CN102028739B - Drug for treating coronary heart disease and preparation method thereof - Google Patents
Drug for treating coronary heart disease and preparation method thereof Download PDFInfo
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- CN102028739B CN102028739B CN200910070679.0A CN200910070679A CN102028739B CN 102028739 B CN102028739 B CN 102028739B CN 200910070679 A CN200910070679 A CN 200910070679A CN 102028739 B CN102028739 B CN 102028739B
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Abstract
The invention relates to a drug for treating coronary heart disease and a preparation method thereof. The preparation method comprises the following steps: extracting salvia with alcohol, extracting notoginseng with water 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 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
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, has hindered 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.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, is deeply subject to clinically patient's welcome.In order to improve the preparation technology of FUFANG DANSHEN DIWAN, the inventor conducts in-depth research from extraction process aspect, from saving 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 active constituents of medicine through following steps, is more further prepared into medicine.
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 is concentrated, lets cool, add acid for adjusting pH value, cold preservation is standing, filters, and filtrate is crossed resin, washes successively low concentration alcohol eluting with water, high concentration alcohol eluting, collects high concentration alcohol eluen, concentrated, dry, obtains salvianolic acid B extract;
Step 3, the Radix Salviae Miltiorrhizae decoction dregs after step 2 alcohol extraction adds Radix Notoginseng, and aqueous alkali is or/and water extraction, and extracting solution is concentrated, adds alcohol, and standing, supernatant concentration, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, the tanshinol extract of step 1, the salvianolic acid B extract of step 2, Salvia miltiorrhiza and Panax notoginseng extract and Borneolum Syntheticum are further made drop pill.
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, dry, obtains tanshinol extract;
Step 2, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and adds 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 medicinal liquid pH value 1-4, standing, filter, filtrate is crossed 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, the Radix Salviae Miltiorrhizae decoction dregs after the alcohol extraction of step 2, adds Radix Notoginseng, the aqueous alkali that adds 2-12 times of pH value 7-10, extracts 1-3 time, then adds 2-12 times of water, extract 1-3 time, filter, filtrate is concentrated, adds ethanol to medicinal liquid and contains alcohol amount 50-80%, standing, separation of supernatant, reclaims ethanol, receives cream to pol 50%-90% or concentrated, dry, pulverizing, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, by the tanshinol extract of step 1, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract mixes with adjuvant with Borneolum Syntheticum, adds any or more than one adjuvants, and the 1-6 that adjuvant addition is active component doubly, makes any oral formulations;
Wherein described in step 2, alcohol extraction mode 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: 3.0.
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, filters, and extracting solution concentrating under reduced pressure, dry, obtains 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 uses 40-90% ethanol elution, collect 40-90% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 2, adds Radix Notoginseng to extract, and the aqueous alkali that adds for the first time 2-12 doubly to measure PH7-8 decocts 1-3 hour, add for the second time 2-12 times of water gaging to decoct 0.5-2 hour, obtain extracting solution, extracting solution is concentrated, adds ethanol to medicinal liquid and contains alcohol amount 50%-80%, standing 12-36 hour, separation of supernatant, reclaims ethanol, receives cream to pol 55%-80%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extract adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill; Wherein described in step 2, alcohol extraction mode is selected from: reflux, extract,, warm macerating extraction, supersound extraction or dynamic countercurrent extraction.
The preferred preparation method of drop pill of the present invention, step is:
Step 1, Radix Salviae Miltiorrhizae adds 2-5 and doubly measures 95% ethanol, reflux, extract, 1-3 time, each 1-3 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains 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 uses 40-70% ethanol elution, collect 40-70% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 2, adds Radix Notoginseng, and the aqueous alkali that adds for the first time 6-12 doubly to measure PH7-8 decocts 1-3 hour, add for the second time 6-12 times of water gaging to decoct 0.5-2 hour, obtain extracting solution, extracting solution is concentrated, adds ethanol to medicinal liquid and contains alcohol amount 50%-75%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 55%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extract adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, 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, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 2, adds Radix Notoginseng, and the aqueous alkali that adds for the first time 6-12 doubly to measure PH7-8 decocts 1-3 hour, 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 contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extract adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The present invention also comprises the application in the medicine of the cardiovascular disease such as a kind of resisting coronary heart disease of preparation, angina pectoris with the medicinal dropping ball for the treatment of 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, 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-perfusion and during postischemic reperfusion, add the medicinal dropping ball for the treatment of coronary heart disease, 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, treats the medicinal dropping ball of coronary heart disease during pre-perfusion during with postischemic reperfusion and all can lay in by increasing cardiac energy, the generation of inhibition lipid peroxide and protecting myocardial cell before ischemia.
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 generation 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 pathology damage degree, and stronger with the medicinal dropping ball dosage increasing effect for the treatment of coronary heart disease.In the myocardial cell of cultivating, carrying out anoxia experiment 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 Bcl-2 expresses, and further shows that the medicinal dropping ball for the treatment of 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 treatment medicinal dropping ball induced by endotoxin 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 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-fiber proliferative of 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.The medicinal dropping ball that Ma Xiao waits quietly observing treatment coronary heart disease with similar method modeling is on damaging the impact of interior film healing situation, 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 obviously alleviates compared with matched group, new intima medium vessels smooth muscle cell and fibrous tissue obviously reduce compared with 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 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.Specificity molecular marker when plasma A membrane granulosa protein-140 (GMP-140) are 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, treatment group angina pectoris symptom, electrocardiogram ischemia improve, blood plasma GMP-140 level significantly reduces compared with matched group (singly taking aspirin), 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, reduces platelet aggregation rate, and total effective rate is 85%, and the average range of decrease is 51.57%.
Owing to treating the medicinal dropping ball of coronary heart disease, there is 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 used for illustrating effect of the present invention: experimental drug is the medicine of the embodiment of the present invention 1.
The comparison of the medicinal dropping ball of table 1 treatment coronary heart disease aspect angina pectoris treatment effect
| Group | n | Effective | Effectively | Invalid | Increase the weight of | Total effective rate/% |
| Treatment group | 51 | 20 | 30 | 1 | 0 | 98.0① |
| Matched group | 51 | 8 | 30 | 12 | 1 | 74.5 |
Note: 1. with matched group comparison, through Radit, analyze U=3.039, P < 0.01.
The comparison of the medicinal dropping ball of table 2 treatment coronary heart disease aspect ECG curative effect
| Group | n | Effective | Effectively | Invalid | Increase the weight of | Total effective rate/% |
| Treatment group | 51 | 10 | 21 | 20 | 0 | 60.8① |
| Matched group | 51 | 2 | 16 | 31 | 2 | 35.3 |
Note: 1. with matched group comparison, through Radit, analyze U=2.685, P < 0.01.
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 comparison (x ± s) of table 4 treatment coronary heart disease
Note: 1. before and after medication, compare P > 0.05; 2. before and after medication, compare P < 0.05.
That the present invention adopts that modern pharmacy technology develops is efficient, quick-acting, the pure TCM Dripping Pills of multiple-effect, prevent and treat coronary heart disease determined curative effect, and can improve blood capillary circulation, to 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, purposes is novel, and preparation method technique is simple, easy to operate, with low cost simultaneously, is applicable to suitability for industrialized production.
The specific embodiment
With embodiment, illustrate the present invention below, embodiment is for the ease of understanding the present invention, and the claim not limiting 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, filters; Medicinal residues add 2 times of amount 95% ethanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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, with 4BV washing, eluent discards; With 4BV15% ethanol, wash, eluent discards again; Finally with 4BV50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 2, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extract adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; 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, filter, extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 85% ethanol extract;
Step 2, gets 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, pulp board filters, upper AB-8 macroporous resin, first washes with water, and eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, the Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, add for the first time the aqueous alkali of 2 times of amounts to decoct 1 hour, add for the second time 2 times of water gagings to decoct 0.5 hour, obtain extracting solution, extracting solution is concentrated into 1.120/80 ± 1 ℃, concentrated solution lets cool 25-30 ℃, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaim ethanol, receive cream to pol 70%-75%, obtain compound Salviae Miltiorrhizae extractum; Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Compound Salviae Miltiorrhizae extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill.
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, filter, extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets step 1 alcohol extraction medicinal residues, adds 8 times of amount 60% alcohol reflux 4hr, filters, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, and filtrate is concentrated into without alcohol, lets 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 washes with water, and eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, gets tanshinol extract, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract, the Borneolum Syntheticum of step 1, adds appropriate mannitol, magnesium oxide, calcium carbonate to mix; Tabletting, makes tablet.
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 of amount 75% ethanol, reflux, extract, twice, each 2 hours, filter, extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 75% ethanol extract;
Step 2, gets step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol ultrasonic extraction 2hr, filters, medicinal residues add 4 times of amount 50% ethanol ultrasonic extraction 1hr, filter, and filtrate is concentrated into without alcohol, lets 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 washes with water, and eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
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, filters, and extracting solution concentrating under reduced pressure, dry, obtains tanshinol extract.
Step 2, gets 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 washes with water, and eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extractum;
Step 4, gets tanshinol extract, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract, the Borneolum Syntheticum of step 1, gets appropriate cane sugar powder, essence adds appropriate water, makes oral liquid.
The preparation of embodiment 6 FUFANG DANSHEN DIWAN, 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, filters; Medicinal residues add 2 times of amount 95% methanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract; Step 2, gets 95% 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 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of embodiment 7 FUFANG DANSHEN DIWAN, 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, filters; Medicinal residues add 2 times of amount 95% normal propyl alcohols, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets step alcohol extraction medicinal residues, adds 2 times of amount 10% ethanol warm macerating and extracts 2hr, filters, medicinal residues add 4 times of amount 90% ethanol warm macerating and extract 1hr, filter, and filtrate is concentrated into without alcohol, lets 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 washes with water, and eluent discards; With 15% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of embodiment 8 FUFANG DANSHEN DIWAN, 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, filters; Medicinal residues add 2 times of amount 95% n-butyl alcohol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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 50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of embodiment 9 FUFANG DANSHEN DIWAN, 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, filters; Medicinal residues add 4 times of amount 80% ethanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 80% ethanol extract;
Step 2, gets 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% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of embodiment 10 FUFANG DANSHEN DIWAN, 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, filters; Medicinal residues add 3 times of amount 75% ethanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 75% ethanol extract;
Step 2, gets 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 20% ethanol, wash, eluent discards again; Finally with 50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
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, filters; Medicinal residues add 5 times of amount 70% ethanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 70% ethanol extract;
Step 2, gets 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 40% ethanol, wash, collect 40% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, gets tanshinol extract, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract, the Borneolum Syntheticum of step 1, gets appropriate vegetable oil, according to soft capsule preparation method, makes soft capsule.
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, filters; Medicinal residues add 4 times of amount 95% ethanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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 45% ethanol, wash, collect 45% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.Step 4, gets tanshinol extract, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract, the Borneolum Syntheticum of step 1, adds appropriate calcium stearate, Pulvis Talci, Macrogol 4000, mixes; Make micropill.
The preparation of the medicine of embodiment 13 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 85%, Radix Notoginseng 12%, Borneolum Syntheticum 3%;
Step 1, Radix Salviae Miltiorrhizae adds 6 times of amount 95% ethanol, and reflux, extract, 3 hours, filters; Medicinal residues add 4 times of amount 95% ethanol, and reflux, extract, 1.5 hours, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 50%-80%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 50%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of the medicine of embodiment 14 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 50%, Radix Notoginseng 48%, Borneolum Syntheticum 2%;
Step 1, Radix Salviae Miltiorrhizae adds 9 times of amount 95% ethanol, and reflux, extract, 4 hours, filters; Medicinal residues add 7 times of amount 95% ethanol, and reflux, extract, 2 hours, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 50%-80%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 90%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, gets tanshinol extract, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract, the Borneolum Syntheticum of step 1, adds appropriate maltose, hydroxypropyl emthylcellulose, mixes, and dry, pulverize, and makes powder.
The preparation of the medicine of embodiment 15 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 90%, Radix Notoginseng 8%, Borneolum Syntheticum 2%;
Step 1, Radix Salviae Miltiorrhizae adds 4 times of amount 95% ethanol, and reflux, extract, 2 hours, filters; Medicinal residues add 3 times of amount 95% ethanol, and reflux, extract, 2 hours, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 50%-80%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 90%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill.
The preparation of the medicine of embodiment 16 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82%, Radix Notoginseng 17%, Borneolum Syntheticum 1%;
Step 1, Radix Salviae Miltiorrhizae adds 3 times of amount 90% ethanol, and reflux, extract, 2.5 hours, filters; Medicinal residues add 2 times of amount 90% ethanol, and reflux, extract, 1.5 hours, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 90% ethanol extract;
Step 2, gets 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, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 50%-80%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 90%, obtains Salvia miltiorrhiza and Panax notoginseng extractum.
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extractum adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill.
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 1, Radix Salviae Miltiorrhizae adds 3 times of amount 95% ethanol, and reflux, extract, 2 hours, filters; Medicinal residues add 2 times of amount 95% ethanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, gets tanshinol extract, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract, the Borneolum Syntheticum of step 1, adds appropriate amylum pregelatinisatum, zinc stearate, calcium stearate, mixes, and makes tablet.
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 1, Radix Salviae Miltiorrhizae adds 3 times of amount 95% ethanol, and reflux, extract, 2 hours, filters; Medicinal residues add 2 times of amount 95% ethanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, get step 1 alcohol extraction medicinal residues, add 5 times of amount 40% alcohol reflux 1.5hr, filter, last medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, 55 ℃ of filtrates are evaporated to below 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, 4BV washing, 4BV15% alcohol wash, 4BV50% alcohol wash, collects 60 ℃ of following concentrating under reduced pressure of 50% alcohol washing liquid, dry, pulverize, cross 100 orders, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, gets tanshinol extract, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract, the Borneolum Syntheticum of step 1, adds appropriate dextrin, refined honey, mixes, and makes pill.
The preparation of the medicine of embodiment 19 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82.87%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.92%;
Step 1, Radix Salviae Miltiorrhizae adds the methanol of 2 times 70, and reflux, extract, is filtered, and extracting solution concentrating under reduced pressure, dry, obtains tanshinol extract;
Step 2, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and adds 2 times of amounts, 10% isopropyl alcohol warm macerating extraction 0.5 hour, filters, last medicinal residues add 2 times of amount alcohol warm macerating and extract 10 hours, 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 D101, washes with water successively, 10% ethanol elution, 60% ethanol elution, collects 60% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;
Step 3, the Radix Salviae Miltiorrhizae decoction dregs after the alcohol extraction of step 1, adds Radix Notoginseng, the aqueous alkali that adds 2-12 times of pH value 7-10, extracts 1-3 time, then adds 2-12 times of water, extract 1-3 time, filter, filtrate is concentrated, adds ethanol to medicinal liquid and contains alcohol amount 50-80%, standing, separation of supernatant, reclaims ethanol, receives cream to pol 50%-90% or concentrated, dry, pulverizing, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, by the tanshinol extract of step 1, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract mixes with adjuvant with Borneolum Syntheticum, adds any or more than one adjuvants, and the 1-6 that adjuvant addition is active component doubly, makes any oral formulations.
The preparation of the medicine of embodiment 20 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82.87%, 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, filters; Medicinal residues add 2 times of amount 95% ethanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and adds 20 times of amount 10% n-propanol extraction 10 hours, filters, last medicinal residues add 20 times of amounts alcohol extraction 1.5 hours, 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 S-8, washes with water successively, 10% ethanol elution, 60% ethanol elution, collects 60% ethanol elution, concentrated, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 1, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, gets tanshinol extract, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract, the Borneolum Syntheticum of step 1, adds appropriate dextrin, refined honey, mixes, and makes pill.
Claims (8)
1. a preparation method for the treatment of the medicine 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 active constituents of medicine through following steps, is more further prepared into medicine:
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, dry, obtains tanshinol extract;
Step 2, gets step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and adds 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 medicinal liquid pH value 1-4, standing, filter, filtrate is crossed 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, the Radix Salviae Miltiorrhizae decoction dregs after the alcohol extraction of step 2, adds Radix Notoginseng, the aqueous alkali that adds 2-12 times of pH value 7-10, extracts 1-3 time, then adds 2-12 times of water, extract 1-3 time, filter, filtrate is concentrated, adds ethanol to medicinal liquid and contains alcohol amount 50-80%, standing, separation of supernatant, reclaims ethanol, receives cream to pol 50%-90% or concentrated, dry, pulverizing, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, by the tanshinol extract of step 1, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract mixes with adjuvant with Borneolum Syntheticum, adds any or more than one adjuvants, and the 1-6 that adjuvant addition is active component doubly, makes any oral formulations;
Wherein described in step 2, alcohol extraction mode 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.
2. the preparation method of claim 1, is characterized in that, preparation process is:
Step 1, Radix Salviae Miltiorrhizae adds 2-5 times of 70-100% ethanol, reflux, extract, 1-3 time, each 1-3 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains 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, 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, wash with water successively, 5-20% alcohol eluting, finally use 40-90% ethanol elution, collect 40-90% ethanol elution, concentrated, dry, obtain salvianolic acid B extract, wherein the model of macroporous resin is selected from S-8, AB-8 or D101 macroporous resin column,
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 2, adds Radix Notoginseng to extract, and the aqueous alkali that adds for the first time 2-12 doubly to measure pH7-8 decocts 1-3 hour, add for the second time 2-12 times of water gaging to decoct 0.5-2 hour, obtain extracting solution, extracting solution is concentrated, adds ethanol to medicinal liquid and contains alcohol amount 50%-80%, standing 12-36 hour, separation of supernatant, reclaims ethanol, receives cream to pol 55%-80%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extract adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill;
Wherein described in step 2, alcohol extraction mode is selected from: reflux, extract,, warm macerating extraction, supersound extraction or dynamic countercurrent extraction.
3. the preparation method of claim 1: it is characterized in that, preparation process is:
Step 1, Radix Salviae Miltiorrhizae adds 2-5 and doubly measures 95% ethanol, reflux, extract, 1-3 time, each 1-3 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains 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, 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, wash with water successively, 10-20% alcohol eluting, finally use 40-70% ethanol elution, collect 40-70% ethanol elution, concentrated, dry, obtain salvianolic acid B extract, wherein the model of macroporous resin is selected from S-8, AB-8 or D101 macroporous resin column,
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 2, adds Radix Notoginseng, and the aqueous alkali that adds for the first time 6-12 doubly to measure pH7-8 decocts 1-3 hour, add for the second time 6-12 times of water gaging to decoct 0.5-2 hour, obtain extracting solution, extracting solution is concentrated, adds ethanol to medicinal liquid and contains alcohol amount 50%-75%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 55%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extract adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
4. the preparation method of claim 1: it is characterized in that, preparation process is:
Step 1, Radix Salviae Miltiorrhizae adds 2-3 and doubly measures 95% ethanol, reflux, extract, 2 times, each 1-2 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 2, adds Radix Notoginseng, and the aqueous alkali that adds for the first time 6-12 doubly to measure pH7-8 decocts 1-3 hour, 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 contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extract adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
5. the preparation method of claim 1, is characterized in that, preparation process is:
Step 1, Radix Salviae Miltiorrhizae adds 3 times of amount 95% ethanol, and reflux, extract, 2 hours, filters; Medicinal residues add 2 times of amount 95% ethanol, and reflux, extract, 1 hour, filters, and extracting solution concentrating under reduced pressure, dry, obtains Radix Salviae Miltiorrhizae 95% ethanol extract;
Step 2, gets 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, with 4BV washing, eluent discards; With 4BV15% ethanol, wash, eluent discards again; Finally with 4BV50% ethanol, wash, collect 50% ethanol washing liquid, 60 ℃ of following concentrating under reduced pressure, dry, obtain salvianolic acid B extract;
Step 3, Radix Salviae Miltiorrhizae decoction dregs after the ethanol extraction of step 2, adds Radix Notoginseng, adds 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, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, standing more than 12 hours, separation of supernatant, reclaims ethanol, receives cream to pol 70%-75%, obtains Salvia miltiorrhiza and Panax notoginseng extract;
Step 4, the tanshinol extract of step 1 is suspended in the PEG-6000 of pre-thawing; Salvia miltiorrhiza and Panax notoginseng extract adds water mix homogeneously, adds salvianolic acid B extract, mix homogeneously; Said two devices mix homogeneously, adds Borneolum Syntheticum, mixes; Material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
6. the arbitrary described preparation method of claim 1-5: it is characterized in that, step 4 is, the tanshinol extract that step 1-3 is obtained, salvianolic acid B extract, Salvia miltiorrhiza and Panax notoginseng extract mixes with adjuvant with Borneolum Syntheticum, add any or more than one adjuvants, described adjuvant is selected from fat-soluble substrate and water-soluble base, and wherein fat-soluble substrate is selected from: stearic acid, glyceryl monostearate, insect wax, Cera Flava, paraffin, hydrogenated vegetable oil, semi-synthetic fatty acid ester; Water-soluble base is selected from Polyethylene Glycol, polyoxyethylene monostearate, poloxamer, sodium stearate, glycerin gelatine; Xylitol and composites of starch, erythritol.
7. the preparation method of claim 6: it is characterized in that, wherein the auxiliary ratio of step 4 medicine is 1: 3.0
8. the preparation method of claim 6: it is characterized in that, wherein said Polyethylene Glycol is PEG-4000.
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