CN102028743A

CN102028743A - Medicament for treating coronary heart disease and preparation method thereof

Info

Publication number: CN102028743A
Application number: CN2009100706837A
Authority: CN
Inventors: 刘顺航; 徐波; 戚可人; 刘岩; 陈红; 丛德刚; 赵国辉
Original assignee: TIANJIN TASLY MODERN CHINESE MEDICINE RESOURCE CO Ltd
Current assignee: TIANJIN TASLY MODERN CHINESE MEDICINE RESOURCE CO Ltd
Priority date: 2009-09-29
Filing date: 2009-09-29
Publication date: 2011-04-27
Anticipated expiration: 2029-09-29
Also published as: CN102028743B

Abstract

The invention relates to a medicament for treating coronary heart disease and a preparation method thereof. An extraction method comprises the steps of ethanol extraction of root of red rooted salvia and root of pseudo-ginseng, ethanol extraction of the decoction dregs of the root of red rooted salvia, and the like. The process can realize industrialization, and the quality is stable and controllable. Related experiments show that: the medicament has high curative effect compared with the prior art; the medicament has high purity, good absorption, stable quality and novel application; and meanwhile, the preparation method is simple and convenient in operation, and low in cost, and is suitable for industrialized production.

Description

A kind of medicine and preparation for the treatment of coronary heart disease

Technical field

The present invention relates to a kind of medicine for the treatment of coronary heart disease, belong to the field of Chinese medicines.

Background technology

Along with the rejuvenation of growth in the living standard, world population aging and morbidity colony, cardiovascular and cerebrovascular vessel patient increases year by year, has become the second largest disease of harm humans health.Angina pectoris is a kind of caused by the temporary transient ischemia of cardiac muscle, anoxia, serves as the clinical syndrome of main performance with ictal chest pain or chest discomfort.Angina pectoris is meant because coronary atherosclerosis or spasm cause myocardial ischemia, the caused angina pectoris of anoxia, accounts for 90% of patient with angina pectoris.

The anginal method of treatment is based on blood vessel dilating, reduction blood viscosity, anti-platelet aggregation, anticoagulation at present.Traditional Western medicine of using is nitrate, nitrous acid ester, beta-blocker, calcium antagonist etc., but all has bigger toxic and side effects, should not take for a long time, mostly is symptomatic treatment and course of disease progress is not had bigger effect.For example take occur sometimes behind the nitroglycerin beating in feeling of fullness in the head, the head, palpitating speed, even faint [referring to 264 pages of new pharmacologies (the 14th edition)], find again in recent years to cause severe hypotension [referring to contemporary Chinese medical journal 1997; 7 (4): 42; Shaanxi medical journal 1996; 25 (5): 315], easily produce toleration [referring to southern nursing magazine 1996; 3 (5): 7～9] etc. problem has hindered its application clinically.

Though the anginal Chinese patent medicine of many treatments is also arranged, wherein ball, loose, cream, pellet, decoction becomes old historical already, the modern seldom uses.There are preparations such as common FUFANG DANSHEN PIAN and capsule to sell in the market, but conventional tablet, capsule manufacture technology fall behind, active constituent content is low, no quality control index, need oral through gastrointestinal absorption, go into blood at liver generation first pass effect post-absorption, bioavailability is low, absorbs slow. can not be fit to the need of angina pectoris patient's first aid.

FUFANG DANSHEN DIWAN is fast, the eutherapeutic therapeutic drug of coronary heart disease of a kind of special effect, is subjected to patient's welcome clinically deeply.In order to improve the preparation technology of FUFANG DANSHEN DIWAN, the inventor furthers investigate from the extraction process aspect, from saving the herb resource aspect, has improved product yield, the comprehensive utilization ratio of the contained effective ingredient of medical material.

Summary of the invention

The invention provides a kind of medicine for the treatment of coronary heart disease.

The medicine of treatment coronary heart disease of the present invention, described medicine is prepared from by following raw materials by weight percent medicine, Radix Salviae Miltiorrhizae 19.8%-97%, Radix Notoginseng 2%-80%, Borneolum Syntheticum 0.2%-3%, described preparation is earlier crude drug to be prepared into active constituents of medicine through following steps, further is prepared into medicine again.

Step 1, Radix Salviae Miltiorrhizae adds alcohol, extracts, and extracting solution is concentrated, dry, obtains the Radix Salviae Miltiorrhizae ethanol extract;

Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, extracts, and filters, and filtrate concentrates, and puts cold, add acid for adjusting pH value, cold preservation is left standstill, and filters, and filtrate is crossed resin, water eluting successively, low concentration alcohol eluting, high concentration alcohol eluting is collected the high concentration alcohol eluen, concentrates, and drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng adds alcohol, extracts, and extracting solution is concentrated, dry, obtains Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after step 2 alcohol extraction add, and aqueous alkali is or/and water extraction, and extracting solution concentrates, and adds alcohol, leaves standstill, and supernatant concentration obtains Radix Salviae Miltiorrhizae extractum;

The Radix Salviae Miltiorrhizae ethanol extract that step 5, step 1 obtain, the salvianolic acid B extract that step 2 obtains, the Radix Notoginseng extract that step 3 obtains, Radix Salviae Miltiorrhizae extractum that step 4 obtains and Borneolum Syntheticum are further made drop pill.

Medicine of the present invention is for oral medicine, the preparation of galenic pharmacy routine techniques is adopted in its preparation, comprise that wherein the adjuvant of oral drug preparation is selected from starch with the blended step of the adjuvant of active constituents of medicine and oral drugs, amylum pregelatinisatum, dextrin, Icing Sugar, lactose, mannitol, calcium sulfate two water things, calcium hydrogen phosphate, magnesium oxide, calcium carbonate, magnesium carbonate, water, ethanol, starch slurry, syrup, liquid glucose, maltose, refined honey, cane sugar powder, citric acid, essence, mucialga of arabic gummy, gelatine size, polyvinylpyrrolidone (PVP), rubber cement, microcrystalline Cellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, magnesium stearate, stearic acid, zinc stearate, calcium stearate, Pulvis Talci, Macrogol 4000, polyethylene glycol 6000, micropowder silica gel, vegetable oil, sodium stearate, glycerin gelatine, stearic acid, glyceryl monostearate, insect wax, one or several combinations of hydrogenated oil and fat.

Oral formulations of the present invention is selected from: all acceptable dosage forms on tablet, dispersible tablet, hard capsule, soft capsule, granule, pill, micropill, powder, drop pill, slow releasing preparation, controlled release preparation, syrup, oral liquid, soft extract and the extractum pharmaceutics.

Its preferred manufacturing procedure of medicine that confession of the present invention is oral, step is:

Step 1, Radix Salviae Miltiorrhizae add methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or the isobutanol of 2-12 times of 70-100%, and reflux, extract, is filtered, and extracting solution concentrating under reduced pressure, drying obtain the Radix Salviae Miltiorrhizae ethanol extract;

Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and is added 2-20 and doubly measured the 10-100% alcohol extraction 0.5-10 hour, filters, last medicinal residues add 2-20 and doubly measured the 10-100% alcohol extraction 0.5-10 hour, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid, leave standstill to medicinal liquid pH value 1-4, filter, filtrate is crossed macroporous resin, successively the water eluting, low concentration alcohol eluting, high concentration alcohol eluting is collected the high concentration alcohol eluen, concentrate, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or the isobutanol of 2-20 times of 50-100%, reflux, extract, 2 times, and each extraction time 0.5-10 hour, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Notoginseng extract;

Step 4, the salvianolic acid B medicinal residues after the alcohol extraction of step 2 add the aqueous alkali of 2-12 times of pH value 7-10, extract 1-3 time, add 2-12 times of water again, extract 1-3 time, filter, filtrate concentrates, add ethanol to medicinal liquid and contain alcohol amount 50-80%, leave standstill separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 50%-90% or concentrated, dry, pulverizing;

Step 5, with the above-mentioned tanshinol extract that obtains, the salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum mixes with adjuvant with Borneolum Syntheticum, adds any or more than one adjuvants, and the adjuvant addition is 1-6 a times of active component, makes any oral formulations;

Wherein the described alcohol extraction mode of step 2 is selected from: reflux, extract,, warm macerating extraction, supersound extraction or dynamic countercurrent extraction,

Described alcohol is selected from: methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol,

Described macroporous resin is selected from: polar resin S-8, low pole Resin A B-8, non-polar resin D101 or polyamide.

The preferred drop pill of medicine of the present invention, the preparation of galenic pharmacy routine techniques is adopted in its preparation, comprises that described adjuvant is selected from fat-soluble substrate and water-soluble base with the blended step of adjuvant of active constituents of medicine and drop pill medicine, and medicine is assisted than being 1: 1-6.Wherein said fat-soluble substrate is selected from: stearic acid, glyceryl monostearate, insect wax, Cera Flava, paraffin, hydrogenated vegetable oil, semi-synthetic fatty acid ester; Water-soluble base is selected from Polyethylene Glycol, polyoxyethylene monostearate, poloxamer, sodium stearate, glycerin gelatine etc.; Xylitol and composites of starch, erythritol; Preferred medicine is auxilliary than being 1: 2.1.

Drop pill preferred manufacturing procedure of the present invention, step is:

Step 1, Radix Salviae Miltiorrhizae add 2-5 times of 70-100% ethanol, reflux, extract, 1-3 time, and each 1-3 hour, to filter, extracting solution concentrating under reduced pressure, drying obtain the Radix Salviae Miltiorrhizae ethanol extract;

Step 2, getting step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues adds 2-15 and doubly measured the 10-90% ethanol extraction 1-8 hour, filter, last medicinal residues add 2-15 and doubly measured the 10-90% ethanol extraction 1-8 hour, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1-3, leave standstill, filter, filtrate is crossed macroporous resin (S-8, AB-8 or D101), water eluting successively, 5-20% alcohol eluting is used the 40-90% ethanol elution at last, collect the 40-90% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add the ethanol of 2-12 times of 50-80%, reflux, extract, 2 times, and each 1-3 hour, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, add for the first time the aqueous alkali that 2-12 doubly measures PH7-8 and decocted 1-3 hour, add 2-12 times of water gaging for the second time and decocted 0.5-2 hour, obtain extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, left standstill separation of supernatant 12-36 hour, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 55%-80%;

Step 5, the Radix Salviae Miltiorrhizae ethanol extract of step 1, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill;

Wherein the described alcohol extraction mode of step 2 is selected from: reflux, extract,, warm macerating extraction, supersound extraction or dynamic countercurrent extraction.

The preferred preparation method of drop pill of the present invention, step is:

Step 1, Radix Salviae Miltiorrhizae add 2-5 and doubly measure 95% ethanol, reflux, extract, 1-3 time, and each 1-3 hour, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, getting step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues adds 2-10 and doubly measured the 30-70% alcohol reflux 1-6 hour, filter, last medicinal residues add 2-10 and doubly measured the 30-70% alcohol reflux 1-6 hour, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to liquid PH value 1-3, leave standstill, filter, filtrate is crossed macroporous resin (S-8, AB-8 or D101), water eluting successively, the 10-20% ethanol elution is used the 40-70% ethanol elution at last, collect the 40-70% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add the ethanol of 4-10 times of 50-80%, reflux, extract, 2 times, and each 1-3 hour, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, add for the first time the aqueous alkali that 6-12 doubly measures PH7-8 and decocted 1-3 hour, add 6-12 times of water gaging for the second time and decocted 0.5-2 hour, obtain extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-75%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 55%-75%;

Step 5, the Radix Salviae Miltiorrhizae ethanol extract of step 1, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill.

The particularly preferred preparation method of drop pill of the present invention, step is:

Step 1, Radix Salviae Miltiorrhizae add 2-3 and doubly measure 95% ethanol, reflux, extract, 2 times, and each 1-2 hour, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, adds the alcohol reflux 2 times that 4-6 doubly measures 40-60%, each 1-2hr, filter, filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid and regulate pH value 1.8-2.0, cold preservation is left standstill more than the 12hr, filters last AB-8 macroporous resin eluting, wash with water earlier, eluent discards; Reuse 15% ethanol is washed,, eluent discards; Wash with 50% ethanol at last, collect 50% ethanol elution, concentrating under reduced pressure, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add doubly 70% ethanol of 6-8, reflux, extract, 2 times, and each 1-2 hour, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, add for the first time the aqueous alkali that 6-12 doubly measures PH7-8 and decocted 1-3 hour, add 8 times of water gagings for the second time and decocted 1 hour, obtain extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;

Step 5, the Radix Salviae Miltiorrhizae ethanol extract of step 1, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.

The present invention also comprises the application of medicinal dropping ball in the medicine of cardiovascular disease such as a kind of resisting coronary heart disease of preparation, angina pectoris with treatment coronary heart disease of the present invention.

The present invention is more more superior than prior art because of the change of technology causes the present invention to treat the medicinal dropping ball of coronary heart disease.

Below data declaration the present invention treats the beneficial effect of the medicinal dropping ball of coronary heart disease by experiment.

Add the medicinal dropping ball of treatment coronary heart disease of the present invention before the myocardial cell anoxia, the intracellular calcium fluorescence intensity obviously descends, and proves that the medicinal dropping ball of treatment coronary heart disease has antagonism myocardial cell calcium overload, the effect of protecting myocardial cell.

Behind the myocardial ischemia-reperfusion, high-energy phosphate compound obviously reduces in the tissue, and the lipid peroxide contents showed increased causes reperfusion injury.The medicinal dropping ball that adds treatment coronary heart disease when pouring into again when before ischemia, pouring in advance and behind the ischemia, high-energy phosphate compound all is higher than ischemic reperfusion notes group in the tissue, two groups of adenosine triphosphate (ATP), cardiac muscular tissue's gland nucleoside total amount (TAN) are all near normal level, and the lipid peroxide level is lower than ischemic reperfusion notes group.This result proves, before ischemia during pre-perfusion with ischemia after treat coronary heart disease when pouring into again medicinal dropping ball all can be by increasing the cardiac energy deposit, the generation of inhibition lipid peroxide and protecting myocardial cell.

Cardiomyocyte cell death is a damage type the most serious in the myocardial ischemia-reperfusion, comprises necrocytosis and apoptosis.The apoptotic regulation and control that expressed by several genes.Myocardial infarction rear section myocardial cell generation apoptosis, relevant with the cell calcium overload due to the ischemia probably with the oxygen-derived free radicals effect.The medicinal dropping ball of treatment coronary heart disease can obviously reduce apoptosis of cardiac muscle quantity behind the myocardial ischemia-reperfusion, dwindles the myocardial infarct size of ischemia-reperfusion rat, significantly alleviates the pathology damage degree, and stronger with the medicinal dropping ball dosage increasing effect of treatment coronary heart disease.Carrying out the anoxia experiment in cardiac muscle cells shows, the medicinal dropping ball intervention of treatment coronary heart disease can obviously be reduced apoptotic proteins Fas and be expressed, slight upregulation of apoptosis Profilin Bcl-2 expresses, and shows that further the protein expression of apoptosis-related genes in the medicinal dropping ball pair cell for the treatment of coronary heart disease has certain influence.

The medicinal dropping ball of treatment coronary heart disease improves blood capillary circulation albumin outside leakage and mast cell degranulation is one of important symbol of microcirculation disturbance.The medicinal dropping ball of treatment coronary heart disease is to the improvement effect of endotoxin and the caused microcirculation disturbance of ischemia-reperfusion, the medicinal dropping ball that confirms treatment coronary heart disease improves significantly to the rat mesentery microcirculation disturbance that ischemia-reperfusion causes, shows: 1. can suppress the early stage albumin outside leakage of ischemia that Radix Salviae Miltiorrhizae can not play a role; 2. effectively suppress mast cell degranulation; 3. suppress the generation of vascular endothelial cell and leukocyte oxide; 4. suppress sticking of leukocyte and vascular endothelial cell; 5. also influential to the interaction of the cell adhesion factor, peroxidating and leukocyte behind the ischemia-reperfusion and endotheliocyte.

The medicinal dropping ball of treatment coronary heart disease has more obviously influence to patient's bulbar Conjunctiva Microcirculation, thrombelastogram, patient's arteriole vessel diameter broadening after the medication, and fine vein blood vessel narrow diameter, arteriole blood flow rate and blood flow have more significantly to be increased.

Medicinal dropping ball antioxidation, antiinflammatory, the protection blood vessel endothelium of treatment coronary heart disease, the balance between the formation of inhibition atherosclerotic plaque and neointimal hyperplasia vascular endothelial cell associated media nitric oxide (NO) and the vasoconstrictive factor endothelin-1 (ET-1) etc. is being kept the stability of blood vessel.The medicinal dropping ball of the treatment coronary heart disease of damage back variable concentrations all obviously alleviates human vascular endothelial damage due to the LPS, illustrate that the medicinal dropping ball for the treatment of coronary heart disease has obvious protective effect to vascular endothelial cell.The medicinal dropping ball of variable concentrations being treated coronary heart disease is used for the culture fluid that hydrogen peroxide damages the modeling front and back, discovery can generate by balance NO at the medicinal dropping ball of prevention and treatment group treatment coronary heart disease, significantly increase cytoactive, endothelial injury due to the hydrogen peroxide is had obvious antagonism.

Atherosclerotic lesion is that a kind of protectiveness inflammation-fiber proliferative to local damage is responded.In the speckle forming process, lipidosis is most important factor.But the medicinal dropping ball treatment hypercholesterolemia reducing (TC) and low density lipoprotein, LDL (LDL) cholesterol levels of treatment coronary heart disease, high density lipoprotein increasing (HDL) cholesterol levels.Ma Xiao waits quietly observing the influence of the medicinal dropping ball of treatment coronary heart disease to film healing situation in damaging with similar method modeling, the medicinal dropping ball group postoperative NO concentration of finding treatment coronary heart disease is apparently higher than matched group, the neointimal hyperplasia degree obviously alleviates than matched group, new intima medium vessels smooth muscle cell and fibrous tissue obviously reduce than matched group, so think that the medicinal dropping ball of treatment coronary heart disease can promote to damage the reparation of inner membrance, reduces neointimal hyperplasia.

The medicinal dropping ball coronary blood flow increasing of treatment coronary heart disease improves the hemorheology hyperlipemia and can cause vascular endothelial injury, come off, platelet adhesion reaction and gathering.The medicinal dropping ball of treatment coronary heart disease can significantly increase the rat coronary flow but not increase heart rate, helps to improve the supply of heart oxygen and nutrient substance.The medicinal dropping ball of treatment coronary heart disease obviously reduces rabbit anteserum TC, triglyceride (TG), LDL, very low density lipoprotein (VLDL) (VLDL) concentration and TC/HDL ratio, and HDL concentration obviously raises.

The medicinal dropping ball inhibition platelet adhesion reaction and the gathering endothelial function for the treatment of coronary heart disease lacked of proper care, endothelium integrity destruction can trigger a series of molecules and biochemical reaction makes the blood flow stagnation, and blood vessel wall reparation, inhibition or antagonism platelet adhesion reaction and gathering are to prevent thrombotic key link.The medicinal dropping ball antiplatelet activation of treatment coronary heart disease and gathering be from the multi-section position, stage construction and many target spots play a role.

The medicinal dropping ball of treatment coronary heart disease all has obvious inhibitory action to adenosine diphosphate (ADP) (ADP), thrombin and collagen-induced rat platelet aggregation, and is dose-dependence.The medicinal dropping ball of treatment coronary heart disease can suppress high fat and feed dog platelet overactivity.The specificity molecular marker of plasma A membrane granulosa protein-140 (GMP-140) when being platelet activation.Before the treatment, treatment group and matched group GMP-140 level are organized apparently higher than healthy people, after the medicinal dropping ball associating aspirin for treatment of treatment coronary heart disease, treatment group angina pectoris symptom, electrocardiogram ischemia improve, blood plasma GMP-140 level significantly reduces than matched group (single clothes aspirin), organize no significant difference with healthy people.To the aspirin resistance person, the medicinal dropping ball that adds with treatment coronary heart disease can obviously improve the aspirin resistance state, reduces platelet aggregation rate, and total effective rate is 85%, and the average range of decrease is 51.57%.

Because the medicinal dropping ball of treatment coronary heart disease has above-mentioned many target spots effect, it is to all kinds coronary heart disease, comprises that the peri-operation period treatment etc. of stable or unstable angina pectoris, myocardial infarction, heart failure, silent ischemia and intervention all has remarkable result.

Following experimental data is used to illustrate effect of the present invention: experimental drug is the medicine of the embodiment of the invention 1.

The comparison of medicinal dropping ball aspect the angina pectoris treatment effect of table 1 treatment coronary heart disease

Group

n

Produce effects

Effectively

Invalid

Increase the weight of

Total effective rate/%

The treatment group

51

22

26

3

0

94.1①

Matched group

51

10

27

12

2

72.5

Annotate: 1. compare, analyze U=3.039, P＜0.01 through Radit with matched group.

The comparison of medicinal dropping ball aspect ECG curative effect of table 2 treatment coronary heart disease

Group	n	Produce effects	Effectively	Invalid	Increase the weight of	Total effective rate/%
							The treatment group	51	13	18	20	0	60.8①
Matched group	51	4	15	30	2	37.3

Annotate: 1. compare, analyze U=2.685, P＜0.01 through Radit with matched group.

Hemorheology index variation before and after the medicinal dropping ball treatment of table 3 treatment coronary heart disease (x ± s)

The medicinal dropping ball medication left ventricular contractile function comparison of table 4 treatment coronary heart disease (x ± s)

Annotate: 1. compare P＞0.05 before and after the medication; 2. compare P＜0.05 before and after the medication.

Efficient, quick-acting, the multi-purpose pure Chinese medicine dripping pills preparation that the present invention adopts the modern pharmacy technology to develop, prevent and treat the coronary heart disease determined curative effect, and can improve the blood capillary circulation,, comprise that diabetic renal papillary necrosis and diabetic nephropathy all have good preventive and therapeutic effect the diabetes microvascular complication.

The invention has the advantages that: this process route can be realized industrialization, and is stable and controllable for quality.Relevant test shows, the present invention is than prior art curative effect height, the product purity height, and good absorbing, steady quality, the purposes novelty, preparation method technology is simple, easy to operate, with low cost simultaneously, is fit to suitability for industrialized production.

The specific embodiment

Specify the present invention with embodiment below, embodiment is for the ease of understanding the present invention, and claim that does not limit the present invention in any way and core content.

The preparation of the medicinal dropping ball of embodiment 1 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82.87%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.92%;

Step 1, Radix Salviae Miltiorrhizae add 3 times of amount 95% ethanol, and reflux, extract, 2 hours is filtered; Medicinal residues add 2 times of amount 95% ethanol, and reflux, extract, 1 hour is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 3 times of amount 20% alcohol reflux 1hr, filters, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, and filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr

Filter, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add the ethanol of 8 times of amounts 70%, and reflux, extract, 2 hours is filtered, and medicinal residues add 6 times of amount 70% ethanol, reflux, extract, 1 hour, and extracting liquid filtering is concentrated into clarification, and decompression recycling ethanol, drying obtain Radix Notoginseng extract;

Step 4, the medicinal residues of salvianolic acid B behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 8 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;

Step 5, the Radix Salviae Miltiorrhizae ethanol extract that obtains after the said extracted, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.

The preparation of the medicinal dropping ball of embodiment 2 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 19.8%, Radix Notoginseng 78.2%, Borneolum Syntheticum 2%;

Step 1, Radix Salviae Miltiorrhizae add 2 times of amount 85% ethanol, reflux, extract, 1 time, and each 1 hour, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 85% ethanol extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds 2 times of amount PH7-8 for the first time decocted 1 hour, added 2 times of water gagings for the second time and decocted 0.5 hour, obtain extracting solution, extracting solution is concentrated into 1.15/80 ± 1 ℃, and concentrated solution is put and is as cold as 25-30 ℃, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, leave standstill more than 12 hours, separation of supernatant reclaims ethanol, receives cream to pol 70%-75%, obtains Radix Salviae Miltiorrhizae extractum;

The preparation of embodiment 3 FUFANG DANSHEN DIWAN, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 97%, Radix Notoginseng 2%, Borneolum Syntheticum 1%,

Step 1, Radix Salviae Miltiorrhizae add 5 times of amount 95% ethanol, reflux, extract, 3 times, and each 3 hours, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 8 times of amount 60% alcohol reflux 4hr, filters, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, and filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr Filter, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 6 times of amount PH7-8 decocted 3 hours, added 6 times of water gagings for the second time and decocted 2 hours, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;

The preparation of embodiment 4 FUFANG DANSHEN DIWAN, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 95%, Radix Notoginseng 2%, Borneolum Syntheticum 3%,

Step 1, Radix Salviae Miltiorrhizae add 2 times of amount 75% ethanol, and warm macerating extracts twice, and each 2 hours, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 75% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol ultrasonic extraction 2hr, filters, medicinal residues add 4 times of amount 50% ethanol ultrasonic extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr Filter, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 10% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 4, Radix Salviae Miltiorrhizae decoction dregs behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;

The preparation of embodiment 5 FUFANG DANSHEN DIWAN, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 19.8%, Radix Notoginseng 80%, Borneolum Syntheticum 0.2%,

Step 1, Radix Salviae Miltiorrhizae add 5 times of amount 95% ethanol, and reflux, extract, twice is filtered, and extracting solution concentrating under reduced pressure, drying obtain the Radix Salviae Miltiorrhizae ethanol extract.

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol dynamic countercurrent extraction 2hr, filters, medicinal residues add 4 times of amount 50% ethanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;

The preparation of the medicine of embodiment 6 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 20.8%, Radix Notoginseng 78.6%, Borneolum Syntheticum 0.6%,

Step 1, Radix Salviae Miltiorrhizae add 3 times of amount 95% methanol, and reflux, extract, 2 hours is filtered; Medicinal residues add 2 times of amount 95% methanol, and reflux, extract, 1 hour is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% alcohol reflux 2hr, filter, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.0-4.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 5 is got the Radix Salviae Miltiorrhizae ethanol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, and the Radix Salviae Miltiorrhizae extractum that the Radix Notoginseng extract that step 2 obtains, step 4 obtain, Borneolum Syntheticum add an amount of vegetable oil, mixing; Make soft capsule according to the soft capsule conventional method.

The preparation of the medicine of embodiment 7 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 29.8%, Radix Notoginseng 68.6%, Borneolum Syntheticum 1.6%,

Step 1, Radix Salviae Miltiorrhizae add 3 times of amount 95% normal propyl alcohols, and reflux, extract, 2 hours is filtered; Medicinal residues add 2 times of amount 95% normal propyl alcohols, and reflux, extract, 1 hour is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, adds the alcohol reflux of 5 times of amounts 60%, 2hr, last medicinal residues add the alcohol reflux 2hr of 4 times of amounts 50%, filter, filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid and regulate pH value 1.8-2.0, cold preservation is left standstill more than the 12hr, filter, last AB-8 macroporous resin eluting washes with water earlier, and eluent discards; Reuse 10% ethanol is washed,, eluent discards; Wash with 40% ethanol at last, collect 40% ethanol elution, concentrating under reduced pressure, drying obtains the salvianolic acid B extract;

Step 5 is got the Radix Salviae Miltiorrhizae ethanol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, and the Radix Salviae Miltiorrhizae extractum that the Radix Notoginseng extract that step 2 obtains, step 4 obtain, Borneolum Syntheticum add an amount of amylum pregelatinisatum, zinc stearate, calcium stearate, and mixing is made tablet.

The preparation of the medicine of embodiment 8 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 86.8%, Radix Notoginseng 12.6%, Borneolum Syntheticum 0.6%,

Step 1, Radix Salviae Miltiorrhizae add 12 times of amount 95% n-butyl alcohol, and reflux, extract, 2 hours is filtered; Medicinal residues add 2 times of amount 95% n-butyl alcohol, and reflux, extract, 1 hour is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol ultrasonic extraction 2hr, filter, medicinal residues add 4 times of amount 50% ethanol ultrasonic extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-4.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 5, get the Radix Salviae Miltiorrhizae ethanol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, the Radix Salviae Miltiorrhizae extractum that the Radix Notoginseng extract that step 2 obtains, step 4 obtain, Borneolum Syntheticum, add an amount of polyvinylpyrrolidone (PVP), rubber cement, microcrystalline Cellulose, sodium carboxymethyl cellulose, mixing; Make controlled release preparation.

The preparation of the medicinal dropping ball of embodiment 9 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 85.8%, Radix Notoginseng 12.6%, Borneolum Syntheticum 1.6%,

Step 1, Radix Salviae Miltiorrhizae add 8 times of amount 80% ethanol, and reflux, extract, 2 hours is filtered; Medicinal residues add 4 times of amount 80% ethanol, and reflux, extract, 1 hour is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 80% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol ultrasonic extraction 2hr, filter, medicinal residues add 4 times of amount 50% ethanol ultrasonic extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.0-2.0, cold preservation is left standstill more than the 12hr, last S-8 macroporous resin, wash with water earlier, eluent discards; Reuse 20% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add the ethanol of 6 times of amounts 70%, and reflux, extract, 1 hour is filtered, and medicinal residues add 8 times of amount 70% ethanol, reflux, extract, 2 hours, and extracting liquid filtering is concentrated into clarification, and decompression recycling ethanol, drying obtain Radix Notoginseng extract;

Step 5, the Radix Salviae Miltiorrhizae ethanol extract that obtains after the said extracted, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 80-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.

The preparation of the medicine of embodiment 10 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 74.8%, Radix Notoginseng 23.6%, Borneolum Syntheticum 1.6%,

Step 1, Radix Salviae Miltiorrhizae add 5 times of amount 75% ethanol, and reflux, extract, 2 hours is filtered; Medicinal residues add 3 times of amount 75% ethanol, and reflux, extract, 1 hour is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 75% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% ethanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-4.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

The preparation of the medicine of embodiment 11 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 58.8%, Radix Notoginseng 40.6%, Borneolum Syntheticum 0.6%,

Step 1, Radix Salviae Miltiorrhizae add 10 times of amount 70% ethanol, and reflux, extract, 2 hours is filtered; Medicinal residues add 5 times of amount 70% ethanol, and reflux, extract, 1 hour is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 70% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% methanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% methanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add the ethanol of 4 times of amounts 70%, and reflux, extract, 1 hour is filtered, and medicinal residues add 8 times of amount 70% ethanol, reflux, extract, 2 hours, and extracting liquid filtering is concentrated into clarification, and decompression recycling ethanol, drying obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 2 times of amount PH7-8 decocted 2 hours, added 2 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;

Step 5 is got the Radix Salviae Miltiorrhizae ethanol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, the Radix Salviae Miltiorrhizae extractum that the Radix Notoginseng extract that step 3 obtains, step 4 obtain, Borneolum Syntheticum add an amount of maltose, hydroxypropyl emthylcellulose, mixing, drying is pulverized, and makes powder.

The preparation of the medicine of embodiment 12 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 28%, Radix Notoginseng 70%, Borneolum Syntheticum 2%;

Step 1, Radix Salviae Miltiorrhizae add 7 times of amount 95% ethanol, and reflux, extract, 2 hours is filtered; Medicinal residues add 4 times of amount 95% ethanol, and reflux, extract, 1 hour is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% methanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% methanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 10% ethanol is washed, and eluent discards; Wash with 45% ethanol at last, collect 45% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add the ethanol of 4 times of amounts 80%, and reflux, extract, 1 hour is filtered, and medicinal residues add 10 times of amount 70% ethanol, reflux, extract, 3 hours, and extracting liquid filtering is concentrated into clarification, and decompression recycling ethanol, drying obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 12 times of amount PH7-8 decocted 2 hours, added 12 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;

Step 5 is got the Radix Salviae Miltiorrhizae ethanol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, and the Radix Salviae Miltiorrhizae extractum that the Radix Notoginseng extract that step 3 obtains, step 4 obtain, Borneolum Syntheticum add an amount of calcium stearate, Pulvis Talci, Macrogol 4000, mixing; Make micropill.

The preparation of the medicine of embodiment 13 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 85%, Radix Notoginseng 12%, Borneolum Syntheticum 3%;

Step 1, Radix Salviae Miltiorrhizae add 6 times of amount 95% ethanol, and reflux, extract, 3 hours is filtered; Medicinal residues add 4 times of amount 95% ethanol, and reflux, extract, 1.5 hours is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% n-butyl alcohol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% n-butyl alcohol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 13% ethanol is washed, and eluent discards; Wash with 65% ethanol at last, collect 65% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add 4 times 80% ethanol, reflux, extract, 3 times, and each 3 hours, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 7 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 50%;

Step 5, the Radix Salviae Miltiorrhizae ethanol extract that obtains after the said extracted, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 80 ℃; The temperature of liquid paraffin is 8 ℃, makes drop pill.

The preparation of the medicine of embodiment 14 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 50%, Radix Notoginseng 48%, Borneolum Syntheticum 2%;

Step 1, Radix Salviae Miltiorrhizae add 9 times of amount 95% ethanol, and reflux, extract, 4 hours is filtered; Medicinal residues add 7 times of amount 95% ethanol, and reflux, extract, 2 hours is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% methanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% methanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last D101 macroporous resin, wash with water earlier, eluent discards; Reuse 10% ethanol is washed, and eluent discards; Wash with 70% ethanol at last, collect 70% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add 10 times 80% ethanol, reflux, extract, 1 time, and each 1 hour, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 7 times of amount PH7-10 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 90%;

Step 5 is got the Radix Salviae Miltiorrhizae ethanol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, and the Radix Salviae Miltiorrhizae extractum that the Radix Notoginseng extract that step 3 obtains, step 4 obtain, Borneolum Syntheticum add an amount of vegetable oil, make soft capsule according to the soft capsule preparation method.

The preparation of the medicine of embodiment 15 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 90%, Radix Notoginseng 8%, Borneolum Syntheticum 2%;

Step 1, Radix Salviae Miltiorrhizae add 4 times of amount 95% ethanol, and reflux, extract, 2 hours is filtered; Medicinal residues add 3 times of amount 95% ethanol, and reflux, extract, 2 hours is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% isobutanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% isobutanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 13% ethanol is washed, and eluent discards; Wash with 65% ethanol at last, collect 65% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add 6 times 75% ethanol, reflux, extract, 2 times, and each 2 hours, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Notoginseng extract;

The preparation of the medicine of embodiment 16 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82%, Radix Notoginseng 17%, Borneolum Syntheticum 1%;

Step 1, Radix Salviae Miltiorrhizae add 3 times of amount 90% ethanol, and reflux, extract, 2.5 hours is filtered; Medicinal residues add 2 times of amount 90% ethanol, and reflux, extract, 1.5 hours is filtered, and extracting solution concentrating under reduced pressure, drying obtain Radix Salviae Miltiorrhizae 90% ethanol extract;

Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% n-butyl alcohol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% n-butyl alcohol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 13% ethanol is washed, and eluent discards; Wash with 70% ethanol at last, collect 70% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add 7 times 80% ethanol, reflux, extract, 3 times, and each 1.5 hours, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 6 times of amount PH7-10 decocted 2 hours, added 9 times of water gagings for the second time and decocted 2 hours, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Salvia miltiorrhiza and Panax notoginseng extractum to pol 90%;

Step 5 is got the Radix Salviae Miltiorrhizae ethanol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, and the Radix Salviae Miltiorrhizae extractum that the Radix Notoginseng extract that step 2 obtains, step 4 obtain, Borneolum Syntheticum add an amount of mannitol, magnesium oxide, calcium carbonate mixing; Tabletting is made tablet.

The preparation of the medicine of embodiment 17 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82.87%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.92%;

Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and is added 2 times of amount 10% isopropyl alcohol warm macerating extraction 0.5 hour, filters, last medicinal residues add 2 times of pure warm macerating of amount and extracted 10 hours, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid, leave standstill to liquid PH value 1-4, filter, filtrate is crossed macroporous resin D101, successively the water eluting, 10% ethanol elution, 60% ethanol elution is collected 60% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;

Step 3, Radix Notoginseng add 50 times 50% ethanol, reflux, extract, 3 times, and each 3 hours, to filter, extracting solution concentrating under reduced pressure, drying obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 5, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 8 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;

Step 5 is got the Radix Salviae Miltiorrhizae ethanol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, and the Radix Salviae Miltiorrhizae extractum that the Radix Notoginseng extract that step 2 obtains, step 4 obtain, Borneolum Syntheticum add microcrystalline Cellulose, sodium carboxymethyl cellulose, gelatine size mixing; Granulate, make granule.

The preparation of the medicine of embodiment 18 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82.87%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.92%;

Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and is added 20 times of amount 10% normal propyl alcohol reflux, extract, 10 hours, filters, last medicinal residues add 20 times of amounts alcohol extraction 1.5 hours, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid, leave standstill to liquid PH value 1-4, filter, filtrate is crossed macroporous resin S-8, successively the water eluting, 10% ethanol elution, 60% ethanol elution is collected 60% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;

Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 8 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;

Step 5 is got the Radix Salviae Miltiorrhizae ethanol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, and the Radix Salviae Miltiorrhizae extractum that the Radix Notoginseng extract that step 2 obtains, step 4 obtain, Borneolum Syntheticum add appropriate amount of starch, Mel mix homogeneously; Make pill.

The preparation of the medicine of embodiment 19 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82.87%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.92%;

Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and is added 2 times of amount 10% normal propyl alcohol warm macerating extraction 0.5 hour, filters, last medicinal residues add 2 times of pure warm macerating of amount and extracted 10 hours, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid, leave standstill to liquid PH value 1-4, filter, filtrate is crossed macroporous resin D101, successively the water eluting, 10% ethanol elution, 60% ethanol elution is collected 60% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;

The preparation of the medicine of embodiment 20 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82.82%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.97%;

Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and is added 2 times of amount 10% normal propyl alcohol supersound extraction 0.5 hour, filters, last medicinal residues add 2 times of pure warm macerating of amount and extracted 10 hours, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid, leave standstill to liquid PH value 1-4, filter, filtrate is crossed macroporous resin D101, successively the water eluting, 10% ethanol elution, 60% ethanol elution is collected 60% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;

Claims

1. medicine for the treatment of coronary heart disease, described medicine is prepared from by following raw materials by weight percent medicine, Radix Salviae Miltiorrhizae 19.8%-97%, Radix Notoginseng 2%-80%, Borneolum Syntheticum 0.2%-3%, described preparation is earlier crude drug to be prepared into active constituents of medicine through following steps, further be prepared into medicine again

2. the medicine of the treatment coronary heart disease of claim 1 is for oral medicine, it is characterized in that preparation process is:

Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and is added 2-20 and doubly measured the 10-100% alcohol extraction 0.5-10 hour, filters, last medicinal residues add 2-20 and doubly measured the 10-100% alcohol extraction 0.5-10 hour, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid, leave standstill to liquid PH value 1-4, filter, filtrate is crossed macroporous resin, successively the water eluting, low concentration alcohol eluting, high concentration alcohol eluting is collected the high concentration alcohol eluen, concentrate, drying obtains the salvianolic acid B extract;

3. the medicine of the treatment coronary heart disease of claim 2 is drop pills, it is characterized in that, preparation process is:

4. the medicine of the treatment coronary heart disease of claim 3: it is characterized in that preparation process is:

Step 2, getting step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues adds 2-10 and doubly measured the 30-70% alcohol reflux 1-6 hour, filter, last medicinal residues add 2-10 and doubly measured the 30-70% alcohol reflux 1-6 hour, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to liquid PH value 1-3, leave standstill, filter, filtrate is crossed macroporous resin (S-8, AB-8 or D101), water eluting successively, 10-20% alcohol eluting is used the 40-70% ethanol elution at last, collect the 40-70% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;

5. the medicine of the treatment coronary heart disease of claim 4: it is characterized in that preparation process is:

6. the medicine of the treatment coronary heart disease of claim 5: it is characterized in that preparation process is:

Step 2 is got step 1 alcohol extraction medicinal residues, adds 3 times of amount 20% alcohol reflux 1hr, filter, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr, pulp board filters, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;

7. the medicine of the arbitrary described treatment coronary heart disease of claim 1-6: it is characterized in that, step 5 is, with the Radix Salviae Miltiorrhizae ethanol extract that obtains after step 1 extraction, the salvianolic acid B extract that step 2 obtains after extracting, the Radix Notoginseng extract that step 3 obtains after extracting, the Radix Salviae Miltiorrhizae extractum that step 4 obtains after extracting mixes with Borneolum Syntheticum and adjuvant, add any or more than one adjuvants, described adjuvant is selected from fat-soluble substrate and water-soluble base, and wherein fat-soluble substrate is selected from: stearic acid, glyceryl monostearate, insect wax, Cera Flava, paraffin, hydrogenated vegetable oil, semi-synthetic fatty acid ester; Water-soluble base is selected from Polyethylene Glycol, polyoxyethylene monostearate, poloxamer, sodium stearate, glycerin gelatine; Xylitol and composites of starch, erythritol.

8. the medicine of the treatment coronary heart disease of claim 7: it is characterized in that wherein step 5 medicine is auxilliary than being 1: 2.1.

9. the medicine of the treatment coronary heart disease of claim 7: it is characterized in that wherein said Polyethylene Glycol is a Polyethylene Glycol-6000.

10. the application of the medicine of the treatment coronary heart disease of claim 1 in the medicine of a kind of resisting coronary heart disease of preparation, angina pectoris cardiovascular disease.