CN1935197A - Medicinal composition and its preparing method - Google Patents

Abstract

The present invention relates to a medicine composition for curinge angiocardiopathy and cerebrovascular diseases and its preparation method. The prescription of said medicine composition is formed from ginseng total saponin (or ginseng stem and leaf saponin) and red peony (or white peony) or its extract, said medicine composition can be made into injection preparation and various oral preparations. Said medicine preparation is mainly used for curing the diseases of coronary heart disease, angina pectoris and myocardial ischemia, etc.

Description

A kind of pharmaceutical composition and preparation method thereof

Technical field

The present invention relates to a kind of pharmaceutical composition that is used for the treatment of cardiovascular and cerebrovascular disease, the preparation method of said composition is provided simultaneously, belong to technical field of medicaments.

Technical background

Cardiovascular and cerebrovascular disease is first of current serious threat human life and the healthy major disease, has become first and second cause of death of world's most countries, and it not only has very high fatality rate, and causes patient's disability rate also high after its morbidity.There is 2,600,000 people every year in China because of cardiovascular and cerebrovascular disease death at present, and therefore plant disease and death with regard to 1 people is arranged per 12 seconds, and wherein coronary heart disease ranks first.It is reported that coronary heart disease has become the important diseases that threatens public's life and health, China dies from the number of various coronary heart disease every year and estimates to surpass 1,000,000.One studies show that, in 10 years, China's males with coronary disease sickness rate will increase by 26.1%, and the women will increase by 19.0%.And the evidence of coronary heart diseases mortality rate is still in rapid rising.At present, the nitrate preparations of clinical Western medicine that is used for coronary heart disease treatment such as nitroglycerin, sorbitrate, 5-single nitric acid sorbitol etc.; Adrenergic such as Propranolol, oxprenolol, alprenolol, pindolol, metoprolol; Calcium channel blocker such as verapamil, nifedipine, diltiazem; Antiplatelet drug such as aspirin, dipyridamole, benzene sulphur azoles sulphur; Adjust hypolipidemic medicine such as nicotinic acid, pravastatin, lovastatin; Thrombolytic agent such as warfarin, heparin, urokinase, streptokinase; But find in the medication process that this type of medicine can be alleviated acute symptom, but the cause of disease is still lacked effective treatment means, and with certain toxic and side effects; And Chinese medicine such as FUFANG DANSHEN DIWAN, FUFANG DANSHEN PIAN, SUXIAO JIUXIN WAN, Heart pill of Musk etc. have demonstrated certain advantage, but it is low to exist bioavailability mostly, and onset is slow, prescription complexity, drawback such as dose is big.So develop prevention and treatment cardiovascular and cerebrovascular disease especially treating coronary heart disease and angina pectoris become the serious and difficult task of pendulum in face of ours.

Coronary heart disease is a kind of because coronary artery stationarity (atheroma sclerosis) or dynamic property (vasospasm) pathological changes, cause the narrow even obstruction of vessel lumen, cause that the myocardial oxygen need are unbalance and cause myocardial ischemia-anoxemia or downright bad a kind of heart disease, also claim ischemic heart desease.Coronary heart disease belongs to categories such as the traditional Chinese medical science " thoracic obstruction ", " pained ", " angina pectoris ", the traditional Chinese medical science thinks that the pathogenesis of coronary heart disease is a deficiency in origin and excess in superficiality, so-called deficiency in origin mainly refers to the void thanks to of the heart, spleen, kidney yin kidney yang QI and blood, the real mainly finger of the so-called mark stagnation of QI, blood stasis, turbid, the YIN-cold of expectorant.So according to the pathogenesis of coronary heart disease deficiency in origin and excess in superficiality. nourishing-to-relaxing is emphasized in treatment by Chinese herbs, and the invigorating middle warmer residence is logical, and through-supplementation is conceived to the adjusting of allomeric function, and reaching gas, to be full of blood capable, the blood vessels tonneau.Simultaneously compare Chinese medicine coronary heart disease with Western medicine, have following advantage: toxic and side effects is less relatively, is suitable for prolonged application; Can act on a plurality of pathology links; To improve that the patient follows as breathe hard, symptom such as weak, spirit depressing and sexual hypofunction is comparatively obvious; Clinical and experimentation shows that Chinese medicine coronary heart disease has coronary artery dilator, improves myocardial ischemia, suppresses platelet aggregation, improves effects such as patient moving ability and quality of life.So, defective that exists at prior art and Chinese medicine excavate motherland's medical treasure-house in the unique advantage of such disease of treatment, and it is capable and vigorous to seek a kind of prescription, determined curative effect, the pure Chinese medicinal preparation that is used for the treatment of as cardiovascular and cerebrovascular diseases such as angina pectoris that has no side effect just seems very urgent.

Summary of the invention

The objective of the invention is to disclose a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease, adopt the preparation that Radix Ginseng total saponins and Radix Paeoniae Rubra (or Radix Paeoniae Alba) or its extract formula are made to be needed; The traditional Chinese medical science thinks that the generation of coronary heart disease is many, and function is deficient because worn with age, yin and yang qi and blood disorder, and the influence of seven emotions six climate exopathogens causes qi depression to blood stasis in addition, and hypofunction of YANG QI in chest is given birth in expectorant is turbid, makes blockage of the cardiac vessels, stagnation of QI and blood may bring about pain.In view of the above as can be known, blood stasis due to qi deficiency be coronary heart disease main diseases because of.According to the pathogenesis of coronary heart disease deficiency in origin and excess in superficiality, nourishing-to-relaxing is emphasized in treatment by Chinese herbs, and invigorating middle warmer residence is logical, and through-supplementation is conceived to the adjusting of allomeric function, and reaching gas, to be full of blood capable, the blood vessels tonneau.Modern pharmacological research shows, Radix Ginseng total saponins has pharmacological action widely: at cardio-cerebrovascular, can reduce the arterial pressure resistance, decreased heart rate, strengthen myocardial hypoxia tolerance, supraventricular tachycardia threshold value due to the rising intracardiac electrode pace-making, significantly improve cardiac muscle to anoxybiotic tolerance, arrhythmia, reduce blood cholesterol, coronary artery dilating increases effects such as coronary blood flow, antiplatelet aggregation, and the old friend joins total saponins has certain preventive and therapeutic effect to common Senile disease such as hypertension, atherosclerosis, coronary heart disease; Simultaneously Radix Ginseng total saponins also has antitumor action, immunoregulation effect, and adaptogen prevents the effect of cell ageing, improves old people's immunologic function, strengthens body antiserum shock, alleviates effects such as old people's fatigue and hypomnesis; Radix Paeoniae Rubra has the animal of increasing coronary flow, anti-platelet aggregation, antithrombotic formation, atherosclerosis, anti-experimental character myocardial ischemia, microcirculation improvement and reduces the portal hypertension effect; rat neurocyte cerebral ischemia sample is damaged; significant protective effect is all arranged; the clinical premonitory apoplexy, cerebral infarction, acute cerebral thrombosis of being used for the treatment of forms; two medicines share, and have strengthened the effect of blood circulation promoting and blood stasis dispelling.The results of pharmacodynamic test of prescription proportioning shows that Radix Ginseng total saponins and Radix Paeoniae Rubra (or Radix Paeoniae Alba) or its extract share, and have stronger physiologically active.Another object of the present invention is to disclose the preparation of drug combination method of this treatment cardiovascular and cerebrovascular disease, comprise multiple injection type and peroral dosage form, effectively avoid the single inconvenience that brings of dosage form of present doctors and patients' medication, satisfied the selection of clinician and extensive patients to a greater degree.

Preparation of the present invention is to constitute like this: calculate according to components by weight percent, it by 10～10000 parts of 0.1～50 part of Radix Ginseng total saponins and Radix Paeoniae Rubra through extracting refining forming; Or the Radix Paeoniae Rubra extract that is obtained after extracting by corresponding weight portion Radix Ginseng total saponins and corresponding weight portion Radix Paeoniae Rubra medical material is made.Specifically, calculate according to components by weight percent, it by 100～5000 parts of 1～30 part of Radix Ginseng total saponins and Radix Paeoniae Rubra through extracting refining forming; Or the Radix Paeoniae Rubra extract that is obtained after extracting by corresponding weight portion Radix Ginseng total saponins and corresponding weight portion Radix Paeoniae Rubra medical material is made.More specifically say, calculate according to parts by weight, it by 1000～3000 parts of 8～20 parts of Radix Ginseng total saponinss and Radix Paeoniae Rubra through extracting refining forming; Or the Radix Paeoniae Rubra extract that is obtained after extracting by corresponding weight portion Radix Ginseng total saponins and corresponding weight portion Radix Paeoniae Rubra medical material is made.

Preparation of the present invention is injection and oral formulations; Injection comprises: be directly used in drug administration by injection injection, need to be used for the concentrated solution for injection of intravenous drip after the dilution, directly for the venous transfusion of intravenous drip and injectable sterile powder and the aseptic block that makes with freeze-drying or spray drying method; Oral formulations comprises: all acceptable dosage forms on tablet, dispersible tablet, effervescent tablet, oral cavity disintegration tablet, capsule, soft capsule, microcapsule, granule, pill, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, soft extract, extractum, gel, membrane and other pharmaceuticss.Preferred preparation is the injection that is directly used in drug administration by injection, need to be used for the concentrated solution for injection of intravenous drip after the dilution, directly for the venous transfusion of intravenous drip and injectable sterile powder and aseptic block, drop pill, capsule, soft capsule, oral cavity disintegration tablet, tablet, pellet, dispersible tablet or the granule that makes with freeze-drying or spray drying method.

Described pharmaceutical composition calculates according to percentage by weight, and wherein the content of Radix Ginseng total saponins is not less than 1% of the total solid after the deduction adjuvant amount and water quantities in the preparation; Content of paeoniflorin is not less than in the preparation 0.1% of total solid after deduction adjuvant amount and the water quantities; Radix Ginseng total saponins in the injection, all can be surveyed the component content sum and are not less than 25% of the total solid after the deduction adjuvant amount and water quantities in the preparation to derive from the glycoside composition of Radix Paeoniae Rubra and other.

Described preparation of drug combination method is: get Radix Paeoniae Rubra, add entry or ethanol extraction, the extracting solution concentrate drying gets the Radix Paeoniae Rubra crude extract, or further adopt water precipitating, precipitate with ethanol, organic solvent extractionprocess, flocculent precipitation, column chromatography one or more unite use carry out suitably refining, get the Radix Paeoniae Rubra extract, with Radix Paeoniae Rubra crude extract or extract and Radix Ginseng total saponins mixing, add adjuvant and be prepared into different preparations with diverse ways.Specifically, get Radix Paeoniae Rubra, add alcohol reflux 1～5 time, merge extractive liquid,, concentrated, add water dissolution, leave standstill, filter, concentrate, or further adopt macroporous resin to carry out purification, concentrate the dry Radix Paeoniae Rubra extract that gets; With Radix Paeoniae Rubra extract and Radix Ginseng total saponins mix homogeneously, add adjuvant and be prepared into different preparations with diverse ways.

Described injection is like this preparation: get Radix Paeoniae Rubra and add 5～15 times of 40～80% alcohol reflux 1～5 time, each 0.5～4 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 1～5 times of water dissolution, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.3～1ml/g medical material .min, use 1～10 times of resinite hydrops and 1～6 times of resin volume 5～15% alcohol flushing impurity successively, use 40～80% alcohol desorptions of 1～7 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, reclaiming and measuring relative density when ethanol is concentrated into 60 ℃ is 1.05～1.15, the dry Radix Paeoniae Rubra extract that gets; With Radix Paeoniae Rubra extract and Radix Ginseng total saponins mix homogeneously, add adjuvant and be prepared into various injections with diverse ways.

Described Injectable sterile block is preparation like this: get Radix Paeoniae Rubra and add 10 times of amount 70% alcohol reflux 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 3 times of water dissolutioies, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 5 times of resinite hydrops and 3 times of resin volume 10% alcohol flushing impurity successively, use 60% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, reclaiming and measuring relative density when ethanol is concentrated into 60 ℃ is 1.05～1.15, the dry Radix Paeoniae Rubra extract that gets; With Radix Paeoniae Rubra extract and Radix Ginseng total saponins mix homogeneously, add the injection blunge make it the dissolving, boil the needle-use activated carbon that the back adds 0.2% (W/V), keep little and boiled 20 minutes, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 6.0～7.5, boil, coarse filtration, fine straining are spent the night in cold preservation (4 ℃); Injection mannitol is added the injection water be mixed with 120mg/ml solution, with above-mentioned filtrate mixing, coarse filtration, fine straining, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and in 12～72 hours differential gradient increased temperature to 10 ℃ progressively, keep 2h, be warming up to 20 ℃, keep 2h, promptly.

The adjuvant that is adopted in the preparation comprises mannitol, galactose, glycine, glucose, sodium chloride, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, sorbitol, tween, poloxamer, dextrin, starch, polyvinylpolypyrrolidone PVPP, CMC-Na, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, the Radix Glycyrrhizae charcoal, stevioside, vegetable oil, soybean oil, sorbitol, Pulvis Talci, Cera Flava, modified starch, magnesium stearate, dimethicone, in the liquid paraffin one or more.

The Radix Paeoniae Rubra extract that the present invention relates to can also be commercially available or adopt other preparation methoies to prepare; Radix Paeoniae Rubra and extract thereof can also be the Radix Paeoniae Alba and the extracts thereof of same ratio.

Described pharmaceutical composition tool is mainly used in cardiovascular and cerebrovascular diseases such as treatment coronary heart disease, angina pectoris, myocardial ischemia.

Compared with prior art, the present invention adopts the extract Radix Ginseng total saponins to be used as medicine, studies show that Radix Ginseng total saponins mainly be applicable to coronary heart disease, angina pectoris, bradycardia, too fast, ventricular premature contraction, disorder of blood pressure, neurasthenia, climacteric syndrome, overfatigue, after being ill, puerperal, postoperative physical weakness etc. symptom, for a long time clothes can life lengthening, and energy physical strength reinforcing, the diseases such as immunologic hypofunction that the treatment cancer patient causes because of radiation and chemotherapy, and the cold-and-heat resistent stress is arranged; Be equipped with to have and invigorate blood circulation, the Radix Paeoniae Rubra of eliminating stasis to stop pain function, cardiovascular and cerebrovascular diseases such as its treatment coronary heart disease, angina pectoris have been strengthened, directly be used as medicine simultaneously with Radix Ginseng total saponins, have the early development less investment, advantage with high content of technology, that added value of product is big, and then can make the preparation of high crude drug amount-preparation ratio, promoted product specification, for the cardiovascular and cerebrovascular disease patient particularly the angina pectoris patient brought new dawn.

The applicant has carried out following experiment, proves the effectiveness of medicine of the present invention.

Experimental example 1: medicament composing prescription experimental study

The research of table 1 prescription pharmacodynamics test

Pilot project	The Radix Ginseng total saponins group	The Radix Paeoniae Rubra group	Of the present invention group
				Myocardial ischemia test due to the dog coronary artery ligation method	Effect is obvious	Effect is obvious	Effect strengthens
Cardiac function and hemodynamics test	Partial action is obvious, and partial action is not obvious	Effect is general	Effect strengthens
				The myocardial oxygen consumption test	Effect is obvious	Effect is general	Effect strengthens
The coronary circulation test	Effect is obvious	Effect is obvious	Effect strengthens
				The blood circulation promoting and blood stasis dispelling test	Effect is general	Effect is obvious	Effect strengthens
To the mice hypoxia endurance test	Effect is obvious	Effect is general	Effect strengthens

Show by table 1 drug efficacy study; after the two herbal medicine use in conjunction; the obvious synergistic synergistic function is arranged aspect blood circulation promoting and blood stasis dispelling; aspect the treatment cardiac-cerebral ischemia obvious synergistic effect is being arranged also; can obviously increase the increase of blood flow coronarius, antagonism myocardial oxygen consumption; improve the blood flow index, thus the better protection ischemic myocardium.

Experimental example 2: technical study

(1) Radix Paeoniae Rubra extracts solvent research

Getting the Radix Paeoniae Rubra fine powder, use 90% ethanol, 70% ethanol, 50% ethanol and 30% alcohol reflux respectively, is evaluation index with the paeoniflorin content.The results are shown in Table 2.

Table 2 different solvents extraction process relatively

Paeoniflorin content (%) meansigma methods

Extract solvent

1 2 3 4 (％)

90% ethanol 7.15 7.21 7.32 7.28 7.24

70% ethanol 7.31 7.29 7.33 7.36 7.32

50% ethanol 7.01 7.08 7.05 7.12 7.06

30% ethanol 6.35 6.28 6.38 6.26 6.31

As shown in Table 2, extract aqueous solvent and ethanol and all the most of glycoside composition in the Radix Paeoniae Rubra can be extracted, when still using 70% ethanol extraction by contrast, the glycoside component content is the highest, but concentration of alcohol is little from 50～90% content difference, determines that therefore 70% ethanol is the optimum solvent that extracts.

The different backflow number of times of table 3 gained extractum paeoniflorin content

Sequence number	Extract 1 extraction ratio (%)	Extract 2 extraction ratios (%)	Extract 3 extraction ratios (%)	Extract 4 extraction ratios (%)
					1	48.52	68.35	77.96	82.45
2	52.18	72.55	83.62	85.74
					3	50.49	71.68	81.25	84.37
Meansigma methods (%)	50.40	70.86	80.94	84.19

As shown in Table 3, extraction time has certain influence to content of paeoniflorin in the Radix Paeoniae Rubra, all can extract effective ingredient to some extent but extract 1～4 time, but it is very little to extract the amplitude that the peoniflorin extraction ratio raises after 3 times, consider production cost, so preferred extraction is best number of times 3 times.

Table 4 different extraction times influence the peoniflorin extraction ratio

Extraction time (h)	0.5	1	1.5	2	2.5
						Peoniflorin extraction ratio (%)	68.78	75.68	84.26	86.43	87.68

As shown in Table 4, there is certain influence extraction time to content of paeoniflorin in the Radix Paeoniae Rubra, but all is in higher at 0.5～2.5h peoniflorin extraction ratio, experiment is found, extract 1.5h paeoniflorin content substantially constant, consider man-hour and extraction ratio, preferred 1.5h is optimum extraction time.

Table 5 solvent load is investigated table as a result

Solvent load (doubly) peoniflorin extraction ratio

Tested number

The second time first time is (%) for the third time

1 8 8 8 82.25

2 10 10 10 84.68

3 13 13 13 86.95

4 13 10 10 85.11

5 13 10 8 83.77

6 10 10 8 83.15

7 10 8 8 82.58

As shown in Table 5: the peoniflorin extraction ratio was the highest when quantity of solvent was 13,13,13 times; The peoniflorin extraction ratio was minimum when quantity of solvent was 8,8,8 times of amounts; But take all factors into consideration solvent load, extraction ratio and energy resource consumption, guaranteeing in order to save cost, to determine that quantity of solvent is that each 10 times of amounts are optimum extraction condition under the sufficient prerequisite of extracts active ingredients.

(2) process for refining research

The applicant has carried out the different model macroporous adsorbent resin to the research of Radix Paeoniae Rubra total glycosides than adsorbance.

The comparison of process for purification: the butanol extraction liquid method: precision is measured Radix Paeoniae Rubra extract, extracts 4 times with water saturated n-butyl alcohol jolting, merges n-butyl alcohol liquid, and evaporate to dryness, residue add methanol makes dissolving; The Amberlyst process precision is measured the Radix Paeoniae Rubra extracting solution, be added on the ZTC-1 type resin column of having handled well, after the water flushing, reuse 65% ethanol elution, collect eluent to effluent colourless till.The results are shown in Table 6.

The screening of table 6 process for purification

Process for purification paeoniflorin content %

N-butanol extraction 52.86

Macroporous adsorbent resin method 70.58

As can be seen from Table 6, select macroporous resin extraction rate height.

The screening of table 7 resin model

Peoniflorin percentage ratio (%) in the resin model adsorbent solution

D101 50.23

ZTC-1 70.26

AB-8 40.68

Table 7 shows: comparatively speaking, ZTC-1 type resin is bigger to the adsorbance of peoniflorin, so we determine with ZTC-1 type resin to be optimal case.

Experimental example 3: injection technical study

(1) pH value of solution is investigated

For adapting to the Human Physiology needs, consider the character of each constituents in the medicinal liquid simultaneously, the applicant has investigated the pH value of medicinal liquid.Select solution appearance and Radix Ginseng total saponins content, paeoniflorin content as evaluation index.

Test method and result: after feeding intake and handle by recipe quantity by above-mentioned condition, with the concentrated solution mix homogeneously, filter, add water to 1000ml, adjust pH when the different pH value that reaches shown in the following table, boils the back standing over night, the variation of observation appearance character under different pH condition, experimental result sees Table 8.

The investigation of table 8 dosing pH value (is evaluation index with the solution appearance)

Sequence number	1 2	3 4 5	6 7
				Dosing pH	5.5 6.0	6.5 7.0 7.5	8.0 8.5
Boil pH	5.0 5.6	6.2 6.8 7.3	7.8 8.2
				Outward appearance	Precipitation appears	No significant change	Color burn

Table 8 is the result show, medicinal liquid boils the back pH value and occur to precipitate at the sample 6.5 below, and pH value is obviously deepened in the color sample more than 7.5, and pH value is that 6.0～7.5 medicinal liquid is relatively stable, and outward appearance does not have significant change.Estimate from content below, the results are shown in Table 9.

The investigation of table 9 dosing pH value (is evaluation index with content)

Sequence number	Dosing pH	Radix Ginseng total saponins content (%)	Paeoniflorin content (%)	Boil back pH	Radix Ginseng total saponins content (%)	Paeoniflorin content (%)
							1	6.0	7.68	6.23	5.7	6.82	6.01
2	6.5	8.23	6.75	6.1	7.69	6.25
							3	7.0	8.89	6.95	6.7	8.31	6.47
4	7.5	9.25	7.03	7.2	9.03	6.62

As shown in Table 9, medicinal liquid is being adjusted the pH value front and back, the not too big variation of index components Radix Ginseng total saponins saponin content and paeoniflorin content.Integrated appearance and changes of contents determine that the pH value 6.0～7.5 of medicinal liquid is suitable pH value.

(2) screening of freeze-dried powder caffolding agent kind

The caffolding agent kind influences the molding of freeze-dried powder, so at first this is screened.The results are shown in Table 10.

The screening of table 10 caffolding agent kind

The caffolding agent kind	Caffolding agent: medicinal liquid (V: V)	Solubility	The finished product outward appearance
				Glucose	1∶1	Generally	Molding, the part atrophy
Sucrose	1∶1	Good	Molding, part is frangible
				Glucosan	1∶1	Generally	Molding
Poloxamer, mannitol	1∶1	Good	Molding, part is subsided
				Mannitol	1∶1	Good	Molding
Alanine	1∶1	Generally	Molding, part is subsided
				Dextran	1∶1	Generally	Molding
Mannitol, Polyethylene Glycol	1∶1	Good	Molding
				Glycine, Polyethylene Glycol	1∶1	Good	Molding, a small amount of broken
Blank medicinal liquid	3ml		Atrophy

As shown in Table 10, selected adjuvant, can molding, but investigate from the solubility angle of yield rate, molding situation and sample, use the effect of mannitol, mannitol and Polyethylene Glycol to be better than other several adjuvants, consider simultaneously to reduce as far as possible and add too much adjuvant, so optimal case is selected to use mannitol as caffolding agent separately.

Concrete embodiment

(part is a unit of weight, as ton, kilogram, gram)

Embodiment 1: 10 parts of 0.1 part of Radix Paeoniae Rubra of Radix Ginseng total saponins

Get Radix Paeoniae Rubra and add 10 times of amount 70% alcohol reflux 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 3 times of water dissolutioies, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 5 times of resinite hydrops and 3 times of resin volume 10% alcohol flushing impurity successively, use 60% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, reclaiming and measuring relative density when ethanol is concentrated into 60 ℃ is 1.05～1.15, the dry Radix Paeoniae Rubra extract that gets; With Radix Paeoniae Rubra extract and Radix Ginseng total saponins mix homogeneously, add the injection blunge make it the dissolving, boil the needle-use activated carbon that the back adds 0.2% (W/V), keep little and boiled 20 minutes, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 6.0～7.5, boil, coarse filtration, fine straining are spent the night in cold preservation (4 ℃); Injection mannitol is added the injection water be mixed with 120mg/ml solution, with above-mentioned filtrate mixing, coarse filtration, fine straining, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and in 12～72 hours differential gradient increased temperature to 10 ℃ progressively, keep 2h, be warming up to 20 ℃, keep 2h, promptly get the aseptic block of lyophilizing.After testing, the Radix Ginseng total saponins in the preparation, peoniflorin and other all can survey the composition sum and account for 38% of the total solid after the deduction adjuvant amount and water quantities in the preparation.

Embodiment 2: 100 parts of 1 part of Radix Paeoniae Rubra of Radix Ginseng total saponins

Get Radix Paeoniae Rubra and add 8 times of 80% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 3 times of water dissolutioies, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 4 times of resinite hydrops and 3 times of resin volume 8% alcohol flushing impurity successively, use 50% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Paeoniae Rubra extract adds injection and blunges and make it dissolving, and medicinal liquid is standby; Get Radix Ginseng total saponins add the injection blunge make it the dissolving, boil, between adjust pH to 5.0～7.0, medicinal liquid is standby; With above-mentioned two medicinal liquid mix homogeneously, regulating pH value is 6.0～7.5, adds 0.2% activated needle-use activated carbon, boil absorption, carbon removal, fine straining, filtrate adds the injection water to ormal weight, spend the night 4 ℃ of cold preservations, coarse filtration, fine straining divide to install in the ampoule bottle sterilization, packing promptly gets the injection with small volume or the concentrated solution for injection that are directly used in drug administration by injection.After testing, the content of Radix Ginseng total saponins accounts in the preparation 3% of total solid after deduction adjuvant amount and the water quantities; Radix Ginseng total saponins in the injection, all can be surveyed the component content sum and account for 36% of the total solid after the deduction adjuvant amount and water quantities in the preparation to derive from the glycoside composition of Radix Paeoniae Rubra and other.

Embodiment 3: 10000 parts of 50 portions of Radix Paeoniae Albas of stem and leaf of Radix Ginseng total saponins

Get the Radix Paeoniae Alba and add 12 times of 60% alcohol reflux 2 times, each 2.0 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 4 times of water dissolutioies, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.6ml/g medical material .min, use 4 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% alcohol desorption of 4 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Paeoniae Alba extract; Add injection and blunge and make it dissolving, filter filtrate for later use; Get Radix Ginseng total saponins, add the dissolving of injection water, regulate between pH value to 5.0～7.0, with above-mentioned two kinds of medicinal liquid mix homogeneously, add the glucose of ormal weight, boil, regulating pH value is 6.0～7.5, adds 0.4% activated needle-use activated carbon, boils absorption, carbon removal, fine straining is spent the night in 4 ℃ of placements, filtrate adds the injection water to ormal weight, packing, sterilization promptly gets the glucose intravenous infusion agent.

Embodiment 4: 10 parts of 50 parts of Radix Paeoniae Rubra of stem and leaf of Radix Ginseng total saponins

Get Radix Paeoniae Rubra and add 6 times of 50% alcohol reflux 5 times, each 0.5 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 5 times of water dissolutioies, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 1ml/g medical material .min, use 5 times of resinite hydrops and 3 times of resin volume 6% alcohol flushing impurity successively, use 80% alcohol desorption of 6 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Paeoniae Rubra extract; With stem and leaf of Radix Ginseng total saponins and Radix Paeoniae Rubra extract mix homogeneously, add and inject the dissolving of blunging, filter, filtrate is boiled the needle-use activated carbon of back by quality percent by volume adding 0.2%, keep little and boiled 30 minutes, cold slightly filtration, filtrate adjust pH 6.0～7.5, boil, 4 ℃ of cold preservations are spent the night, and coarse filtration, fine straining add an amount of 0.9% sodium chloride solution through boiling, be diluted to ormal weight with water for injection, promptly get the sodium chloride infusion solution

Embodiment 5: 5000 parts of 20 portions of Radix Paeoniae Albas of Radix Ginseng total saponins

Get the Radix Paeoniae Alba and add 10 times of 70% alcohol reflux 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 4 times of water dissolutioies, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.6ml/g medical material .min, use 5 times of resinite hydrops and 4 times of resin volume 8% alcohol flushing impurity successively, use 60% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the dry Radix Paeoniae Alba extract that gets adds the water for injection dissolving, and medicinal liquid is standby; Get Radix Ginseng total saponins, add the dissolving of injection water, regulate between pH5.0～7.0, medicinal liquid is standby; Above-mentioned two kinds of solution are mixed, by volume add 2% needle-use activated carbon, boil, keep little 20min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, and adjust pH 6.0～7.5 boils, and spends the night 4 ℃ of cold preservations, coarse filtration, fine straining divide to install in the enamel tray, temperature-40 ℃, pre-freeze time 10h;-35 ℃ of evacuation keep 8h; Be warming up to-30 ℃ again, keep 8h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, keep 4h; Be warming up to 0 ℃, keep 4h; Be warming up to 10 ℃, keep 2h; Be warming up to 20 ℃, keep 2h, under aseptic condition, divide to install in the cillin bottle, promptly get the freeze dry sterile powder end.After testing, content of paeoniflorin accounts in the preparation 0.2% of total solid after deduction adjuvant amount and the water quantities; Radix Ginseng total saponins, all can be surveyed the component content sum and account for 36% of the total solid after the deduction adjuvant amount and water quantities in the preparation to derive from the glycoside composition of Radix Paeoniae Rubra and other.

Embodiment 6: 100 parts of 20 parts of Radix Paeoniae Rubra of stem and leaf of Radix Ginseng total saponins

Get Radix Paeoniae Rubra and add 8 times of 80% alcohol reflux 3 times, each 1.0 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 3 times of water dissolutioies, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.7ml/g medical material .min, use 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity successively, use 65% alcohol desorption of 4 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Paeoniae Rubra extract; With Radix Paeoniae Rubra extract and Radix Ginseng total saponins mix homogeneously, add an amount of water for injection stirring and dissolving, add the needle-use activated carbon of 0.3% (W/V), boil, keep little 40min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 6.0～7.5 boils, and spends the night 5 ℃ of cold preservations, coarse filtration, fine straining, in inlet temperature is 150 ℃, and leaving air temp is 70 ℃, and air velocity is 18ms ^-1Condition under spray drying get powder, packing promptly gets the spray drying sterilized powder.

Embodiment 7: 50 parts of 8 parts of Radix Paeoniae Rubra of Radix Ginseng total saponins

Getting Radix Paeoniae Rubra adds 10 times of decoctings and boils 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add ethanol precipitate with ethanol twice, make that to contain the alcohol amount be 60% for the first time, make that to contain the alcohol amount be 80% for the second time, reclaiming and measuring relative density when ethanol is concentrated into 60 ℃ is 1.05～1.15, the dry Radix Paeoniae Rubra extract that gets; Radix Ginseng total saponins and Radix Paeoniae Rubra extract are merged, add appropriate amount of PEG-400, mix homogeneously, heating and melting stirs, and is transferred to the drop pill machine, is coolant with the liquid paraffin, drips system, collects drop pill, removes the liquid paraffin on surface, promptly gets drop pill.After testing, the content of Radix Ginseng total saponins accounts in the preparation 4.12% of total solid after deduction adjuvant amount and the water quantities.

Embodiment 8: 1000 parts of 15 portions of Radix Paeoniae Albas of stem and leaf of Radix Ginseng total saponins

Get the Radix Paeoniae Alba, add 10 times of decoctings and boil 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 50 ℃ is 1.35～1.40, with Radix Paeoniae Alba extract and stem and leaf of Radix Ginseng total saponins mixing, make soft material, drying is ground into fine powder, add stevioside and starch is an amount of, mixing is used 65% alcohol granulation, drying, encapsulated, promptly get capsule.

Embodiment 9: 10 parts of 50 parts of Radix Paeoniae Alba extracts of stem and leaf of Radix Ginseng total saponins

With stem and leaf of Radix Ginseng total saponins and Radix Paeoniae Alba extract mixing, add the vegetable oil of 0.8 times of medicated powder weight and 3% Cera Flava, the dropping preparation method pill, compacting promptly gets soft capsule.After testing: content of paeoniflorin accounts in the preparation 0.25% of total solid after deduction adjuvant amount and the water quantities;

Embodiment 10: 20 parts of 30 parts of Radix Paeoniae Rubra extracts of Radix Ginseng total saponins

With Radix Ginseng total saponins and Radix Paeoniae Rubra extract mix homogeneously, be ground into fine powder, adding MCC and hydroxypropyl starch are an amount of, and tabletting promptly gets oral cavity disintegration tablet.

Embodiment 11: 3000 parts of 1 portion of Radix Paeoniae Albas of Radix Ginseng total saponins

Getting the Radix Paeoniae Alba adds 10 times of decoctings and boils 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.35～1.40, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 80% for the second time, reclaiming and measuring relative density when ethanol is concentrated into 60 ℃ is 1.35～1.40, make soft material, drying is ground into fine powder, sieves, add above-mentioned Radix Ginseng total saponins mix homogeneously, it is an amount of to add stevioside and starch, and mixing is granulated, dry, tabletting, coating promptly gets tablet.

Embodiment 12: 5000 parts of 28 parts of Radix Paeoniae Rubra of Radix Ginseng total saponins

Get Radix Paeoniae Rubra and add 10 times of 70% alcohol reflux 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds 4 times of water dissolutioies, filters, concentrate, drying is pulverized, add Radix Ginseng total saponins, add The addition of C MC-Na and low-substituted hydroxypropyl cellulose mixing, it is moistening to add 75% ethanol, system material, granulate, tabletting promptly gets dispersible tablet.

Embodiment 13: 10000 parts of 0.1 part of Radix Paeoniae Rubra of stem and leaf of Radix Ginseng total saponins leaf

Get Radix Paeoniae Rubra and add 10 times of decoctings and boil 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 60% for the first time, make for the second time that to contain the alcohol amount be 80%, reclaiming and measuring relative density when ethanol is concentrated into 60 ℃ is 1.05～1.15, drying, pulverize, add above-mentioned stem and leaf of Radix Ginseng total saponins, mixing, add 30% ethanol, the spheronization pill promptly gets pellet.

Embodiment 14: 10 parts of 50 portions of Radix Paeoniae Albas of Radix Ginseng total saponins

Get the Radix Paeoniae Alba and add 8 times of 80% alcohol reflux 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds 3 times of water dissolutioies, filters, concentrate, the dry Radix Paeoniae Alba extract that gets is with Radix Ginseng total saponins and Radix Paeoniae Alba extract mixing, the system soft material, drying is ground into fine powder, add stevioside and starch is an amount of, mixing is granulated, drying promptly gets granule.

Claims (13)

1, a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease is characterized in that: calculate according to components by weight percent, it by 10～10000 parts of 0.1～50 part of Radix Ginseng total saponins and Radix Paeoniae Rubra through extracting refining forming; Or the Radix Paeoniae Rubra extract that is obtained after extracting by corresponding weight portion Radix Ginseng total saponins and corresponding weight portion Radix Paeoniae Rubra medical material is made.

2, according to the pharmaceutical composition of the described treatment cardiovascular and cerebrovascular disease of claim 1, it is characterized in that: calculate according to components by weight percent, it by 100～5000 parts of 1～30 part of Radix Ginseng total saponins and Radix Paeoniae Rubra through extracting refining forming; Or the Radix Paeoniae Rubra extract that is obtained after extracting by corresponding weight portion Radix Ginseng total saponins and corresponding weight portion Radix Paeoniae Rubra medical material is made.

3, according to the pharmaceutical composition of claim 1 or 2 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: calculate according to parts by weight, it by 1000～3000 parts of 8～20 parts of Radix Ginseng total saponinss and Radix Paeoniae Rubra through extracting refining forming; Or the Radix Paeoniae Rubra extract that is obtained after extracting by corresponding weight portion Radix Ginseng total saponins and corresponding weight portion Radix Paeoniae Rubra medical material is made.

4, according to the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease of claim 1～3, it is characterized in that: preparation of the present invention is injection and oral formulations; Injection comprises: be directly used in drug administration by injection injection, need to be used for the concentrated solution for injection of intravenous drip after the dilution, directly for the venous transfusion of intravenous drip and injectable sterile powder and the aseptic block that makes with freeze-drying or spray drying method; Oral formulations comprises: all acceptable dosage forms on tablet, dispersible tablet, effervescent tablet, oral cavity disintegration tablet, capsule, soft capsule, microcapsule, granule, pill, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, soft extract, extractum, gel, membrane and other pharmaceuticss.

5, according to the pharmaceutical composition of the described treatment cardiovascular and cerebrovascular disease of claim 4, it is characterized in that: preparation of the present invention is the injection that is directly used in drug administration by injection, need to be used for the concentrated solution for injection of intravenous drip after the dilution, directly for the venous transfusion of intravenous drip and injectable sterile powder and aseptic block, drop pill, capsule, soft capsule, oral cavity disintegration tablet, tablet, pellet, dispersible tablet or the granule that makes with freeze-drying or spray drying method.

6, according to the pharmaceutical composition of claim 4 or 5 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: calculate according to percentage by weight, wherein the content of Radix Ginseng total saponins is not less than 1% of the total solid after the deduction adjuvant amount and water quantities in the preparation; Content of paeoniflorin is not less than in the preparation 0.1% of total solid after deduction adjuvant amount and the water quantities; Radix Ginseng total saponins in the injection, all can be surveyed the component content sum and are not less than 25% of the total solid after the deduction adjuvant amount and water quantities in the preparation to derive from the glycoside composition of Radix Paeoniae Rubra and other.

7, according to the preparation of drug combination method of claim 4 or 5 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Radix Paeoniae Rubra, add entry or ethanol extraction, the extracting solution concentrate drying gets the Radix Paeoniae Rubra crude extract, or further adopt water precipitating, precipitate with ethanol, organic solvent extractionprocess, flocculent precipitation, column chromatography one or more unite use carry out suitably refining, get the Radix Paeoniae Rubra extract, with Radix Paeoniae Rubra crude extract or extract and Radix Ginseng total saponins mixing, add adjuvant and be prepared into different preparations with diverse ways.

8, according to the preparation of drug combination method of the described treatment cardiovascular and cerebrovascular disease of claim 7, it is characterized in that: get Radix Paeoniae Rubra, add alcohol reflux 1～5 time, merge extractive liquid,, concentrate, add water dissolution, leave standstill, filter, concentrate, or further adopt macroporous resin to carry out purification, concentrate the dry Radix Paeoniae Rubra extract that gets; With Radix Paeoniae Rubra extract and Radix Ginseng total saponins mix homogeneously, add adjuvant and be prepared into different preparations with diverse ways.

9, preparation of drug combination method according to claim 7 or 8 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: injection is like this preparation: get Radix Paeoniae Rubra and add 5～15 times of 40～80% alcohol reflux 1～5 time, each 0.5～4 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 1～5 times of water dissolution, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.3～1ml/g medical material .min, use 1～10 times of resinite hydrops and 1～6 times of resin volume 5～15% alcohol flushing impurity successively, use 40～80% alcohol desorptions of 1～7 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Paeoniae Rubra extract; With Radix Paeoniae Rubra extract and Radix Ginseng total saponins mix homogeneously, add adjuvant and be prepared into various injections with diverse ways.

10, preparation of drug combination method according to any described treatment cardiovascular and cerebrovascular disease of claim 7～9, it is characterized in that: the Injectable sterile block is preparation like this: get Radix Paeoniae Rubra and add 10 times of amount 70% alcohol reflux 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 3 times of water dissolutioies, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 5 times of resinite hydrops and 3 times of resin volume 10% alcohol flushing impurity successively, use 60% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, reclaiming and measuring relative density when ethanol is concentrated into 60 ℃ is 1.05～1.15, the dry Radix Paeoniae Rubra extract that gets; With Radix Paeoniae Rubra extract and Radix Ginseng total saponins mix homogeneously, add the injection blunge make it the dissolving, boil the needle-use activated carbon that the back adds 0.2% (W/V), keep little and boiled 20 minutes, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 6.0～7.5, boil, coarse filtration, fine straining are spent the night in cold preservation (4 ℃); Injection mannitol is added the injection water be mixed with 120mg/ml solution, with above-mentioned filtrate mixing, coarse filtration, fine straining, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and in 12～72 hours differential gradient increased temperature to 10 ℃ progressively, keep 2h, be warming up to 20 ℃, keep 2h, promptly.

11, according to the preparation of drug combination method of any described treatment cardiovascular and cerebrovascular disease in the claim 7～9, it is characterized in that: the adjuvant that is adopted in the preparation comprises mannitol, galactose, glycine, glucose, sodium chloride, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, sorbitol, tween, poloxamer, dextrin, starch, polyvinylpolypyrrolidone PVPP, CMC-Na, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, the Radix Glycyrrhizae charcoal, stevioside, vegetable oil, soybean oil, sorbitol, Pulvis Talci, Cera Flava, modified starch, magnesium stearate, dimethicone, in the liquid paraffin one or more.

12, according to the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease in the claim 1～3,7～10, it is characterized in that: Radix Paeoniae Rubra extract can also be commercially available or adopt other preparation methoies to prepare; Radix Paeoniae Rubra and extract thereof can also be the Radix Paeoniae Alba and the extracts thereof of same ratio.

13, according to the application of the described pharmaceutical composition of claim 1～3 in disease medicaments such as preparation treatment angina pectoris, myocardial ischemia.