CN102028747A - Drug for treating coronary heart disease and extraction method - Google Patents

Drug for treating coronary heart disease and extraction method Download PDF

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CN102028747A
CN102028747A CN2009100706875A CN200910070687A CN102028747A CN 102028747 A CN102028747 A CN 102028747A CN 2009100706875 A CN2009100706875 A CN 2009100706875A CN 200910070687 A CN200910070687 A CN 200910070687A CN 102028747 A CN102028747 A CN 102028747A
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extract
alcohol
add
ethanol
amount
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CN102028747B (en
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刘顺航
徐波
戚可人
刘岩
陈红
丛德刚
赵国辉
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TIANJIN TASLY MODERN CHINESE MEDICINE RESOURCE CO Ltd
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TIANJIN TASLY MODERN CHINESE MEDICINE RESOURCE CO Ltd
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Abstract

The invention relates to a drug for treating coronary heart disease and an extraction method. The extraction method comprises the following steps: extracting salvia with alcohol; extracting dregs of salvia, adding a solvent to notoginseng; reflowing and extracting the mixture, extracting dreg decoction of salvianolic acid B 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

A kind of medicine and extracting method for the treatment of coronary heart disease
Technical field
The present invention relates to a kind of medicine for the treatment of coronary heart disease, belong to the field of Chinese medicines.
Background technology
Along with the rejuvenation of growth in the living standard, world population aging and morbidity colony, cardiovascular and cerebrovascular vessel patient increases year by year, has become the second largest disease of harm humans health.Angina pectoris is a kind of caused by the temporary transient ischemia of cardiac muscle, anoxia, serves as the clinical syndrome of main performance with ictal chest pain or chest discomfort.Angina pectoris is meant because coronary atherosclerosis or spasm cause myocardial ischemia, the caused angina pectoris of anoxia, accounts for 90% of patient with angina pectoris.
The anginal method of treatment is based on blood vessel dilating, reduction blood viscosity, anti-platelet aggregation, anticoagulation at present.Traditional Western medicine of using is nitrate, nitrous acid ester, beta-blocker, calcium antagonist etc., but all has bigger toxic and side effects, should not take for a long time, mostly is symptomatic treatment and course of disease progress is not had bigger effect.For example take occur sometimes behind the nitroglycerin beating in feeling of fullness in the head, the head, palpitating speed, even faint [referring to 264 pages of new pharmacologies (the 14th edition)], find again in recent years to cause severe hypotension [referring to contemporary Chinese medical journal 1997; 7 (4): 42; Shaanxi medical journal 1996; 25 (5): 315], easily produce toleration [referring to southern nursing magazine 1996; 3 (5): 7~9] etc. problem has hindered its application clinically.
Though the anginal Chinese patent medicine of many treatments is also arranged, wherein ball, loose, cream, pellet, decoction becomes old historical already, the modern seldom uses.There are preparations such as common FUFANG DANSHEN PIAN and capsule to sell in the market, but conventional tablet, capsule manufacture technology fall behind, active constituent content is low, no quality control index, need oral through gastrointestinal absorption, go into blood at liver generation first pass effect post-absorption, bioavailability is low, absorbs slow. can not be fit to the need of angina pectoris patient's first aid.
FUFANG DANSHEN DIWAN is fast, the eutherapeutic therapeutic drug of coronary heart disease of a kind of special effect, is subjected to patient's welcome clinically deeply.In order to improve the preparation technology of FUFANG DANSHEN DIWAN, the inventor furthers investigate from the extraction process aspect, from saving the herb resource aspect, has improved product yield, the comprehensive utilization ratio of the contained effective ingredient of medical material.
Summary of the invention
The invention provides a kind of medicine for the treatment of coronary heart disease.
The medicine of treatment coronary heart disease of the present invention, described medicine is prepared from by following raw materials by weight percent medicine, Radix Salviae Miltiorrhizae 19.8%-97%, Radix Notoginseng 2%-80%, Borneolum Syntheticum 0.2%-3%, described preparation is earlier crude drug to be prepared into active constituents of medicine through following steps, further is prepared into medicine again.
Step 1, Radix Salviae Miltiorrhizae adds alcohol, extracts, and filters, and extracting solution concentrates, and leaves standstill, and filters, and precipitation is dry, obtains first's tanshinone extract; Filtrate is crossed resin, with low concentration alcohol eluting, collects eluent, concentrates, and leaves standstill, and filters, and precipitation is dry, obtains the cryptotanshinone extract; Reuse high concentration alcohol eluting, the collection eluent concentrates, and leaves standstill, and filters, and precipitation is dry, gets second portion tanshinone extract, and two parts merge, and obtain the tanshinone extract;
Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, extracts, and filters, and filtrate concentrates, and puts cold, add acid for adjusting pH value, cold preservation is left standstill, and filters, and filtrate is crossed resin, water eluting successively, low concentration alcohol eluting, high concentration alcohol eluting is collected the high concentration alcohol eluen, concentrates, and drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add the solvent reflux, extract,, extracting liquid filtering, and filtrate is concentrated into does not have the alcohol flavor, adding distil water, last macroporous resin, first water eluting, eluent discards, and reuse alcohol eluting is collected alcohol eluen, concentrates, and drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues after step 2 alcohol extraction add, and aqueous alkali is or/and water extraction, and extracting solution concentrates, and adds alcohol, leaves standstill, and supernatant concentration obtains Radix Salviae Miltiorrhizae extractum;
Tanshinone extract that step 5, step 1 obtain and cryptotanshinone extract, the salvianolic acid B extract that step 2 obtains, the Radix Notoginseng extract that step 3 obtains, Radix Salviae Miltiorrhizae extractum that step 4 obtains and Borneolum Syntheticum are further made drop pill;
Wherein the described solvent of step 3 is selected from: the methanol of water, aqueous slkali, 50-100%, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol.
Medicine of the present invention is for oral medicine, the preparation of galenic pharmacy routine techniques is adopted in its preparation, comprise that wherein the adjuvant of oral drug preparation is selected from starch with the blended step of the adjuvant of active constituents of medicine and oral drugs, amylum pregelatinisatum, dextrin, Icing Sugar, lactose, mannitol, calcium sulfate two water things, calcium hydrogen phosphate, magnesium oxide, calcium carbonate, magnesium carbonate, water, ethanol, starch slurry, syrup, liquid glucose, maltose, refined honey, cane sugar powder, citric acid, essence, mucialga of arabic gummy, gelatine size, polyvinylpyrrolidone (PVP), rubber cement, microcrystalline Cellulose, sodium carboxymethyl cellulose, hydroxypropyl emthylcellulose, magnesium stearate, stearic acid, zinc stearate, calcium stearate, Pulvis Talci, Macrogol 4000, polyethylene glycol 6000, micropowder silica gel, vegetable oil, sodium stearate, glycerin gelatine, stearic acid, glyceryl monostearate, insect wax, one or several combinations of hydrogenated oil and fat.
Oral formulations of the present invention is selected from: all acceptable dosage forms on tablet, dispersible tablet, hard capsule, soft capsule, granule, pill, micropill, powder, drop pill, slow releasing preparation, controlled release preparation, syrup, oral liquid, soft extract and the extractum pharmaceutics.
Its preferred manufacturing procedure of medicine that confession of the present invention is oral, step is:
Step 1, Radix Salviae Miltiorrhizae add 2-20 doubly to be measured 60%~100% alcohol extraction 1-10 hour, filters, and medicinal residues are doubly measured 60%~100% alcohol with 2-20, extract 1-10 hour, filters, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.2-5 times of medical material amount, leaves standstill filtration; Precipitation is dry, obtains first's tanshinone extract; Macroporous resin on the filtrate (polar resin S-8, low pole Resin A B-8 or non-polar resin D101), the 50-85% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 20-40%, leaves standstill, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use the 85-100% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 65-85%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2, get step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and add 2-20 and doubly measured the 10-100% alcohol extraction 0.5-10 hour, filter, last medicinal residues add 2-20 and doubly measured alcohol extraction 0.5-10 hour, filter, filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, adds dilute hydrochloric acid to liquid PH value 1-4, leave standstill, filter, filtrate is crossed macroporous resin (polar resin S-8, low pole Resin A B-8, non-polar resin D101 or polyamide), water eluting successively, low concentration alcohol eluting, high concentration alcohol eluting, collect the high concentration alcohol eluen, concentrate, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add alcohol reflux 1-2 time of 2-20 times of 50-100%, each extraction time 0.5-10 hour, extracting liquid filtering, filtrate are concentrated into does not have the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, last macroporous resin (S-8, AB-8 or D101), first water eluting, eluent discards, reuse 30-100% methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol eluting are collected alcohol eluen, concentrate, drying promptly gets Radix Notoginseng extract;
Step 4, the salvianolic acid B medicinal residues after the alcohol extraction of step 2 add the aqueous alkali of 2-12 times of pH value 7-10, extract 1-3 time, add 2-12 times of water again, extract 1-3 time, filter, filtrate concentrates, add ethanol to medicinal liquid and contain alcohol amount 50-80%, leave standstill separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 50%-90% or concentrated, dry, pulverizing;
Step 5 is with the above-mentioned tanshinone extract that obtains, cryptotanshinone extract, the salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum mixes with adjuvant with Borneolum Syntheticum, add any or more than one adjuvants, the adjuvant addition is 1-6 a times of active component, makes any oral formulations;
Wherein alcohol is selected from described in the step 1 and 2: methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol alcohol, described extracting mode is selected from: reflux, extract,, warm macerating extraction, merceration extraction, percolation extraction, supersound extraction, dynamic countercurrent extraction or microwave extraction.
The preferred drop pill of medicine of the present invention, the preparation of galenic pharmacy routine techniques is adopted in its preparation, comprises that described adjuvant is selected from fat-soluble substrate and water-soluble base with the blended step of adjuvant of active constituents of medicine and drop pill medicine, and medicine is assisted than being 1: 1-6.Wherein said fat-soluble substrate is selected from: stearic acid, glyceryl monostearate, insect wax, Cera Flava, paraffin, hydrogenated vegetable oil, semi-synthetic fatty acid ester; Water-soluble base is selected from Polyethylene Glycol, polyoxyethylene monostearate, poloxamer, sodium stearate, glycerin gelatine etc.; Xylitol and composites of starch, erythritol; Preferred medicine is auxilliary than being 1: 4.0.
Drop pill preferred manufacturing procedure of the present invention, step is:
Step 1, Radix Salviae Miltiorrhizae add 2-15 doubly to be measured 60%~100% alcohol extraction 1-8 hour, filters, and medicinal residues are doubly measured 60%~100% alcohol with 2-15, extract 1-8 hour, filters, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.2-3 times of medical material amount, leaves standstill filtration; Precipitation is dry, obtains first's tanshinone extract; Macroporous resin on the filtrate (polar resin S-8, low pole Resin A B-8 or non-polar resin D101), the 50-85% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 20-40%, leaves standstill, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Reuse 85-100% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 65-85%, leaves standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merge, and obtain the tanshinone extract;
Step 2, getting step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues adds 2-15 and doubly measured the 10-90% alcohol extraction 1-8 hour, filter, last medicinal residues add 2-15 and doubly measured the 10-90% alcohol extraction 1-8 hour, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1-3, leave standstill, filter, filtrate is crossed macroporous resin (S-8, AB-8 or D101), water eluting successively, the 5-20% ethanol elution is used the 40-90% ethanol elution at last, collect the 40-90% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add alcohol reflux 1-2 time of 2-10 times of 60-80%, each extraction time 0.5-3 hour, extracting liquid filtering, filtrate are concentrated into does not have the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, last macroporous resin (S-8, AB-8 or D101), first water eluting, eluent discards, reuse 30-60% ethanol elution is collected alcohol eluen, concentrates, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, add for the first time the aqueous alkali that 2-12 doubly measures PH7-8 and decocted 1-3 hour, add 2-12 times of water gaging for the second time and decocted 0.5-2 hour, obtain extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, left standstill separation of supernatant 12-36 hour, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 55%-80%;
Step 5, the tanshinone extract of step 1, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill.
The preferred preparation method of drop pill of the present invention, step is:
Step 1, Radix Salviae Miltiorrhizae add 2-10 doubly to be measured 80%~100% alcohol reflux 1-5 hour, filters, and medicinal residues are doubly measured 80%~100% alcohol with 2-10, reflux, extract, 1-5 hour, filter, medicinal residues are used for salvianolic acid B and extract, filtrate is concentrated into 0.2-1 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; Macroporous resin on the filtrate (S-8, AB-8 or D101), the 60-85% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 20-40%, leaves standstill, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use the 85-100% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 65-85%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2, getting step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues adds 2-10 and doubly measured the 30-70% alcohol reflux 1-6 hour, filter, last medicinal residues add 2-10 and doubly measured the 30-70% alcohol reflux 1-6 hour, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to liquid PH value 1-3, leave standstill, filter, filtrate is crossed macroporous resin (S-8, AB-8 or D101), water eluting successively, the 10-20% ethanol elution is used the 40-70% ethanol elution at last, collect the 40-70% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add alcohol reflux 1-2 time of 5-10 times of 60-80%, each extraction time 0.5-3 hour, extracting liquid filtering, filtrate are concentrated into does not have the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, last macroporous resin (S-8, AB-8 or D101), first water eluting, eluent discards, reuse 40-60% ethanol elution is collected alcohol eluen, concentrates, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, add for the first time the aqueous alkali that 6-12 doubly measures PH7-8 and decocted 1-3 hour, add 6-12 times of water gaging for the second time and decocted 0.5-2 hour, obtain extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-75%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 55%-75%;
The tanshinone extract that step 5, above-mentioned steps obtain, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill.
The particularly preferred preparation method of drop pill of the present invention, step is:
Step 1, Radix Salviae Miltiorrhizae add 3-5 and doubly measure 95% alcohol reflux 2 times, and each 1-2 hour, filter, medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.4-0.5 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; Macroporous resin AB-8 on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merge, and obtain the tanshinone extract;
Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, adds the alcohol reflux 2 times that 4-6 doubly measures 40-60%, each 1-2hr, filter, filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid and regulate pH value 1.8-2.0, cold preservation is left standstill more than the 12hr, filters last AB-8 macroporous resin eluting, wash with water earlier, eluent discards; Reuse 15% ethanol is washed,, eluent discards; Wash with 50% ethanol at last, collect 50% ethanol elution, concentrating under reduced pressure, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add the alcohol reflux 2 times of 5-10 times of 60-80%, each extraction time 1-2 hour, extracting liquid filtering, filtrate are concentrated into does not have the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, last macroporous resin (S-8, AB-8 or D101), first water eluting, eluent discards, reuse 40-60% ethanol elution is collected alcohol eluen, concentrates, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, add for the first time the aqueous alkali that 6-12 doubly measures PH7-8 and decocted 1-3 hour, add 8 times of water gagings for the second time and decocted 1 hour, obtain extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, above-mentioned steps obtain the tanshinone extract, and cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The present invention also comprises the application of medicinal dropping ball in the medicine of cardiovascular disease such as a kind of resisting coronary heart disease of preparation, angina pectoris with treatment coronary heart disease of the present invention.
The present invention is more more superior than prior art because of the change of technology causes the present invention to treat the medicinal dropping ball of coronary heart disease.
Below data declaration the present invention treats the beneficial effect of the medicinal dropping ball of coronary heart disease by experiment.
Add the medicinal dropping ball of treatment coronary heart disease of the present invention before the myocardial cell anoxia, the intracellular calcium fluorescence intensity obviously descends, and proves that the medicinal dropping ball of treatment coronary heart disease has antagonism myocardial cell calcium overload, the effect of protecting myocardial cell.
Behind the myocardial ischemia-reperfusion, high-energy phosphate compound obviously reduces in the tissue, and the lipid peroxide contents showed increased causes reperfusion injury.The medicinal dropping ball that adds treatment coronary heart disease when pouring into again when before ischemia, pouring in advance and behind the ischemia, high-energy phosphate compound all is higher than ischemic reperfusion notes group in the tissue, two groups of adenosine triphosphate (ATP), cardiac muscular tissue's gland nucleoside total amount (TAN) are all near normal level, and the lipid peroxide level is lower than ischemic reperfusion notes group.This result proves, before ischemia during pre-perfusion with ischemia after treat coronary heart disease when pouring into again medicinal dropping ball all can be by increasing the cardiac energy deposit, the generation of inhibition lipid peroxide and protecting myocardial cell.
Cardiomyocyte cell death is a damage type the most serious in the myocardial ischemia-reperfusion, comprises necrocytosis and apoptosis.The apoptotic regulation and control that expressed by several genes.Myocardial infarction rear section myocardial cell generation apoptosis, relevant with the cell calcium overload due to the ischemia probably with the oxygen-derived free radicals effect.The medicinal dropping ball of treatment coronary heart disease can obviously reduce apoptosis of cardiac muscle quantity behind the myocardial ischemia-reperfusion, dwindles the myocardial infarct size of ischemia-reperfusion rat, significantly alleviates the pathology damage degree, and stronger with the medicinal dropping ball dosage increasing effect of treatment coronary heart disease.Carrying out the anoxia experiment in cardiac muscle cells shows, the medicinal dropping ball intervention of treatment coronary heart disease can obviously be reduced apoptotic proteins Fas and be expressed, slight upregulation of apoptosis Profilin Bcl-2 expresses, and shows that further the protein expression of apoptosis-related genes in the medicinal dropping ball pair cell for the treatment of coronary heart disease has certain influence.
The medicinal dropping ball of treatment coronary heart disease improves blood capillary circulation albumin outside leakage and mast cell degranulation is one of important symbol of microcirculation disturbance.The medicinal dropping ball of treatment coronary heart disease is to the improvement effect of endotoxin and the caused microcirculation disturbance of ischemia-reperfusion, the medicinal dropping ball that confirms treatment coronary heart disease improves significantly to the rat mesentery microcirculation disturbance that ischemia-reperfusion causes, shows: 1. can suppress the early stage albumin outside leakage of ischemia that Radix Salviae Miltiorrhizae can not play a role; 2. effectively suppress mast cell degranulation; 3. suppress the generation of vascular endothelial cell and leukocyte oxide; 4. suppress sticking of leukocyte and vascular endothelial cell; 5. also influential to the interaction of the cell adhesion factor, peroxidating and leukocyte behind the ischemia-reperfusion and endotheliocyte.
The medicinal dropping ball of treatment coronary heart disease has more obviously influence to patient's bulbar Conjunctiva Microcirculation, thrombelastogram, patient's arteriole vessel diameter broadening after the medication, and fine vein blood vessel narrow diameter, arteriole blood flow rate and blood flow have more significantly to be increased.
Medicinal dropping ball antioxidation, antiinflammatory, the protection blood vessel endothelium of treatment coronary heart disease, the balance between the formation of inhibition atherosclerotic plaque and neointimal hyperplasia vascular endothelial cell associated media nitric oxide (NO) and the vasoconstrictive factor endothelin-1 (ET-1) etc. is being kept the stability of blood vessel.The medicinal dropping ball of the treatment coronary heart disease of damage back variable concentrations all obviously alleviates human vascular endothelial damage due to the LPS, illustrate that the medicinal dropping ball for the treatment of coronary heart disease has obvious protective effect to vascular endothelial cell.The medicinal dropping ball of variable concentrations being treated coronary heart disease is used for the culture fluid that hydrogen peroxide damages the modeling front and back, discovery can generate by balance NO at the medicinal dropping ball of prevention and treatment group treatment coronary heart disease, significantly increase cytoactive, endothelial injury due to the hydrogen peroxide is had obvious antagonism.
Atherosclerotic lesion is that a kind of protectiveness inflammation-fiber proliferative to local damage is responded.In the speckle forming process, lipidosis is most important factor.But the medicinal dropping ball treatment hypercholesterolemia reducing (TC) and low density lipoprotein, LDL (LDL) cholesterol levels of treatment coronary heart disease, high density lipoprotein increasing (HDL) cholesterol levels.Ma Xiao waits quietly observing the influence of the medicinal dropping ball of treatment coronary heart disease to film healing situation in damaging with similar method modeling, the medicinal dropping ball group postoperative NO concentration of finding treatment coronary heart disease is apparently higher than matched group, the neointimal hyperplasia degree obviously alleviates than matched group, new intima medium vessels smooth muscle cell and fibrous tissue obviously reduce than matched group, so think that the medicinal dropping ball of treatment coronary heart disease can promote to damage the reparation of inner membrance, reduces neointimal hyperplasia.
The medicinal dropping ball coronary blood flow increasing of treatment coronary heart disease improves the hemorheology hyperlipemia and can cause vascular endothelial injury, come off, platelet adhesion reaction and gathering.The medicinal dropping ball of treatment coronary heart disease can significantly increase the rat coronary flow but not increase heart rate, helps to improve the supply of heart oxygen and nutrient substance.The medicinal dropping ball of treatment coronary heart disease obviously reduces rabbit anteserum TC, triglyceride (TG), LDL, very low density lipoprotein (VLDL) (VLDL) concentration and TC/HDL ratio, and HDL concentration obviously raises.
The medicinal dropping ball inhibition platelet adhesion reaction and the gathering endothelial function for the treatment of coronary heart disease lacked of proper care, endothelium integrity destruction can trigger a series of molecules and biochemical reaction makes the blood flow stagnation, and blood vessel wall reparation, inhibition or antagonism platelet adhesion reaction and gathering are to prevent thrombotic key link.The medicinal dropping ball antiplatelet activation of treatment coronary heart disease and gathering be from the multi-section position, stage construction and many target spots play a role.
The medicinal dropping ball of treatment coronary heart disease all has obvious inhibitory action to adenosine diphosphate (ADP) (ADP), thrombin and collagen-induced rat platelet aggregation, and is dose-dependence.The medicinal dropping ball of treatment coronary heart disease can suppress high fat and feed dog platelet overactivity.The specificity molecular marker of plasma A membrane granulosa protein-140 (GMP-140) when being platelet activation.Before the treatment, treatment group and matched group GMP-140 level are organized apparently higher than healthy people, after the medicinal dropping ball associating aspirin for treatment of treatment coronary heart disease, treatment group angina pectoris symptom, electrocardiogram ischemia improve, blood plasma GMP-140 level significantly reduces than matched group (single clothes aspirin), organize no significant difference with healthy people.To the aspirin resistance person, the medicinal dropping ball that adds with treatment coronary heart disease can obviously improve the aspirin resistance state, reduces platelet aggregation rate, and total effective rate is 85%, and the average range of decrease is 51.57%.
Because the medicinal dropping ball of treatment coronary heart disease has above-mentioned many target spots effect, it is to all kinds coronary heart disease, comprises that the peri-operation period treatment etc. of stable or unstable angina pectoris, myocardial infarction, heart failure, silent ischemia and intervention all has remarkable result.
Following experimental data is used to illustrate effect of the present invention: experimental drug is the medicine of the embodiment of the invention 1.
The comparison of medicinal dropping ball aspect the angina pectoris treatment effect of table 1 treatment coronary heart disease
Group n Produce effects Effectively Invalid Increase the weight of Total effective rate/%
The treatment group 51 22 26 3 0 94.1①
Matched group 51 8 29 11 3 72.5
Annotate: 1. compare, analyze U=3.039, P<0.01 through Radit with matched group.
The comparison of medicinal dropping ball aspect ECG curative effect of table 2 treatment coronary heart disease
Group n Produce effects Effectively Invalid Increase the weight of Total effective rate/%
The treatment group 51 15 18 18 0 64.7①
Matched group 51 2 17 30 2 37.3
Annotate: 1. compare, analyze U=2.685, P<0.01 through Radit with matched group.
Hemorheology index variation before and after the medicinal dropping ball treatment of table 3 treatment coronary heart disease (x ± s)
Figure B2009100706875D0000091
The medicinal dropping ball medication left ventricular contractile function comparison of table 4 treatment coronary heart disease (x ± s)
Annotate: 1. compare P>0.05 before and after the medication; 2. compare P<0.05 before and after the medication.
Efficient, quick-acting, the multi-purpose pure Chinese medicine dripping pills preparation that the present invention adopts the modern pharmacy technology to develop, prevent and treat the coronary heart disease determined curative effect, and can improve the blood capillary circulation,, comprise that diabetic renal papillary necrosis and diabetic nephropathy all have good preventive and therapeutic effect the diabetes microvascular complication.
The invention has the advantages that: this process route can be realized industrialization, and is stable and controllable for quality.Relevant test shows, the present invention is than prior art curative effect height, the product purity height, and good absorbing, steady quality, the purposes novelty, preparation method technology is simple, easy to operate, with low cost simultaneously, is fit to suitability for industrialized production.
The specific embodiment
Specify the present invention with embodiment below, embodiment is for the ease of understanding the present invention, and claim that does not limit the present invention in any way and core content.
Embodiment 1
The preparation of the medicine of treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82.87%, Radix Notoginseng 16.21%, Borneolum Syntheticum 0.92%;
Step 1, Radix Salviae Miltiorrhizae add 5 times of amount 95% ethanol, and reflux, extract, 2 hours is filtered, and medicinal residues are measured 95% ethanol with 3 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.4-0.5 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; AB-8 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 3 times of amount 20% alcohol reflux 1hr, filters, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, and filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr
Figure B2009100706875D0000101
Filter, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 8 times of amount 70% alcohol reflux 2hr, and last medicinal residues add 6 times of amount 70% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 2 times medical material amount, last AB-8 macroporous resin, elder generation's water eluting, eluent discards, reuse 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, the medicinal residues of salvianolic acid B behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 8 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of the medicine of embodiment 2 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 19.8%, Radix Notoginseng 78.2%, Borneolum Syntheticum 2%;
Step 1, Radix Salviae Miltiorrhizae add 2 times of amount 95% ethanol, and reflux, extract, 1 hour is filtered, and medicinal residues are measured 95% ethanol with 20 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.4-0.6 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; AB-8 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 20%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract
Step 2 is got step 1 alcohol extraction medicinal residues, adds 3 times of amount 20% alcohol reflux 1hr, filter, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr, filter, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 8 times of amount 70% alcohol reflux 1hr, and last medicinal residues add again, 6 times of amount 70% alcohol reflux 1.5hr, extracting liquid filtering, being concentrated into does not have the alcohol flavor, adding distil water to 2 times medical material amount, last AB-8 macroporous resin, first water eluting, eluent discards, reuse 50% ethanol elution is collected 50% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds 2 times of amount PH7-8 for the first time decocted 1 hour, added 2 times of water gagings for the second time and decocted 0.5 hour, obtain extracting solution, extracting solution is concentrated into 1.120, and concentrated solution is put and is as cold as 25-30 ℃, adds ethanol to medicinal liquid and contains alcohol amount 60%-70%, leave standstill more than 12 hours, separation of supernatant reclaims ethanol, receives cream to pol 70%-75%, obtains Radix Salviae Miltiorrhizae extractum;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of the 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 add 2 times of amount 95% ethanol, and reflux, extract, 1 hour is filtered, and medicinal residues are measured 95% ethanol with 20 times, and reflux, extract, 10 hours is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.2 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; AB-8 macroporous resin on the filtrate, 50% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 85% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 65%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 8 times of amount 60% alcohol reflux 4hr, filters, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, and filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr
Figure B2009100706875D0000121
Filter, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 6 times of amount 70% alcohol reflux 2hr, and last medicinal residues add 7 times of amount 70% alcohol reflux 3hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last AB-8 macroporous resin, elder generation's water eluting, eluent discards, reuse 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 6 times of amount PH7-8 decocted 3 hours, added 6 times of water gagings for the second time and decocted 2 hours, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of the medicine of embodiment 4 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 95%, Radix Notoginseng 2%, Borneolum Syntheticum 3%,
Step 1, Radix Salviae Miltiorrhizae add 15 times of amount 95% ethanol, and reflux, extract, 3 hours is filtered, and medicinal residues are measured 95% ethanol with 15 times, and reflux, extract, 10 hours is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 5 times of medical material amounts, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; S-8 macroporous resin on the filtrate, 85% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 30%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 100% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 85%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol ultrasonic extraction 2hr, filter, medicinal residues add 4 times of amount 50% ethanol ultrasonic extraction 1hr, filter, filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr, pulp board filters, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 8 times of amount 60% alcohol reflux 1hr, and last medicinal residues add 6 times of amount 80% alcohol reflux 3hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 3 times medical material amount, last AB-8 macroporous resin, elder generation's water eluting, eluent discards, reuse 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, Radix Salviae Miltiorrhizae decoction dregs behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, Borneolum Syntheticum add and can press starch, mixing in right amount; Make tablet.
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 add 2 times of amount 95% ethanol, and reflux, extract, 3 hours is filtered, and medicinal residues are measured 95% ethanol with 15 times, and reflux, extract, 2 hours is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 1 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; D101 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 25%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% ethanol dynamic countercurrent extraction 1hr, filter, filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr, pulp board filters, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 2 times of amount 70% alcohol reflux 2hr, and last medicinal residues add 20 times of amount 70% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 2 times medical material amount, last AB-8 macroporous resin, elder generation's water eluting, eluent discards, reuse 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, Borneolum Syntheticum are got an amount of vegetable oil, make soft capsule according to the soft capsule preparation method.
The preparation of the medicine of embodiment 6 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 20.8%, Radix Notoginseng 78.6%, Borneolum Syntheticum 0.6%,
Step 1, Radix Salviae Miltiorrhizae add 10 times of amount 95% ethanol, and reflux, extract, 3 hours is filtered, and medicinal residues are measured 95% ethanol with 2 times, and reflux, extract, 2 hours is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 1 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; D101 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% alcohol reflux 2hr, filter, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.0-4.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 5 times of amount 60% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 60% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last S-8 macroporous resin, elder generation's water eluting, eluent discards, reuse 50% methanol-eluted fractions, collect 50% meoh eluate, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of the medicine of embodiment 7 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 29.8%, Radix Notoginseng 68.6%, Borneolum Syntheticum 1.6%,
Step 1, Radix Salviae Miltiorrhizae add 10 times of amount 60% ethanol, and reflux, extract, 3 hours is filtered, and medicinal residues are measured 60% ethanol with 8 times, and reflux, extract, 2 hours is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 1 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; D101 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 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 does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr
Figure B2009100706875D0000151
Filter, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 10% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 5 times of amount 60% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 60% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 40% normal propyl alcohol eluting, collect 40% normal propyl alcohol eluent, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the Tanshinone I I A extract, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, the Borneolum Syntheticum that obtain after the said extracted add an amount of mannitol, magnesium oxide, calcium carbonate mixing; Tabletting is made tablet.
The preparation of the medicine of embodiment 8 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 86.8%, Radix Notoginseng 12.6%, Borneolum Syntheticum 0.6%,
Step 1, Radix Salviae Miltiorrhizae add 10 times of amount 100% ethanol, and reflux, extract, 3 hours is filtered, and medicinal residues are measured 60% ethanol with 8 times, and reflux, extract, 2 hours is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 1 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; D101 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 35%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol ultrasonic extraction 2hr, filter, medicinal residues add 4 times of amount 50% ethanol ultrasonic extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-4.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 20% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 5 times of amount 60% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 60% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 60% isopropyl alcohol alcohol eluting, collect 60% isopropyl alcohol eluent, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 80-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of the medicine of embodiment 9 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 85.8%, Radix Notoginseng 12.6%, Borneolum Syntheticum 1.6%,
Step 1, Radix Salviae Miltiorrhizae add 10 times of amount 95% ethanol, and reflux, extract, 10 hours is filtered, and medicinal residues are measured 95% ethanol with 8 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 1 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; D101 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 38%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol ultrasonic extraction 2hr, filter, medicinal residues add 4 times of amount 50% ethanol ultrasonic extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.0-2.0, cold preservation is left standstill more than the 12hr, last S-8 macroporous resin, wash with water earlier, eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 5 times of amount 60% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 60% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 40% ethanol elution, collect 40% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, Borneolum Syntheticum add appropriate amount of starch, Mel mix homogeneously; Make pill.
The preparation of the medicine of embodiment 10 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 74.8%, Radix Notoginseng 23.6%, Borneolum Syntheticum 1.6%,
Step 1, Radix Salviae Miltiorrhizae add 10 times of amount 95% ethanol, and reflux, extract, 3 hours is filtered, and medicinal residues are measured 95% ethanol with 8 times, and reflux, extract, 2 hours is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 1 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; D101 macroporous resin on the filtrate, 60% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 85% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 65%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% ethanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% ethanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-4.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 5 times of amount 60% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 60% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 40% ethanol elution, collect 40% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, Borneolum Syntheticum add crystallite Cellulose, Sodium carboxymethyl cellulose, Bright GlueThe slurry mixing; Granulate, make granule.
The preparation of the medicine of embodiment 11 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 58.8%, Radix Notoginseng 40.6%, Borneolum Syntheticum 0.6%,
Step 1, Radix Salviae Miltiorrhizae add 4 times of amount 95% ethanol, and reflux, extract, 1 hour is filtered, and medicinal residues are measured 95% ethanol with 5 times, and reflux, extract, 2 hours is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.2 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; D101 macroporous resin on the filtrate, 60% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 85% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 65%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% methanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% methanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 40% ethanol at last, collect 40% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 6 times of amount 50% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 50% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 30% ethanol elution, collect 30% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 2 times of amount PH7-8 decocted 2 hours, added 2 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 80-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
The preparation of the medicine of embodiment 12 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 28%, Radix Notoginseng 70%, Borneolum Syntheticum 2%;
Step 1, Radix Salviae Miltiorrhizae add 10 times of amount 65% methanol, and reflux, extract, 1 hour is filtered, and medicinal residues are measured 95% methanol with 5 times, and reflux, extract, 5 hours is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.8 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; D101 macroporous resin on the filtrate, 85% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 100% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 85%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% methanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% methanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 10% ethanol is washed, and eluent discards; Wash with 45% ethanol at last, collect 45% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 6 times of amount 50% methanol eddies and extract 2hr, and last medicinal residues add 18 times of amount 50% methanol eddies again and extract 1hr, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 12 times of amount PH7-8 decocted 2 hours, added 12 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 80 ℃; The temperature of liquid paraffin is 8 ℃, makes drop pill.
The preparation of the medicine of embodiment 13 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 85%, Radix Notoginseng 12%, Borneolum Syntheticum 3%;
Step 1, Radix Salviae Miltiorrhizae add 5 times of amount 95% normal propyl alcohols, and reflux, extract, 2 hours is filtered, and medicinal residues are measured 95% normal propyl alcohols with 3 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.4-0.5 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; AB-8 macroporous resin on the filtrate, 70% ethanol elution, eluent discards, and continues to use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure gets second portion tanshinone extract, and two parts merge, and obtain the tanshinone extract
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% n-butyl alcohol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% n-butyl alcohol dynamic countercurrent extraction 1hr, filter, filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, adds dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, and last AB-8 macroporous resin washes with water earlier, collect eluent, be concentrated into and contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure gets the cryptotanshinone extract; Reuse 13% ethanol is washed, and eluent discards; Wash with 65% ethanol at last, collect 65% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 5 times of amount 60% normal propyl alcohol reflux, extract, 2hr, and last medicinal residues add 10 times of amount 60% normal propyl alcohol reflux, extract, 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 40% ethanol elution, collect 40% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 7 times of amount PH7-8 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 50%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, Borneolum Syntheticum add an amount of dextrin, mucialga of arabic gummy mixing, granulate; Incapsulate, make capsule.
The preparation of the medicine of embodiment 14 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 50%, Radix Notoginseng 48%, Borneolum Syntheticum 2%;
Step 1, Radix Salviae Miltiorrhizae add 5 times of amount 95% isopropyl alcohols, and reflux, extract, 2 hours is filtered, and medicinal residues are measured 95% isopropyl alcohols with 3 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.4-0.5 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; AB-8 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 20%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% methanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% methanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last D101 macroporous resin, wash with water earlier, eluent discards; Reuse 10% ethanol is washed, and eluent discards; Wash with 70% ethanol at last, collect 70% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 6 times of amount 50% isopropyl alcohol reflux, extract, 2hr, and last medicinal residues add 18 times of amount 50% isopropyl alcohol reflux, extract, 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 7 times of amount PH7-10 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 71%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, Borneolum Syntheticum add appropriate amount of starch, mixing, tabletting is made tablet.
The preparation of the medicine of embodiment 15 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 90%, Radix Notoginseng 8%, Borneolum Syntheticum 2%;
Step 1, Radix Salviae Miltiorrhizae add 5 times of amount 95% n-butyl alcohol, and reflux, extract, 2 hours is filtered, and medicinal residues are measured 95% n-butyl alcohol with 3 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.4-0.5 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; AB-8 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 20%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% isobutanol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% isobutanol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 13% ethanol is washed, and eluent discards; Wash with 65% ethanol at last, collect 65% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 6 times of amount 50% n-butyl alcohol reflux, extract, 2hr, and last medicinal residues add 7 times of amount 50% n-butyl alcohol reflux, extract, 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 7 times of amount PH7-10 decocted 2 hours, added 6 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 90%;
Step 5, the tanshinone extract that obtains after the said extracted, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, Borneolum Syntheticum add an amount of mannitol, magnesium oxide, calcium carbonate mixing; Tabletting is made tablet.
The preparation of the medicine of embodiment 16 treatment coronary heart disease, each component consists of in the weight percent of crude drug effective ingredient: Radix Salviae Miltiorrhizae 82%, Radix Notoginseng 17%, Borneolum Syntheticum 1%;
Step 1, Radix Salviae Miltiorrhizae add 5 times of amount 95% isobutanol, and reflux, extract, 2 hours is filtered, and medicinal residues are measured 95% isobutanol with 3 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.4-0.5 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains the Tanshinone I I A of first extract; AB-8 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 28%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains Tanshinone I I A extract
Step 2 is got step 1 alcohol extraction medicinal residues, adds 4 times of amount 50% n-butyl alcohol dynamic countercurrent extraction 2hr, filter, medicinal residues add 4 times of amount 50% n-butyl alcohol dynamic countercurrent extraction 1hr, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 2.0-3.0, cold preservation is left standstill more than the 12hr, last AB-8 macroporous resin, wash with water earlier, eluent discards; Reuse 13% ethanol is washed, and eluent discards; Wash with 70% ethanol at last, collect 70% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 6 times of amount 50% isobutanol reflux, extract, 1hr, and last medicinal residues add 10 times of amount 50% isobutanol reflux, extract, 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 2 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 6 times of amount PH7-10 decocted 2 hours, added 9 times of water gagings for the second time and decocted 2 hours, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Salvia miltiorrhiza and Panax notoginseng extractum to pol 70%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 80 ℃; The temperature of liquid paraffin is 8 ℃, makes drop pill.
The preparation of the medicine of embodiment 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 add 5 times of amount 95% ethanol, and reflux, extract, was filtered in 2 hours, and medicinal residues are measured 95% ethanol with 3 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 2 times of medical material amounts, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; S-8 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 33%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract
Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and is added 2 times of amount 10% isopropyl alcohol warm macerating extraction 0.5 hour, filters, last medicinal residues add 2 times of pure warm macerating of amount and extracted 10 hours, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid, leave standstill to liquid PH value 1-4, filter, filtrate is crossed macroporous resin D101, successively the water eluting, 10% ethanol elution, 60% ethanol elution is collected 60% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 6 times of amount 50% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 50% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last D101 macroporous resin, elder generation's water eluting, eluent discards, reuse 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 5, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 8 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 80 ℃; The temperature of liquid paraffin is 8 ℃, makes drop pill.
The preparation of the medicine of embodiment 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 add 5 times of amount 95% ethanol, and reflux, extract, 2 hours is filtered, and medicinal residues are measured 95% ethanol with 3 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 3 times of medical material amounts, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; AB-8 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract
Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and is added 20 times of amount 10% normal propyl alcohol reflux, extract, 10 hours, filters, last medicinal residues add 20 times of amounts alcohol extraction 1.5 hours, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid, leave standstill to liquid PH value 1-4, filter, filtrate is crossed macroporous resin S-8, successively the water eluting, 10% ethanol elution, 60% ethanol elution is collected 60% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 6 times of amount 50% alcohol reflux 2hr, and last medicinal residues add 18 times of amount 50% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 1 times medical material amount, last AB-8 macroporous resin, elder generation's water eluting, eluent discards, reuse 60% ethanol elution, collect 60% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 8 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum, Borneolum Syntheticum add and can press starch, mixing in right amount; Make tablet.

Claims (10)

1. medicine for the treatment of coronary heart disease, described medicine is prepared from by following raw materials by weight percent medicine, Radix Salviae Miltiorrhizae 19.8%-97%, Radix Notoginseng 2%-80%, Borneolum Syntheticum 0.2%-3%, described preparation is earlier crude drug to be prepared into active constituents of medicine through following steps, further be prepared into medicine again
Step 1, Radix Salviae Miltiorrhizae adds alcohol, extracts, and filters, and extracting solution concentrates, and leaves standstill, and filters, and precipitation is dry, obtains first's tanshinone extract; Filtrate is crossed resin, with low concentration alcohol eluting, collects eluent, concentrates, and leaves standstill, and filters, and precipitation is dry, obtains the cryptotanshinone extract; Reuse high concentration alcohol eluting, the collection eluent concentrates, and leaves standstill, and filters, and precipitation is dry, gets second portion tanshinone extract, and two parts merge, and obtain the tanshinone extract;
Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, extracts, and filters, and filtrate concentrates, and puts cold, add acid for adjusting pH value, cold preservation is left standstill, and filters, and filtrate is crossed resin, water eluting successively, low concentration alcohol eluting, high concentration alcohol eluting is collected the high concentration alcohol eluen, concentrates, and drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add the solvent reflux, extract,, extracting liquid filtering, and filtrate is concentrated into does not have the alcohol flavor, adding distil water, last macroporous resin, first water eluting, eluent discards, and reuse alcohol eluting is collected alcohol eluen, concentrates, and drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues after step 2 alcohol extraction add, and aqueous alkali is or/and water extraction, and extracting solution concentrates, and adds alcohol, leaves standstill, and supernatant concentration obtains Radix Salviae Miltiorrhizae extractum;
Tanshinone I I extract that step 5, step 1 obtain and cryptotanshinone extract, the salvianolic acid B extract that step 2 obtains, the Radix Notoginseng extract that step 3 obtains, Radix Salviae Miltiorrhizae extractum that step 4 obtains and Borneolum Syntheticum are further made drop pill;
Wherein the described solvent of step 3 is selected from: the methanol of water, aqueous slkali, 50-100%, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol.
2. the medicine of the treatment coronary heart disease of claim 1 is for oral medicine, it is characterized in that preparation process is:
Step 1, Radix Salviae Miltiorrhizae add 2-20 doubly to be measured 60%~100% alcohol extraction 1-10 hour, filters, and medicinal residues are doubly measured 60%~100% alcohol with 2-20, extract 1-10 hour, filters, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.2-5 times of medical material amount, leaves standstill filtration; Precipitation is dry, obtains first's tanshinone extract; Macroporous resin on the filtrate (polar resin S-8, low pole Resin A B-8 or non-polar resin D101), the 50-85% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 20-40%, leaves standstill, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use the 85-100% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 65-85%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2, get step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues and add 2-20 and doubly measured the 10-100% alcohol extraction 0.5-10 hour, filter, last medicinal residues add 2-20 and doubly measured alcohol extraction 0.5-10 hour, filter, filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, adds dilute hydrochloric acid to liquid PH value 1-4, leave standstill, filter, filtrate is crossed macroporous resin (polar resin S-8, low pole Resin A B-8, non-polar resin D101 or polyamide), water eluting successively, low concentration alcohol eluting, high concentration alcohol eluting, collect the high concentration alcohol eluen, concentrate, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add alcohol reflux 1-2 time of 2-20 times of 50-100%, each extraction time 0.5-10 hour, extracting liquid filtering, filtrate are concentrated into does not have the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, last macroporous resin (S-8, AB-8 or D101), first water eluting, eluent discards, reuse 30-100% methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol eluting are collected alcohol eluen, concentrate, drying promptly gets Radix Notoginseng extract;
Step 4, the salvianolic acid B medicinal residues after the alcohol extraction of step 2 add the aqueous alkali of 2-12 times of pH value 7-10, extract 1-3 time, add 2-12 times of water again, extract 1-3 time, filter, filtrate concentrates, add ethanol to medicinal liquid and contain alcohol amount 50-80%, leave standstill separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 50%-90% or concentrated, dry, pulverizing;
Step 5 is with the above-mentioned tanshinone extract that obtains, cryptotanshinone extract, the salvianolic acid B extract, Radix Notoginseng extract, Radix Salviae Miltiorrhizae extractum mixes with adjuvant with Borneolum Syntheticum, add any or more than one adjuvants, the adjuvant addition is 1-6 a times of active component, makes any oral formulations;
Wherein alcohol is selected from described in the step 1 and 2: methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol or isobutanol alcohol, described extracting mode is selected from: reflux, extract,, warm macerating extraction, merceration extraction, percolation extraction, supersound extraction, dynamic countercurrent extraction or microwave extraction.
3. the medicine of the treatment coronary heart disease of claim 2 is drop pills, it is characterized in that, preparation process is:
Step 1, Radix Salviae Miltiorrhizae add 2-15 doubly to be measured 60%~100% alcohol extraction 1-8 hour, filters, and medicinal residues are doubly measured 60%~100% alcohol with 2-15, extract 1-8 hour, filters, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.2-3 times of medical material amount, leaves standstill filtration; Precipitation is dry, obtains first's tanshinone extract; Macroporous resin on the filtrate (polar resin S-8, low pole Resin A B-8 or non-polar resin D101), the 50-85% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 20-40%, leaves standstill, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Reuse 85-100% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 65-85%, leaves standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merge, and obtain the tanshinone extract;
Step 2, getting step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues adds 2-15 and doubly measured the 10-90% alcohol extraction 1-8 hour, filter, last medicinal residues add 2-15 and doubly measured the 10-90% alcohol extraction 1-8 hour, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1-3, leave standstill, filter, filtrate is crossed macroporous resin (S-8, AB-8 or D101), water eluting successively, the 5-20% ethanol elution is used the 40-90% ethanol elution at last, collect the 40-90% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add alcohol reflux 1-2 time of 2-10 times of 60-80%, each extraction time 0.5-3 hour, extracting liquid filtering, filtrate are concentrated into does not have the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, last macroporous resin (S-8, AB-8 or D101), first water eluting, eluent discards, reuse 30-60% ethanol elution is collected alcohol eluen, concentrates, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, add for the first time the aqueous alkali that 2-12 doubly measures PH7-8 and decocted 1-3 hour, add 2-12 times of water gaging for the second time and decocted 0.5-2 hour, obtain extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-80%, left standstill separation of supernatant 12-36 hour, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 55%-80%;
Step 5, the tanshinone extract of step 1, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill.
4. the medicine of the treatment coronary heart disease of claim 3: it is characterized in that preparation process is:
Step 1, Radix Salviae Miltiorrhizae add 2-10 doubly to be measured 80%~100% alcohol reflux 1-5 hour, filters, and medicinal residues are doubly measured 80%~100% alcohol with 2-10, reflux, extract, 1-5 hour, filter, medicinal residues are used for salvianolic acid B and extract, filtrate is concentrated into 0.2-1 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; Macroporous resin on the filtrate (S-8, AB-8 or D101), the 60-85% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 20-40%, leaves standstill, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use the 85-100% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 65-85%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2, getting step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues adds 2-10 and doubly measured the 30-70% alcohol reflux 1-6 hour, filter, last medicinal residues add 2-10 and doubly measured the 30-70% alcohol reflux 1-6 hour, filter, and filtrate is concentrated into does not have alcohol, put and be chilled to below 10 ℃, add dilute hydrochloric acid to liquid PH value 1-3, leave standstill, filter, filtrate is crossed macroporous resin (S-8, AB-8 or D101), water eluting successively, the 10-20% ethanol elution is used the 40-70% ethanol elution at last, collect the 40-70% ethanol elution, concentrate, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add alcohol reflux 1-2 time of 5-10 times of 60-80%, each extraction time 0.5-3 hour, extracting liquid filtering, filtrate are concentrated into does not have the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, last macroporous resin (S-8, AB-8 or D101), first water eluting, eluent discards, reuse 40-60% ethanol elution is collected alcohol eluen, concentrates, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, add for the first time the aqueous alkali that 6-12 doubly measures PH7-8 and decocted 1-3 hour, add 6-12 times of water gaging for the second time and decocted 0.5-2 hour, obtain extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 50%-75%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 55%-75%;
The tanshinone extract that step 5, above-mentioned steps obtain, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 0-10 ℃, makes drop pill.
5. the medicine of the treatment coronary heart disease of claim 4: it is characterized in that preparation process is:
Step 1, Radix Salviae Miltiorrhizae add 3-5 and doubly measure 95% alcohol reflux 2 times, and each 1-2 hour, filter, medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.4-0.5 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; Macroporous resin AB-8 on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merge, and obtain the tanshinone extract;
Step 2 is got step 1 Radix Salviae Miltiorrhizae alcohol extraction medicinal residues, adds the alcohol reflux 2 times that 4-6 doubly measures 40-60%, each 1-2hr, filter, filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid and regulate pH value 1.8-2.0, cold preservation is left standstill more than the 12hr, filters last AB-8 macroporous resin eluting, wash with water earlier, eluent discards; Reuse 15% ethanol is washed,, eluent discards; Wash with 50% ethanol at last, collect 50% ethanol elution, concentrating under reduced pressure, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add the alcohol reflux 2 times of 5-10 times of 60-80%, each extraction time 1-2 hour, extracting liquid filtering, filtrate are concentrated into does not have the alcohol flavor, adds the distilled water of 1-3 times of medical material amount, last macroporous resin (S-8, AB-8 or D101), first water eluting, eluent discards, reuse 40-60% ethanol elution is collected alcohol eluen, concentrates, drying promptly gets Radix Notoginseng extract;
Step 4, salvianolic acid B medicinal residues behind the ethanol extraction of step 2, add for the first time the aqueous alkali that 6-12 doubly measures PH7-8 and decocted 1-3 hour, add 8 times of water gagings for the second time and decocted 1 hour, obtain extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, above-mentioned steps obtain the tanshinone extract, and cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
6. the medicine of the treatment coronary heart disease of claim 5: it is characterized in that preparation process is:
Step 1, Radix Salviae Miltiorrhizae add 5 times of amount 95% ethanol, and reflux, extract, 2 hours is filtered, and medicinal residues are measured 95% ethanol with 3 times, and reflux, extract, 1 hour is filtered, and medicinal residues are used for salvianolic acid B and extract, and filtrate is concentrated into 0.4-0.5 times of medical material amount, leaves standstill, and filters; Precipitation is dry, obtains first's tanshinone extract; AB-8 macroporous resin on the filtrate, 70% ethanol elution is collected eluent, is concentrated into to contain alcohol amount 40%, cold preservation is left standstill more than the 12hr, filter, the precipitation drying under reduced pressure, the cryptotanshinone extract; Continue use 95% ethanol elution, collect eluent, be concentrated into and contain alcohol amount 80%, leave standstill, filter, the precipitation drying under reduced pressure, second portion tanshinone extract, two parts merging obtains the tanshinone extract;
Step 2 is got step 1 alcohol extraction medicinal residues, adds 3 times of amount 20% alcohol reflux 1hr, filters, medicinal residues add 4 times of amount 50% alcohol reflux 1hr, filter, and filtrate is concentrated into does not have alcohol, puts to be chilled to below 10 ℃, add dilute hydrochloric acid to medicinal liquid pH value 1.8-2.0, cold preservation is left standstill more than the 12hr
Figure F2009100706875C0000051
Filter, last AB-8 macroporous resin washes with water earlier, and eluent discards; Reuse 15% ethanol is washed, and eluent discards; Wash with 50% ethanol at last, collect 50% ethanol washing liquid, concentrating under reduced pressure below 60 ℃, drying obtains the salvianolic acid B extract;
Step 3, Radix Notoginseng add 8 times of amount 70% alcohol reflux 2hr, and last medicinal residues add 6 times of amount 70% alcohol reflux 1hr again, extracting liquid filtering, being concentrated into does not have alcohol flavor, adding distil water to 2 times medical material amount, last AB-8 macroporous resin, elder generation's water eluting, eluent discards, reuse 50% ethanol elution, collect 50% ethanol elution, concentrating under reduced pressure, drying promptly gets Radix Notoginseng extract;
Step 4, the medicinal residues of salvianolic acid B behind the ethanol extraction of step 2, the aqueous alkali that adds for the first time 8 times of amount PH7-8 decocted 2 hours, added 8 times of water gagings for the second time and decocted 1 hour, obtained extracting solution, extracting solution concentrates, add ethanol to medicinal liquid and contain alcohol amount 60%-70%, leave standstill more than 12 hours separation of supernatant, reclaim ethanol, receive cream, obtain Radix Salviae Miltiorrhizae extractum to pol 70%-75%;
Step 5, the tanshinone extract that obtains after the said extracted, cryptotanshinone extract, salvianolic acid B extract, Radix Notoginseng extract are suspended among the PEG-6000 of pre-thawing successively; Radix Salviae Miltiorrhizae extractum adds the water mix homogeneously; The said two devices mix homogeneously; Add Borneolum Syntheticum again, mixing; Changing the material temperature is 60-100 ℃; The temperature of liquid paraffin is 5-10 ℃, makes drop pill.
7. the medicine of the arbitrary described treatment coronary heart disease of claim 1-6: it is characterized in that, step 5 is, with the Tanshinone I I extract that obtains after step 1 extraction, the cryptotanshinone extract, the salvianolic acid B extract that step 2 obtains after extracting, the Radix Notoginseng extract that step 3 obtains after extracting, the Radix Salviae Miltiorrhizae extractum that step 4 obtains after extracting mixes with Borneolum Syntheticum and adjuvant, add any or more than one adjuvants, described adjuvant is selected from fat-soluble substrate and water-soluble base, and wherein fat-soluble substrate is selected from: stearic acid, glyceryl monostearate, insect wax, Cera Flava, paraffin, hydrogenated vegetable oil, semi-synthetic fatty acid ester; Water-soluble base is selected from Polyethylene Glycol, polyoxyethylene monostearate, poloxamer, sodium stearate, glycerin gelatine; Xylitol and composites of starch, erythritol.
8. the medicine of the treatment coronary heart disease of claim 7: it is characterized in that wherein step 3 medicine is auxilliary than being 1: 4.0.
9. the medicine of the treatment coronary heart disease of claim 7: it is characterized in that wherein said Polyethylene Glycol is a Polyethylene Glycol-6000.
10. the application of the medicine of the treatment coronary heart disease of claim 1 in the medicine of a kind of resisting coronary heart disease of preparation, angina pectoris cardiovascular disease.
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Publication number Priority date Publication date Assignee Title
CN102351819A (en) * 2011-10-27 2012-02-15 广州汉方现代中药研究开发有限公司 Extraction, purification and preparation method of high-purity salvianolic acid B
CN103919849A (en) * 2013-01-15 2014-07-16 天津天士力现代中药资源有限公司 Purification method for cryptotanshinone extract
CN104547027A (en) * 2013-10-23 2015-04-29 天津天士力现代中药资源有限公司 Preparation method and application of salvia miltiorrhiza leave and panax pseudo-ginseng leave extract
CN114949050A (en) * 2022-06-28 2022-08-30 琛蓝(美国)营养制品股份有限公司 Traditional Chinese medicine extract composition for promoting blood vessel health and preparation method thereof

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* Cited by examiner, † Cited by third party
Title
国家药典委员会: "《中华人民共和国药典2005版一部》", 31 December 2005, 化学工业出版社 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102351819A (en) * 2011-10-27 2012-02-15 广州汉方现代中药研究开发有限公司 Extraction, purification and preparation method of high-purity salvianolic acid B
CN102351819B (en) * 2011-10-27 2014-05-14 广州白云山汉方现代药业有限公司 Extraction, purification and preparation method of high-purity salvianolic acid B
CN103919849A (en) * 2013-01-15 2014-07-16 天津天士力现代中药资源有限公司 Purification method for cryptotanshinone extract
CN104547027A (en) * 2013-10-23 2015-04-29 天津天士力现代中药资源有限公司 Preparation method and application of salvia miltiorrhiza leave and panax pseudo-ginseng leave extract
CN104547027B (en) * 2013-10-23 2020-05-22 天津天士力现代中药资源有限公司 Preparation method and application of salvia miltiorrhiza leave and panax notoginseng leaf extract
CN114949050A (en) * 2022-06-28 2022-08-30 琛蓝(美国)营养制品股份有限公司 Traditional Chinese medicine extract composition for promoting blood vessel health and preparation method thereof

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