CN102028743B

CN102028743B - Medicament for treating coronary heart disease and preparation method thereof

Info

Publication number: CN102028743B
Application number: CN200910070683.7A
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: 2014-12-24
Anticipated expiration: 2029-09-29
Also published as: CN102028743A

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 growth in the living standard, world population ages and morbidity colony rejuvenation, 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 myocardium ischemia, anoxia, with ictal chest pain or the uncomfortable clinical syndrome for main manifestations of chest.Angina pectoris refers to the angina pectoris because coronary atherosclerosis or spasm cause caused by myocardial ischemia, anoxia, accounts for 90% of patient with angina pectoris.

The anginal method of current treatment is based on blood vessel dilating, reduction blood viscosity, anti-platelet aggregation, anticoagulation.Traditional Western medicine of application is nitrate, nitrous acid ester, beta-blocker, calcium antagonist etc., but all there is larger toxic and side effects, unsuitable long-term taking, mostly is symptomatic treatment and to course advancement without larger effect.Such as, occur sometimes after taking nitroglycerin beating in feeling of fullness in the head, head, palpitating speed, even faint [see new pharmacology (the 14th edition) 264 pages], find that there is again in recent years and cause severe hypotension [see contemporary Chinese medical journal 1997; 7 (4): 42; Shaanxi medical journal 1996; 25 (5): 315] toleration, is easily produced [see southern nursing magazine 1996; The problem such as 3 (5): 7 ~ 9], hinders its application clinically.

Although also there is the anginal Chinese patent medicine of many treatments, wherein ball, loose, cream, pellet, decoction become ancient history already, and modern seldom applies.The preparations such as common FUFANG DANSHEN PIAN and capsule are had to sell in the market, but conventional tablet, capsule manufacturing techniques 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. the need of the first aid of Patients With Angina Pectoris can not be applicable to.

FUFANG DANSHEN DIWAN is fast, the eutherapeutic therapeutic drug of coronary heart disease of a kind of special effect, clinically deeply by the welcome of patient.In order to improve the preparation technology of FUFANG DANSHEN DIWAN, the present inventor conducts in-depth research from extraction process aspect, from saving herb resource aspect, improves product yield, the comprehensive utilization ratio of effective ingredient contained by 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 first crude drug is prepared into active constituents of medicine through following steps, then be prepared into medicine further.

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

Step 2, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, extracts, and filters, and filtrate concentrates, and lets cool, add acid for adjusting pH value, cold preservation leaves standstill, and filter, filtrate crosses resin, washes with water successively, low concentration alcohol eluting, high concentration alcohol eluting, collects high concentration alcohol eluen, concentrated, dry, obtains salvianolic acid B extract;

Step 3, Radix Notoginseng adds alcohol, extracts, and extracting solution is concentrated, dry, obtains 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 concentrates, and adds alcohol, and leave standstill, supernatant concentration, obtains 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 make drop pill further.

Medicine of the present invention is for oral medicine, its preparation adopts the preparation of galenic pharmacy routine techniques, comprise the step mixed with the adjuvant of oral drugs by active constituents of medicine, wherein the adjuvant of oral drug preparation is selected from starch, amylum pregelatinisatum, dextrin, Icing Sugar, lactose, mannitol, calcium sulfate two water thing, 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 the methanol of 2-12 times of 70-100%, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol, reflux, extract, and filter, extracting solution concentrating under reduced pressure, drying, obtain tanshinol extract;

Step 2, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and adds 2-20 times amount 10-100% alcohol extraction 0.5-10 hour, filters, remaining medicinal residues add 2-20 times amount 10-100% alcohol extraction 0.5-10 hour, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 1-4, leave standstill, filter, filtrate crosses macroporous resin, washes with water successively, low concentration alcohol eluting, high concentration alcohol eluting, collects high concentration alcohol eluen, concentrated, dry, obtain salvianolic acid B extract;

Step 3, Radix Notoginseng adds the methanol of 2-20 times of 50-100%, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol, reflux, extract, 2 times, each extraction time 0.5-10 hour, and 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 alcohol content 50-80%, leave standstill, 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, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum mixes with adjuvant with Borneolum Syntheticum, adds any one or more than one adjuvants, and adjuvant addition is 1-6 times of active component, makes any one oral formulations;

Wherein described in step 2, alcohol extraction mode is selected from: the extraction of reflux, extract, warm macerating, 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, and comprise the step mixed with the adjuvant of drop pill medicine by active constituents of medicine, 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; The auxiliary ratio of preferred medicine is 1: 2.1.

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, and filter, extracting solution concentrating under reduced pressure, drying, obtain tanshinol extract;

Step 2, get step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and add 2-15 times amount 10-90% ethanol extraction 1-8 hour, filter, remaining medicinal residues add 2-15 times amount 10-90% ethanol extraction 1-8 hour, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 1-3, leave standstill, filter, filtrate crosses macroporous resin (S-8, AB-8 or D101), wash with water successively, 5-20% alcohol eluting, finally uses 40-90% ethanol elution, collect 40-90% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;

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

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, the aqueous alkali that first time adds 2-12 times amount PH7-8 decocts 1-3 hour, and second time adds 2-12 times amount soak by water 0.5-2 hour, obtains extracting solution, extracting solution concentrates, add ethanol to medicinal liquid alcohol content 50%-80%, leave standstill 12-36 hour, separation of supernatant, reclaim ethanol, receive cream to pol 55%-80%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, the tanshinol extract of step 1, salvianolic acid B extract, Radix Notoginseng extract is suspended in the pre-PEG-6000 melted successively; Radix Salviae Miltiorrhizae extractum adds water mix homogeneously; Said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Material temperature is 60-100 DEG C; The temperature of liquid paraffin is 0-10 DEG C, makes drop pill; Wherein described in step 2, alcohol extraction mode is selected from: the extraction of reflux, extract, warm macerating, supersound extraction or dynamic countercurrent extraction.

Step 1, Radix Salviae Miltiorrhizae adds 2-5 times amount 95% ethanol, reflux, extract, 1-3 time, each 1-3 hour, and filter, 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 and add 2-10 times amount 30-70% alcohol reflux 1-6 hour, filter, remaining medicinal residues add 2-10 times amount 30-70% alcohol reflux 1-6 hour, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to liquid PH value 1-3, leave standstill, filter, filtrate crosses macroporous resin (S-8, AB-8 or D101), wash with water successively, 10-20% ethanol elution, finally use 40-70% ethanol elution, collect 40-70% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;

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

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, the aqueous alkali that first time adds 6-12 times amount PH7-8 decocts 1-3 hour, and second time adds 6-12 times amount soak by water 0.5-2 hour, obtains extracting solution, extracting solution concentrates, add ethanol to medicinal liquid alcohol content 50%-75%, leave standstill 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, salvianolic acid B extract, Radix Notoginseng extract is suspended in the pre-PEG-6000 melted successively; Radix Salviae Miltiorrhizae extractum adds water mix homogeneously; Said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Material temperature is 60-100 DEG C; The temperature of liquid paraffin is 0-10 DEG C, 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 times amount 95% ethanol, reflux, extract, 2 times, each 1-2 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, adds the alcohol reflux 2 times of 4-6 times amount 40-60%, each 1-2hr, filter, filtrate is concentrated into without alcohol, lets cool to less than 10 DEG C, add dilute hydrochloric acid adjust ph 1.8-2.0, cold preservation leaves standstill more than 12hr, filters, upper AB-8 macroporous resin eluting, first wash with water, eluent discards; Wash with 15% ethanol again, eluent discards; Finally wash with 50% ethanol, collect 50% ethanol elution, concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

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

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, the aqueous alkali that first time adds 6-12 times amount PH7-8 decocts 1-3 hour, and second time adds 8 times amount soak by water 1 hour, obtains extracting solution, extracting solution concentrates, add ethanol to medicinal liquid alcohol content 60%-70%, leave standstill 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, salvianolic acid B extract, Radix Notoginseng extract is suspended in the pre-PEG-6000 melted successively; Radix Salviae Miltiorrhizae extractum adds water mix homogeneously; Said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Material temperature is 60-100 DEG C; The temperature of liquid paraffin is 5-10 DEG C, makes drop pill.

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

Illustrate that the present invention treats the beneficial effect of the medicinal dropping ball of coronary heart disease below by way of experimental data.

Before Myocytes Anoxia, add the medicinal dropping ball for the treatment of coronary heart disease of the present invention, intracellular calcium fluorescence intensity obviously declines, 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 lipid peroxide contents showed increased, causes reperfusion injury.Before ischemia during pre-filled and postischemic reperfusion time add treatment coronary heart disease medicinal dropping ball, in tissue, high-energy phosphate compound is all higher than ischemic reperfusion note group, two groups of adenosine triphosphate (ATP), cardiac muscular tissue's gland nucleoside total amount (TAN) are all close to normal level, and LPO levels is lower than ischemic reperfusion note group.This result proves, before ischemia during pre-filled and postischemic reperfusion time give to treat the medicinal dropping ball of coronary heart disease all by increasing cardiac energy deposit, the generation of anti-lipid peroxidation thing and protecting myocardial cell.

Cardiomyocyte cell death is damage type the most serious in myocardial ischemia-reperfusion, comprises necrocytosis and apoptosis.The regulation and control that apoptotic generation is expressed by several genes.Myocardial infarction rear section myocardial cell generation apoptosis, probably overloads with the cell calcium caused by ischemia relevant with Scavenging Oxygen Free Radical.The medicinal dropping ball for the treatment of coronary heart disease obviously can reduce apoptosis of cardiac muscle quantity after myocardial ischemia-reperfusion, reduces the myocardial infarct size of ischemia-reperfusion rat, significantly alleviates pathology damage degree, and stronger with the medicinal dropping ball dosage increasing effect for the treatment of coronary heart disease.Anoxia experiment display is carried out in cultured myocyte, the medicinal dropping ball intervention for the treatment of coronary heart disease obviously can be lowered apoptotic proteins Fas and be expressed, slight upregulation of apoptosis Profilin Bcl-2 expresses, and the medicinal dropping ball of display treatment coronary heart disease has certain influence to the protein expression of apoptosis-related genes in cell further.

The medicinal dropping ball for the treatment of coronary heart disease improves microcirculation albumin outside leakage and mast cell degranulation is one of important symbol of microcirculation disturbance.The improvement result of the treatment medicinal dropping ball induced by endotoxin of coronary heart disease and the microcirculation disturbance caused by ischemia-reperfusion, confirm that the medicinal dropping ball for the treatment of coronary heart disease improves significantly to the Rat Mesenteric Microcirculation obstacle that ischemia-reperfusion causes, show: the early stage albumin outside leakage of the ischemia that 1. Radix Salviae Miltiorrhizae can be suppressed not play a role; 2. effectively mast cell degranulation is suppressed; 3. the generation of vascular endothelial cell and leukocyte oxide is suppressed; 4. sticking of leukocyte and vascular endothelial cell is suppressed; 5. also impact is had 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 on patient's bulbar Conjunctiva Microcirculation, thrombelastogram has more obviously affects, after medication, patient's arteriole vessel diameter is broadening, and fine vein blood vessel narrow diameter, arteriole blood flow rate and blood flow have to be increased more significantly.

Medicinal dropping ball antioxidation, antiinflammatory, the protection blood vessel endothelium for the treatment of coronary heart disease, suppress atherosclerotic plaque formation and the balance between neointimal hyperplasia vascular endothelial cell associated media nitric oxide (NO) and vasoconstrictive factor endothelin-1 (ET-1) etc. to maintain the stability of blood vessel.After damage, the medicinal dropping ball of the treatment coronary heart disease of variable concentrations all obviously alleviates human vascular endothelial damage caused by LPS, illustrates 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 in the culture fluid before and after Hydroperoxide injury modeling, find that can balance NO at the medicinal dropping ball of prevention and therapy group treatment coronary heart disease generates, significantly increase cytoactive, have obvious antagonism to endothelial injury caused by hydrogen peroxide.

Atherosclerotic lesion is that a kind of protectiveness inflammation-Fibroproliferative to local damage is responded.In Mottling formation process, lipidosis is most important factor.The medicinal dropping ball treatment for the treatment of coronary heart disease can reduce T-CHOL (TC) 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 the impact of film healing situation in damage 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, neointimal hyperplasia degree comparatively matched group obviously alleviates, new intima medium vessels smooth muscle cell and fibrous tissue comparatively matched group obviously reduce, therefore think that the medicinal dropping ball for the treatment of coronary heart disease can promote to damage the reparation of inner membrance, reduce neointimal hyperplasia.

The medicinal dropping ball for the treatment of coronary heart disease increases coronary flow, improves lectin from hemolymph hyperlipemia 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 rat coronary flow but not increase heart rate, contributes to the supply improving 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, obvious raising HDL levels.

The medicinal dropping ball for the treatment of coronary heart disease suppresses platelet adhesion reaction and gathering Endothelial dysfunction, endothelium integrity violations can trigger a series of molecule and biochemical reaction makes blood flow cessation, and blood vessel wall reparation, suppression or antagonism platelet adhesion reaction and gathering prevent thrombotic key link.Medicinal dropping ball D-dimer and the gathering for the treatment of coronary heart disease play a role from multiple location, stage construction and Mutiple Targets.

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 in dose-dependence.The medicinal dropping ball for the treatment of coronary heart disease can suppress high fat to feed dog platelet overactivity.Specificity molecular marker when plasma A granule membrane protein140 (GMP-140) is platelet activation.Before treatment, treatment group and matched group GMP-140 level are apparently higher than Healthy People group, after the medicinal dropping ball associating aspirin for treatment for the treatment of coronary heart disease, the improvement for the treatment of group angina pectoris symptom, electrocardiogram ischemia, Plasma C reflect pro tein level comparatively matched group (singly taking aspirin) significantly reduce, with Healthy People group without significant difference.To aspirin resistance person, the medicinal dropping ball of add-on coronary heart disease can obviously improve aspirin resistance state, and reduce platelet aggregation rate, total effective rate is 85%, and mean reduction 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, comprise stable or unstable angina pectoris, myocardial infarction, heart failure, silent ischemia and intervention perioperative treatment etc. all have remarkable result.Following experimental data is for illustration of effect of the present invention: experimental drug is the medicine of the embodiment of the present invention 1.

The comparison of medicinal dropping ball in angina pectoris treatment effect of coronary heart disease treated by table 1

Group	n	Effective	Effectively	Invalid	Increase the weight of	Total effective rate/%
							Treatment group	51	22	26	3	0	94.1①
Matched group	51	10	27	12	2	72.5

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

The comparison of medicinal dropping ball in ECG curative effect of coronary heart disease treated by table 2

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

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

Medicinal dropping ball treatment front and back hemorheology index change (x ± s) of coronary heart disease treated by table 3

The medicinal dropping ball medication left ventricular contractile function that coronary heart disease treated by table 4 compares (x ± s)

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

The pure TCM Dripping Pills of efficient, quick-acting, the multiple-effect that the present invention adopts modern pharmacy technology to develop, prevent and treat coronary heart disease determined curative effect, and can microcirculation be improved, to Diabetic microvascular complication, comprise diabetic renal papillary necrosis and diabetic nephropathy all has good preventive and therapeutic effect.

The invention has the advantages that: this process route can realize 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, steady quality, and purposes is novel, and preparation method technique is simple simultaneously, easy to operate, with low cost, is applicable to suitability for industrialized production.

Detailed description of the invention

Illustrate the present invention with embodiment below, 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.

Embodiment 1 treats the preparation of the medicinal dropping ball of coronary heart disease, and 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 amount 95% ethanol, reflux, extract, 2 hours, filters; Medicinal residues add 2 times amount 95% ethanol, reflux, extract, 1 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 3 times amount 20% alcohol reflux 1hr, filters, medicinal residues add 4 times amount 50% alcohol reflux 1hr, and filter, filtrate is concentrated into without alcohol, lets cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation leaves standstill more than 12hr filter, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 15% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

Step 3, Radix Notoginseng adds the ethanol of 8 times amount 70%, reflux, extract, 2 hours, and filter, medicinal residues add 6 times 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 after the ethanol extraction of step 2, the aqueous alkali that first time adds 8 times amount PH7-8 decocts 2 hours, and second time adds 8 times amount soak by water 1 hour, obtains extracting solution, extracting solution concentrates, add ethanol to medicinal liquid alcohol content 60%-70%, leave standstill 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 is suspended in the pre-PEG-6000 melted successively; Radix Salviae Miltiorrhizae extractum adds water mix homogeneously; Said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Material temperature is 60-100 DEG C; The temperature of liquid paraffin is 5-10 DEG C, makes drop pill.

Embodiment 2 treats the preparation of the medicinal dropping ball of coronary heart disease, and 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 amount 85% ethanol, reflux, extract, 1 time, each 1 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 85% ethanol extract;

Step 4, salvianolic acid B medicinal residues after the ethanol extraction of step 2, the aqueous alkali that first time adds 2 times amount PH7-8 decocts 1 hour, and second time adds 2 times amount soak by water 0.5 hour, obtain extracting solution, extracting solution is concentrated into 1.15/80 ± 1 DEG C, and concentrated solution lets cool 25-30 DEG C, adds ethanol to medicinal liquid alcohol content 60%-70%, leave standstill more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtain 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 adds 5 times amount 95% ethanol, reflux, extract, 3 times, each 3 hours, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 8 times amount 60% alcohol reflux 4hr, filters, medicinal residues add 4 times amount 50% alcohol reflux 1hr, and filter, filtrate is concentrated into without alcohol, lets cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation leaves standstill more than 12hr filter, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 15% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

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

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

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% ethanol ultrasonic extraction 2hr, filters, medicinal residues add 4 times amount 50% ethanol ultrasonic extraction 1hr, and filter, filtrate is concentrated into without alcohol, lets cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation leaves standstill more than 12hr filter, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 10% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

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

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 adds 5 times amount 95% ethanol, reflux, extract, twice, and filter, extracting solution concentrating under reduced pressure, drying, obtain tanshinol extract.

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% ethanol dynamic countercurrent extraction 2hr, filters, medicinal residues add 4 times amount 50% ethanol dynamic countercurrent extraction 1hr, and filter, filtrate is concentrated into without alcohol, lets cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation leaves standstill more than 12hr filter, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 15% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

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

Embodiment 6 treats the preparation of the medicine of coronary heart disease, and 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 amount 95% methanol, reflux, extract, 2 hours, filters; Medicinal residues add 2 times amount 95% methanol, reflux, extract, 1 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% alcohol reflux 2hr, filter, medicinal residues add 4 times amount 50% alcohol reflux 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 1.0-4.0, cold preservation leaves standstill more than 12hr, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 15% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

Step 5, gets the tanshinol 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 vegetable oil, mixing; Soft capsule is made according to soft capsule conventional method.

Embodiment 7 treats the preparation of the medicine of coronary heart disease, and 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 amount 95% normal propyl alcohols, reflux, extract, 2 hours, filters; Medicinal residues add 2 times amount 95% normal propyl alcohols, reflux, extract, 1 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, adds the alcohol reflux of 5 times amount 60%, 2hr, remaining medicinal residues add the alcohol reflux 2hr of 4 times amount 50%, filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid adjust ph 1.8-2.0, cold preservation leaves standstill more than 12hr, filter, upper AB-8 macroporous resin eluting, first wash with water, eluent discards; Wash with 10% ethanol again, eluent discards; Finally wash with 40% ethanol, collect 40% ethanol elution, concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

Step 5, gets the tanshinol 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 amylum pregelatinisatum, zinc stearate, calcium stearate, and mixing, makes tablet.

Embodiment 8 treats the preparation of the medicine of coronary heart disease, and 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 amount 95% n-butyl alcohol, reflux, extract, 2 hours, filters; Medicinal residues add 2 times amount 95% n-butyl alcohol, reflux, extract, 1 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% ethanol ultrasonic extraction 2hr, filter, medicinal residues add 4 times amount 50% ethanol ultrasonic extraction 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 2.0-4.0, cold preservation leaves standstill more than 12hr, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 15% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

Step 5, get the tanshinol 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 appropriate polyvinylpyrrolidone (PVP), rubber cement, microcrystalline Cellulose, sodium carboxymethyl cellulose, mixing; Make controlled release preparation.

Embodiment 9 treats the preparation of the medicinal dropping ball of coronary heart disease, and 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 amount 80% ethanol, reflux, extract, 2 hours, filters; Medicinal residues add 4 times amount 80% ethanol, reflux, extract, 1 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 80% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% ethanol ultrasonic extraction 2hr, filter, medicinal residues add 4 times amount 50% ethanol ultrasonic extraction 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 1.0-2.0, cold preservation leaves standstill more than 12hr, upper S-8 macroporous resin, first wash with water, eluent discards; Wash with 20% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

Step 3, Radix Notoginseng adds the ethanol of 6 times amount 70%, reflux, extract, 1 hour, and filter, medicinal residues add 8 times 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 tanshinol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract is suspended in the pre-PEG-6000 melted successively; Radix Salviae Miltiorrhizae extractum adds water mix homogeneously; Said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Material temperature is 80-100 DEG C; The temperature of liquid paraffin is 5-10 DEG C, makes drop pill.

Embodiment 10 treats the preparation of the medicine of coronary heart disease, and 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 amount 75% ethanol, reflux, extract, 2 hours, filters; Medicinal residues add 3 times amount 75% ethanol, reflux, extract, 1 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 75% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% ethanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times amount 50% ethanol dynamic countercurrent extraction 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 2.0-4.0, cold preservation leaves standstill more than 12hr, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 15% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

Embodiment 11 treats the preparation of the medicine of coronary heart disease, and 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 amount 70% ethanol, reflux, extract, 2 hours, filters; Medicinal residues add 5 times amount 70% ethanol, reflux, extract, 1 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 70% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% methanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times amount 50% methanol dynamic countercurrent extraction 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation leaves standstill more than 12hr, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 15% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

Step 3, Radix Notoginseng adds the ethanol of 4 times amount 70%, reflux, extract, 1 hour, and filter, medicinal residues add 8 times 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 after the ethanol extraction of step 2, the aqueous alkali that first time adds 2 times amount PH7-8 decocts 2 hours, and second time adds 2 times amount soak by water 1 hour, obtains extracting solution, extracting solution concentrates, add ethanol to medicinal liquid alcohol content 60%-70%, leave standstill more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, gets the tanshinol 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 appropriate maltose, hydroxypropyl emthylcellulose, mixing, dry, pulverize, make powder.

Embodiment 12 treats the preparation of the medicine of coronary heart disease, and 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 amount 95% ethanol, reflux, extract, 2 hours, filters; Medicinal residues add 4 times amount 95% ethanol, reflux, extract, 1 hour, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% methanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times amount 50% methanol dynamic countercurrent extraction 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation leaves standstill more than 12hr, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 10% ethanol, eluent discards again; Finally wash with 45% ethanol, collect 45% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

Step 3, Radix Notoginseng adds the ethanol of 4 times amount 80%, reflux, extract, 1 hour, and filter, medicinal residues add 10 times 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 after the ethanol extraction of step 2, the aqueous alkali that first time adds 12 times amount PH7-8 decocts 2 hours, and second time adds 12 times amount soak by water 1 hour, obtains extracting solution, extracting solution concentrates, add ethanol to medicinal liquid alcohol content 60%-70%, leave standstill more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, gets the tanshinol 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 appropriate calcium stearate, Pulvis Talci, Macrogol 4000, mixing; Make micropill.

Embodiment 13 treats the preparation of the medicine of coronary heart disease, and 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 amount 95% ethanol, reflux, extract, 3 hours, filters; Medicinal residues add 4 times amount 95% ethanol, reflux, extract, 1.5 hours, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% n-butyl alcohol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times amount 50% n-butyl alcohol dynamic countercurrent extraction 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation leaves standstill more than 12hr, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 13% ethanol, eluent discards again; Finally wash with 65% ethanol, collect 65% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

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

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

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

Embodiment 14 treats the preparation of the medicine of coronary heart disease, and 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 amount 95% ethanol, reflux, extract, 4 hours, filters; Medicinal residues add 7 times amount 95% ethanol, reflux, extract, 2 hours, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% methanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times amount 50% methanol dynamic countercurrent extraction 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation leaves standstill more than 12hr, upper D101 macroporous resin, first wash with water, eluent discards; Wash with 10% ethanol, eluent discards again; Finally wash with 70% ethanol, collect 70% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

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

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

Step 5, gets the tanshinol 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 appropriate vegetable oil, makes soft capsule according to soft capsule preparation method.

Embodiment 15 treats the preparation of the medicine of coronary heart disease, and 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 amount 95% ethanol, reflux, extract, 2 hours, filters; Medicinal residues add 3 times amount 95% ethanol, reflux, extract, 2 hours, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 95% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% isobutanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times amount 50% isobutanol dynamic countercurrent extraction 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation leaves standstill more than 12hr, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 13% ethanol, eluent discards again; Finally wash with 65% ethanol, collect 65% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

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

Embodiment 16 treats the preparation of the medicine of coronary heart disease, and 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 amount 90% ethanol, reflux, extract, 2.5 hours, filters; Medicinal residues add 2 times amount 90% ethanol, reflux, extract, 1.5 hours, and filter, extracting solution concentrating under reduced pressure, drying, obtain Radix Salviae Miltiorrhizae 90% ethanol extract;

Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times amount 50% n-butyl alcohol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times amount 50% n-butyl alcohol dynamic countercurrent extraction 1hr, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation leaves standstill more than 12hr, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 13% ethanol, eluent discards again; Finally wash with 70% ethanol, collect 70% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

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

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

Step 5, gets the tanshinol 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, adds appropriate mannitol, magnesium oxide, calcium carbonate mixing; Tabletting, makes tablet.

Embodiment 17 treats the preparation of the medicine of coronary heart disease, and 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, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and adds 2 times amount 10% isopropyl alcohol warm macerating and extract 0.5 hour, filters, remaining medicinal residues add 2 times amount alcohol warm macerating and extract 10 hours, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to liquid PH value 1-4, leave standstill, filter, filtrate crosses macroporous resin D101, washes with water successively, 10% ethanol elution, 60% ethanol elution, collects 60% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;

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

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

Step 5, gets the tanshinol 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, adds microcrystalline Cellulose, sodium carboxymethyl cellulose, gelatine size mixing; Granulate, make granule.

Embodiment 18 treats the preparation of the medicine of coronary heart disease, and 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, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and adds 20 times amount 10% normal propyl alcohol reflux, extract, 10 hours, filters, remaining medicinal residues add 20 times amount alcohol extraction 1.5 hours, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to liquid PH value 1-4, leave standstill, filter, filtrate crosses macroporous resin S-8, washes with water successively, 10% ethanol elution, 60% ethanol elution, collects 60% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;

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

Step 5, gets the tanshinol 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.

Embodiment 19 treats the preparation of the medicine of coronary heart disease, and 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, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and adds 2 times amount 10% normal propyl alcohol warm macerating and extract 0.5 hour, filters, remaining medicinal residues add 2 times amount alcohol warm macerating and extract 10 hours, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to liquid PH value 1-4, leave standstill, filter, filtrate crosses macroporous resin D101, washes with water successively, 10% ethanol elution, 60% ethanol elution, collects 60% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;

Embodiment 20 treats the preparation of the medicine of coronary heart disease, and 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, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and adds 2 times amount 10% normal propyl alcohol supersound extraction 0.5 hour, filters, remaining medicinal residues add 2 times amount alcohol warm macerating and extract 10 hours, and filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to liquid PH value 1-4, leave standstill, filter, filtrate crosses macroporous resin D101, washes with water successively, 10% ethanol elution, 60% ethanol elution, collects 60% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;

Claims

1. treat the preparation method of the medicine of coronary heart disease for one kind, 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 first crude drug is prepared into active constituents of medicine through following steps, then be prepared into medicine further

Step 2, gets step 1 alcohol extraction medicinal residues, adds 3 times amount 20% alcohol reflux 1 hour, filter, medicinal residues add 4 times amount 50% alcohol reflux 1 hour, filter, filtrate is concentrated into without alcohol, let cool to less than 10 DEG C, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation leaves standstill more than 12 hours, pulp board filters, upper AB-8 macroporous resin, first wash with water, eluent discards; Wash with 15% ethanol, eluent discards again; Finally wash with 50% ethanol, collect 50% ethanol washing liquid, less than 60 DEG C concentrating under reduced pressure, dry, obtain salvianolic acid B extract;

Step 4, get the medicinal residues after the ethanol extraction salvianolic acid B of step 2, the aqueous alkali that first time adds 8 times amount pH7-8 decocts 2 hours, and second time adds 8 times amount soak by water 1 hour, obtains extracting solution, extracting solution concentrates, add ethanol to medicinal liquid alcohol content 60%-70%, leave standstill more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain Radix Salviae Miltiorrhizae extractum;

Step 5, Radix Salviae Miltiorrhizae 95% ethanol extract obtained after said extracted, salvianolic acid B extract, Radix Notoginseng extract is suspended in the pre-PEG-6000 melted successively; Radix Salviae Miltiorrhizae extractum adds water mix homogeneously; Said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Material temperature is 60-100 DEG C; The temperature of liquid paraffin is 5-10 DEG C, makes drop pill.