CN1778336A - A kind of preparation method of compound danshen dripping pill - Google Patents

Abstract

A composite Danshen dripping pill is prepared from red sage root, notoginseng and borneol through extracting the liquid extract from red sage root and notoginseng in water or alcohol, clarifying, ultrafiltering, concentrating, adding borneol and preparing dripping pills.

Description

A kind of preparation method of compound danshen dripping pill

technical field

The invention relates to a preparation method of compound danshen dripping pills for treating coronary heart disease, belonging to the field of traditional Chinese medicines.

Background technique

With the improvement of living standards, the aging of the world's population and the rejuvenation of the disease population, cardiovascular and cerebrovascular patients are increasing year by year, and have become the second largest disease that endangers human health. Angina pectoris is a clinical syndrome caused by temporary myocardial ischemia and hypoxia, with episodic chest pain or chest discomfort as the main manifestation. Coronary heart disease angina pectoris refers to angina pectoris caused by myocardial ischemia and hypoxia due to coronary artery sclerosis or spasm, accounting for about 90% of angina pectoris patients.

The current methods of treating angina pectoris mainly focus on dilating blood vessels, reducing blood viscosity, anti-platelet aggregation, and anti-coagulation. The traditional western medicines used are nitrates, nitrites, β-receptor blockers, calcium antagonists, etc., but all of them have relatively large toxic and side effects, and should not be taken for a long time. great effect. For example, after taking nitroglycerin, sometimes there will be dizziness, throbbing pain in the head, rapid heartbeat, and even fainting [see the new pharmacology [14th edition] page 264], and it has been found to cause severe hypotension in recent years [see Chinese Journal of Modern Medicine 1997; 7(4): 42; Shaanxi Medical Journal 1996; 25(5): 315], prone to tolerance [see Southern Nursing Journal 1996; 3(5): 7～9] and other issues, which hinder its use in clinical application.

Although there are many Chinese patent medicines for treating angina pectoris, pills, powders, creams, pills, and decoctions have long been ancient and are rarely used by modern people. At present, there are ordinary compound Danshen tablets and capsules on the market, but the production process of ordinary tablets and capsules is relatively backward, the content of active ingredients is low, and there is no quality control standard. They need to be taken orally and absorbed through the gastrointestinal tract, and the first-pass effect occurs in the liver. After being absorbed into the blood, the bioavailability is low and the absorption is slow, so it is not suitable for the first aid needs of patients with angina pectoris.

Compound Danshen Dripping Pill is a kind of drug for the treatment of coronary heart disease with fast onset and good curative effect, which is very popular among patients in clinic. In order to improve the preparation technology of compound danshen dripping pills, the inventor has carried out in-depth research on the extraction technology and completed the present invention.

Contents of the invention

The purpose of the present invention is to provide a new preparation process of compound danshen dripping pills.

The present invention is implemented through the following schemes:

The present invention is realized through the following technical steps: using salvia miltiorrhiza, notoginseng and borneol as raw materials, it is prepared according to the following steps:

(1) Mix Salvia Miltiorrhiza and Panax notoginseng or make water extract or alcohol extract separately;

(2) Carry out preliminary clarification treatment to described extract;

(3) further carry out ultrafiltration treatment to described extract;

(4) Concentrate the ultrafiltrate into an extract, mix the obtained extract with borneol and auxiliary materials evenly, and make dropping pills.

The weight percentages of the above raw materials are 20%-97% of Danshen, 2%-79% of Sanqi, and 0.2%-3% of Borneol; preferably 63.0%-94% of Danshen, 4.0%-35.0% of Radix Notoginseng, and 0.5%-0.5% of Borneol. 2.0%; more preferably 75.2% to 90% of Danshen, 9% to 23.5% of Panax notoginseng, 0.5% to 1.3% of borneol; the best is 82.87% of Danshen, 16.21% of notoginseng, and 0.92% of borneol. The sum of the percentages by weight of salvia miltiorrhiza, notoginseng and borneol is 100%.

In the technical step (1) of the present invention, the alcohol extract can be lower alcohols of different concentrations such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, etc., or extracts of their mixtures. The alcohol extract can be subjected to the next preliminary clarification treatment without concentration or after proper concentration.

In the technical step (2) of the present invention, preliminary clarification treatment can carry out rough filtration with general material such as gauze, silk silk etc., also can carry out microfiltration with more professional material such as ceramic membrane, also can get supernatant after high-speed centrifugation Liquid, also can use flocculant such as chitosan flocculation clarifier, 101 fruit juice clarifier, ZTC1+1 natural clarifier, egg white flocculant etc. Some impurities. The above clarification methods can be used alone or in combination, such as coarse filtration-adsorption clarification, adsorption clarification-high-speed centrifugation, coarse filtration-microfiltration, coarse filtration-alcohol precipitation, etc. The solution that has been preliminarily clarified can be subjected to the next step of ultrafiltration without concentration or after being properly concentrated; preferably, the next step of ultrafiltration is performed without concentration.

In the technical step (3) of the present invention, the ultrafiltration membrane used for ultrafiltration can be cellulose diacetate membrane (CA), cellulose triacetate membrane (CTA), cyanoethyl cellulose acetate membrane (CN-CA), polyester Sulfone membrane (PS), sulfonated polysulfone membrane (SPS), polyethersulfone membrane (PES), sulfonated polyethersulfone membrane (SPES), polysulfone amide membrane (PSA), phenolphthalein side group polyarylsulfone membrane (PDS) ), polyvinylidene fluoride film (PVDF), polyacrylonitrile film (PAN), polyimide film (N), cellulose film, methyl methacrylate-acrylonitrile copolymer film (MMA-AN), poly Acrylonitrile/cellulose diacetate (PAN/CA) blend membranes, dynamically formed ultrafiltration membranes, and modified membranes of the above membranes. Preferably cellulose diacetate membrane (CA), cellulose triacetate membrane (CTA), polysulfone membrane (PS), sulfonated polysulfone membrane (SPS), polyethersulfone membrane (PES), sulfonated polyethersulfone membrane (SPES), polysulfoneamide membrane (PSA), polyvinylidene fluoride membrane (PVDF), polyacrylonitrile membrane (PAN).

The molecular weight cut-off of the ultrafiltration membrane is generally 6000-80000, preferably 10000-70000, most preferably 20000-50000.

Ultrafiltration can be either cross-flow filtration or dead-end filtration, but cross-flow filtration is preferred.

The operating conditions of the ultrafiltration process are as follows:

(1) The inlet pressure of the ultrafiltration is 0.1-0.5MPa, preferably 0.1-0.35Mpa, and most preferably 0.25-0.35Mpa; the outlet pressure of the ultrafiltration is 0.5-0.25kPa lower than the inlet pressure. In the initial stage of ultrafiltration, a lower pressure is used, and then the pressure is gradually increased; in the process of ultrafiltration, periodic pressure fluctuations are adopted, and the pressure fluctuation difference is 0.1-0.2Mpa.

(2) The flow rate of the feed liquid is 1.0-4.0 m/s, preferably 2.0-3.0 m/s. During the ultrafiltration process, periodic flow fluctuations are used to generate pulsating flow or unsteady flow in the membrane channel, and the flow velocity fluctuation difference is 1.0-2.0m/s.

(3) In the ultrafiltration system, high-pressure inert gas such as nitrogen is fed intermittently to form a gas-liquid pulse flow, and the cycle is 0.5h-2h to ventilate once, each time for 1 minute.

(3) The feed liquid temperature is 15-50°C, preferably 20-40°C.

(4) When the stock solution is concentrated by 1/15 to 1/5, add water or dilute alcohol solution for ultrafiltration 1 to 2 times; preferably when the stock solution is concentrated by 1/12 to 1/8, add water Or dilute alcohol solution ultrafiltration 1 to 2 times.

(5) The pH value of the feed liquid is controlled at 5 to 9, preferably 6.0 to 7.5;

(6) Backwashing conditions: Backwashing pressure is 0.15-2.5MPa, backwashing cycle is 0.5-1.5h, and backwashing time is 1min-10min. When the ultrafiltration modules are connected in parallel to use the method of alternate backflushing, one or several sets perform normal ultrafiltration and part of the filtrate is flowed out to backwash the ultrafiltration membrane of another set or several sets of components, and exchange after a period of time To carry out, generally work for 10 to 20 minutes, and recoil for 30 seconds to 3 minutes.

(7) The chemical cleaning cycle is 0.5 months to 2 months. The chemical cleaning agents are generally dilute acids, dilute alkalis, and surfactants, preferably dilute alkalis such as 0.5% to 4.0% sodium hydroxide, 1.5% sodium hydroxide and The mixed solution of 2% sodium hypochlorite, etc., the pH value is 10-12, and the cleaning working pressure is 0.05-1.0MPa. After cleaning with chemical cleaners, rinse with water until nearly neutral.

In the ultrafiltration process, periodic pressure fluctuations or periodic flow fluctuations or periodic inert gas injections can be used alone, or in combination, that is, periodic pressure fluctuations and periodic flow fluctuations are used in combination, or periodic pressure fluctuations It is used in combination with periodic inert gas injection, or in combination with periodic flow fluctuations and inert gas injection, or in combination with the three.

In the technical step (4) of the present invention, after the ultrafiltrate is concentrated into an extractum, after mixing evenly with borneol and auxiliary materials, the chemical material is heated, moved into the dropping tank of the dropping pill machine, and the medicinal liquid is dropped into low-temperature liquid paraffin to remove the liquid Paraffin, choose pills.

Among them: the auxiliary material is polyethylene glycol-6000, its freezing point is 53-58 °C, and the addition amount is 2-6 times the weight of the extract and borneol; the temperature of the chemical material is 60-100 °C; the temperature of the liquid paraffin is 0-10 °C. ℃ (optimally 5-10 ℃); pellet weight 5-50mg/granule, diameter 1.95-4.29mm.

The compound danshen dripping pill prepared by the method of the invention has outstanding curative effect in treating angina pectoris caused by coronary heart disease.

Clinical Observation of Experimental Case of Compound Danshen Dripping Pills in Treating Angina Pectoris of Coronary Heart Disease

1 clinical data

1.1 Case selection All cases were diagnosed according to the standards revised by the 1979 National Symposium on the Prevention and Treatment of Coronary Heart Disease and Angina Pectoris with Integrative Traditional Chinese and Western Medicine, and according to the "ischemic disease" formulated by the International Society of Cardiology and Association and the World Health Organization Clinical Nomenclature Standardization Joint Task Force in 1979. Classification of angina pectoris in the Nomenclature of Cardiac Diseases. 102 patients with angina pectoris attack more than 5 times per week were randomly divided into treatment group and control group. The treatment group consisted of 51 cases, 30 males and 21 females; aged 39-76 years; disease course 1-20 years; 41 cases of stable exertional angina, 10 cases of unstable angina (including 1 case of post-infarct angina); There were 15 cases of blood pressure disease, 2 cases of diabetes, and 1 case of old myocardial infarction. The control group consisted of 51 cases, including 29 males and 22 females; aged 40-75 years; disease course 1-20 years; 42 cases of stable exertional angina, 9 cases of unstable angina (including 1 case of post-infarction angina); There were 14 cases of blood pressure disease, 2 cases of diabetes, and 1 case of old myocardial infarction. The two groups were comparable in terms of age, sex, course of disease, and condition (P>0.05).

1.2 Treatment method The patient stopped taking anti-angina pectoris drugs one week before treatment, and could take nitroglycerin tablets if the angina pectoris occurs, and record the dosage. The treatment group took Compound Danshen Dripping Pills, 3 times/day, 10 capsules each time; the control group took Xiaoxintong, 3 times/day, 10 mg each time. The course of treatment is 4 weeks. During the treatment period, except for nitroglycerin tablets in the mouth when angina pectoris attacks, other anti-angina pectoris drugs were stopped.

1.3 Observation method Before treatment, record the number of angina pectoris attack, pain degree, duration, dose of nitroglycerin tablets in mouth, heart rate, blood pressure, and do electrocardiogram examination. After taking the medicine, a routine electrocardiogram was performed once a week, and the above-mentioned indicators were recorded. Before and after treatment, do blood and urine routine, chest X-ray, liver and kidney function tests, blood rheology tests, and echocardiography.

1.4 Efficacy Evaluation Standards Efficacy evaluation standards refer to the "Draft Guidelines for Clinical Research of Cardiovascular System Drugs" formulated by the Ministry of Health in 1987.

1.4.1 Evaluation criteria for clinical efficacy Marked effect: the same level of exertion does not cause angina pectoris attack or the number of attacks is reduced by more than 80%, and the consumption of nitroglycerin is reduced by more than 80%. Effective: the number of angina attacks and the consumption of nitroglycerin are reduced by 50% to 80%. Ineffective: The number of angina attacks and the consumption of nitroglycerin were reduced by less than 50%. Aggravation: the number of angina attacks increases, the degree increases, the duration increases, and the consumption of nitroglycerin increases. Significant effect plus effective calculation of the total effective rate.

1.4.2 ECG Efficacy Evaluation Criteria Significantly effective: the resting ECG returns to normal, the limited exercise test turns from positive to negative or the exercise tolerance increases by more than 2 grades. Effective: Resting ECG ischemic ST-segment depression recovers below 0.15mV, T wave inversion becomes shallower by more than 50%, or exercise tolerance increases by 1 grade. Ineffective: The resting electrocardiogram remains unchanged from before treatment. Aggravation: resting ECG ST segment depression, decreased by > 0.05mV compared with before treatment, T wave inversion deepened > 50%, or T wave changed from upright to flat, or from flat to inverted. Significant effect plus effective calculation of the total effective rate.

1.5 Statistical data processing x ± s means, using t test and Ridit analysis for data processing.

2 results

2.1 Curative effect of angina pectoris symptoms Ridit analysis showed that there was a very significant difference between the two groups, indicating that the curative effect of Compound Danshen Dripping Pills on angina pectoris symptoms was significantly better than that of Xiaoxintong, see Table 1.

Table 1 Comparison of the therapeutic effects of the two groups on angina pectoris group no markedly effective efficient invalid aggravate Total effective rate/% Treatment group Control group 5151 208 2829 313 01 94.1①72.5

Note: ①Compared with the control group, by Radit analysis, U=3.039, P<0.01.

2.2 The curative effect of electrocardiogram According to Radit analysis, the improvement of electrocardiogram by Compound Danshen Dripping Pills is significantly better than that of Xiaoxintong, see Table 2.

Table 2 Comparison of the curative effect of the electrocardiogram between the two groups group no markedly effective efficient invalid aggravate Total effective rate/% Treatment group Control group 5151 112 2017 2030 02 60.8 ^① 37.3

Note: ①Compared with the control group, analyzed by Rtdit, U=2.685, P<0.01.

2.3 Changes in hemorrheology indexes The high-shear, low-shear, plasma viscosity, and erythrocyte aggregation index in the treatment group were significantly lower than those before treatment; although the above parameters in the control group were reduced to a certain extent, there was no statistical significance (P<0.05 ). Comparison between the two groups: the curative effect of the Compound Danshen Dripping Pill group was significantly higher than that of the Xiaoxintong group, P<0.01 or P<0.05. See Table 3.

Table 3 Changes of hemorheology indexes in the two groups before and after treatment (x±s) group no project Whole blood viscosity high shear/mPa.s Whole blood viscosity low cut/mPa.s Plasma viscosity/mPa.s erythrocyte aggregation index control group treatment group before treatment after treatment before treatment after treatment 5.43±3.155.39±0.365.12±0.134.01±0.11 1138±1.1211.26±1.3311.32±1.267.16±1.19 2.51±0.122.49±0.162.45±0.151.98±0.68 5.43±3.155.39±0.365.12±0.134.01±0.11 5.43±3.155.39±0.365.12±0.134.01±0.11

2.4 Effects on left ventricular systolic function Compound Danshen Dripping Pills re-examined echocardiographic images after 1 month of treatment: left ventricular systolic function, SV, CO, EF and FS all increased, and the difference was significant (P<0.05 ), while the control group had no significant change before and after treatment, as shown in Table 4.

Table 4 Comparison of left ventricular systolic function between the two groups before and after treatment (x±s) group no project SV/mL Po ^-1 CO/L·min ^-1 EF/% FS/% Treatment group Control group 5151 before treatment after treatment before treatment after treatment 71±1876±22 ^① 61±2062±29 ^① 5.2±2.05.6±2.0 ^① 4.6±1.44.4±1.7 ^① 53±1256±12 ^① 58±1156±12 ^⑦ 29±1831±8 ^① 31±830±8 ^①

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

Through the clinical research on Compound Danshen Dripping Pills, it is believed that Compound Danshen Dripping Pills can dilate coronary arteries, improve coronary flow, increase myocardial blood oxygen supply, and cause myocardial ischemic damage and myocardial repolarization caused by ST-T changes and Q-T prolongation. The symptoms of cardiac dysfunction such as palpitation, chest tightness and precordial pain caused by myocardial ischemia are relieved (the total effective rate is over 90%). After oral administration of Compound Danshen Dripping Pills, not only the onset of effect is fast (mostly within 4-5 minutes), but also the duration is 2-3 hours, which is longer than that of nitroglycerin. Therefore, it has the clinical value of protecting and saving the heart.

Detailed ways

The present invention will be further elaborated below in conjunction with embodiment. These examples are for illustrative purposes only and do not limit the invention in any way.

Embodiment one

The raw materials are 55.8g of Danshen, 3.4g of Radix Notoginseng, and 0.8g of Borneol.

Extracting the salvia miltiorrhiza and notoginseng with ethanol to obtain the ethanol extract of the salvia miltiorrhiza and notoginseng, filtering the extract with gauze, and collecting the filtrate. The filtrate was ultrafiltered with a cellulose diacetate membrane with a molecular weight cut-off of 6000, and the filtration method was cross-flow filtration. The operating conditions of the ultrafiltration process are: the pressure of the liquid inlet of the ultrafiltration is 0.1Mpa, and the pressure of the liquid outlet of the ultrafiltration is 0.5kPa lower than the pressure of the liquid inlet. In the initial stage of ultrafiltration, a lower pressure is used, and then the pressure is gradually increased; in the process of ultrafiltration, periodic pressure fluctuations are used, and the pressure fluctuation difference is 0.1Mpa. The flow rate of the feed liquid is 1.0m/s. During the ultrafiltration process, periodic flow fluctuations are used to generate pulsating flow or unstable flow in the membrane channel. The difference in flow rate fluctuations is 1.0m/s. Nitrogen is intermittently fed into the ultrafiltration system , to form a gas-liquid pulse flow, and the period is 0.5h to ventilate once, each time for 1 minute. The temperature of the feed liquid is 15°C. When the original feed liquid is concentrated by 1/15, add water or dilute alcohol solution for ultrafiltration once, and the pH value of the feed liquid is controlled at 5. The backwash pressure is 0.15MPa, the backwash cycle is 0.5h, and the backwash time is 1min. When the ultrafiltration modules are connected in parallel to use the method of alternate backflushing, one or several sets perform normal ultrafiltration and part of the filtrate is flowed out to backwash the ultrafiltration membrane of another set or several sets of components, and exchange after a period of time Carry out, work for 10min, recoil for 30sec. The chemical cleaning cycle is 0.5 months, the chemical cleaning agent is a mixed solution of 0.5%-4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, the pH value is 10-12, and the cleaning working pressure is 0.05MPa. After cleaning with chemical cleaners, rinse with water until nearly neutral.

Concentrating the ultrafiltrate to obtain an extract with a relative density of 1.35-1.39 (55° C.). Take the extract and borneol, mix them evenly with 18g of polyethylene glycol-6000, heat to a temperature of 85°C, and after 20-120 minutes to make the material, move it to a dropping tank of a dripping machine whose tank temperature is kept at 85-90°C. Drop the drug solution into liquid paraffin at 7-8°C, take out the dropping pills, remove the oil, select the pills through a sieve, and make 1000 dropping pills.

Embodiment two

The raw materials used are Danshen 59.3g, Panax notoginseng 6.38g and Borneol 0.34g.

Decoct the coarsely crushed Salvia miltiorrhiza in 5 times the amount of water for 2 hours, filter, and extract the filter residue for the second time, add 4 times the amount of water, fry for 1 hour, filter, discard the filter residue, and combine the filtrates to obtain the salvia miltiorrhiza extract . Extract the notoginseng with 70% ethanol to obtain the notoginseng extract. The above-mentioned Danshen extract and Panax notoginseng extract were combined, allowed to stand, and filtered. The filtrate was ultrafiltered with a polysulfone membrane with a molecular weight cut-off of 80,000, and the filtration method was dead-end filtration. The operating conditions of the ultrafiltration process are: the pressure of the liquid inlet of the ultrafiltration is 0.5Mpa, and the pressure of the liquid outlet of the ultrafiltration is 0.25kPa lower than the pressure of the liquid inlet. In the initial stage of ultrafiltration, a lower pressure is used, and then the pressure is gradually increased; in the process of ultrafiltration, periodic pressure fluctuations are adopted, and the pressure fluctuation difference is 0.2Mpa. The flow rate of the feed liquid is 4.0m/s. During the ultrafiltration process, periodic flow fluctuations are used to generate pulsating flow or unstable flow in the membrane channel. The difference in flow rate fluctuations is 2.0m/s. Nitrogen is intermittently fed into the ultrafiltration system , to form a gas-liquid pulse flow, and the period is 2h to ventilate once, each time for 1 minute. The temperature of the feed liquid is 50°C. When the raw liquid of the feed liquid is concentrated by 1/5, add water or dilute alcohol solution for ultrafiltration twice, and the pH value of the feed liquid is controlled at 9. The backwash pressure is 2.5MPa, the backwash cycle is 1.5h, and the backwash time is 10min. When the ultrafiltration modules are connected in parallel to use the method of alternate backflushing, one or several sets perform normal ultrafiltration and part of the filtrate is flowed out to backwash the ultrafiltration membrane of another set or several sets of components, and exchange after a period of time Carry out, work for 20 minutes, recoil for 3 minutes. The chemical cleaning cycle is 2 months, the chemical cleaning agent is a mixed solution of 0.5% to 4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, the pH value is 10 to 12, and the cleaning working pressure is 1.0MPa. After cleaning with chemical cleaners, rinse with water until nearly neutral.

Concentrating the ultrafiltrate to obtain an extract with a relative density of 1.35-1.39 (55° C.). Take the extract and borneol, mix them evenly with 20g of polyethylene glycol-6000, heat to a temperature of 85°C, and after 20-120 minutes to make the material, move it to a dropping tank of a dripping machine whose tank temperature is kept at 85-90°C. Drop the drug solution into liquid paraffin at 7-8°C, take out the dropping pills, remove the oil, select the pills through a sieve, and make 1000 dropping pills.

Embodiment three

The raw materials are 36.0g of Danshen, 23.2g of Radix Notoginseng, and 0.8g of Borneol.

The salvia miltiorrhiza and notoginseng are extracted with 80% ethanol to obtain the ethanol extract of the salvia miltiorrhiza and notoginseng, the extract is centrifuged at high speed and the supernatant is collected. The liquid is ultrafiltered with a polysulfone membrane with a molecular weight cut-off of 50,000, and the filtration method adopts cross-flow filtration. The operating conditions of the ultrafiltration process are: the pressure of the liquid inlet of the ultrafiltration is 0.35Mpa, and the pressure of the liquid outlet of the ultrafiltration is 0.20kPa lower than the pressure of the liquid inlet. In the initial stage of ultrafiltration, a lower pressure is used, and then the pressure is gradually increased; in the process of ultrafiltration, periodic pressure fluctuations are adopted, and the pressure fluctuation difference is 0.2Mpa. The flow rate of the feed liquid is 3.0m/s. During the ultrafiltration process, periodic flow fluctuations are used to generate pulsating or unstable flows in the membrane channel. The difference in flow rate fluctuations is 2.0m/s. Nitrogen is intermittently fed into the ultrafiltration system , to form a gas-liquid pulse flow, and the period is 2h to ventilate once, each time for 1 minute. The temperature of the feed liquid is 40°C. When the original feed liquid is concentrated by 1/8, add water or dilute alcohol solution for ultrafiltration twice, and the pH value of the feed liquid is controlled at 7.5. The backwash pressure is 2.5MPa, the backwash cycle is 1.5h, and the backwash time is 10min. When the ultrafiltration modules are connected in parallel to use the method of alternate backflushing, one or several sets perform normal ultrafiltration and part of the filtrate is flowed out to backwash the ultrafiltration membrane of another set or several sets of components, and exchange after a period of time Carry out, work for 20 minutes, recoil for 3 minutes. The chemical cleaning cycle is 2 months, the chemical cleaning agent is a mixed solution of 0.5% to 4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, the pH value is 10 to 12, and the cleaning working pressure is 1.0MPa. After cleaning with chemical cleaners, rinse with water until nearly neutral.

Concentrating the ultrafiltrate to obtain an extract with a relative density of 1.35-1.39 (55° C.). Take the extract and borneol, mix evenly with 20g of polyethylene glycol-6000, heat to a temperature of 60°C, and after 20-120 minutes of compounding, move to a dripping tank of a dripping machine whose tank temperature is kept at 90°C. Drop the drug solution into methyl silicone oil at 7-8°C, take out the dropping pills, remove the oil, select the pills through a screen, and make 1000 dropping pills, to get ready.

Embodiment four

The raw materials used are Danshen 41.1g, Panax notoginseng 8.0g, and Borneol 0.46g.

Put the coarsely crushed Danshen and Panax notoginseng into the extraction tank, add 5 times the amount of water, decoct for 2 hours, filter, and extract the filter residue for the second time, add 4 times the amount of water, fry for 1 hour, filter, and discard the filter residue To, combine the filtrates. The filtrate was ultrafiltered with a cellulose diacetate membrane with a molecular weight cut-off of 6000, and the filtration method was cross-flow filtration. The operating conditions of the ultrafiltration process are: the pressure of the liquid inlet of the ultrafiltration is 0.1Mpa, and the pressure of the liquid outlet of the ultrafiltration is 0.5kPa lower than the pressure of the liquid inlet. In the initial stage of ultrafiltration, a lower pressure is used, and then the pressure is gradually increased; in the process of ultrafiltration, periodic pressure fluctuations are used, and the pressure fluctuation difference is 0.1Mpa. The flow rate of the feed liquid is 1.0m/s. During the ultrafiltration process, periodic flow fluctuations are used to generate pulsating flow or unstable flow in the membrane channel. The difference in flow rate fluctuations is 1.0m/s. Nitrogen is intermittently fed into the ultrafiltration system , to form a gas-liquid pulse flow, and the period is 0.5h to ventilate once, each time for 1 minute. The temperature of the feed liquid is 15°C. When the original feed liquid is concentrated by 1/15, add water or dilute alcohol solution for ultrafiltration once, and the pH value of the feed liquid is controlled at 5. The backwash pressure is 0.15MPa, the backwash cycle is 0.5h, and the backwash time is 1min. When the ultrafiltration modules are connected in parallel to use the method of alternate backflushing, one or several sets perform normal ultrafiltration and part of the filtrate is flowed out to backwash the ultrafiltration membrane of another set or several sets of components, and exchange after a period of time Carry out, work for 10min, recoil for 30sec. The chemical cleaning cycle is 0.5 months, the chemical cleaning agent is a mixed solution of 0.5%-4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, the pH value is 10-12, and the cleaning working pressure is 0.05MPa. After cleaning with chemical cleaners, rinse with water until nearly neutral.

Concentrating the ultrafiltrate to obtain an extract with a relative density of 1.35-1.39 (55° C.). Take the extract and borneol, mix evenly with 21g of polyethylene glycol 6000, heat to a temperature of 60°C, and after 20 to 120 minutes of compounding, move to a dropping tank of a dripping machine whose tank temperature is kept at 90°C. Drop the drug solution into liquid paraffin at 7-8°C, take out the dropping pills, remove the oil, select the pills through a sieve, and make 1000 dropping pills.

Embodiment five

The raw materials used are 29.0g of Danshen, 30.6g of Radix Notoginseng, and 0.6g of Borneol.

Put the coarsely crushed Danshen and Panax notoginseng into the extraction tank, add 5 times the amount of water, decoct for 2 hours, filter, and extract the filter residue for the second time, add 4 times the amount of water, fry for 1 hour, filter, and discard the filter residue To, combine the filtrates. The filtrate was ultrafiltered with a polysulfone membrane with a molecular weight cut-off of 80,000, and the filtration method was dead-end filtration. The operating conditions of the ultrafiltration process are: the pressure of the liquid inlet of the ultrafiltration is 0.5Mpa, and the pressure of the liquid outlet of the ultrafiltration is 0.25kPa lower than the pressure of the liquid inlet. In the initial stage of ultrafiltration, a lower pressure is used, and then the pressure is gradually increased; in the process of ultrafiltration, periodic pressure fluctuations are adopted, and the pressure fluctuation difference is 0.2Mpa. The flow rate of the feed liquid is 4.0m/s. During the ultrafiltration process, periodic flow fluctuations are used to generate pulsating flow or unstable flow in the membrane channel. The difference in flow rate fluctuations is 2.0m/s. Nitrogen is intermittently fed into the ultrafiltration system , to form a gas-liquid pulse flow, and the period is 2h to ventilate once, each time for 1 minute. The temperature of the feed liquid is 50°C. When the raw liquid of the feed liquid is concentrated by 1/5, add water or dilute alcohol solution for ultrafiltration twice, and the pH value of the feed liquid is controlled at 9. The backwash pressure is 2.5MPa, the backwash cycle is 1.5h, and the backwash time is 10min. When the ultrafiltration modules are connected in parallel to use the method of alternate backflushing, one or several sets perform normal ultrafiltration and part of the filtrate is flowed out to backwash the ultrafiltration membrane of another set or several sets of components, and exchange after a period of time Carry out, work for 20 minutes, recoil for 3 minutes. The chemical cleaning cycle is 2 months, the chemical cleaning agent is a mixed solution of 0.5% to 4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, the pH value is 10 to 12, and the cleaning working pressure is 1.0MPa. After cleaning with chemical cleaners, rinse with water until nearly neutral.

Concentrate the ultrafiltrate to obtain an extract with a relative density of 1.32 to 1.40 (55° C.), take the extract and borneol, mix with 20 g of polyethylene glycol-6000, heat to a temperature of 60° C. After 120 minutes, move to the dripping tank of the dropping pill machine where the tank temperature is maintained at 90°C. Drop the drug solution into liquid paraffin at 7-8°C, take out the dropping pills, remove the oil, select the pills through a sieve, and make 1000 dropping pills.

Embodiment six

The raw materials are 21.0g of Danshen, 38.0g of Panax notoginseng, and 0.4g of borneol.

Take the coarsely crushed Danshen and Panax notoginseng medicinal materials into the extraction tank, add 0.89g sodium bicarbonate, add 4 times the amount of water, decoct for 2 hours, filter, and extract the filter residue for the second time, add 4 times the amount of water, decoct After 1 hour, filter, discard the filter residue, and combine the filtrates. The filtrate was ultrafiltered with a polysulfone membrane with a molecular weight cut-off of 50,000, and the filtration method was cross-flow filtration. The operating conditions of the ultrafiltration process are: the pressure of the liquid inlet of the ultrafiltration is 0.35Mpa, and the pressure of the liquid outlet of the ultrafiltration is 0.20kPa lower than the pressure of the liquid inlet. In the initial stage of ultrafiltration, a lower pressure is used, and then the pressure is gradually increased; in the process of ultrafiltration, periodic pressure fluctuations are adopted, and the pressure fluctuation difference is 0.2Mpa. The flow rate of the feed liquid is 3.0m/s. During the ultrafiltration process, periodic flow fluctuations are used to generate pulsating or unstable flows in the membrane channel. The difference in flow rate fluctuations is 2.0m/s. Nitrogen is intermittently fed into the ultrafiltration system , to form a gas-liquid pulse flow, and the period is 2h to ventilate once, each time for 1 minute. The temperature of the feed liquid is 40°C. When the original feed liquid is concentrated by 1/8, add water or dilute alcohol solution for ultrafiltration twice, and the pH value of the feed liquid is controlled at 7.5. The backwash pressure is 2.5MPa, the backwash cycle is 1.5h, and the backwash time is 10min. When the ultrafiltration modules are connected in parallel to use the method of alternate backflushing, one or several sets perform normal ultrafiltration and part of the filtrate is flowed out to backwash the ultrafiltration membrane of another set or several sets of components, and exchange after a period of time Carry out, work for 20 minutes, recoil for 3 minutes. The chemical cleaning cycle is 2 months, the chemical cleaning agent is a mixed solution of 0.5% to 4.0% sodium hydroxide, 1.5% sodium hydroxide and 2% sodium hypochlorite, the pH value is 10 to 12, and the cleaning working pressure is 1.0MPa. After cleaning with chemical cleaners, rinse with water until nearly neutral.

Concentrate the ultrafiltrate to obtain an extract with a relative density of 1.32 to 1.40 (55° C.), take the extract and borneol, mix it with polyethylene glycol-6000 18 g, heat to a temperature of 85° C. After 120 minutes, move to the dropping tank of the dropping pill machine whose tank temperature is kept at 85-90°C. Drop the drug solution into liquid paraffin at 7-8°C, take out the dropping pills, remove the oil, select the pills through a sieve, and make 1000 dropping pills.

Claims (14)

1. a kind of preparation method of compound danshen dripping pill is made with salvia miltiorrhiza, Radix Notoginseng and Borneolum as raw material medicine, it is characterized in that the processing step of its preparation is: (1) Mix Salvia Miltiorrhiza and Panax notoginseng or make water extract or alcohol extract separately; (2) Carry out preliminary clarification treatment to described extract; (3) further carry out ultrafiltration treatment to described extract; (4) Concentrate the ultrafiltrate, mix the obtained extract with borneol and auxiliary materials evenly, and make dropping pills. 2. the preparation method according to claim 1 is characterized in that the weight percent distribution ratio of described crude drug is: Salvia miltiorrhiza 20%～97%, Panax notoginseng 2%～79%, Borneol 0.2% to 3%. 3. preparation method according to claim 2 is characterized in that the weight percent of described raw material is: Salvia miltiorrhiza 63.0%～94%, Chuanxiong 4.0%～35.0%, Borneol 0.5% ~ 2.0%. 4. preparation method according to claim 3 is characterized in that the weight percent of described raw material is: Danshen 75.2% ~ 90%, Chuanxiong 9%～23.5%, Borneol 0.5% ~ 1.3%. 5. according to the described preparation method of claim 1～4, it is characterized in that described alcohol extraction liquid is the extraction liquid of the lower alcohol or its mixture selected from following: methanol, ethanol, n-propanol, isopropanol, n-propanol, Butanol, isobutanol. 6. The preparation method according to claims 1-4, characterized in that the alcohol extract is an ethanol extract. 7. The preparation method according to claims 1-4, characterized in that what is obtained in the step (a) is the ethanol extract prepared by mixing Salvia miltiorrhiza and Radix Notoginseng. 8. The preparation method according to claims 1-4, characterized in that what is obtained in the step (a) is the water extract prepared by mixing Salvia miltiorrhiza and Radix Notoginseng. 9. The preparation method according to claims 1 to 4, wherein said step (a) is as follows: take the coarsely crushed Danshen and Panax notoginseng medicinal materials into the extraction tank, add an appropriate amount of sodium bicarbonate, add water and decoct twice , filtered, and the filter residue was discarded, and the filtrates were combined to obtain an extract. 10. The preparation method according to claims 1-4, characterized in that the preliminary clarification treatment is coarse filtration-adsorption clarification, adsorption clarification-high-speed centrifugation, coarse filtration-microfiltration or coarse filtration-alcohol precipitation. 11. The preparation method according to claims 1 to 4, characterized in that the ultrafiltration membrane used in the ultrafiltration treatment is selected from: cellulose diacetate membrane, cellulose triacetate membrane, cyanoethyl cellulose acetate membrane, Polysulfone membrane, sulfonated polysulfone membrane, polyethersulfone membrane, sulfonated polyethersulfone membrane, polysulfone amide membrane, polyarylsulfone membrane with phenolphthalein side group, polyvinylidene fluoride membrane, polyacrylonitrile membrane, polyimide Membranes, cellulose membranes, methyl methacrylate-acrylonitrile copolymer membranes, polyacrylonitrile/cellulose diacetate blend membranes, dynamically formed ultrafiltration membranes, and modified membranes of the above membranes; the ultrafiltration membranes The molecular weight cut-off is 6000-80000. 12. The preparation method according to claim 11, wherein the ultrafiltration membrane is selected from the group consisting of: cellulose diacetate membrane, cellulose triacetate membrane, polysulfone membrane, sulfonated polysulfone membrane, polyethersulfone membrane, Sulfonated polyethersulfone membrane, polysulfoneamide membrane, polyvinylidene fluoride membrane, polyacrylonitrile membrane; the molecular weight cut-off of the ultrafiltration membrane is 10,000-70,000. 13. The preparation method according to claims 1 to 4, characterized in that the operating conditions of the ultrafiltration treatment are as follows: the pressure of the liquid inlet of the ultrafiltration is 0.1 to 0.5 MPa, and the pressure of the liquid outlet of the ultrafiltration is higher than that of the inlet The pressure at the liquid port is 0.25-0.5kPa lower; the temperature of the feed liquid is 15-50°C; the pH value of the feed liquid is controlled at 5-9; when the raw liquid of the feed liquid is concentrated by 1/15-1/5, add water or dilute alcohol solution Ultrafiltration 1 to 2 times. 14. The preparation method according to claim 13, characterized in that, in the process of the ultrafiltration, the following methods are used alone or in combination: periodic pressure fluctuations, periodic flow fluctuations, intermittently feeding inert gas; wherein The pressure fluctuation difference of the periodic pressure fluctuation is 0.1-0.2Mpa, the flow velocity fluctuation difference of the periodic flow fluctuation is 1.0-2.0 m/s, and the inert gas is intermittently injected every 0.5-2 hours for 1 minute each time.