CN1935148A - Medicinal composition and its preparing method - Google Patents

Abstract

The present invention relates to a medicine composition for curing angiocardiopathy and cerebrovascular disease and its preparation method. It is made up by using ginseng total saponin (or ginseng stem and leaf total saponin) and red peony total saponin (or white peony total saponin) through a certain preparation process. Said medicine composition can be made into injection preparation and oral preparation.

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.Chinese invention patent 93103012.9 in the prior art, name is called " a kind of Chinese patent medicine for the treatment of angina pectoris " and number of patent application 01131789.2, name is called " a kind of Chinese medicine and method for making thereof that is used for the treatment of coronary heart disease " and all is used as medicine with the Radix Paeoniae Alba, the Radix Paeoniae Alba is through extraction separation, behind the purification refine, content of effective still has certain difference, and the factor that influences the Chinese medicine curative effect is a lot, as breed difference, place of production difference, collecting season, medicinal part, holding conditions or the like, make that the curative effect of preparation different manufacturers of same prescription is different, for fear of this type of problem, pharmaceutical producing enterprise has been done certain work, such as height according to content of effective what and clinical integrated application degree, stipulate the input amount of different cultivars aborning, although aspect curative effect, play a role, bring very big inconvenience to production, select medicine also to bring very big inconvenience to the patient simultaneously.Just become a new focus so seek the medication of making things convenient for the people self to select of the identical curative effect zero difference of a kind of prescription.

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 Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides or Radix Paeoniae Alba total glucosides prescription to make preparation; 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.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.The main diseases of coronary heart disease is because of being blood stasis due to qi deficiency.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, 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.Studies show that Radix Ginseng total saponins has pharmacological action widely at cardiovascular system: 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, increase coronary blood flow, effects such as antiplatelet aggregation, the old friend joins total saponins to hypertension, atherosclerosis, common Senile disease such as coronary heart disease has certain preventive and therapeutic effect, and Radix Ginseng total saponins also has antitumor action simultaneously, immunoregulation effect, adaptogen prevents the effect of cell ageing, improves old people's immunologic function, strengthen body antiserum shock, alleviate effects such as old people's fatigue and hypomnesis; Radix Paeoniae Rubra total glycosides is the total extract of Radix Paeoniae Rubra; Radix Paeoniae Rubra is traditional drug for invigorating blood circulation and eliminating stasis; modern study shows; the total extract Radix Paeoniae Rubra total glycosides of Radix Paeoniae Rubra is to the effect that has clear improvement unusually of blood stasis hemorheology of rat; can increase animal coronary flow, anti-platelet aggregation, antithrombotic formation, atherosclerosis, anti-experimental character myocardial ischemia, microcirculation improvement and reduce the portal hypertension effect, damage has significant protective effect to rat neurocyte cerebral ischemia sample.The clinical cardiovascular and cerebrovascular diseases such as coronary heart disease, angina pectoris, ischemic cerebrovascular that are used for the treatment of.The results of pharmacodynamic test of prescription proportioning shows that Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides two medicines share, and preparation ginsenoside sheet has stronger physiologically active separately.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 is made for 99～1 parts by 1～99 part of Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides.Specifically, calculate according to components by weight percent, it is made for 90～10 parts by 10～90 parts of Radix Ginseng total saponinss and Radix Paeoniae Rubra total glycosides.Say that more specifically calculate according to components by weight percent, it is made for 70～30 parts by 30～70 parts of Radix Ginseng total saponinss and Radix Paeoniae Rubra total glycosides.

Preparation of the present invention is injection and oral formulations, and 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 infusion solution 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 preparation of drug combination method is that Radix Ginseng total saponins is mixed with Radix Paeoniae Rubra total glycosides, adds adjuvant and makes various preparations.

Described injection is preparation like this: take by weighing Radix Ginseng total saponins and join in a certain amount of water for injection, regulate pH value and be 5.0～7.0 and make dissolving, get Radix Paeoniae Rubra total glycosides again, add the injection blunge make it the dissolving, with above-mentioned two medicinal liquid mix homogeneously, regulating pH value is 6.0～7.5, add 0.1～2% needle-use activated carbon, boil absorption, carbon removal, fine straining, filtrate add different auxiliary material and are prepared into various injections.

Described Injectable sterile block is preparation like this: take by weighing Radix Ginseng total saponins and join in a certain amount of water for injection, regulate pH value and be 5.0～7.0 and make dissolving, get Radix Paeoniae Rubra total glycosides again, add the injection blunge make it the dissolving, with above-mentioned two solution mix homogeneously, regulating pH value is 6.0～7.5, add 0.2% activated needle-use activated carbon, boil absorption, carbon removal, fine straining, filtrate for later use; Injection mannitol is added the injection water be mixed with 100mg/ml solution,, add the injection water to ormal weight 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 comprises mannitol, galactose, glycine, glucose, glucosan, sodium chloride, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, sorbitol, tween, poloxamer, dextrin, starch, crospolyvinylpyrrolidone, carboxymethyl starch sodium, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, polyoxyethylene monostearate, polyethers 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.

Radix Ginseng total saponins that the present invention relates to and Radix Paeoniae Rubra total glycosides can be commercially available or by the following method extraction separation obtain: get Radix Ginseng or Stem and leaf of Radix Ginseng part or Radix Ginseng Rubra or Radix Codonopsis, Radix Paeoniae Rubra, add water or ethanol extraction respectively, extracting solution gets the medical material crude extract respectively through suitably concentrating, one or more that further adopt water precipitating, precipitate with ethanol, organic solvent extractionprocess, flocculent precipitation, column chromatography unite use carry out suitably refining, respectively Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides.

Described pharmaceutical composition is used for the treatment of diseases such as angina pectoris, ischemic cerebral vascular.

Compared with prior art, the present invention is used as medicine with Chinese medicine extract Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides (or Radix Paeoniae Alba total glucosides), has avoided the extraction separation that directly is used as medicine with the Chinese medicine medical material, the research of purification refine technology, directly reference is fruitful simultaneously, has shortened the R﹠D cycle, has reduced the research and development fund; Also have: raw material is had the definite quantitative index, know a kind of at least or an effective constituents; The harmful components major part is removed, thereby improves greatly in safety; The impurity that influences preparation is removed, thereby can make the preparation of high crude drug amount-preparation ratio, has promoted product specification; Pharmacology, drug effect, safety evaluatio etc. are modern system, and be international, helps advancing the modernization of Chinese medicine, the process of internationalization of tcm.Compare with Western medicine, the present invention is based on the Chinese medicine theory, still from the cause of disease of coronary heart disease deficiency in origin and excess in superficiality, be used as medicine with Chinese medicine extract, treating both the principal and secondary aspects of a disease has no side effect simultaneously, be suitable for taking for a long time, can improve the quality of living simultaneously, bring into play the advantage of Chinese medicine aspect cardiovascular and cerebrovascular disease, avoid taking for a long time the toxic and side effects and the unconspicuous deficiency of curative effect of Western medicine again.The Radix Ginseng total saponins of prescription of the present invention, Radix Paeoniae Rubra total glycosides are all comparatively sophisticated Chinese medicine extract of research such as chemical constituent, pharmacological effect or clinical practice at present, with two medicine composition of prescription, further investigate technology, the drug effect of its prescription, select for the treatment of cardiovascular and cerebrovascular disease provides new medication.Up to now, do not find the preparation of two extract compatibilities.

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

Group

Of the present invention group of Radix Ginseng total saponins group Radix Paeoniae Rubra total glycosides group

Evaluation index

Dog coronary artery ligation method institute

Effect positive effect positive effect strengthens

Cause the myocardial ischemia test

Cardiac function and blood flow partial action are obvious, portion

The general effect of effect strengthens

The effect of mechanical test branch is not obvious

The general effect of myocardial oxygen consumption test effect positive effect strengthens

Coronary circulation test effect positive effect positive effect strengthens

The general effect positive effect of blood circulation promoting and blood stasis dispelling test effect strengthens

The general effect of the general effect of mice hypoxia endurance test effect strengthens

The general effect of immunomodulating test effect positive effect strengthens

Show by table 1 drug efficacy study, after the two herbal medicine use in conjunction, aspect the treatment cardiac-cerebral ischemia obvious synergistic effect is being arranged, simultaneously can obviously increase blood flow coronarius, the increase of antagonism myocardial oxygen consumption improves the blood flow index, can also improve immunologic function simultaneously, anti-stress, and then the quality of life of obviously improving human body.

Experimental example 2: 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, Radix Ginseng total saponins content, paeoniflorin content as evaluation index.

Test method and result: after feeding intake and handle by recipe quantity,, filter with the concentrated solution mix homogeneously by described condition, add water to 1000ml, adjust pH is when the different pH value that reaches shown in the following table, boil the back standing over night, observe the variation of appearance character under different pH condition.Experimental result sees Table 2.

The investigation of table 2 dosing pH value (is evaluation index with the solution appearance)

Sequence number	1 2	3 4 5 6	7 8
				Dosing pH	5.0 5.5	6.0 6.5 7.0 7.5	8.0 8.5
Boil pH	4.6 5.1	5.6 6.2 6.8 7.3	7.8 8.2
				Outward appearance	Precipitation appears	No significant change	Color burn

Table 2 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 3.

The investigation of table 3 dosing pH value (is evaluation index with content)

Sequence number	Dosing pH	Radix Ginseng total saponins content (%)	Boil back pH	Radix Ginseng total saponins content (%)
					1	6.0	16.82	5.5	15.96
2	6.5	17.21	6.1	16.59
					3	7.0	17.64	6.7	17.05
4	7.5	17.28	7.1	16.84

As shown in Table 3, medicinal liquid is being adjusted the pH value front and back, the not too big variation of index components Radix Ginseng total saponins content and paeoniflorin content.The appearance character of comprehensive above-mentioned medicinal liquid and changes of contents, the pH value of medicinal liquid is transferred between 6.0～7.5 when determining dosing.

(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 4.

The screening of table 4 caffolding agent kind

The caffolding agent kind	Caffolding agent: medicinal liquid (V: V)	Solubility	The finished product outward appearance
				Mannitol	3∶2	Good	Molding
Galactose	3∶2	Generally	Molding, a small amount of atrophy
				Glycine	3∶2	Generally	Molding, the part atrophy
Glucose	3∶2	Good	Molding, part is frangible
				Dextran	3∶2	Generally	Molding
Propylene glycol, poloxamer	3∶2	Good	Molding, part is frangible
				Mannitol, Polyethylene Glycol	3∶2	Good	Molding
Sorbitol, tween	3∶2	Good	Molding
				Glucosan	3∶2	Generally	Molding
Blank medicinal liquid	3ml		Atrophy

As shown in Table 4, in the adjuvant that is screened, all adjuvants are all plastic, but investigate from the solubility angle of yield rate, molding situation and sample, use the effect of mannitol, mannitol and Polyethylene Glycol, sorbitol and tween to be better than other several adjuvants, consider simultaneously to reduce as far as possible and add too much adjuvant, therefore select to use mannitol separately as caffolding agent.

(3) lyophilization conditional filtering

Lyophilization is a veryer long dry run, also is the process of a power consumption simultaneously.An ideal lyophilisation condition not only can make the samples met standard, simultaneously also can save the energy and man-hour, so we are optimized screening to lyophilisation condition, sees Table 5.

Table 5 lyophilization conditional filtering

The time

Condition I condition II condition III cold-trap between temperature

(℃)

-45 (pre-freezes) 10-8

-40 (pre-freeze)-8-

-40 (evacuation) 10-8

-35 (evacuation) 10 58

-25 (evacuation) 10 58 keeps

55 5-70 ℃ of-15 (evacuation)

0 (evacuation) 555

10 (evacuation) 222

20 (evacuation) 222

30 (evacuation) 2-2

Experimental result shows: finished product appearance character that condition I, II, III make and the equal conformance with standard of moisture.Consider the practical situation of production, the finally selected less and overall time spent of energy expenditure, i.e. lyophilization condition was than the condition II that lacks: pre-freeze temperature-40 ℃, pre-freeze time 8h; The beginning evacuation, and be warming up to-35 ℃, keep 5h; Be warming up to-25 ℃ again, keep 5h; Be warming up to-15 ℃, keep 5h; Be warming up to 0 ℃, keep 2h; Be warming up to 10 ℃, keep 2h; Be warming up to 20 ℃, keep 2h, get finished product.

Test example 3: dispersible tablet disintegrating agent screening

The kind of disintegrating agent, quantity directly have influence on the dispersing uniformity of preparation in the dispersible tablet, are the leading indicators of weighing the dispersible tablet quality, thus we to select disintegration time for use be that performance assessment criteria is investigated different disintegrating agents, the results are shown in Table 6.

Table 6 disintegrating agent table of merit rating

Disintegrating agent	With the ointment ratio	Disintegration time (minute)
			Crospolyvinylpyrrolidone	0.8∶1	2.4
Low-substituted hydroxypropyl cellulose	0.8∶1	2.8
			Carboxymethyl starch sodium	0.8∶1	2.5
Carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose	0.8∶1	2.0
			Low-substituted hydroxypropyl cellulose, microcrystalline Cellulose	0.8∶1	2.4

From the result of above-mentioned test as can be seen, most of disintegrating agent can improve the disintegration time of dispersible tablet, all can reach the requirement of dispersible tablet.But by contrast, after employing carboxymethyl starch sodium and the low-substituted hydroxypropyl cellulose combination, the disintegrate best results.

Test example 4: drop pill substrate screening

The inventor is prepared into the required substrate of drop pill to extract and investigates by a large amount of tests, and different etc. with fusion situation, the ball method of double differences of drop pill outward appearance, principal agent and substrate serves as to investigate index, optimizes and has screened the substrate that influences the drop pill quality, result of the test such as table 7.

Method: substrate is put in the small beaker, be heated to 85-95 ℃, after treating whole fusions, the mixed material that adds Radix Ginseng extract and Radix Paeoniae Rubra extract, investigate the fusion situation of substrate and material, (drip the system condition: expect 80 ℃ of temperature, coolant is a dimethicone to the system of dripping to select the fusion situation to write out a prescription preferably, drip apart from 3～6cm, drip 30～40 droplets/minute of speed).

Table 7 substrate screening test

Sequence number	1	2	3	4	5
						Material heavy (g)	15	15	15	15	15
PEG4000	30	25	-	-	-
						PEG6000	-	-	-	15	15
Polyoxyethylene monostearate	-	5	15	-	-
						Polyethers	-	-	-	15	-
Poloxamer	-	-	15	-	15
						Substrate and material merge situation	Better	Good	Relatively poor	Better	Better
The drop pill outward appearance	Smooth, roundness is better	Smooth, roundness is good	Roundness is poor	Smooth, roundness is good	Smooth, roundness is good
						The ball method of double differences is different	6.4％	6.1％	12％	7.8％	6.5％

From above table as can be seen, most of substrate can satisfy the needs of preparations shaping, is substrate but take all factors into consideration with PEG4000, and batching is convenient, is easy to control the drop pill quality, therefore selects for use PEG4000 to optimize back substrate.

Concrete embodiment

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

Embodiment 1: 99 parts of 1 part of Radix Paeoniae Rubra total glycosidess of Radix Ginseng total saponins

Getting Radix Ginseng total saponins joins in a certain amount of water for injection, regulate pH value and be 5.0～7.0 and make dissolving, get Radix Paeoniae Rubra total glycosides again, add injection and blunge and make it dissolving, join in the above-mentioned Radix Ginseng total saponins solution, mix homogeneously, regulating pH value is 5.5～7.0, adds 0.2% activated needle-use activated carbon, boil absorption, carbon removal, fine straining, filtrate for later use; Injection mannitol is added the injection water be mixed with 100mg/ml solution,, add the injection water to ormal weight with above-mentioned filtrate mixing, coarse filtration, fine straining, packing, lyophilization, lyophilisation condition is: pre-freeze temperature-40 ℃, pre-freeze time 10h; The beginning evacuation, and be warming up to-35 ℃, keep 8h; Be warming up to-25 ℃ again, keep 8h; Be warming up to-15 ℃, keep 8h; Be warming up to 0 ℃, keep 5h; Be warming up to 10 ℃, keep 4h; Be warming up to 20 ℃, keep 2h; Be warming up to 30 ℃, keep 2h, promptly get the aseptic block of lyophilizing.

Embodiment 2: 1 part of 99 parts of Radix Paeoniae Alba total glucosides of Radix Ginseng total saponins

Get Radix Ginseng total saponins and join in a certain amount of water for injection, regulate pH value and be 5.0～7.0 and make dissolving, get Radix Paeoniae Alba total glucosides again, add the injection blunge make it the dissolving, join in the above-mentioned Radix Ginseng total saponins solution mix homogeneously, regulating pH value is 5.5～7.0, adds 0.2% activated needle-use activated carbon, boils 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, in vapor (steam) temperature is 105 ℃, and actual pressure is at 110kN/m ³Pressure sterilizing is 40 minutes under the condition, promptly gets the injection with small volume or the concentrated solution for injection that are directly used in drug administration by injection.

Embodiment 3: 40 parts of 60 parts of Radix Paeoniae Rubra total glycosidess of Radix Ginseng total saponins

Get Radix Ginseng total saponins and join in a certain amount of water for injection, regulate pH value and be 5.0～7.0 and make dissolving, get Radix Paeoniae Rubra total glycosides again, add the injection blunge make it the dissolving, join in the above-mentioned Radix Ginseng total saponins solution mix homogeneously, the glucose that adds ormal weight, regulating pH value is 5.5～7.5, adds 0.3% activated needle-use activated carbon, boil absorption, carbon removal, 5 ℃ of placements are spent the night, fine straining, filtrate add the injection water to ormal weight, packing, 110 ℃ of sterilizations 40 minutes, promptly get the glucose infusion liquid agent.

Embodiment 4: 80 parts of 20 parts of Radix Paeoniae Alba total glucosidess of stem and leaf of Radix Ginseng total saponins

Getting stem and leaf of Radix Ginseng total saponins joins in a certain amount of water for injection, regulate pH value and be 5.0～7.0 and make dissolving, get Radix Paeoniae Alba total glucosides again, add the injection blunge make it the dissolving, join in the above-mentioned stem and leaf of Radix Ginseng total saponins solution mix homogeneously, the sodium chloride of adding ormal weight, regulating pH value is 5.0～7.0, add 0.3% activated needle-use activated carbon, boil absorption, carbon removal, 5 ℃ of placements are spent the night, fine straining, filtrate add the injection water to ormal weight, packing, 110 ℃ of sterilizations 40 minutes, promptly get the sodium chloride infusion solution.

Embodiment 5: 30 parts of 70 parts of Radix Paeoniae Rubra total glycosidess of Radix Ginseng total saponins

Get Radix Ginseng total saponins and mix with Radix Paeoniae Rubra total glycosides, make soft material, drying is ground into fine powder, sieves, and adding stevioside and starch are an amount of, and mixing is granulated, drying, and tabletting, coating promptly gets tablet.

Embodiment 6: 65 parts of 35 parts of Radix Paeoniae Alba total glucosidess of Radix Ginseng total saponins

Radix Ginseng total saponins and Radix Paeoniae Alba total glucosides mixing, the system soft material, drying is ground into fine powder, and it is an amount of to add stevioside, starch and dextrin, and mixing is granulated, and drying promptly gets granule.

Embodiment 7: 45 parts of 55 parts of Radix Paeoniae Rubra total glycosidess of stem and leaf of Radix Ginseng total saponins

Get stem and leaf of Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides and merge, add appropriate amount of PEG-4000, mix homogeneously, heating and melting stirs, and is transferred to the drop pill machine, with the methyl-silicone oil is coolant, drip system, the water dropper internal diameter is 3mm, external diameter 4.5mm, drip apart from 4mm, collect drop pill, remove the methyl-silicone oil on surface, promptly get drop pill.

Embodiment 8: 42 parts of 38 parts of Radix Paeoniae Rubra total glycosidess of Radix Ginseng total saponins

Get Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides mixing, make soft material, drying is ground into fine powder, adds stevioside and starch is an amount of, and mixing is used 65% alcohol granulation, and drying is encapsulated, promptly gets capsule.

Embodiment 9: 1 part of 1 part of Radix Paeoniae Rubra total glycosides of Radix Ginseng total saponins

Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides mixing add the soybean oil of 0.8 times of medicated powder weight and 2% Cera Flava; The dropping preparation method pill, compacting promptly gets soft capsule.

Embodiment 10: 99 parts of 99 parts of Radix Paeoniae Alba total glucosidess of Radix Ginseng total saponins

Get Radix Ginseng total saponins and Radix Paeoniae Alba total glucosides mixing, add hydroxypropyl starch, the ratio that adds the combination of carboxymethyl starch sodium and low-substituted hydroxypropyl cellulose is that 0.8: 1 mixing disintegrating agent and stevioside is an amount of, and tabletting promptly gets oral cavity disintegration tablet.

Embodiment 11: 99 parts of 1 part of Radix Paeoniae Rubra total glycosidess of Radix Ginseng total saponins

Get Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides mixing, add modified starch, the spheronization pill with Radix Glycyrrhizae charcoal coating, promptly gets pellet.

Embodiment 12: 1 part of 99 parts of Radix Paeoniae Alba total glucosides of Radix Ginseng total saponins

Get Radix Ginseng total saponins and Radix Paeoniae Alba total glucosides mix homogeneously, add an amount of carboxymethyl starch sodium and low-substituted hydroxypropyl cellulose (0.8: 1) mixing, it is moistening to add 70% ethanol, system material, granulate, and tabletting promptly gets dispersible tablet.

Claims (11)

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 is to be made for 99～1 parts by 1～99 part of Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides.

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 is to be made for 90～10 parts by 10～90 parts of Radix Ginseng total saponinss and Radix Paeoniae Rubra total glycosides.

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 components by weight percent, it is to be made for 70～30 parts by 30～70 parts of Radix Ginseng total saponinss and Radix Paeoniae Rubra total glycosides.

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, and 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 infusion solution 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 preparation of drug combination method of claim 4 or 5 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: Radix Ginseng total saponins is mixed with Radix Paeoniae Rubra total glycosides, add adjuvant and make various preparations.

7, according to the preparation of drug combination method of the described treatment cardiovascular and cerebrovascular disease of claim 6, it is characterized in that: injection is preparation like this: take by weighing Radix Ginseng total saponins and join in a certain amount of water for injection, regulate pH value and be 5.0～7.0 and make dissolving, get Radix Paeoniae Rubra total glycosides again, add the injection blunge make it the dissolving, with above-mentioned two medicinal liquid mix homogeneously, regulating pH value is 6.0～7.5, add 0.1～2% needle-use activated carbon, boil absorption, carbon removal, fine straining, filtrate adds different auxiliary material and is prepared into various injections.

8, according to the preparation of drug combination method of claim 6 or 7 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the Injectable sterile block is preparation like this: take by weighing Radix Ginseng total saponins and join in a certain amount of water for injection, regulate pH value and be 5.0～7.0 and make dissolving, get Radix Paeoniae Rubra total glycosides again, add the injection blunge make it the dissolving, with above-mentioned two solution mix homogeneously, regulating pH value is 6.0～7.5, add 0.2% activated needle-use activated carbon, boil absorption, carbon removal, fine straining, filtrate for later use; Injection mannitol is added the injection water be mixed with 100mg/ml solution,, add the injection water to ormal weight with above-mentioned filtrate mixing, coarse filtration, fine straining, packing, temperature-40 ℃, pre-freeze time 10h, beginning evacuation, and differential gradient increased temperature to 10 ℃ progressively, keep 2h, be warming up to 20 ℃, keep 2h, be warming up to 30 ℃, keep 2h, promptly.

9, according to the preparation of drug combination method of any described treatment cardiovascular and cerebrovascular disease of claim 6～7, it is characterized in that: the adjuvant that is adopted in the preparation comprises mannitol, galactose, glycine, glucose, glucosan, sodium chloride, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, sorbitol, tween, poloxamer, dextrin, starch, crospolyvinylpyrrolidone, carboxymethyl starch sodium, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, polyoxyethylene monostearate, polyethers 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.

10, according to claim 1～3, the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease in 6～8, it is characterized in that: Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides can be commercially available or by the following method extraction separation obtain: get Radix Ginseng or Stem and leaf of Radix Ginseng the part or Radix Ginseng Rubra or Radix Codonopsis, Radix Paeoniae Rubra, add water or ethanol extraction respectively, extracting solution gets the medical material crude extract respectively through suitably concentrating, further adopt water precipitating, precipitate with ethanol, organic solvent extractionprocess, flocculent precipitation, one or more of column chromatography are united use and are carried out suitably making with extra care, and get Radix Ginseng total saponins or stem and leaf of Radix Ginseng total saponins and Radix Paeoniae Rubra total glycosides respectively.

11, according to the application of the described pharmaceutical composition of claim 1～3 in disease medicaments such as preparation treatment angina pectoris, ischemic cerebral vascular.