondary.

(2) obtain sample, that is, PRP (blood plasma rich in blood platelet) under the conditions of 20~25 DEG C centrifugal speed with 500r/min, Time 5Min or so, uses horizontal type centrifuger.(3) it slowly stalls, further takes out naturally to centrifuge, in case cell flows into PRP, It such as finds that still a moment should be centrifuged under the above conditions containing RBC in PRP.Aggregation inducing agent ADP and fibrin ferment, measurement blood platelet is most Big aggregation rate

2.3 statistical analysis data are with means standard deviationIt indicates.Using corresponding journey in SPSS (10.0 editions) Sequence carries out statistical disposition to data.Statistical analysis uses one-way analysis of variance (one-way ANOVA), and p < 0.05 is statistics Learning difference has conspicuousness.

3, result normal rat stomach-filling strength gastrodia elata-cortex capsule raw medicine or test medicine 1,2,3,4,54 weeks after, take blood into The experiment of row extracorporeal platelet aggregation.The result shows that: the platelet aggregation with rats in normal control group external ADP and thrombin induction Rate compares, and gives raw medicine and 5 kinds of test medicines can significantly reduce the platelet aggregation rate of ADP and thrombin induction.As a result it is detailed in Table 1, table 2.

4, conclusion strength gastrodia elata-cortex capsule raw medicine and test medicine 1,2,3,4,5 all have the work for inhibiting platelet aggregation With.

The inhibiting effect (mean ± SD, N=10) of the platelet aggregation of the ADP induction external to normal rat of table 1

Group	Dosage	The platelet aggregation rate (%) of ADP induction
			Normal group	--	55.70±5.65
Raw medicine group	350mg/kg	42.51±8.22**
			1 group of medicine of test	300mg/kg	44.49±7.98*
2 groups of medicine of test	67mg/kg	49.64±13.74
			3 groups of medicine of test	283mg/kg	43.43±12.69**
4 groups of medicine of test	70mg/kg	45.29±8.79*
			5 groups of medicine of test	89mg/kg	41.94±13.10**

Note: normal group of administration group VS, * P < 0.05, * * P < 0.01.

Inhibiting effect (mean ± SD, N=10) of the table 2 to the platelet aggregation of the external thrombin induction of normal rat

Group	Dosage	The platelet aggregation rate (%) of Thrombin induction
			Normal group	--	85.00±8.46
Raw medicine group	350mg/kg	44.64±21.62**
			1 group of medicine of test	300mg/kg	45.55±24.55**
2 groups of medicine of test	67mg/kg	47.36±27.44**
			3 groups of medicine of test	283mg/kg	46.61±20.93**
4 groups of medicine of test	70mg/kg	43.95±21.72**
			5 groups of medicine of test	89mg/kg	44.87±19.43**

Note: normal group of administration group VS, * * P < 0.01.

5, overall merit: although 5 kinds are tested the effect of medicine (new process) and raw medicine in inhibition platelet aggregation without conspicuousness Difference, but test 1 group of medicine (new process 1) and 3 groups of medicine of test (new processes 3) do not have trend of obvious reduced on dosage, say It is bright that changing, technique (reducing medication dose) directive significance is little, and test 2 groups of medicine (new processes 2) is although obvious on dosage It reduces, but pharmacological action is not so good as other groups (other new processes), it is therefore possible to use active principle is damaged in macroporous resin purification processing Consumption is too big, so the method is not suitable for this product technology of preparing, tests 4 groups of medicine (new processes 4) and 5 groups of medicine (new process 5) results of test It is ideal, but 5 groups of the medicine inhibiting effect in the platelet aggregation induced the external ADP of normal rat are tested than testing medicine 4 Group is obvious, the reason is that the dregs of a decoction do not utilize after Rhizoma Gastrodiae alcohol extracting, may have lost water soluble ingredient, comprehensively consider, and the 5th kind of selection new Process modification research direction of the process route as strength gastrodia elata-cortex capsule, i.e. Rhizoma Gastrodiae alcohol extracting, the dregs of a decoction merge with other medicinal materials Water extract-alcohol precipitation.

(3) pharmacodynamics confirmatory experiment purpose: after known strength gastrodia elata-cortex capsule raw medicine is used clinically for headstroke The diseases such as ache tendon and vessel, extremity numbness, inconvenient walking, waist and leg ache, headache and dizziness caused by disease are lost, are had a good effect, and Patients with Stroke hemorheology can be improved and inhibit platelet aggregation.Strength gastrodia elata-cortex capsule raw medicine has platelet aggregation Inhibiting effect, using strength gastrodia elata-cortex capsule raw medicine as positive control drug, observation strength gastrodia elata-cortex capsule tests medicine 5 for this experiment (hereinafter referred to as test medicine) blocks the neuroprotection of 2 hours/reperfusion injury to intraluminal middle cerebral artery occlusion in rats and its in brain The influence of wind rat blood rheology and platelet aggregation.

1, experimental material

1.1 experimental animal Sprague-Dawley (SD) rats, male, weight 280-320g, cleaning grade, by University Of Suzhou Laboratory animal center of medical college offer (production licence XCYK (Soviet Union): No 2002-0008, it uses licensing SYXK (Soviet Union): No2002-0037.Feeding conditions are as follows: six cages, and 22 DEG C of room temperature, humidity 50-60%, well-ventilated, artificial (12h/ round the clock 12h), it freely ingests water.Before experiment, animal is adapted to 1 week in feeding environment.

1.2 laboratory apparatus TYXN-96 multifunctional intellectual blood pool instrument, Shanghai General Machinery & Electric technology Inst.；80-2 platform Formula low speed centrifuge, surgical instrument factory, Shanghai Medical instrument Co., Ltd.

1.3 drugs and reagent strength gastrodia elata-cortex capsule raw medicine and strength gastrodia elata-cortex capsule test medicine 5 are (by seminar There is provided) suspension is made into distilled water；Sodium dihydrogen phosphate (production of Dihydrogen Phosphate Chinese medicines group, lot number F20090624)；Disodium hydrogen phosphate (production of Disodium Phosphate Chinese medicines group, product batch number 20090915)；Chinese holly edge acid Sodium (production of Sodium Citrate Shanghai Reagent One Plant, product batch number 96-02-03)；ADP (solarbio production, product batch number A8290)；Fibrin ferment (Thrombin) (Sigma produces product batch number 9002-04-4).

2, experimental method

2.1 experimental design health male SD rats 60, weight 280-320g, it is quasi- to be divided into 6 groups, every group 10, respectively Sham-operation group, ischemia/reperfusion control group, (raw medicine group, 350mg/kg are equivalent to and take daily strength gastrodia elata-cortex capsule raw medicine group Measure 4.2g) and test medicine 178mg/kg group (being equivalent to a day dosing 2.14g), 89mg/kg group (being equivalent to a day dosing 1.07g) and 44.5mg/kg (is equivalent to a day dosing 0.535g).Neurological deficit score is carried out according to 6 point-scores within 2 hours after cerebral ischemic reperfusion in rats, Rat is assigned to ischemia/reperfusion control group and each administration group at random according to neurological deficit score (table 1).Then stomach-filling strength Rhizoma Gastrodiae Eucommia bark capsules raw medicine and test medicine, sham-operation group and model group rats press 0.2ml/100g stomach-filling distilled water, 1 time a day, continuous 4 Week.Rat uses the two kinds of sides Corner Test and Cylinder Test in preoperative and postoperative 1d, 3d, 7d, 14d, 21d and 28 day Method measures nervous symptoms, and measures abdominal aortic blood survey after administration in rat last of weight (postoperative 28 days) 2 hours weekly Determine the high, medium and low viscosity, plasma viscosity, fibrinogen, hematocrit, erythrocyte sedimentation rate, erythrocyte aggregation index, red thin of cutting of whole blood The aggregation of the blood platelet maximum of the hemorheology indexs such as born of the same parents' rigidity index and erythrocyte electrophoresis index and ADP and thrombin induction Rate；And after broken end takes rat whole brain to take a picture, brain is cut into 5 with specific rat brain mould, every thickness is 3mm, after photograph The volume of measurement damage side remaining brain tissue.Then brain piece is fixed with 4% formaldehyde, after row paraffin embedding, does HE dyeing, light microscopic The degree of impairment of lower observation damage side brain tissue nerve cell (see attached drawing 2).

The nervous symptoms scoring after 2 hours of 12 hours/Reperfu- sion of each group rat ischemia of table

2.2 establish intraluminal middle cerebral artery occlusion in rats obstruction Reperfu- sion cerebral ischemic model with 4% chloraldurate (350mg/kg, ip) fiber crops Rat back position is fixed after liquor-saturated, neck median incision separates right carotid and to wear 2 sutures spare, then separates in neck, outside neck Artery, and ligature external carotid artery.In separated arteria carotis communis proximal part suture ligature, distal end blocks blood with artery clamp Stream, between, cuts an osculum, and heating one end is inserted into osculum at the nylon wire (4-0) of round bead shape (diameter < 0.3mm), is gone Fall artery clamp, nylon wire is slowly pushed into arteriae cerebri starting point (18-19mm), by blocking the blood supply of arteria cerebri media to make At arteria cerebri media ischemic, Reperfu- sion after ischemic two hours.Skin suture.Sham-operation tissue separates artery but not plug wire.Whole During a anesthesia, using automatic temperature control heating pad by rat anus temperature control system at 37 ± 0.5 DEG C.

Behaviouristics is carried out according to 6 point-scores and is commented within 2 hours after 2.3 rat behaviors measurement 2 hours/Reperfu- sion of rat cerebral ischemia Divide [6]: 0 point: there is no neurologically handicapped.1 point: obstruction branch hole eyelid reduces or ipsilateral forward pawl not tensible.2 points: animal persistence Turn great circle to ipsilateral.3 points: animal is persistent to ipsilateral ringlet or the repeatability of turning to ipsilateral rotation.4 points: animal almost lies It is motionless in opposite side.5 points: Animal Anesthesia is dead after restoring.Rat uses in preoperative and postoperative 1d, 3d, 7d, 14d, 21d and 28 day Corner two methods of Test and Cylinder Test measure nervous symptoms, Corner Test (angle method of testing): i.e. rat It is placed among the cardboard in angle, it, can be forward or to enterprising into then turning to another end opening and count after rat deeply enters Every mouse of rat deflection number is tested 20 times.Then the ratio of turn right number and total degree is calculated.Rat has only had It just calculates effectively at the full back side that turns to.Cylinder Test: rat is placed in cylinder barrel, and observation rat is cooked vertical along cylinder barrel wall The access times of limb, measure 20 times altogether in 10 minutes when straight movement or so.Final scoring is (before non-damaging forelimb movements-damage Limb forelimb movements)/(non-damaging forelimb movements+2 movements) meter.

The measurement rat broken end of 2.4 Damage of Rats side remaining Brain tissue volumes takes brain, removes olfactory bulb, cerebellum and low level brain It is dry, it is divided into 5 with coronal 4 knives of cutting of specific rat brain mould, the first knife pole and optic chiasma line midpoint, second knife before brain At optic chiasma position, third knife at infundibular stalk, the 4th knife infundibular stalk and leaf tail and between.Every thickness is 3mm, is surveyed after photograph The volume of side remaining brain tissue is hurt in setting loss, is indicated with damaging side Brain tissue volume/non-damaging side Brain tissue volume.

Abdominal aorta takes whole blood behind administrations in measurement rat last (postoperative 28 days) 2 hours of 2.5 hemorheology, uses MVIS-2000 fully automatic blood rheological analysis system measurement whole blood is high, medium and low to cut viscosity, plasma viscosity, fibrinogen, red The hemorheology indexs such as cell pack, erythrocyte sedimentation rate, erythrocyte aggregation index, erythrocyte mechanical fragility and erythrocyte electrophoresis index.

Abdominal aortic blood measurement blood is small behind administrations in measurement rat last (postoperative 28 days) 2 hours of 2.6 platelet aggregations The maximum aggregation rate of plate.Follow these steps to operate: (1) anti-coagulants is sour using 3.28% Chinese holly edge, the ratio of blood drawing amount and anti-coagulants It should be 9: 1, fall to mix 2~3 times immediately.(2) obtain sample, that is, PRP (blood plasma rich in blood platelet) under the conditions of 20~25 degree from Heart speed uses horizontal type centrifuger with 500r/mIn, time 5Min or so.(3) it slowly stalls, further takes out naturally to centrifuge, In order to avoid cell flows into PRP, as found that still a moment should be centrifuged under the above conditions containing RBC in PRP.Aggregation inducing agent with ADP with Fibrin ferment measures maximum platelet aggregation rate.

2.7 statistical analysis data are with means standard deviationIt indicates.Using corresponding journey in SPSS (10.0 editions) Sequence carries out statistical disposition to data.Statistical analysis uses one-way analysis of variance (one-way ANOVA), and P < 0.05 is statistics Learning difference has conspicuousness.

3, result

3.1 strength gastrodia elata-cortex capsule raw medicines and test medicine make the improvement of Cerebral Ischemia/Reperfusion rat behavior symptom With.Corner Test the result shows that: ischemia-reperfusion control rats to the right (strong side) turning percentage compare sham-operation group It obviously increases.Compared with ischemia-reperfusion control rats, extend with the stomach-filling time, raw medicine 350mg/kg and test medicine 178mg/ The number that kg and 89mg/kg rat is turned to the right substantially reduces, and postoperative stomach-filling 3-7d starts to work, postoperative stomach-filling 28d rat The number turned to the right reduces most obvious.Test medicine 44.5mg/kg rat onset time is postoperative stomach-filling 14d, and stomach-filling 28d subtracts It is few most significant.As a result see Table 1 for details.Cylinder test the result shows that: ischemia-reperfusion control rats are due to left limb function Energy obstacle, is obviously increased using the number of strong side forelimb (right side forelimb) than artificial hand group；With ischemia-reperfusion control rats phase Than extending with the stomach-filling time, giving forelimb access times on the right side of the rat 178mg/kg and 89mg/kg of raw medicine and test and obviously subtract Few, i.e. involvement forelimb (left side forelimb) access times obviously increase.Postoperative stomach-filling 14d starts to work, and postoperative stomach-filling 28d effect is most Obviously.As a result see Table 2 for details.As a result prompt: strength gastrodia elata-cortex capsule raw medicine and test medicine are to cerebral ischemia/reperfusion injury rat Behaviouristics defect has improvement result.

The influence brain of 3.2 strength gastrodia elata-cortex capsule raw medicines and test medicine to cerebral ischemia/reperfusion injury rat body weight lacks The equal very little of body weight evolution of the postoperative first week each group rat of blood/reperfusion injury gives raw medicine and test medicine increase with time The rat body weight increase of 178mg/kg and 89mg/kg is obviously fast compared with ischemia/reperfusion control group.But test medicine 44.5mg/kg rat Weight gain and ischemia/reperfusion control group are without significant difference.As a result see Table 2 for details.As a result prompt: strength gastrodia elata-cortex capsule is former Medicine and test medicine can promote the recovery of cerebral ischemia/reperfusion injury rat body weight.

The influence of 3.3 strength gastrodia elata-cortex capsule raw medicines and test medicine to Cerebral Ischemia/Reperfusion Damage of Rats side brain volume. Ischemia Injury damage early stage since there are apparent brain edemas, damages side Brain tissue volume and significantly increases according to the literature. And significant atrophy occurs in cerebral ischemic injury later period (after cerebral ischemia 4 weeks) damage side brain tissue, volume becomes smaller.Therefore, brain lacks Courage and uprightness damage the later period measurement damage side remaining Brain tissue volume can between reaction brain tissue degree of injury.With document report one It causes, shrinking of brain tissues is surveyed in damage in 4 weeks after this research proves cerebral ischemia/reperfusion injury of rats, and volume obviously becomes smaller, and gives original The Damage of Rats side Brain tissue volume of medicine and test medicine 178mg/kg and 89mg/kg are dramatically increased compared with ischemia/reperfusion control group.It gives Prediction reagent 44.5mg/kg rat also increased damage side Brain tissue volume, but the not up to statistical level of signifiance. As a result see Table 4 for details.As a result it prompts: brain tissue of the strength gastrodia elata-cortex capsule raw medicine with test medicine to cerebral ischemia/reperfusion injury With protective effect.

The influence that 3.4 strength gastrodia elata-cortex capsule raw medicines and test medicine change Cerebral Ischemia/Reperfusion cerebral morphology. HE coloration result shows: after cerebral ischemia/reperfusion injury of rats 4 weeks, the cell number of damage zone brain tissue is obviously less, and gives The cell number of the Damage of Rats area brain tissue of raw medicine and test medicine 178mg/kg and 89mg/kg is significant compared with ischemia/reperfusion control group Increase.Strength gastrodia elata-cortex capsule raw medicine and test medicine can improve Cerebral Ischemia/Reperfusion rat cerebral tissue morphology.

3.5 strength gastrodia elata-cortex capsule raw medicine lattice are tested medicine and are made to the improvement of Cerebral Ischemia/Reperfusion hemorheology of rat Changing generation, development with cerebral infarction with hemorheology has close relationship.Patient or rat after headstroke according to the literature Its hemorheology is abnormal, and shows as blood viscosity raising, erythrocyte aggregation increases, fibrinogen content increase Deng.Consistent with document report, 4 weeks rat whole bloods are high, medium and low after cerebral ischemia/reperfusion injury of rats cuts viscosity compared with sham-operation group Apparent increase, fibrinogen content and hematocrit also dramatically increase, though erythrocyte aggregation index and rigidity index are Increase, but the not up to statistical level of signifiance.Strength gastrodia elata-cortex capsule raw medicine and test medicine 178mg/kg and 89mg/kg It can significantly reduce within stomach-filling 4 weeks that whole blood is high, medium and low to cut viscosity, hence it is evident that it reduces fibrinogen content and reduces hematocrit, Test medicine 178mg/kg and 89mg/kg can also significantly reduce the rigidity index of erythrocyte aggregation index.Test medicine 44.5mg/kg Also have the tendency that improving hemorheology of rat hair, but in addition to cutting viscosity in whole blood and significantly reducing, other indexs are not up to statistics The level of signifiance on.As a result see Table 5 for details.As a result prompt: strength gastrodia elata-cortex capsule raw medicine and test medicine are to cerebral ischemia/fill again Infusing hemorheology of rat has improvement result.

3.6 strength gastrodia elata-cortex capsule raw medicines and test medicine to normal rat and Cerebral Ischemia/Reperfusion rats in vitro ADP and The inhibiting effect of the platelet aggregation of fibrin ferment (Thrombin) induction.Normal rat stomach-filling strength gastrodia elata-cortex capsule raw medicine or After test medicine 4 weeks, blood is taken to carry out extracorporeal platelet aggregation experiment.It gives raw medicine and tests medicine rat ADP and thrombin induction Platelet aggregation rate is substantially reduced, and testing medicine group is in dose dependent.As a result see Table 6 for details, table 7.Further experiment is seen It examines strength gastrodia elata-cortex capsule raw medicine and test medicine lures Cerebral Ischemia/Reperfusion rats in vitro ADP and fibrin ferment (Thrombin) The influence for the platelet aggregation led.Cerebral Ischemia/Reperfusion rat oral gavage strength gastrodia elata-cortex capsule raw medicine or test take blood in medicine 4 weeks Carry out extracorporeal platelet aggregation experiment.As the result is shown: Cerebral Ischemia/Reperfusion rat by ADP and thrombin induction platelet aggregation Collection rate is all remarkably higher than sham-operation group, and the platelet aggregation rate for giving raw medicine and test medicine rat ADP and thrombin induction compares brain Ischemia/reperfusion rat is substantially reduced, and testing medicine group is in dose dependent.As a result see Table 8 for details, table 9.As a result it prompts: strong Power gastrodia elata-cortex capsule raw medicine and test medical instrument play the role of inhibiting platelet aggregation.

Improvement result (mean ± SD, N=10) of the table 2 to Cerebral Ischemia/Reperfusion rat behavior symptom

Note: ischemia/reperfusion control group VS sham-operation group,^##P < 0.01；Administration group VS ischemia/reperfusion control group, * * P < 0.01。

Influence (mean ± SD, N=10) of the table 3 to Cerebral Ischemia/Reperfusion rat body weight

Note: ischemia/reperfusion control group VS sham-operation group,^##P < 0.01；Administration group VS ischemia/reperfusion control group, * P < 0.05, * * P < 0.01.

Table 4 surveys the influence (mean ± SD, N=10) of brain volume to Cerebral Ischemia/Reperfusion Damage of Rats

Improvement result (mean ± SD, N=10) of the table 5 to Cerebral Ischemia/Reperfusion hemorheology of rat

Inhibiting effect (mean ± SD, N=10) of the table 6 to the normal rat ADP platelet aggregation induced

Note: normal group of administration group VS, * * P < 0.01.

Inhibiting effect (mean ± SD, N=10) of the table 7 to normal rat thrombin induction platelet aggregation

Note: normal group of administration group VS, * * P < 0.01.

Inhibiting effect (mean ± SD, N=10) of the table 8 to the ischemia/reperfusion rat ADP platelet aggregation induced

Note: ischemia/reperfusion control group VS sham-operation group,^##P < 0.01；Administration group VS ischemia/reperfusion control group * * P < 0.01。

The inhibiting effect for the platelet aggregation that table 9 induces Cerebral Ischemia/Reperfusion rat fibrin ferment (Thrombin) (mean ± SD, N=10)

4, conclusion: test medicine (new process preparation) middle dosage blocks 2 hours/reperfusion injury to intraluminal middle cerebral artery occlusion in rats There was no significant difference with raw medicine for neuroprotection and its influence to headstroke rat blood rheology and platelet aggregation, there is increasing Strong trend, but test medicine (new process preparation) high dose group and be substantially better than raw medicine, it is provided for process modification innovation feasible reliable Theoretical foundation.

Two, preparation process thereof and quality versus's research

(1) Study on Preparation

1, prescription: Rhizoma Gastrodiae 139.2g, Cortex Eucommiae (salt system) 147.8g, wild aconite root 17.4g, monkshood (system) 17.4g, Radix Angelicae Pubescentis 86.8g, rhizoma ligustici 102.6g, radix scrophulariae 102.6g, Radix Angelicae Sinensis 174g, glutinous rehmannia 278.2g, radix cyathulae 102.6g, mistletoe 102.6g, Qiang 174g living.

2, preparation method: taking prescription medicine, and Rhizoma Gastrodiae adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration, Ethanol extract is spare, the dregs of a decoction are spare, and Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste of Rhizoma Et Radix Notopterygii add 6 times of amount water 6 small through steam distillation extraction When, separation, it is spare to obtain volatile oil, and aqueous solution filtering is spare, the dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae, radix aconiti agrestis, monkshood, radix scrophulariae, glutinous rehmannia, Radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, and 3 hours for the first time, second 2 hours, filtration merged above-mentioned water-soluble Liquid, filtrate are concentrated into the medical fluid that concentration containing crude drug is 1: 1, let cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content up to 60%, stand 12 hours, supernatant liquid filtering is taken to obtain ethanol, merged with Rhizoma Gastrodiae alcohol extract, recycle ethyl alcohol and be concentrated into relative density be 1.25~ The medicinal extract of 1.35 (60 DEG C) is spare；Taking polyethylene glycol -6000 and polyethylene glycol-4000 mix heating melting, and volatile oil, leaching is added Cream stirs evenly, and is transferred in pill dripping machine and keeps the temperature 10 minutes in 60 DEG C, dripping pelletization, de-oiling, low temperature drying is filling, is made 1000 to get.

3, process flow chart (see attached drawing 3):

4, it extracts, purifying process research

4.1 Extraction Process of Volatile Oil are preferred

4.1.1 plus the investigation measured again of water is in prescription ratio, weighs Radix Angelicae Pubescentis 43.4g, rhizoma ligustici 51.3, Radix Angelicae Sinensis 87g, Rhizoma Et Radix Notopterygii 87g Equal four traditional Chinese medicines material, takes three parts, every part of 268.7g altogether, respectively plus 4 times of amounts, 5 times of amounts, 6 times of amount water distillating extracting oils, each extraction 5 hours, distillate is received, with petroleum ether condenser pipe and volatile oil extractor inner wall, merges petroleum ether liquid and oil-water fluid, with Three times, each 15ml merges petroleum ether liquid to petroleum ether extraction, is dehydrated and is filtered with anhydrous sodium sulfate, with the leakage of 10ml petroleum ether Bucket, low temperature are vaporized petroleum ether to constant weight, weigh the weight of volatile oil to get.It the results are shown in Table 1.

The investigation that table 1 plus water are measured again

Water is added to measure again	The amount (g) of volatile oil
		4 times of amounts	1.5742
5 times of amounts	1.6047
		6 times of amounts	1.6125

As seen from the experiment, add the amount of 4 times of water amount gained volatile oil lower；Add 5 times of water amounts and volatile oil obtained by 6 times of amounts Amount it is substantially suitable, and relatively plus 4 times of water amounts be more.Therefore last determine adds water to measure again for 5 times of amounts.

4.1.2 pretreatment mode weighs Radix Angelicae Pubescentis 43.4g, rhizoma ligustici 51.3, Radix Angelicae Sinensis 87g, Rhizoma Et Radix Notopterygii 87g etc. four in prescription ratio Taste medicinal material takes three parts, every part of 268.7g altogether, and totally three parts, every part adds 5 times of amount water, and first part of direct distillating extracting oil 5 is small When, second part is cold soaking 1 hour first, and redistillation is extracted volatile oil 5 hours, and third part is first heated to 80 DEG C of temperature leachings 1 hour, redistillation It extracts volatile oil 5 hours, receives distillate respectively, with petroleum ether condenser pipe and volatile oil extractor inner wall, merge petroleum Ether liquid and oil-water fluid, three times with petroleum ether extraction, each 15ml merge petroleum ether liquid, are dehydrated and are filtered with anhydrous sodium sulfate, with 10ml petroleum ether funnel, and low temperature is vaporized petroleum ether to constant weight, weigh the weight of volatile oil to get；Gained volatile oil is another Device is collected spare.It the results are shown in Table 2.

The investigation of 2 pretreatment mode of table

Pretreatment mode	The amount (g) of volatile oil
		Directly distillation is extracted	1.5984
First cold soaking 1 hour, redistillation are extracted	1.6077
		First 80 DEG C temperature leaching 1 hour, redistillation is extracted	1.6294

As seen from the experiment, be first heated to 80 DEG C temperature leaching 1 hour, redistillation extract then volatile oil extraction efficiency compared with Height, therefore last determine first is heated to 80 DEG C of temperature leachings 1 hour, redistillation is extracted volatile oil 5 hours.

4.1.3 the investigation of distillation time weighs Radix Angelicae Pubescentis 43.4g, rhizoma ligustici 51.3, Radix Angelicae Sinensis 87g, Rhizoma Et Radix Notopterygii 87g in prescription ratio Equal four traditional Chinese medicines material, takes three parts, every part of 268.7g altogether, totally three parts, respectively plus 5 times of amount water, is first heated to 80 DEG C of temperature and soaks 1 hour, then 4 hours, 5 hours, 6 hours are extracted in distillation respectively, distillate are received, in petroleum ether condenser pipe and volatile oil extractor Wall merges petroleum ether liquid and oil-water fluid, and three times with petroleum ether extraction, each 15ml merges petroleum ether liquid, de- with anhydrous sodium sulfate Water filtration, with 10ml petroleum ether funnel, and low temperature is vaporized petroleum ether to constant weight, weigh the weight of volatile oil to get；Gained The another device of volatile oil is collected spare.It the results are shown in Table 3.

The investigation of 3 distillation time of table

Distillation time	The amount (g) of volatile oil
		4 hours	1.5943
5 hours	1.6239
		6 hours	1.6287

As seen from the experiment, insufficient due to distilling, the amount for distilling 4 hours gained volatile oil is lower；Distillation 5 hours with 6 hours efficiency is substantially suitable, to save time and the energy, determines selection distillation 5 hours.In summary it tests, this preparation Extraction Process of Volatile Oil are as follows: take four taste such as Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, Rhizoma Et Radix Notopterygii to add 5 times of amount water, after being heated to 80 DEG C of temperature leachings 1 hour, Distillation is extracted 5 hours.In mass production, it is made since volatile oil is not easy to extract, volatile oil yield is extremely low in production.To make this work Skill more adapts to the needs of mass production, and the distillation of four tastes such as Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, Rhizoma Et Radix Notopterygii is extracted 6 hours in this product, receives distillate, 20% sodium chloride is added, sets and stands refrigeration 24 hours in freezer, be layered grease, point take volatilization oil reservoir to get.

4.2 Rhizoma Gastrodiae alcohol extraction processes are preferred

4.2.1 determining alcohol investigates the content assaying method referring to Rhizoma Gastrodiae in Chinese Pharmacopoeia version in 2010, respectively with 30% second Alcohol, 50% ethyl alcohol, 70% alcohol reflux extract 3 hours, measure the content of Gastrodin in Rhizoma Gastrodiae, the results are shown in Table 4.

The investigation of 4 Rhizoma Gastrodiae technique of table

Determining alcohol (%)	Gastrodin content (mg/g)
		30	2.495
50	2.605
		70	2.505

As seen from the experiment, the content of Gastrodin in Gastrodia eleta Bl. has certain difference with Extraction solvent concentration difference；With Content highest when 50% ethyl alcohol extracts, it is identical as official method Diluted Alcohol, therefore select the alcohol extracted using 50% ethyl alcohol as Rhizoma Gastrodiae Concentration.

4.2.2 other alcohol extracting factors are investigated

(1) factor level, which establishes the factor for influencing to extract, mainly the following aspects: alcohol adding amount, extraction time, extraction Number etc..Therefore we have carried out the horizontal orthogonal investigation of 3 factor 3 to these three principal elements, with preferred optimal processing parameter. The factor level table of orthogonal test is shown in Table 5.

5 Rhizoma Gastrodiae alcohol extracting orthogonal test factor level table of table

(2) index selects and the extracted amount of evaluation result Gastrodin using in extract is as orthogonal test evaluation index；It is dry Cream yield directly affects the regulation for taking daily dosage and single oral dose, therefore also using it as one of orthogonal test evaluation index.This examination Test proposed adoption comprehensive scoring method carry out process conditions it is preferred, due to dried cream yield with take daily dosage and single oral dose it is related, it is specified that It, which is weighed, is divided into 40 points, and Gastrodin is effective component in side, can directly reflect extraction effect, therefore provide the tradeoff of the two indexs Dividing is 60 points.

(3) sample preparation takes 50g Rhizoma Gastrodiae coarse powder, carries out alcohol extracting by each orthogonal test condition of table 6, extracting solution is concentrated and determines Hold to 100ml, it is spare.

(4) Gastrodin extracted amount measurement takes reserve liquid 2ml to be settled to 25ml, measures gastrodin content, calculates Gastrodin Extracted amount.

(5) the medical fluid 20ml after dried cream yield measurement precision takes each orthogonal test to be concentrated, sets dried to constant weight respectively In evaporating dish, water bath method, residue is 3 hours dry in 105 DEG C, takes out, sets in drier and place 30 minutes, weighs, and calculates dry Cream yield.It the results are shown in Table 6.

6 Rhizoma Gastrodiae alcohol extracting orthogonal experiments table of table

Note: dried cream yield scoring=(dried cream yield/maximum dried cream yield) × 40

Gastrodin extracted amount scoring=(Gastrodin extracted amount/maximum Gastrodin extracted amount) × 60

Comprehensive score=dried cream yield scoring+Gastrodin extracted amount scoring

7 Rhizoma Gastrodiae alcohol extracting analysis of variance table of table

Soruces of variation	Quadratic sum	Freedom degree	It is square	F value	Factor influences
						Alcohol adding amount A	255.06	2	127.53	4.26	It is not significant
Extraction time B	46.45	2	23.22	0.77	It is not significant
						Extraction time C	1226.33	2	613.16	20.46	Significantly
Error	23.63	2	0.06

Note: F_0.05(2,2)=19.00；F_0.01(2,2)=99.00

Result is analyzed from table 6,7 it is found that each factor effect primary and secondary is C > A > B；C is because being known as significant difference, in A factor A₃> A₂> A₁, so selection A₃；B in B factor₂> B₃> B₁, so selection B₂；C in C factor₃> C₂> C₁, so selection C₃。 Therefore optimised process is A₃B₂C₃.Difference is influenced with factor in view of production is practical, quasi- Rhizoma Gastrodiae alcohol extraction process is plus 5 times are measured 50% Ethyl alcohol extracts 3 times, extracts 2 hours every time.

4.3 extraction process by water are preferred

4.3.1 the factor that factor level establishes that influence water mentions mainly has the following aspects: amount of water, mentions extraction time Take number etc..Therefore we have carried out the horizontal orthogonal investigation of 3 factor 3 to these three principal elements, with preferred optimised process ginseng Number.The factor level table of orthogonal test is shown in Table 8.

8 water of table proposes orthogonal test factor level table

4.3.2 index selects the extracted amount of the Gastrodin using in extract as orthogonal test evaluation index；Prescription Chinese medicinal materials Also containing fat-soluble active ingredients such as phenols, terpene, alkaloids, in order to sufficiently reflect extraction effect, we are measured in extract The content of 60% ethanol soluble extraction, and orthogonal test evaluation index is also made with it；In addition, dried cream yield is also evaluation extraction effect Conventional index, therefore also using it as one of orthogonal test evaluation index.This test intended carries out technique item using comprehensive scoring method Part is preferred, and since dried cream yield is not proportional with effect amount, it is specified that its tradeoff is divided into 20 points, Gastrodin and 60% ethyl alcohol are leached Object is effective component in side, can directly reflect extraction effect, therefore provides that the tradeoff point of the two indexs is 40 points.

4.3.3 sample preparation takes 1/5 recipe quantity medicinal material, and part medicinal material collects the dregs of a decoction, by table 8 after the extraction of 1,2 techniques Each orthogonal test condition carries out water and mentions, and after 300 mesh filter-cloth filterings of medical fluid, is concentrated and is settled to 500ml.It is spare.

4.3.4 Gastrodin extracted amount measurement takes reserve liquid 10ml to be settled to 25ml, measures gastrodin content, calculates Rhizoma Gastrodiae The extracted amount of element.

4.3.5 the medical fluid 20ml after dried cream yield measurement precision takes each orthogonal test to be concentrated, sets dried to constant weight respectively Evaporating dish in, water bath method, residue is 3 hours dry in 105 DEG C, takes out, sets in drier and places 30 minutes, weigh, calculating Dried cream yield.

4.3.6 ethyl alcohol (60%) determination of extractives takes reserve liquid 50ml, and respectively plus ethyl alcohol makes alcohol content up to 60%, stands cold 24 hours, hiding, filtration, filtrate water bath method, residue is 3 hours dry in 105 DEG C, takes out, is placed in drier and places 30 minutes, Weighing calculates extract yield.It the results are shown in Table 9

9 water of table mentions orthogonal experiments table

Note: dried cream yield scoring=(dried cream yield/maximum dried cream yield) × 20

60% ethanol soluble extraction scoring=(extract yield/maximum extract yield) × 40

Gastrodin extracted amount scoring=(Gastrodin extracted amount/maximum Gastrodin extracted amount) × 40

Comprehensive score=+ 60% ethanol soluble extraction scoring of dried cream yield scoring+Gastrodin extracted amount scoring

10 water of table mentions analysis of variance table

Soruces of variation	Quadratic sum	Freedom degree	It is square	F value	Factor influences
						A	2.26	2	1.13	0.01	It is not significant
B	3098.34	2	1549.17	19.41	Significantly
						C	19.87	2	9.93	0.12	It is not significant
Error	159.62	2	79.81

Note: F_0.05(2,2)=19.00；F_0.01(2,2)=99.00

Result is analyzed from table 9,10 it is found that each factor effect primary and secondary is B > C > A；B is because being known as significant difference, A factor Middle A₂> A₃> A₁, so selection A₂；B in B factor₂> B₃> B₁, so selection B₂；C in C factor₂> C₃> C₁, so selection C₂, therefore optimised process is A₂B₂C₂.In view of production cost, so extracting 2 times to add 10 times of amount water, it is small that 3 are extracted for the first time When, second extract 2 hours.

4.4 alcohol precipitation processes are preferred

4.4.1 factor level, which establishes the factor for influencing alcohol precipitation, mainly the following aspects: liquor strength, alcohol precipitation are pure and strong Degree, time of repose etc..Therefore we have carried out the horizontal orthogonal investigation of 3 factor 3 to these three principal elements, with preferred best work Skill parameter.The factor level table of orthogonal test is shown in Table 11.

11 alcohol precipitation orthogonal test factor level table of table

4.4.2 the extracted amount of evaluation index and the preparation method Gastrodin using in extract is as orthogonal test evaluation index； Prescription Chinese medicinal materials also contain the fat-soluble active ingredients such as phenols, terpene, alkaloid, this technique is purified with 60% alcohol precipitation, dry cream Yield is direct reflection alcohol precipitation purification effect, while also directly affecting the regulation for taking daily dosage and single oral dose, therefore also with its work For one of orthogonal test evaluation index.This test intended is preferred using comprehensive scoring method progress process conditions, since dried cream yield is straight It connects influence and takes daily dosage and single oral dose, can reflect alcohol precipitation purification effect, it is specified that its tradeoff is divided into 40 points, Gastrodin Fang Zhongyou Ingredient is imitated, can directly reflect extraction effect, therefore provides that the tradeoff point of the two indexs is 60 points.

4.4.3 sample preparation takes recipe quantity medicinal material, and part medicinal material collects the dregs of a decoction, by table 11 after the extraction of 1,2,3 techniques Each orthogonal test condition carries out water and mentions, and after 300 mesh filter-cloth filterings of medical fluid, is concentrated and is settled to 500ml.It is spare.

4.4.4 Gastrodin extracted amount measurement takes reserve liquid 2ml to be settled to 25ml, measures gastrodin content, calculates Gastrodin Extracted amount.

4.4.5 the medical fluid 20ml after dried cream yield measurement precision takes each orthogonal test to be concentrated, sets dried to constant weight respectively Evaporating dish in, water bath method, residue is 3 hours dry in 105 DEG C, takes out, sets in drier and places 30 minutes, weigh, calculating Dried cream yield.It the results are shown in Table 12

12 alcohol precipitation orthogonal experiments table of table

13 alcohol precipitation analysis of variance table of table

Note: F_0.05(2,2)=19.00；F_0.01(2,2)=99.00

Result is analyzed from table 12,13 it is found that each factor effect primary and secondary is A > B > C；A is because being known as significant difference, A factor Middle A₁> A₂> A₃, so selection A₁；B in B factor₃> B₂> B₁, so selection B₃；C in C factor₁> C₂> C₃, so selection C₁, therefore optimised process is A₁B₃C₁.In view of production technology reality, so selecting alcohol precipitation process for liquor strength is 1ml medical fluid It is equivalent to 1.0g crude drug in whole, adds ethyl alcohol to alcohol content up to 60%, stands 12 hours.

5, preparations shaping technical study

The preparation of 5.1 medicinal extract is prepared by extraction, purifying process.The another device of volatile oil is collected, and medicinal extract part reduced pressure is concentrated into Relative density is 1.25~1.35 (60 DEG C), spare.

The selection of 5.2 matrix and coolant

5.2.1 the selection of coolant is by prerun, and when using atoleine as coolant, pellet sedimentation is very fast, and it is poor to form； When using dimethicone as coolant, pellet sedimentation is slower, can form；When using vegetable oil as coolant, pellet sedimentation is slow, molding Difference；So selecting dimethicone preferable for coolant.

5.2.2 the selection of matrix combines our clinical application and prescription containing volatile oil and medicinal extract feature easy to moisture absorption, presses Following table progress matrix is preferred, is coolant with dimethicone, and dripping temperature is 60 DEG C, and water dropper bore is 1/2mm (inside/outside diameter mm).To disperse situation, mobility and form situation as evaluation index, each index is 3 points, 2 points and 1 point by good extremely poor scoring, with Cumulative score is comprehensive score.

14 Screening matrix result of table

Composition	1	2	3	4	5	6	7	8	9	10	11	12
													Drug	50	50	50	50	50	50	60	60	60	60	40	40
PEG-4000	50	25	0	0	0	25	20	0	0	20	40	20
													PEG-6000	0	25	50	0	25	0	20	40	20	0	20	40
PEG-8000	0	0	0	50	25	25	0	0	20	20	0	0
													Dispersion situation	1	3	2	2	2	2	2	2	2	1	2	2
Mobility	1	2	2	1	1	1	2	1	1	2	1	2
													Form situation	1	1	1	1	2	2	2	2	2	1	2	2
Comprehensive score	3	6	5	4	5	5	6	5	5	4	5	6

To the judge that each proportioning test carries out, the preferable proportion composition of screening has drug respectively: PEG-4000: PEG-6000 (2: 1: 1,3: 1: 1 and 2: 1: 2), it is contemplated that drugloading rate and preparation take magnitude relation, selection with PEG-4000: PEG-6000 (1: It 1) is matrix；Drug: matrix (3: 2) is molding formula proportion.

With (1: 1) PEG-4000: PEG-6000 for matrix, dimeticone is coolant dripping for the screening of 5.2 moulding process Pelletization, using the weight differential coefficient of variation of dripping pill as index, screen water dropper internal-and external diameter size, drop speed, drop away from and coolant 4 factor of temperature design, 3 horizontal quadrature screening test, be shown in Table 15.With roundness (shortest diameter/shortest diameter), the opposite mark of ball weight Quasi- deviation (RSD), yield rate are index, and the optimum determining value of each index is set to 100 points, and the importance according to each factor determines Its tradeoff is divided into 30,30,40, obtains formula: comprehensive score=roundness/maximum roundness × 30+ most piller weight RSD/ ball weight RSD × 30+ yield rate/maximum yield rate × 40, test result are shown in Table 16, variance analysis and are shown in Table 17.

15 moulding process of table screens factor level table

16 moulding process screening scheme of table and result

17 moulding process of table screens variance analysis

Note: F_0.05(2,2)=19.00；F_0.01(2,2)=99.00

From table analysis result it is found that each factor effect primary and secondary is C > A > B > D；A, C is because being known as significant difference, A factor Middle A₂> A₃> A₁, so selection A₂；B in B factor₁> B₂> B₃, so selection B₁；C in C factor₃> C₂> C₁, so selection C₃；D in D factor₂> D₃> D₁, so selection D₂, therefore best moulding process is A₂B₁C₃D₂, i.e. coolant temperature is 10~15 DEG C, water dropper internal-and external diameter is 1/3mm, and drop is away from being 10cm, and drop speed is 40 drops/min.

4.3 pilot scale researches take 20 times of recipe quantity medicinal materials, by process route progress scale up test is worked out to obtain, to production work Skill index carries out comprehensive assessment, carries out performance rating to medicinal material and finished product, carries out tracing detection to each principle active component, as a result It is shown in Table 18.

18 pilot plant test result of table

Scale up test the result shows that, this product items technical parameter stablize, illustrate feasible process, it is suitable for mass production.

(2) quality versus's research takes 10 times of recipe quantity medicinal materials, and finished product is made by former preparation process thereof；Separately take at 10 times Finished product is made by technique is improved in side's amount medicinal material, and simulation listing packaging is right using thermostatic accelerated experiment (T=37 DEG C, RH=75%) Two kinds of products make comprehensive comparative study, as a result see the table below 18, table 19.

18 process ration explanation of table

19 different process manufactured goods quality stability comparing result of table

Three, formulation efficacy experimental study

Strength day eucommia bark capsules (concentrated type) are the new drug that Sanli Pharmaceutical Co., Ltd., Guizhou develops, and mainly contain day The ingredients such as fiber crops, Cortex Eucommiae.The court is entrusted by the said firm, is tested to the anti-cerebral ischemia pharmacological action of strength gastrodia elata-cortex capsule Experimental observations, are now reported as follows by observation:

(1) test material

1. drug and reagent test drug: strength gastrodia elata-cortex capsule is public by three power pharmacy Limited Liability of client Guizhou Department provides, lot number: 2009001, state: uniform pellet shape；Quantity: 8kg；Positive control drug is former preparation strength gastrodia tuber eucommia glue Capsule is produced by Sanli Pharmaceutical Co., Ltd., Guizhou, lot number: 100306；State: uniform powder；Quantity: 5kg.Test drug Facing the used time with positive drug with distilled water is made into suspension.Red tetrazolium (TTC) is the production of Shanghai Ling Jin Fine Chemical Co., Ltd Product, lot number: 20050508.

2. animal SD male rat, 250 ± 30g of weight；Kunming mouse, half male and half female, 20 ± 2g of weight, by Soviet Union State University Hospital portion Experimental Animal Center provides, quality certification number: 2007003.

3. instrument LBY-NJ2 type platelet aggregation instrument (Beijing Pu Sheng instrument company), 7170 automatic clinical chemistry analyzers (Hitachi, Japan), BS110S precision electronic balance (Beijing Sai Duolisi joint-stock company), SHA-C temperature controlled water bath oscillator (all over the country industrial corporation in Shenzhen), LXB-B low speed large capacity centrifuge (Town in Shanghai pavilion instrument and equipment factory), FASCO type are complete certainly Move quick blood viscosity analyzer (University Of Chongqing ties up more biology Gong Wu research institutes).

(2) method and result

1. mouse resist oxygen lack is tested

The influence mouse of 1.1 pairs of mouse oxygen deficit tolerances 50 is randomly divided into 5 groups, i.e. blank control group, reagent strength Gastrodia elata-cortex capsule low dose group (0.375g/kg), middle dose group (0.75g/kg), high dose group (1.5g/kg), original product group (0.48g/kg) every group 10.Gastric infusion, once a day, successive administration 7 days, mouse was placed in by 1h after not secondary administration respectively In 250ml wide-mouth bottle, 10g soda lime is placed in bottle, seals bottleneck with vaseline.Mouse is measured to stop in bottle from closing to breathing Time only, as a result compared with blank control group, with t test and judge, it has that there was no significant difference.The results show that with control group ratio Compared with strength gastrodia elata-cortex capsule is low, middle dose group extends the mouse survival time, but without obvious statistical difference (P > 0.05), high dose group can be obviously prolonged mouse normal pressure time-to-live (p < 0.05), the results are shown in Table 1.

Influence of the 1 strength gastrodia elata-cortex capsule of table to mouse normobaric hypoxia

Compared with the control group,^*P < 0.05

Dehisce caused by 1.2 pairs of mouse broken end breathing time influence grouping and medication with 1.1.After not secondary administration 1h, Break end rapidly in mouse ear lower part, record each group mouse broken end after dehisce the snorting time, with t test and judge its whether there is or not conspicuousnesses Difference.The results show that compared with the control group, strength gastrodia elata-cortex capsule high dose group can be obviously prolonged mouse and dehisce breathing time (p < 0.05), low, middle dose group extend mouse breathing time of dehiscing, but without obvious statistical difference (P > 0.05), It the results are shown in Table 2.

2 strength gastrodia elata-cortex capsule of table dehisces the influence of breathing time to mouse broken end

Compared with the control group, * P < 0.05

2. influence of the strength gastrodia elata-cortex capsule to intraluminal middle cerebral artery occlusion in rats focal cerebral ischemia

2.1 modellings prepare middle cerebral artery infarction model, SD male rat, 10% chloraldurate using line brush After (350mg/kg) intraperitoneal anesthesia, along neck midsection skin, separate that right neck is total, neck is outer and internal carotid.In in neck, neck always moves It is closed at arteries and veins with artery clamp folder, ligatures external carotid artery proximal part and distal end, centre is cut.It will be moved in external carotid artery free-end and neck Arteries and veins is in alignment, and nylon wire is inserted by external carotid artery, is ligatured after insertion with No. 0 silk thread, to prevent bleeding, opens internal carotid Locate artery clamp, nylon wire is inserted into internal carotid, is continued into encephalic, the stopping when there is light resistance, insertion depth is about 2cm.Only removed after sham-operation group Animal Anesthesia neck is total, in neck and external carotid artery is without ligaturing).

2.2 animal packets and administration rat are randomly divided into 6 groups, respectively sham-operation group, model group (arteria cerebri media stalk Plug group) strength gastrodia tuber eucommia low dose group, middle dose group, high dose group, positive drug comparison medicine (original product) group.Sham-operation group: Only separate that neck is total, in neck and external carotid artery is without ligaturing after rat anesthesia.It is gastric infusion 1 time daily before each reagent group molding, even Continuous administration 5 days, molding after not secondary administration 1h, 6h is administered once again after middle cerebral artery infarction.Sham-operation group and model group are corresponding The capacity physiological saline such as time stomach-filling.

2.3 nervous symptoms score groups of animals in the brain artery occlusion for 24 hours after, by Bederson^[3]Method to every Mouse scores.It is classified according to its symptom degree, totally 10 points.Specific methods of marking is as follows.

The results show that the nervous symptoms scoring of sham-operation group is 0, model group is 6.2 ± 2.3, apparent nerve barrier occurs Hindering symptom, the middle and high dosage group rat nerve symptom of strength gastrodia elata-cortex capsule is obviously improved, and scoring is respectively 3.4 ± 2.1, 2.9 ± 2.2 (p < 0.05), low dose group effect is not significant, the results are shown in Table 3.

Rear rat broken end takes brain to 2.4 cerebral infarct sizes measurement infraction for 24 hours, sets 20min in -20 DEG C of refrigerators of brain, removal is smelt Ball, cerebellum and low brain stem averagely cut five knives along coronal-plane.Then brain piece is placed in 5ml, red four nitrogen that concentration is 2% rapidly Azoles (contains 0.1mol/LK₂HPO₄) in solution, be protected from light 37 DEG C of incubation 30min, stir therebetween every 7-8min once, through dyeing Afterwards, normal cerebral tissue takes on a red color, and infarct tissue is white, carefully takes out white infarct area and weighs, with blocking tissue's weight Amount accounts for full brain weight percentage and calculates it as infarction size.With t test and judge, it has that there was no significant difference.The results show that sham-operation Group brain is in uniform rose, does not occur ischemic necrosis；Model group is shown in obvious cerebral infarction stove.With model control group ratio Compared with the middle and high dosage group cerebral infarction degree of strength gastrodia elata-cortex capsule significantly reduces (P < 0.05), is shown in Table 3.

The influence that table 3 scores to focal cerebral ischemia in rats Range of Cerebral Infarction and nervous symptoms

Compared with model group, * P < 0.05

2.5 histopathology histological observation rat cerebral ischemias for 24 hours after, broken end takes brain routinely fixed, takes cerebral infarction district's groups It knits, paraffin embedding, HE dyeing.Sham-operation group corresponding region has no damage under light microscopic, and eucaryotic cell structure is complete.Model group cortical cell Structural damage, space between cells increase, and see neuron oedema；Hippocampal CA 1 cell arrangement is loose, and endochylema contaminates deeply, nuclear pyknosis.By force For power gastrodia elata-cortex capsule high dose group compared with model group, cortical cell damages substantially reduced, rarely seen respective cells oedema, hippocampus The area CA1 cellular morphology is substantially complete, without obvious karyopyknosis.In, low dose group cortex and Hippocampal CA 1 neural cell injury Pathology is not improved.

2.6 strength gastrodia elata-cortex capsules are active on focal cerebral ischemia in rats serum lactic dehydrogenase (SLDH) (LDH) to be influenced greatly Mouse middle cerebral artery infarction for 24 hours after, with 10% chloraldurate (350mg/kg) intraperitoneal anesthesia, abdominal aortic blood 2ml, 3000 Turn/min, be centrifuged 10min, serum is taken to measure LDH activity.T test and judge its have that there was no significant difference.The results show that with artificial hand Art group compares, and model group rats Serum LDHs activity is significantly raised (P < 0.05), the middle and high dosage group of strength gastrodia elata-cortex capsule with Model group group compares, and Serum LDH activity is substantially reduced (P < 0.05), and low dose group LDH activity is declined, but without statistics Difference (P > 0.05), the results are shown in Table 4.

Table 4 is on the active influence of Level In Rats With Focal Cerebral Ischemia Serum LDH

Compared with sham-operation group,^#P < 0.05；Compared with model group,^*P < 0.05

Influence intraluminal middle cerebral artery occlusion in rats of the 2.7 strength gastrodia elata-cortex capsules to focal cerebral ischemia in rats hemorheology After blocking for 24 hours, 10% chloraldurate (350mg/kg) intraperitoneal anesthesia, abdominal aortic blood 5ml injects in anticoagulant test tube, slow up and down After slow rotation blood mixes them thoroughly, hemorheological indexes are measured.The results show that compared with sham-operation group, model Control group plasma viscosity, whole blood viscosity (high, medium and low to cut), blood reduced viscosity, hematocrit apparent increase (P < 0.05).Compared with model group, strength gastrodia elata-cortex capsule high dose group is to plasma viscosity, whole blood viscosity (high, medium and low to cut), complete Blood reduced viscosity, hematocrit significantly reduce (P < 0.05).It is (high, medium and low that middle dose group can be substantially reduced whole blood viscosity Cut) (equal P < 0.05), other indexs are had no significant effect；Low dose group effect is unobvious, the results are shown in Table 5.

Influence of the table 5 to Level In Rats With Focal Cerebral Ischemia hemorheology

Compared with sham-operation group, * p < 0.05；Compared with model group,^#P < 0.05.

3. influence grouping and administration of the strength gastrodia elata-cortex capsule to rats after cerebral ischemic reperfusion cerebral index, brain water content With 2,1h after not secondary administration, 10% chloraldurate of rat (350mg/kg) intraperitoneal anesthesia ligatures bilateral common carotid arteries 30min, then After perfusion for 24 hours, brain is taken in rat breaks end rapidly on ice pan, removal brain stem is weighed with lower portion, calculates cerebral index.It is placed in 105 It bakes in DEG C oven to constant weight, calculates its brain water content.

Cerebral index=full brain wet weight/weight × 100% brain water content=(brain wet weight-brain stem weight)/brain wet weight × 100%

The results show that model group brain water content dramatically increases (P < 0.05), and cerebral index has increase compared with sham-operation group Trend, but it is not statistically significant.The middle and high dosage group of strength gastrodia elata-cortex capsule is compared with model group, cerebral index and brain water content It is substantially reduced (P < 0.05), the results are shown in Table 6.

Influence of the table 6 to cerebral ischemia-reperfusion injury in rats cerebral index, brain water content

Compared with sham-operation group,^#P < 0.05；Compared with model group, * p < 0.05

4. influence of the strength gastrodia elata-cortex capsule to thrombosis and platelet aggregation

The anti-Rat Experimental thrombosis of 4.1 strength gastrodia elata-cortex capsules acts on SD rat male and female dual-purpose, is randomly divided into 5 Group: saline control group, strength gastrodia tuber eucommia low, middle and high dose groups (respectively 0.09g/kg, 0.18g/kg, 0.36g/ ) and positive drug Nimodipine group kg.Daily gastric infusion 1 time, continuous 5 days, 60min, yellow Jackets 30mg/ after the last administration Kg Intravenous Anesthesia layback position is fixed, and neck median incision, separates right carotid and left side vena jugularis externa is spare.Take internal diameter The siliconized polyethylene Guan Yigen of 1.5mm, long 12cm are placed in No. 4 surgical threads of a length 6cm, are filled with heparin-saline in pipe Then the both ends of pipe are inserted into left vena jugularis externa and right common carotid artery respectively, form arteria carotis-jugular vein access by (50U/ml), Open blood flow 15min takes out silk thread weighing in managing, subtracts silk thread original weight amount, as wet weight of thrombus.With t test and judge its whether there is or not Significant difference.The results show that the middle and high dosage group of strength gastrodia elata-cortex capsule has obvious inhibiting effect to thrombosis, Its inhibiting rate is respectively 19.4% and 20.1%, the results are shown in Table 7.

Influence of the 7 strength gastrodia elata-cortex capsule of table to thrombosis

Compared with saline control group, * p < 0.05

Influence rabbit of the 4.2 strength gastrodia elata-cortex capsules to platelet aggregation 24, is randomly divided into 4 groups, every group 6 Only, strength gastrodia tuber eucommia re-glue capsule 0.18g/kg group, 0.36g/kg group, saline control group and original product 0.48g/kg group. Medication is with 4.1, and 60min, yellow Jackets 30mg/kg Intravenous Anesthesia are faced upward position and fixed after the last administration, and neck center is cut Mouthful, right carotid is separated, insertion polyethylene pipe takes blood 20ml, is placed in the anticoagulant centrifuge tube of sodium citrate (9: 1), is centrifuged 800rpm, 5min, sucting a layer suspension is platelet rich plasma (PRP)；It is centrifuged 3000rpm, 10min again, sucts suspension and is made Platelet poor plasma (PPP).4 cuvettes are taken, an addition PPP200ul, another three are separately added into PRP200ul, set aggregation 37 DEG C of preheating 3min in instrument first survey the platelet count of PPP in measurement hole, then survey PRP platelet count, then dilute PRP with PPP Platelet count is to measuring aequum.PRP the and PPP measuring cup for mixing up platelet count is set in platelet aggregation instrument measurement hole, in Equipped with stirring rod one is added in PRP glasss, 7.5 μm of ol/ of adenosine diphosphate (Adenosine diphosphate:ADP) are added Curve of platelet aggregation is recorded after L or fibrin ferment (Thrombin:Thr) 3.5u/ml, 5min.According to administration group and physiological saline The aggregation curve of group with observation 1,3,5min aggregation intensity and maximum aggregation intensity (MA), and calculates aggregation and inhibits percentage.With T test and judge its have that there was no significant difference.

The results show that each dosage of strength gastrodia elata-cortex capsule can obviously inhibit the blood of ADP induction compared with physiological saline group Platelet aggregation, is shown in Table 8.On the platelet aggregation of Thr induction, only high dose group generates obvious inhibiting effect influence, the results are shown in Table 9.

Influence of the table 8 to the ADP platelet aggregation induced

Compared with physiology salt group water, * p < 0.05, * * p < 0.01

Influence of the table 9 to the fibrin ferment Thr platelet aggregation induced

Compared with physiological saline group, * p < 0.05, * p < 0.01

(3) conclusion experiment uses mouse resist oxygen lack model, intraluminal middle cerebral artery occlusion in rats focal cerebral ischemia and ischemia-reperfusion Two models, observe the effect of strength gastrodia elata-cortex capsule anti-cerebral ischemia, and observe the anti-blood closely related with cerebral ischemia Bolt is formed and the influence to platelet aggregation, conclusion are as follows:

1. strength gastrodia elata-cortex capsule 0.72g/kg can be obviously prolonged the mouse normal pressure time-to-live and when broken end dehisces to breathe Between.

2. strength gastrodia elata-cortex capsule 0.18g/kg, 0.36g/kg can significantly reduce cerebral infarction to focal cerebral ischemia in rats Range improves nervous symptoms, reduces serum lactic dehydrogenase (SLDH) activity；Cerebral index is substantially reduced to cerebral ischemia-reperfusion injury in rats And brain water content, the preventive and therapeutic effect of strength gastrodia elata-cortex capsule 0.36g/kg are similar to original product 0.48g/kg.Histopathology Histological findings show, strength gastrodia elata-cortex capsule 0.36g/kg can cortex and hippocampus caused by substantially reduced cerebral infarction The area CA1 neure damage degree.

3. the platelet aggregation that strength gastrodia elata-cortex capsule obviously inhibits ADP and THR to induce, 0.18g/kg and 0.36/kg The formation of obvious Inhibition test thrombus, inhibiting rate is respectively 19.4% and 20.1%.Strength gastrodia elata-cortex capsule is substantially reduced Experimental cerebral ischemia rat plasma viscosity, whole blood viscosity (high, medium and low to cut), blood reduced viscosity and hematocrit.

Four, acute toxicity test is studied

Acute toxicity of the abstract observation strength gastrodia elata-cortex capsule to mouse.Mouse single oral gavage is administered without death, can not Median lethal dose is found out, using maximum dosage-feeding 40g/kg.d^-1(three times per day stomach-filling) is observed continuously 14 days, has no that mouse is dead It dies, general status is good, discovery without exception, shows that strength gastrodia elata-cortex capsule is very low to Mouse Acute Toxicity.

1 experimental material

1.1 animal Kunming mouses, half male and half female, weight 18-22g.It is mentioned by University Of Suzhou's medical board Experimental Animal Center For quality certification number: SCXK (Soviet Union) 2009-12.

1.2 drug strength gastrodia elata-cortex capsules (lot number: 2009001, specification: it is not added with the strength gastrodia tuber eucommia glue of auxiliary material Sac extract) it is provided by Sanli Pharmaceutical Co., Ltd., Guizhou.Strength gastrodia elata-cortex capsule is worn into carefully with mortar before experiment It is spare to be configured to suspension with distilled water for powder.

2 experimental methods

2.1 measurement median lethal dose (LD₅₀) mouse 40 are taken, half male and half female, weight 18-22g is randomly divided into 4 group (10 Only/group): it is respectively blank control group (same volume distilled water), strength gastrodia elata-cortex capsule 10.5g/kg.d^-1、11.3g/kg.d^-1、12.1g/kg.d^-1、13g/kg.d^-1(maximum suspension concentration), after fasting (can't help water) 12 hours, single oral gavage administration (0.4ml/10g), observe mouse ordinary circumstance (changes of weight, diet, fur, behavior, secretion, excreta etc.) and in Poison, death condition, are observed continuously 14 days.

2.2 maximum dosage-feeding experiment mices 40, half male and half female, weight 18-22g are randomly divided into blank control group, strong Power gastrodia elata-cortex capsule group.Strength gastrodia elata-cortex capsule presses 40g/kg.d^-1Gastric infusion (0.4ml/10g) in three times, blank pair Same volume distilled water is given according to group, the general activity situation and death toll of mouse is observed, is observed continuously 14 days.

3 results

Have no dead during each administration group mouse experiment of 3.1 strength gastrodia elata-cortex capsules, general status good (weight, drink Food, fur, behavior, secretion, excreta etc.), median lethal dose (LD can not be found out₅₀)。

3.2 use maximum dosage-feeding 40g/kg.d^-1(110 times that are approximately equivalent to clinical daily dose) stomach-filling, experiment periods Between mouse weight increase, with blank control group without significant difference (being shown in Table 1), diet and activity are normal, and fur is smooth, mouth, nose, The no abnormality seens secretion such as eye, only the 1st day brown soft stool of defecating after administration urinate no abnormality seen.

The comparison of 1 strength gastrodia elata-cortex capsule maximum dosage-feeding experiment mice weight of table

Detailed description of the invention

Fig. 1 is the Technology Roadmap influenced on normal rat extracorporeal platelet aggregation；

Fig. 2 is the Technology Roadmap that om observation damages side brain tissue nerve cell；

Fig. 3 is preparation technology flow chart.

Specific embodiment

Embodiment 1: Rhizoma Gastrodiae 139.2g, Cortex Eucommiae (salt system) 147.8g, wild aconite root 17.4g, monkshood (system) 17.4g, Radix Angelicae Pubescentis 86.8g, rhizoma ligustici 102.6g, radix scrophulariae 102.6g, Radix Angelicae Sinensis 174g, glutinous rehmannia 278.2g, radix cyathulae 102.6g, mistletoe 102.6g, Qiang 174g living.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii It extracts 6 hours, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, Huang, radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, and 3 hours for the first time, second 2 hours, combined extract, filter It crosses, filtrate is concentrated into the medical fluid that concentration containing crude drug is 1: 1, lets cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content up to 60%, stands 24 hours, supernatant liquid filtering is taken to obtain ethanol, merged with Rhizoma Gastrodiae alcohol extract, recycle ethyl alcohol and be concentrated into relative density be 1.05~ The medicinal extract of 1.40 (60 DEG C) is spare；Taking polyethylene glycol -6000 and polyethylene glycol-4000 mix heating melting, and volatile oil, leaching is added Cream stirs evenly, and is transferred in pill dripping machine and keeps the temperature 10 minutes in 60 DEG C, dripping pelletization, de-oiling, and low temperature drying is filling in hollow In capsule, 1000 are made to get capsule of the present invention, specification: every dress 0.3g.Usage and dosage: it is oral, once two grains, one day 2 times.

Embodiment 2: Rhizoma Gastrodiae 1392g, Cortex Eucommiae (salt system) 1478g, wild aconite root 174g, monkshood (system) 174g, Radix Angelicae Pubescentis 868g, ligusticumic This 1026g, radix scrophulariae 1026g, Radix Angelicae Sinensis 1740g, glutinous rehmannia 2782g, radix cyathulae 1026g, mistletoe 1026g, Rhizoma Et Radix Notopterygii 1740g.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii It extracts 6 hours, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, Huang, radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, and 3 hours for the first time, second 2 hours, combined extract, filter It crosses, filtrate is concentrated into the medical fluid that concentration containing crude drug is 1: 1, lets cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content up to 60%, stands 24 hours, supernatant liquid filtering is taken to obtain ethanol, merged with Rhizoma Gastrodiae alcohol extract, recycle ethyl alcohol and be concentrated into relative density be 1.05~ The medicinal extract of 1.40 (60 DEG C) is spare；Taking polyethylene glycol -6000 and polyethylene glycol-4000 mix heating melting, and volatile oil, leaching is added Cream stirs evenly, and is transferred in pill dripping machine and keeps the temperature 10 minutes in 60 DEG C, dripping pelletization, de-oiling, and low temperature drying is filling in hollow In capsule, 10000 are made to get capsule of the present invention, specification: every dress 0.3g.Usage and dosage: it is oral, once two grains, one Day 2 times.

Embodiment 3: Rhizoma Gastrodiae 139.2g, Cortex Eucommiae (salt system) 147.8g, wild aconite root 17.4g, monkshood (system) 17.4g, Radix Angelicae Pubescentis 86.8g, rhizoma ligustici 102.6g, radix scrophulariae 102.6g, Radix Angelicae Sinensis 174g, glutinous rehmannia 278.2g, radix cyathulae 102.6g, mistletoe 102.6g, Qiang 174g living.

Rhizoma Gastrodiae raw medicinal material is weighed, 3 times of 90% alcohol refluxs of amount is added to extract 1 time, is extracted 4 hours, is merged, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii It extracts 10 hours, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, Huang, radix cyathulae, mistletoe merge, and 12 times of amount water is added to extract 1 time, extract 4 hours, filtration, and it is 1 that filtrate, which is concentrated into concentration containing crude drug, : 1 medical fluid is let cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content up to 40%, stands 12 hours, supernatant liquid filtering is taken to obtain ethyl alcohol Liquid merges with Rhizoma Gastrodiae alcohol extract, recycle ethyl alcohol and be concentrated into relative density be 1.05~1.40 (60 DEG C) medicinal extract it is spare；It takes poly- Ethylene glycol -6000 and polyethylene glycol-4000 mix heating melting, and volatile oil, medicinal extract is added, stirs evenly, is transferred to pill dripping machine In in 60 DEG C keep the temperature 10 minutes, dripping pelletization, de-oiling, low temperature drying is filling in Capsules, be made 1000 to get this Invention capsule, specification: every dress 0.3g.Usage and dosage: it is oral, once two grains, 2 times a day.

Embodiment 4: embodiment 1: Rhizoma Gastrodiae 139.2g, Cortex Eucommiae (salt system) 147.8g, wild aconite root 17.4g, monkshood (system) 17.4g, Radix Angelicae Pubescentis 86.8g, rhizoma ligustici 102.6g, radix scrophulariae 102.6g, Radix Angelicae Sinensis 174g, glutinous rehmannia 278.2g, radix cyathulae 102.6g, mistletoe 102.6g, Rhizoma Et Radix Notopterygii 174g.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 8 times of 30% alcohol refluxs of amount to extract 4 times, 1 hour every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii It extracts 4 hours, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, Huang, radix cyathulae, mistletoe merge, and add 6 times of amount water to extract 4 times, 1 hour every time, filtration, it was 2 that filtrate, which is concentrated into concentration containing crude drug: 1 medical fluid is let cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content up to 80%, stands 48 hours, supernatant liquid filtering is taken to obtain ethyl alcohol Liquid merges with Rhizoma Gastrodiae alcohol extract, recycle ethyl alcohol and be concentrated into relative density be 1.05~1.40 (60 DEG C) medicinal extract it is spare；It takes poly- Ethylene glycol -6000 and polyethylene glycol-4000 mix heating melting, and volatile oil, medicinal extract is added, stirs evenly, is transferred to pill dripping machine In in 60 DEG C keep the temperature 10 minutes, dripping pelletization, de-oiling, low temperature drying is filling in Capsules, be made 1000 to get this Invention capsule, specification: every dress 0.3g.Usage and dosage: it is oral, once two grains, 2 times a day.

Embodiment 5: Rhizoma Gastrodiae 139.2g, Cortex Eucommiae (salt system) 147.8g, wild aconite root 17.4g, monkshood (system) 17.4g, Radix Angelicae Pubescentis 86.8g, rhizoma ligustici 102.6g, radix scrophulariae 102.6g, Radix Angelicae Sinensis 174g, glutinous rehmannia 278.2g, radix cyathulae 102.6g, mistletoe 102.6g, Qiang 174g living.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii It extracts 6 hours, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, Huang, radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, and 3 hours for the first time, second 2 hours, combined extract, filter It crosses, filtrate is concentrated into the medical fluid that concentration containing crude drug is 1: 1, lets cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content up to 60%, stands 24 hours, supernatant liquid filtering is taken to obtain ethanol, merged with Rhizoma Gastrodiae alcohol extract, recycle ethyl alcohol and be concentrated into relative density be 1.05~ The medicinal extract of 1.40 (60 DEG C) is dried, crushed into fine powder, and right amount of auxiliary materials is added, grinds well, is pressed into 10000, obtain flexible glue of the present invention Capsule, specification: every dress 0.3g.Usage and dosage: it is oral, once two grains, 2 times a day.

Embodiment 6: Rhizoma Gastrodiae 13.92g, Cortex Eucommiae (salt system) 14.78g, wild aconite root 1.74g, monkshood (system) 1.74g, Radix Angelicae Pubescentis 8.68g, rhizoma ligustici 10.26g, radix scrophulariae 10.26g, Radix Angelicae Sinensis 17.4g, glutinous rehmannia 27.82g, radix cyathulae 10.26g, mistletoe 10.26g, Qiang 17.4g living.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 30% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii It extracts 6 hours, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, Huang, radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, 3 hours for the first time, second 2 hours, merge, filtration, filtrate It is concentrated into the medical fluid that concentration containing crude drug is 1: 1, is let cool to room temperature, ethyl alcohol, which is added, makes solution alcohol content up to 60%, 24 hours are stood, It takes supernatant liquid filtering to obtain ethanol, merges with Rhizoma Gastrodiae alcohol extract, recycling ethyl alcohol and being concentrated into relative density is 1.05~1.40 (60 DEG C) medicinal extract it is spare；Taking polyethylene glycol -6000 and polyethylene glycol-4000 mix heating melting, and volatile oil, medicinal extract, stirring is added Uniformly, be transferred in pill dripping machine in 60 DEG C keep the temperature 10 minutes, dripping pelletization, de-oiling, low temperature drying, be made 1000 balls to get this Invention pill, specification: every ball weight 30mg.Usage and dosage: oral, 20 balls, 2 times a day.

Embodiment 7: Rhizoma Gastrodiae 139.2g, Cortex Eucommiae (salt system) 147.8g, wild aconite root 17.4g, monkshood (system) 17.4g, Radix Angelicae Pubescentis 86.8g, rhizoma ligustici 102.6g, radix scrophulariae 102.6g, Radix Angelicae Sinensis 174g, glutinous rehmannia 278.2g, radix cyathulae 102.6g, mistletoe 102.6g, Qiang 174g living.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 30% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii It extracts 6 hours, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, Huang, radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, 3 hours for the first time, second 2 hours, merge, filtration, filtrate It is concentrated into the medical fluid that concentration containing crude drug is 1: 1, is let cool to room temperature, ethyl alcohol, which is added, makes solution alcohol content up to 60%, 24 hours are stood, It takes supernatant liquid filtering to obtain ethanol, merges with Rhizoma Gastrodiae alcohol extract, recycling ethyl alcohol and being concentrated into relative density is 1.05~1.40 (60 DEG C) medicinal extract, right amount of auxiliary materials is added, mixes, pelletizes, it is dry, moderate lubrication agent is added, mixes, tabletting, film coating is made 10000 to get Tablets, specification: every slice weight 0.3g.Usage and dosage: it is oral, one time 2,2 times a day.

Embodiment 8: Rhizoma Gastrodiae 28.9g, Cortex Eucommiae (salt system) 166.2g, wild aconite root 21.7g, monkshood (system) 21.7g, Radix Angelicae Pubescentis 101.2g, rhizoma ligustici 108.4g, radix scrophulariae 108.4g, Radix Angelicae Sinensis 187.9g, glutinous rehmannia 296.3g, radix cyathulae 108.4g, mistletoe 102.4g, Rhizoma Et Radix Notopterygii 187.9g.

Embodiment 9: Rhizoma Gastrodiae 260g, Cortex Eucommiae (salt system) 137.3g, wild aconite root 7.2g, monkshood (system) 7.2g, Radix Angelicae Pubescentis 72.3g, Rhizoma ligustici 93.9g, radix scrophulariae 93.9g, Radix Angelicae Sinensis 160g, glutinous rehmannia 267.4g, radix cyathulae 93.9g, mistletoe 93.9g, Rhizoma Et Radix Notopterygii 160g.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii It extracts 6 hours, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, Huang, radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, and 3 hours for the first time, second 2 hours, combined extract, filter It crosses, filtrate is concentrated into the medical fluid that concentration containing crude drug is 1.0: 1, lets cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content up to 60%, quiet It sets 24 hours, supernatant liquid filtering is taken to obtain ethanol, merge with Rhizoma Gastrodiae alcohol extract, recycling ethyl alcohol and being concentrated into relative density is 1.05 The medicinal extract of~1.40 (60 DEG C) is spare；Taking polyethylene glycol -6000 and polyethylene glycol-4000 mixing heating melting, addition volatile oil, Medicinal extract stirs evenly, and is transferred in pill dripping machine and keeps the temperature 10 minutes in 60 DEG C, dripping pelletization, de-oiling, and low temperature drying is filling in sky In heart-soothing capsule, 1000 are made to get capsule of the present invention, specification: every dress 0.3g.Usage and dosage: it is oral, once two grains, one Day 2 times.

Embodiment 10: Rhizoma Gastrodiae 6.96kg, Cortex Eucommiae (salt system) 7.39kg, wild aconite root 0.87kg, monkshood (system) 0.87kg, Radix Angelicae Pubescentis 4.33kg, rhizoma ligustici 5.13kg, radix scrophulariae 5.13kg, Radix Angelicae Sinensis 8.7kg, glutinous rehmannia 13.91kg, radix cyathulae 5.13kg, mistletoe 5.13kg, Rhizoma Et Radix Notopterygii 8.7kg.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material steam distillation of Rhizoma Et Radix Notopterygii It extracts 6 hours, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, Huang, radix cyathulae, mistletoe merge, and 10 times of amount water is added to extract 2 times, and 3 hours for the first time, second 2 hours, combined extract, filter It crosses, filtrate is concentrated into the medical fluid that concentration containing crude drug is 1.0: 1, lets cool to room temperature, and ethyl alcohol, which is added, makes solution alcohol content up to 60%, quiet It sets 24 hours, supernatant liquid filtering is taken to obtain ethanol, merge with Rhizoma Gastrodiae alcohol extract, recycling ethyl alcohol and being concentrated into relative density is 1.05 The medicinal extract of~1.40 (60 DEG C) is spare；Taking polyethylene glycol -6000 and polyethylene glycol-4000 mixing heating melting, addition volatile oil, Medicinal extract stirs evenly, and is transferred in pill dripping machine and keeps the temperature 10 minutes in 60 DEG C, dripping pelletization, de-oiling, and low temperature drying is filling in sky In heart-soothing capsule, 50000 are made to get capsule of the present invention, specification: every dress 0.3g.Usage and dosage: it is oral, once two grains, 2 times a day.

Embodiment 11: Rhizoma Gastrodiae 139.2g, Cortex Eucommiae (salt system) 147.8g, wild aconite root 17.4g, monkshood (system) 17.4g, Radix Angelicae Pubescentis 86.8g, rhizoma ligustici 102.6g, radix scrophulariae 102.6g, Radix Angelicae Sinensis 174g, glutinous rehmannia 278.2g, radix cyathulae 102.6g, mistletoe 102.6g, Qiang 174g living.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material supercritical CO of Rhizoma Et Radix Notopterygii₂ It extracts, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, river ox Knee, mistletoe merge, and 10 times of amount water is added to extract 2 times, and 3 hours for the first time, second 2 hours, combined extract, filtration, filtrate It is concentrated into the medical fluid that concentration containing crude drug is 1.0: 1, lets cool to room temperature, is added on large pore resin absorption column, with 60% ethanol elution, Eluent is collected, is merged with Rhizoma Gastrodiae alcohol extract, ethyl alcohol is recycled and is concentrated into the medicinal extract that relative density is 1.05~1.40 (60 DEG C) It is spare；Taking polyethylene glycol -6000 and polyethylene glycol-4000 mix heating melting, and volatile oil, medicinal extract is added, stirs evenly, and shift 10 minutes are kept the temperature in 60 DEG C into pill dripping machine, dripping pelletization, de-oiling, low temperature drying is filling in Capsules, is made 50000 Grain is to get capsule of the present invention, specification: every dress 0.3g.Usage and dosage: it is oral, once two grains, 2 times a day.

Embodiment 12: Rhizoma Gastrodiae 1392g, Cortex Eucommiae (salt system) 1478g, wild aconite root 174g, monkshood (system) 174g, Radix Angelicae Pubescentis 868g, Rhizoma ligustici 1026g, radix scrophulariae 1026g, Radix Angelicae Sinensis 1740g, glutinous rehmannia 2782g, radix cyathulae 1026g, mistletoe 1026g, Rhizoma Et Radix Notopterygii 1740g.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 3 times of 30% alcohol refluxs of amount to extract 2 times, 1 hour every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material supercritical CO of Rhizoma Et Radix Notopterygii₂ It extracts, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, river ox Knee, mistletoe merge, and 12 times of amount water is added to extract 1 time, extract 4 hours, and filtration, filtrate is concentrated into the medicine that concentration containing crude drug is 2: 1 Liquid lets cool to room temperature, is added on polyamide resin column, with 80% ethanol elution, collects eluent, merges with Rhizoma Gastrodiae alcohol extract, Recycling ethyl alcohol and be concentrated into relative density be 1.05~1.40 (60 DEG C) medicinal extract it is spare；Taking polyethylene glycol -6000 and poly- second two Alcohol -4000 mixes heating melting, and volatile oil, medicinal extract is added, stirs evenly, and is transferred in pill dripping machine and keeps the temperature 10 minutes in 60 DEG C, Dripping pelletization, de-oiling, low temperature drying is filling in Capsules, is made 10000 to get capsule of the present invention, specification: every Grain dress 0.3g.Usage and dosage: it is oral, once two grains, 2 times a day.

Embodiment 13: Rhizoma Gastrodiae 1392g, Cortex Eucommiae (salt system) 1478g, wild aconite root 174g, monkshood (system) 174g, Radix Angelicae Pubescentis 868g, Rhizoma ligustici 1026g, radix scrophulariae 1026g, Radix Angelicae Sinensis 1740g, glutinous rehmannia 2782g, radix cyathulae 1026g, mistletoe 1026g, Rhizoma Et Radix Notopterygii 1740g.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 8 times of 90% alcohol refluxs of amount to extract 1 time, 4 hours every time, filtration obtained ethyl alcohol extraction Liquid is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material supercritical CO of Rhizoma Et Radix Notopterygii₂It extracts, point From it is spare to obtain volatile oil；The remaining dregs of a decoction are posted with the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, radix cyathulae, Mongolian oak Intercrescence simultaneously, adds 8 times of amount water to extract 4 times, and 1 hour every time, filtration, filtrate was concentrated into the medical fluid that concentration containing crude drug is 1: 1, let cool to Room temperature is added on polyamide resin column, with 40% ethanol elution, is collected eluent, is merged with Rhizoma Gastrodiae alcohol extract, and recycling ethyl alcohol is simultaneously It is spare to be concentrated into the medicinal extract that relative density is 1.05~1.40 (60 DEG C)；Taking polyethylene glycol -6000 and polyethylene glycol-4000 mix Heating melting is added volatile oil, medicinal extract, stirs evenly, and is transferred in pill dripping machine and keeps the temperature 10 minutes in 60 DEG C, and dripping pelletization takes off Oil, low temperature drying is filling in Capsules, is made 10000 to get capsule of the present invention, specification: every dress 0.3g.With Method dosage: it is oral, once two grains, 2 times a day.

Embodiment 14: Rhizoma Gastrodiae 139.2g, Cortex Eucommiae (salt system) 147.8g, wild aconite root 17.4g, monkshood (system) 17.4g, Radix Angelicae Pubescentis 86.8g, rhizoma ligustici 102.6g, radix scrophulariae 102.6g, Radix Angelicae Sinensis 174g, glutinous rehmannia 278.2g, radix cyathulae 102.6g, mistletoe 102.6g, Qiang 174g living.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration, filtrate Recycling ethyl alcohol is simultaneously concentrated into the medicinal extract that relative density is 1.05~1.40 (60 DEG C), and it is spare to obtain Rhizoma Gastrodiae alcohol-extracted extract, remaining Rhizoma Gastrodiae The dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material supercritical CO of Rhizoma Et Radix Notopterygii₂It extracts, it is standby to obtain volatile oil for separation With；The remaining dregs of a decoction merge with the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, radix cyathulae, mistletoe, add 10 times It measures water to extract 2 times, 3 hours for the first time, second 2 hours, combined extract, filtration, filtrate is filtered by ceramic membrane separation, received Collect filtered fluid, it is spare that filter is concentrated into the medicinal extract that relative density is 1.05~1.40 (60 DEG C)；Taking polyethylene glycol -6000 and poly- second two Alcohol -4000 mixes heating melting, and volatile oil, medicinal extract is added, stirs evenly, and is transferred in pill dripping machine and keeps the temperature 10 minutes in 60 DEG C, Dripping pelletization, de-oiling, low temperature drying is filling in Capsules, is made 1000 to get capsule of the present invention, specification: every Fill 0.3g.Usage and dosage: it is oral, once two grains, 2 times a day.

Embodiment 15: Rhizoma Gastrodiae 1392g, Cortex Eucommiae (salt system) 1478g, wild aconite root 174g, monkshood (system) 174g, Radix Angelicae Pubescentis 868g, Rhizoma ligustici 1026g, radix scrophulariae 1026g, Radix Angelicae Sinensis 1740g, glutinous rehmannia 2782g, radix cyathulae 1026g, mistletoe 1026g, Rhizoma Et Radix Notopterygii 1740g.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration, filtrate Recycling ethyl alcohol is simultaneously concentrated into the medicinal extract that relative density is 1.05~1.40 (60 DEG C), and it is spare to obtain Rhizoma Gastrodiae alcohol-extracted extract, remaining Rhizoma Gastrodiae The dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material supercritical CO of Rhizoma Et Radix Notopterygii₂It extracts, it is standby to obtain volatile oil for separation With；The remaining dregs of a decoction merge with the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, radix cyathulae, mistletoe, add 10 times It measures water to extract 2 times, 3 hours for the first time, second 2 hours, combined extract, filtration, filtrate is filtered by ceramic membrane separation, received Collect filtered fluid, it is spare that filter is concentrated into the medicinal extract that relative density is 1.05~1.40 (60 DEG C)；Taking polyethylene glycol -6000 and poly- second two Alcohol -4000 mixes heating melting, and volatile oil, medicinal extract is added, stirs evenly, and is transferred in pill dripping machine and keeps the temperature 10 minutes in 60 DEG C, Dripping pelletization, de-oiling, low temperature drying is filling in Capsules, is made 10000 to get capsule of the present invention, specification: every Grain dress 0.3g.Usage and dosage: it is oral, once two grains, 2 times a day.

Rhizoma Gastrodiae raw medicinal material is weighed, adds 5 times of 50% alcohol refluxs of amount to extract 3 times, 2 hours every time, merges, filtration obtains second Alcohol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material supercritical CO of Rhizoma Et Radix Notopterygii₂ It extracts, it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and the Rhizoma Gastrodiae dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, river ox Knee, mistletoe merge, and 10 times of amount water is added to extract 2 times, and 3 hours for the first time, second 2 hours, combined extract, filtration, filtrate It is concentrated into the medical fluid that concentration containing crude drug is 1: 1, lets cool to room temperature, is added on large pore resin absorption column, with 60% ethanol elution, is received Collect eluent, merge with Rhizoma Gastrodiae alcohol extract, recycle ethyl alcohol and be concentrated into the medicinal extract that relative density is 1.05~1.40 (60 DEG C), does It is dry, it is ground into fine powder, right amount of auxiliary materials is added, grinds well, is pressed into 10000, obtain soft capsule of the present invention, specification: every dress 0.25g.Usage and dosage: it is oral, once two grains, 2 times a day.

Claims

1. a kind of preparation method for preventing and treating cerebrovascular disease medicament preparation, the Chinese medicine material of the pharmaceutical preparation is by weight percentage Are as follows: Rhizoma Gastrodiae 9.6%, Cortex Eucommiae processed 10.3%, wild aconite root 1.2%, radix aconiti lateralis preparata 1.2%, Radix Angelicae Pubescentis 6.0%, rhizoma ligustici 7.1%, radix scrophulariae 7.1%, Radix Angelicae Sinensis 12.0%, glutinous rehmannia 19.3%, radix cyathulae 7.1%, mistletoe 7.1%, Rhizoma Et Radix Notopterygii 12.0%；It is characterized by:

The method that above-mentioned Chinese medicine material is prepared into pharmaceutical preparation are as follows: weigh Rhizoma Gastrodiae raw medicinal material, add 5 times of 50% alcohol refluxs of amount It extracts 3 times, 2 hours every time, merges, filtration obtains that ethanol extract is spare, and the remaining Rhizoma Gastrodiae dregs of a decoction are spare；Weigh Radix Angelicae Pubescentis, rhizoma ligustici, Radix Angelicae Sinensis, four taste raw medicinal material of Rhizoma Et Radix Notopterygii are extracted 6 hours with steam distillation, and it is spare to obtain volatile oil for separation；The remaining dregs of a decoction and Rhizoma Gastrodiae The dregs of a decoction, Cortex Eucommiae processed, wild aconite root, radix aconiti lateralis preparata, radix scrophulariae, glutinous rehmannia, radix cyathulae, mistletoe merge, and add 10 times of amount water extractions 2 times, and first Secondary 3 hours, second 2 hours, combined extract filtered, and filtrate is concentrated into the medical fluid that concentration containing crude drug is 1: 1, let cool to room Temperature, ethyl alcohol, which is added, makes solution alcohol content up to 60%, stands 24 hours, supernatant liquid filtering is taken to obtain ethanol, close with Rhizoma Gastrodiae alcohol extract And recycle ethyl alcohol and be concentrated into the medicinal extract that 60 DEG C of relative densities are 1.05~1.40, merge volatile oil, adds auxiliary material by normal Different pharmaceutical preparations is made in rule preparation process.