CN102028744B

CN102028744B - Drug for treating coronary heart disease and preparation method

Info

Publication number: CN102028744B
Application number: CN2009100706841A
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: 2013-12-11
Anticipated expiration: 2029-09-29
Also published as: CN102028744A

Abstract

The invention relates to a drug for treating coronary heart disease and a preparation method. The preparation method comprises the following steps: extracting salvia and notoginseng with alcohol, extracting dregs of salvia with alcohol and the like. The invention has the following advantages: the process route can realize industrialization and the quality is stable and controllable. Relevant experiments show that the drug has the advantages of high curative effect and product purity, good absorbability, stable quality and novel application compared with the prior art, and meanwhile, the preparation method is simple in process, convenient to operate, low in cost and suitable for industrial production.

Description

A kind of medicine and preparation method 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, Patients with geriatric cardiovascular and cerebrovascular diseases 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, take the clinical syndrome that ictal chest pain or chest discomfort be main manifestations.Angina pectoris refers to 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 for the treatment of be take blood vessel dilating, reduction blood viscosity, anti-platelet aggregation, anticoagulation as main at present.Traditional Western medicine of application is nitrate, nitrous acid ester, beta-blocker, calcium antagonist etc., but all has larger toxic and side effects, unsuitable long-term taking, mostly be symptomatic treatment and to course advancement without larger effect.For example take after nitroglycerin occur sometimes beating in feeling of fullness in the head, head, palpitating speed, even faint [referring to 264 pages of new pharmacologies (the 14th edition)], find that there is again in recent years and 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, hindered its application clinically.

Although the anginal Chinese patent medicine of many treatments is also arranged, wherein ball, loose, cream, pellet, decoction become ancient history already, and the modern seldom applies.There are in the market the preparations such as common FUFANG DANSHEN PIAN and capsule to sell, but conventional tablet, capsule manufacture technique fall behind, active constituent content is low, without quality control index, need oral through gastrointestinal absorption, absorbed into serum after liver generation first pass effect, bioavailability is low, absorbs slow. can not be applicable to the need of the first aid of Patients With Angina Pectoris.

FUFANG DANSHEN DIWAN is fast, the eutherapeutic therapeutic drug of coronary heart disease of a kind of special effect, deeply is subject to clinically patient's welcome.In order to improve the preparation technology of FUFANG DANSHEN DIWAN, the inventor conducts in-depth research 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 for the treatment of coronary heart disease of the present invention, described medicine is prepared from by the crude drug of following percentage by weight, Radix Salviae Miltiorrhizae 19.8%-97%, Radix Notoginseng 2%-80%, Borneolum Syntheticum 0.2%-3%, described preparation is first crude drug to be prepared into to active constituents of medicine through following steps, more further is prepared into medicine.

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

Step 2, get step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, extracts, and filters, and filtrate is concentrated, lets cool, acid adding is regulated pH value, and cold preservation is standing, filters, and filtrate is crossed resin, washes successively low concentration alcohol eluting with water, high concentration alcohol eluting, collect the high concentration alcohol eluen, and concentrated, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds the solvent reflux, extract,, extracting liquid filtering, filtrate is concentrated into without the alcohol flavor, adding distil water, upper macroporous resin, first wash with water, and eluent discards, then uses pure eluting, collects alcohol eluen, and concentrated, drying, obtain Radix Notoginseng extract;

Step 4, the salvianolic acid B medicinal residues after step 2 alcohol extraction add, and aqueous alkali is or/and water extraction, and extracting solution is concentrated, adds alcohol, and standing, supernatant concentration, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract that step 1 obtains, the salvianolic acid B extract that step 2 obtains, the Radix Notoginseng extract that step 3 obtains, the Radix Salviae Miltiorrhizae extractum that step 4 obtains and Borneolum Syntheticum are further made drop pill;

Wherein the described solvent of step 3 is selected from: water, aqueous slkali or acid solution, wherein acid solution is selected from: the methanol of 50-100%, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol.

Medicine of the present invention is for oral medicine, its preparation adopts the preparation of galenic pharmacy routine techniques, comprise the step that active constituents of medicine is mixed with the adjuvant of oral drugs, wherein the adjuvant of oral drug preparation is selected from starch, 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 extractum pharmaceutics.

Its preferred preparation method of medicine that confession of the present invention is oral, step is:

Step 1, Radix Salviae Miltiorrhizae adds 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 tanshinol extract;

Step 2, get step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and add 2-20 and doubly measure 10-100% alcohol extraction 0.5-10 hour, filters, last medicinal residues add 2-20 and doubly measure 10-100% alcohol extraction 0.5-10 hour, filter, and filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to liquid PH value 1-4, standing, filter, filtrate is crossed macroporous resin, washes with water successively, low concentration alcohol eluting, high concentration alcohol eluting, collect the high concentration alcohol eluen, concentrated, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds alcohol reflux 1-2 time of 2-20 times of 50-100%, each extraction time 0.5-10 hour, extracting liquid filtering, filtrate is concentrated into without the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, upper macroporous resin (S-8, AB-8 or D101), first wash with water, eluent discards, use again 30-100% methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol eluting, collect alcohol eluen, concentrated, drying, obtain Radix Notoginseng extract;

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

Step 5, by tanshinol extract obtained above, 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 1-6 that the adjuvant addition is active component doubly, 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, its preparation adopts the preparation of galenic pharmacy routine techniques, comprises the step that active constituents of medicine is mixed with the adjuvant of drop pill medicine, and described adjuvant is selected from fat-soluble substrate and water-soluble base, and the auxiliary ratio of medicine is 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; Preferably the auxiliary ratio of medicine is 1: 2.7.

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

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

Step 2, getting step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues adds 2-15 and doubly measures 10-90% ethanol extraction 1-8 hour, filter, last medicinal residues add 2-15 and doubly measure 10-90% ethanol extraction 1-8 hour, filter, and filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1-3, standing, filter, filtrate is crossed macroporous resin (S-8, AB-8 or D101), wash with water successively, 5-20% alcohol eluting, finally use the 40-90% ethanol elution, collect the 40-90% ethanol elution, concentrated, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds alcohol reflux 1-2 time of 2-10 times of 60-80%, each extraction time 0.5-3 hour, extracting liquid filtering, filtrate is concentrated into without the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, upper macroporous resin (S-8, AB-8 or D101), first wash with water, eluent discards, use again the 30-60% ethanol elution, collect alcohol eluen, concentrated, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, the aqueous alkali that adds for the first time 2-12 doubly to measure PH7-8 decocts 1-3 hour, adds for the second time 2-12 times of water gaging to decoct 0.5-2 hour, obtains extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 50%-80%, standing 12-36 hour, separation of supernatant containing alcohol, reclaim ethanol, receive cream to pol 55%-80%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract of step 1, the salvianolic acid B extract, Radix Notoginseng extract is suspended in the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add again Borneolum Syntheticum, mix; 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.

Step 1, Radix Salviae Miltiorrhizae adds 2-5 and doubly measures 95% ethanol, reflux, extract, 1-3 time, each 1-3 hour, filter, and 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 measures 30-70% alcohol reflux 1-6 hour, filter, last medicinal residues add 2-10 and doubly measure 30-70% alcohol reflux 1-6 hour, filter, and filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to liquid PH value 1-3, standing, filter, filtrate is crossed macroporous resin (S-8, AB-8 or D101), wash with water successively, 10-20% alcohol eluting, finally use the 40-70% ethanol elution, collect the 40-70% ethanol elution, concentrated, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds alcohol reflux 1-2 time of 5-10 times of 60-80%, each extraction time 0.5-3 hour, extracting liquid filtering, filtrate is concentrated into without the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, upper macroporous resin (S-8, AB-8 or D101), first wash with water, eluent discards, use again the 40-60% ethanol elution, collect alcohol eluen, concentrated, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, the aqueous alkali that adds for the first time 6-12 doubly to measure PH7-8 decocts 1-3 hour, adds for the second time 6-12 times of water gaging to decoct 0.5-2 hour, obtains extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 50%-75% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 55%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract of step 1, the salvianolic acid B extract, Radix Notoginseng extract is suspended in the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add again Borneolum Syntheticum, mix; 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 adds 2-3 and doubly measures 95% ethanol, reflux, extract, 2 times, each 1-2 hour, filter, and extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, get 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 without alcohol, lets cool to below 10 ℃, add dilute hydrochloric acid and regulate pH value 1.8-2.0, more than the standing 12hr of cold preservation, filter upper AB-8 macroporous resin eluting, first wash with water, eluent discards; With 15% ethanol, wash again,, eluent discards; Finally with 50% ethanol, wash, collect 50% ethanol elution, concentrating under reduced pressure, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds the alcohol reflux 2 times of 5-10 times of 60-80%, each extraction time 1-2 hour, extracting liquid filtering, filtrate is concentrated into without the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, upper macroporous resin (S-8, AB-8 or D101), first wash with water, eluent discards, use again the 40-60% ethanol elution, collect alcohol eluen, concentrated, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, the aqueous alkali that adds for the first time 6-12 doubly to measure PH7-8 decocts 1-3 hour, adds for the second time 8 times of water gagings to decoct 1 hour, obtains extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract of step 1, the salvianolic acid B extract, Radix Notoginseng extract is suspended in the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add again Borneolum Syntheticum, mix; 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 the cardiovascular disease such as a kind of resisting coronary heart disease of preparation, angina pectoris by treatment coronary heart disease of the present invention.

The present invention is more more superior than prior art because the change of technique 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.

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

After myocardial ischemia-reperfusion, in tissue, high-energy phosphate compound obviously reduces, and the lipid peroxide contents showed increased, cause reperfusion injury.Add the medicinal dropping ball for the treatment of coronary heart disease during pre-perfusion and during postischemic reperfusion before ischemia, in tissue, high-energy phosphate compound is all higher than ischemic reperfusion notes group, two groups of adenosine triphosphate (ATP), cardiac muscular tissue's gland nucleoside total amount (TAN) all approach normal level, and LPO levels is lower than ischemic reperfusion notes group.This result proves, the medicinal dropping ball for the treatment of coronary heart disease before ischemia during pre-perfusion during with postischemic reperfusion all can be by increasing the cardiac energy deposit, the generation of inhibition lipid peroxide and protecting myocardial cell.

Cardiomyocyte cell death is damage type the most serious in myocardial ischemia-reperfusion, comprises necrocytosis and apoptosis.The apoptotic regulation and control that expressed by several genes.Myocardial infarction rear section myocardial cell apoptosis, probably relevant with Scavenging Oxygen Free Radical with the cell calcium overload due to ischemia.The medicinal dropping ball for the treatment of coronary heart disease can obviously reduce apoptosis of cardiac muscle quantity after 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 for the treatment of coronary heart disease.Carrying out the anoxia experiment in the myocardial cell of cultivating shows, the medicinal dropping ball intervention for the treatment of coronary heart disease can obviously be lowered apoptotic proteins Fas and be expressed, slight upregulation of apoptosis Profilin Bc1-2 expresses, and further the medicinal dropping ball of demonstration treatment coronary heart disease has certain influence to the protein expression of apoptosis-related genes in cell.

The medicinal dropping ball for the treatment of 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 induced by endotoxin for the treatment of coronary heart disease and the improvement effect of the caused microcirculation disturbance of ischemia-reperfusion, the Rat Mesenteric Microcirculation obstacle that the medicinal dropping ball of confirmation treatment coronary heart disease causes ischemia-reperfusion improves significantly, and 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 molecules after ischemia-reperfusion, peroxidating and leukocyte and endotheliocyte.

The medicinal dropping ball for the treatment of coronary heart disease has more obviously impact to patient's bulbar Conjunctiva Microcirculation, thrombelastogram, patient's arteriole vessel diameter broadening after 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 for the treatment of coronary heart disease, the balance between the formation of inhibition atherosclerotic plaque and neointimal hyperplasia vascular endothelial cell associated media nitric oxide (NO) and vasoconstrictive factor endothelin-1 (ET-1) etc. is maintaining the stability of blood vessel.After damage, the medicinal dropping ball for the treatment of coronary heart disease of variable concentrations all obviously alleviates human vascular endothelial damage due to LPS, illustrate that the medicinal dropping ball for the treatment of coronary heart disease has obvious protective effect to vascular endothelial cell.Variable concentrations is treated to the medicinal dropping ball of coronary heart disease for the culture fluid before and after the Hydroperoxide injury modeling, discovery generates at the medicinal dropping ball energy balance NO of prevention and treatment group treatment coronary heart disease, significantly increase cytoactive, endothelial injury due to hydrogen peroxide is had to obvious antagonism.

Atherosclerotic lesion is that a kind of protectiveness inflammation to local damage-fiber proliferative is responded.In the Mottling formation process, lipidosis is most important factor.The medicinal dropping ball treatment for the treatment of coronary heart disease can reduce T-CHOL (T ℃) and low density lipoprotein, LDL (LDL) cholesterol levels, high density lipoprotein increasing (HDL) cholesterol levels.Ma Xiao waits quietly observing the medicinal dropping ball for the treatment of coronary heart disease to damaging the impact of interior film healing situation with similar method modeling, find that the postoperative NO concentration of medicinal dropping ball group for the treatment of 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, therefore think that the medicinal dropping ball for the treatment of coronary heart disease can promote to damage the reparation of inner membrance, reduces neointimal hyperplasia.

The medicinal dropping ball for the treatment of coronary heart disease increases coronary flow, improves blood flow and uprises lipidemia and can cause vascular endothelial injury, come off, platelet adhesion reaction and gathering.The medicinal dropping ball for the treatment of coronary heart disease can significantly increase the rat coronary flow but not increase heart rate, contributes to improve the supply of heart oxygen and nutrient substance.The medicinal dropping ball for the treatment of 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 for the treatment of coronary heart disease suppresses platelet adhesion reaction and gathering Endothelial dysfunction, endothelium integrity destruction can trigger a series of molecules and biochemical reaction is stagnated blood flow, and blood vessel wall reparation, inhibition or antagonism platelet adhesion reaction and gathering are to prevent thrombotic key link.Medicinal dropping ball D-dimer and the gathering for the treatment of coronary heart disease are to play a role from multiple location, stage construction and many target spots.

The medicinal dropping ball for the treatment of 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 for the treatment of 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) while being platelet activation.Before treatment, treatment group and matched group GMP-140 level are apparently higher than the Healthy People group, after the medicinal dropping ball associating aspirin for treatment for the treatment of coronary heart disease, treatment group angina pectoris symptom, electrocardiogram ischemia improve, blood plasma GMP-140 level is than the remarkable reduction of matched group (singly taking aspirin), with the Healthy People group without significant difference.To the aspirin resistance person, the medicinal dropping ball of add-on 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 for the treatment of coronary heart disease has above-mentioned multiple target effect, it is to all kinds coronary heart disease, comprises that the perioperative treatment etc. of stable or unstable angina pectoris, myocardial infarction, heart failure, silent ischemia and intervention all has remarkable result.

Following experimental data is for illustrating effect of the present invention: the medicine that experimental drug is the embodiment of the present 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/%
							Treatment group	51	23	27	1	0	98.1①
Matched group	51	10	29	11	1	78

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

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/%
							Treatment group	51	10	21	20	0	60.8①
Matched group	51	3	17	29	2	39.2

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

Before and after the medicinal dropping ball treatment of table 3 treatment coronary heart disease, hemorheology index changes (x ± s)

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

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

That the present invention adopts the modern pharmacy technology to develop is efficient, quick-acting, the pure TCM Dripping Pills of multiple-effect, prevent and treat the coronary heart disease determined curative effect, and can improve the blood capillary circulation, to the diabetes microvascular complication, comprise that diabetic renal papillary necrosis and diabetic nephropathy all have good preventive and therapeutic effect.

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

The specific embodiment

Below with embodiment, illustrate the present invention, embodiment is for the ease of understanding the present invention, and the claim do not limited 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 adds 3 times of amount 95% ethanol, and reflux, extract, 2 hours, filter; Medicinal residues add 2 times of amount 95% ethanol, and reflux, extract, 1 hour, filter, and extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, get step 1 Radix Salviae Miltiorrhizae 95% alcohol extraction medicinal residues, adds 5 times of amount 40% alcohol reflux 1.5hr, filter, last medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, and filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, more than the standing 12hr of cold preservation, AB-8 macroporous resin on filtrate, first wash with water, eluent discards; Use 15% alcohol wash, eluent discards again; Finally use 50% alcohol wash, collect 50% pure washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 8 times of amount 70% alcohol reflux 2hr, and last medicinal residues add 6 times of amount 70% alcohol reflux 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 2 times medical material amount, upper AB-8 macroporous resin, first wash with water, eluent discards, then uses 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, the medicinal residues of salvianolic acid B after the ethanol extraction of step 2, add for the first time the aqueous alkali of 8 times of amount PH7-8 to decoct 2 hours, add for the second time 8 times of water gagings to decoct 1 hour, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract obtained after said extracted, the salvianolic acid B extract, Radix Notoginseng extract is suspended in the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add again Borneolum Syntheticum, mix; 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 adds 2 times of amount 85% ethanol, reflux, extract, 1 time, each 1 hour, to filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 85% ethanol extract;

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, more than the standing 12hr of cold preservation, filter, upper AB-8 macroporous resin, first wash with water, and eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 8 times of amount 70% alcohol reflux 1hr, and last medicinal residues add 6 times of amount 70% alcohol reflux 1.5hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 2 times medical material amount, upper AB-8 macroporous resin, first wash with water, eluent discards, then uses 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, add the aqueous alkali of 2 times of amount PH7-8 to decoct for the first time 1 hour, adds for the second time 2 times of water gagings to decoct 0.5 hour, obtain extracting solution, extracting solution is concentrated into 1.12/80 ± 1 ℃, and concentrated solution lets cool 25-30 ℃, adds ethanol to medicinal liquid and measures 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtains Radix Salviae Miltiorrhizae extractum;

The preparation of the medicine of embodiment 3 treatment coronary heart disease, 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 adds 5 times of amount 95% ethanol, reflux, extract, 3 times, each 3 hours, to filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, get step 1 alcohol extraction medicinal residues, adds 8 times of amount 60% alcohol reflux 4hr, filter, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, more than the standing 12hr of cold preservation, filter, upper AB-8 macroporous resin, first wash with water, and eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 6 times of amount 70% alcohol reflux 2hr, and last medicinal residues add 7 times of amount 70% alcohol reflux 3hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper AB-8 macroporous resin, first wash with water, eluent discards, then uses 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, add for the first time the aqueous alkali of 6 times of amount PH7-8 to decoct 3 hours, add for the second time 6 times of water gagings to decoct 2 hours, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, add Borneolum Syntheticum, mixes; Add appropriate dextrin, mucialga of arabic gummy to mix, granulate; Incapsulate, make capsule.

The preparation of the medicine of embodiment 4 treatment coronary heart disease, 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 adds 2 times of amount 75% ethanol, reflux, extract, twice, each 2 hours, to filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 75% ethanol extract;

Step 2, get 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, filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, more than the standing 12hr of cold preservation, pulp board filters, upper AB-8 macroporous resin, first wash with water, and eluent discards; With 10% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 8 times of amount 60% alcohol reflux 1hr, and last medicinal residues add 6 times of amount 80% alcohol reflux 3hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 3 times medical material amount, upper AB-8 macroporous resin, first wash with water, eluent discards, then uses 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 2, add for the first time the aqueous alkali of 8 times of amount PH7-8 to decoct 2 hours, add for the second time 6 times of water gagings to decoct 1 hour, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, add Borneolum Syntheticum, mixes; Add microcrystalline Cellulose, sodium carboxymethyl cellulose, gelatine size to mix; Granulate, the granulation agent.

The preparation of the medicine of embodiment 5 treatment coronary heart disease, 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 adds 5 times of amount 95% ethanol, and reflux, extract, twice, filter, and extracting solution concentrating under reduced pressure, drying, obtain the tanshinol extract.

Step 2, get 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, filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, more than the standing 12hr of cold preservation, pulp board filters, upper AB-8 macroporous resin, first wash with water, and eluent discards; With 20% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 2 times of amount 70% alcohol reflux 2hr, and last medicinal residues add 20 times of amount 70% alcohol reflux 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 2 times medical material amount, upper AB-8 macroporous resin, first wash with water, eluent discards, then uses 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, add for the first time the aqueous alkali of 8 times of amount PH7-8 to decoct 2 hours, add for the second time 6 times of water gagings to decoct 1 hour, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

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

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.0-4.0, more than the standing 12hr of cold preservation, upper AB-8 macroporous resin, first wash with water, eluent discards; With 10% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 5 times of amount 60% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 60% alcohol reflux 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper S-8 macroporous resin, first wash with water, eluent discards, then uses 50% methanol-eluted fractions, collect 50% meoh eluate, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

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

Step 2, get step alcohol extraction medicinal residues, adds 2 times of amount 10% ethanol warm macerating and extract 2hr, filter, medicinal residues add 4 times of amount 90% ethanol warm macerating and extract 1hr, filter, filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, more than the standing 12hr of cold preservation, filter, upper AB-8 macroporous resin, first wash with water, and eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 40% ethanol, wash, collect 40% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 5 times of amount 60% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 60% alcohol reflux 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 40% normal propyl alcohol eluting, collect 40% normal propyl alcohol eluent, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 5, the tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, add Borneolum Syntheticum, mixes; Add appropriate mannitol, magnesium oxide, calcium carbonate to mix; Tabletting, make 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 adds 12 times of amount 95% n-butyl alcohol, and reflux, extract, 2 hours, filter; Medicinal residues add 2 times of amount 95% n-butyl alcohol, and reflux, extract, 1 hour, filter, and extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-4.0, more than the standing 12hr of cold preservation, upper AB-8 macroporous resin, first wash with water, eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 60% ethanol, wash, collect 60% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 5 times of amount 60% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 60% alcohol reflux 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 60% isopropyl alcohol alcohol eluting, collect 60% isopropyl alcohol eluent, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 5, the tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, add Borneolum Syntheticum, mixes; Add appropriate vegetable oil, according to the soft capsule preparation method, make soft capsule.

The preparation of the medicine 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 adds 8 times of amount 80% ethanol, and reflux, extract, 2 hours, filter; Medicinal residues add 4 times of amount 80% ethanol, and reflux, extract, 1 hour, filter, and extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 80% ethanol extract;

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.0-2.0, more than the standing 12hr of cold preservation, upper S-8 macroporous resin, first wash with water, eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% n-butyl alcohol, wash, collect 50% n-butyl alcohol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 5 times of amount 60% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 60% alcohol reflux 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 40% ethanol elution, collect 40% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 5, the tanshinol extract obtained after said extracted, the salvianolic acid B extract, Radix Notoginseng extract is suspended in the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add again Borneolum Syntheticum, mix; 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 adds 5 times of amount 75% ethanol, and reflux, extract, 2 hours, filter; Medicinal residues add 3 times of amount 75% ethanol, and reflux, extract, 1 hour, filter, and extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 75% ethanol extract;

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-4.0, more than the standing 12hr of cold preservation, upper AB-8 macroporous resin, first wash with water, eluent discards; With 13% ethanol, wash, eluent discards again; Finally use 50% isobutyl alcohol wash, collect 50% isobutanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 5, the tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, add Borneolum Syntheticum, mixes; Add appropriate calcium stearate, Pulvis Talci, Macrogol 4000, mix; Make micropill.

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

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, more than the standing 12hr of cold preservation, upper AB-8 macroporous resin, first wash with water, eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 6 times of amount 50% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 50% alcohol reflux 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 30% ethanol elution, collect 30% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, add for the first time the aqueous alkali of 2 times of amount PH7-8 to decoct 2 hours, add for the second time 2 times of water gagings to decoct 1 hour, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, add Borneolum Syntheticum, mixes; Add appropriate amylum pregelatinisatum, zinc stearate, calcium stearate, mix, make tablet.

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

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, more than the standing 12hr of cold preservation, upper AB-8 macroporous resin, first wash with water, eluent discards; With 10% ethanol, wash, eluent discards again; Finally with 55% ethanol, wash, collect 55% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 6 times of amount 50% methanol eddies and extracts 2hr, and last medicinal residues add 18 times of amount 50% methanol eddies again and extract 1hr, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, add for the first time the aqueous alkali of 12 times of amount PH7-8 to decoct 2 hours, add for the second time 12 times of water gagings to decoct 1 hour, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

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

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

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, more than the standing 12hr of cold preservation, upper AB-8 macroporous resin, first wash with water, eluent discards; With 13% ethanol, wash, eluent discards again; Finally with 65% ethanol, wash, collect 65% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 5 times of amount 60% normal propyl alcohol reflux, extract, 2hr, and last medicinal residues add 10 times of amount 60% normal propyl alcohol reflux, extract, 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 40% ethanol elution, collect 40% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, add for the first time the aqueous alkali of 7 times of amount PH7-8 to decoct 2 hours, add for the second time 6 times of water gagings to decoct 1 hour, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 50%-80% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 50%, obtain Radix Salviae Miltiorrhizae extractum;

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

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, more than the standing 12hr of cold preservation, upper D101 macroporous resin, first wash with water, eluent discards; With 10% ethanol, wash, eluent discards again; Finally with 70% ethanol, wash, collect 70% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 6 times of amount 50% isopropyl alcohol reflux, extract, 2hr, and last medicinal residues add 18 times of amount 50% isopropyl alcohol reflux, extract, 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, add for the first time the aqueous alkali of 7 times of amount PH7-10 to decoct 2 hours, add for the second time 6 times of water gagings to decoct 1 hour, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 50%-80% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 90%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, add Borneolum Syntheticum, mixes; Add appropriate vegetable oil, mix; Make soft capsule according to the soft capsule conventional method.

The preparation of the medicinal dropping ball 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 adds 4 times of amount 95% ethanol, and reflux, extract, 2 hours, filter; Medicinal residues add 3 times of amount 95% ethanol, and reflux, extract, 2 hours, filter, and extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, more than the standing 12hr of cold preservation, upper AB-8 macroporous resin, first wash with water, eluent discards; With 13% ethanol, wash, eluent discards again; Finally with 65% ethanol, wash, collect 65% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 6 times of amount 50% n-butyl alcohol reflux, extract, 2hr, and last medicinal residues add 7 times of amount 50% n-butyl alcohol reflux, extract, 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

The preparation of the medicinal dropping ball 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 adds 3 times of amount 90% ethanol, and reflux, extract, 2.5 hours, filter; Medicinal residues add 2 times of amount 90% ethanol, and reflux, extract, 1.5 hours, filter, and extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 90% ethanol extract;

Step 2, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, more than the standing 12hr of cold preservation, upper AB-8 macroporous resin, first wash with water, eluent discards; With 13% ethanol, wash, eluent discards again; Finally with 70% ethanol, wash, collect 70% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 6 times of amount 50% isobutanol reflux, extract, 1hr, and last medicinal residues add 10 times of amount 50% isobutanol reflux, extract, 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 2 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, add for the first time the aqueous alkali of 6 times of amount PH7-10 to decoct 2 hours, add for the second time 9 times of water gagings to decoct 2 hours, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 50%-80% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 90%, obtain Salvia miltiorrhiza and Panax notoginseng extractum;

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, get 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 without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-2.5, more than the standing 12hr of cold preservation, upper AB-8 macroporous resin, first wash with water, eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds 6 times of amount 50% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 50% alcohol reflux 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper D101 macroporous resin, first wash with water, eluent discards, then uses 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 5, add 8 times of amount PH7-8 for the first time, and 0.2% sodium bicarbonate solution decocts 2 hours, add for the second time 8 times of water gagings to decoct 1 hour, obtain extracting solution, extracting solution is concentrated, adds ethanol to medicinal liquid and measures 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtains Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, add Borneolum Syntheticum, mixes; Add appropriate dextrin, refined honey, mix, make pill.

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, get step 1 alcohol extraction medicinal residues, adds 5 times of amount 40% alcohol reflux 1.5hr, filter, last medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, filtrate is evaporated to below 55 ℃ without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, more than the standing 12hr of cold preservation, filter, upper AB-8 macroporous resin, first wash with water, and eluent discards; With 15% ethanol, wash again,, eluent discards; Finally with 50% ethanol, wash, collect 50% ethanol elution, concentrating under reduced pressure, drying, obtain the salvianolic acid B extract.

Step 3, Radix Notoginseng adds 6 times of amount 50% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 50% alcohol reflux 1hr again, extracting liquid filtering, be concentrated into without alcohol flavor, adding distil water to 1 times medical material amount, upper AB-8 macroporous resin, first wash with water, eluent discards, then uses 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying, obtain Radix Notoginseng extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, add for the first time the aqueous alkali of 8 times of amount PH7-8 to decoct 2 hours, add for the second time 8 times of water gagings to decoct 1 hour, obtain extracting solution, extracting solution is concentrated, add ethanol to medicinal liquid and measure 60%-70% containing alcohol, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, add Borneolum Syntheticum, mixes; Add to fit and can press starch, mix; Make tablet.

Claims

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

Step 3, Radix Notoginseng adds alcohol reflux 1-2 time of 2-20 times of 50-100%, each extraction time 0.5-10 hour, extracting liquid filtering, filtrate is concentrated into without the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, upper S-8, AB-8 or D101 macroporous resin, first wash with water, eluent discards, use again 30-100% methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol eluting, collect alcohol eluen, concentrated, 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 again 2-12 times of water, extract 1-3 time, filter, filtrate is concentrated, add ethanol to medicinal liquid and measure 50-80% containing alcohol, standing, separation of supernatant, reclaim ethanol, receive cream to pol 50%-90% or concentrated, dry, pulverizing, obtain Radix Salviae Miltiorrhizae extractum;

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

Step 2, getting step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues adds 2-15 and doubly measures 10-90% ethanol extraction 1-8 hour, filter, last medicinal residues add 2-15 and doubly measure 10-90% ethanol extraction 1-8 hour, filter, and filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1-3, standing, filter, filtrate is crossed S-8, AB-8 or D101 macroporous resin, wash with water successively, 5-20% alcohol eluting, finally use the 40-90% ethanol elution, collect the 40-90% ethanol elution, concentrated, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds alcohol reflux 1-2 time of 2-10 times of 60-80%, each extraction time 0.5-3 hour, extracting liquid filtering, filtrate is concentrated into without the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, upper S-8, AB-8 or D101 macroporous resin, first wash with water, eluent discards, use again the 30-60% ethanol elution, collect alcohol eluen, concentrated, drying, obtain Radix Notoginseng extract;

3. the medicine of the treatment coronary heart disease of claim 1: 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 measures 30-70% alcohol reflux 1-6 hour, filter, last medicinal residues add 2-10 and doubly measure 30-70% alcohol reflux 1-6 hour, filter, and filtrate is concentrated into without alcohol, let cool to below 10 ℃, add dilute hydrochloric acid to liquid PH value 1-3, standing, filter, filtrate is crossed S-8, AB-8 or 9101 macroporous resins, wash with water successively, 10-20% alcohol eluting, finally use the 40-70% ethanol elution, collect the 40-70% ethanol elution, concentrated, drying, obtain the salvianolic acid B extract;

Step 3, Radix Notoginseng adds alcohol reflux 1-2 time of 5-10 times of 60-80%, each extraction time 0.5-3 hour, extracting liquid filtering, filtrate is concentrated into without the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, upper S-8, AB-8 or D101 macroporous resin, first wash with water, eluent discards, use again the 40-60% ethanol elution, collect alcohol eluen, concentrated, drying, obtain Radix Notoginseng extract;

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

Step 3, Radix Notoginseng adds the alcohol reflux 2 times of 5-10 times of 60-80%, each extraction time 1-2 hour, extracting liquid filtering, filtrate is concentrated into without the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, upper S-8, AB-8 or D101 macroporous resin, first wash with water, eluent discards, use again the 40-60% ethanol elution, collect alcohol eluen, concentrated, drying, obtain Radix Notoginseng extract;

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

6. the medicine of the arbitrary described treatment coronary heart disease of claim 1-5: it is characterized in that, step 5 is, the tanshinol extract obtained after step 1 is extracted, 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, 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.

7. the medicine of the treatment coronary heart disease of claim 6: it is characterized in that, wherein the auxiliary ratio of step 5 medicine is 1: 2.7.

8. the medicine of the treatment coronary heart disease of claim 6: it is characterized in that, wherein said Polyethylene Glycol is PEG-4000.

9. 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.