CN1778323A - A drug drop pill for treating cardiovascular disease - Google Patents

Abstract

A Chinese medicine in the form of dripping pill for treating cardiovascular disease is prepared from Chuan-xiong rhizome, notoginseng and borneol through extracting the liquid extract from Chuan-xiong rhizome and notoginseng in water or alcohol, clarifying, ultrafiltration, concentrating, adding borneol and preparing dripping pills.

Description

A drug drop pill for treating cardiovascular disease

technical field

The invention relates to a medicinal dripping pill for treating cardiovascular diseases, which belongs 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 Chuanxiong Dropping Pills is a drug for the treatment of coronary heart disease with fast onset and good curative effect, and is very popular among patients in clinic. The present inventor has carried out in-depth research from the extraction technology aspect, has completed the present invention.

Contents of the invention

The object of the present invention is to provide a kind of traditional Chinese medicine dripping pill for treating cardiovascular disease.

The present invention is implemented through the following schemes:

The medicine of the present invention is realized through the following technical steps: taking Rhizoma Chuanxiong, Radix Notoginseng and Borneolum as raw materials, prepare according to the following steps:

(1) Mix Rhizoma Chuanxiong 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 a drop pill preparation.

The weight percentages of the above-mentioned raw materials are: Rhizoma Chuanxiong 20%～97%, Radix Notoginseng 2%～79%, Borneol 0.2%～3%; Preferably Chuanxiong 63.0%%～94%, Radix Notoginseng 4.0%～35.0%, Borneol 0.5% %～2.0%; more preferably Chuanxiong 75.2%～90%, Panax notoginseng 9%～23.5%, Borneol 0.5%～1.3%. The sum of the percentages by weight of Rhizoma Chuanxiong, Panax 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 medicine of the invention has outstanding curative effect in treating angina pectoris of coronary heart disease.

Experimental example Chinese medicine dripping pill of the present invention treats clinical curative effect observation of coronary heart disease angina pectoris

normal information

1. Case selection: 52 outpatients and inpatients with coronary heart disease and angina pectoris in our hospital were selected, including 38 inpatients and 14 outpatients who met the WHO diagnostic criteria for coronary heart disease and angina pectoris: 36 cases of stable angina (SA), unstable Type angina pectoris (VA) in 14 cases, accompanied by arrhythmia in 20 cases; male 36 cases, female 16 cases, aged 40 to 68 years old (54.52 ± 10.08 years).

2, method: Chinese medicine dripping pill of the present invention, every day is taken orally 3 times, each 10, and the course of treatment is 2 months. The onset of angina pectoris, changes in electrocardiogram, and changes in hemorrheology were observed before and after treatment. Plasma viscosity (PV) and whole blood viscosity (WBV) were checked using an internationally recognized cone-plate blood viscometer, (manufactured by Chengdu Instrument Factory NXE-I type) hematocrit (Hct) and fibrin (Fib), with microcapillary Methods, the CR-III platelet aggregation instrument was completed at the same time, and PAG MAX was the maximum aggregation rate of the MG platelet aggregation instrument.

Efficacy Judgment Criteria

1. Symptoms of angina pectoris: It is markedly effective if the angina pectoris completely disappears or the number of attacks is reduced by more than 90% before treatment; it is effective if the number of attacks is reduced by more than 50% but less than 90% before treatment; there is no reduction in symptoms of angina pectoris or the number of attacks is less than before treatment 50% of the total is invalid.

2. Electrocardiogram: Observe the ST-T changes of ECG before and after treatment. After treatment, ST-T returns to normal or has a significant decline and returns to near normal. It is effective if the stress ECG test turns from positive to negative. There is no change after treatment, and the stress ECG test remains unchanged. Those who are positive are invalid.

3. Arrhythmia: It is effective if the arrhythmia disappears or decreases by ≥50% after treatment.

Statistical method

The means of various data are represented by (x±s), and the comparison of means is by t test, and the comparison of rates is by X ² test.

result

1. Observation of clinical curative effect on symptoms of angina pectoris. The traditional Chinese medicine dripping pills of the present invention have better effect on stable angina than unstable angina, and the effective rates are respectively 90.48% and 74.1%. See Table 1.

Table 1 Curative effect observation of angina pectoris group Number of cases (n) Significant efficiency (%) Efficient(%) Total effective rate (%) SAVA 3418 60.2432.35 30.2442.55 90.4874.90

2. Improvement of electrocardiogram There were 41 cases with abnormal ST-T of electrocardiogram before treatment, and 22 cases were effective after treatment, the effective rate was 53.6%.

3. Arrhythmia improved in 20 cases accompanied by arrhythmia, 10 cases were effective after treatment, and the effective rate was 50%.

4. Changes in blood rheology The results of measuring platelet aggregation rate, whole blood viscosity high cut value, plasma viscosity, hematocrit, fibrinogen and other indicators before and after treatment showed that compound Chuanxiong dripping pills had a significant effect on platelet aggregation rate and blood viscosity. Improvement effect. See Table 2.

Table 2 Chinese medicine dripping pills of the present invention have influence on hemorrheology of patients with coronary heart disease angina pectoris Observation indicators Before treatment After treatment P PAG Max(%)WBV230 ^s-1 PVHCTFib 79.69±15.727.49±1.242.24±0.7544.3±5.62510.4±1.62 56.94±15.025.12±1.021.94±0.5641.09±4.023.24±1.5 <0.05<0.05<0.05>0.05<0.01

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 Rhizoma Chuanxiong, 3.4g of Radix Notoginseng, and 0.8g of Borneol.

Extract Chuanxiong and Sanqi with ethanol to obtain the ethanol extract of Chuanxiong and Sanqi, filter the extract with gauze, and collect 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 evenly with polyethylene glycol 6000 18g, heat to a temperature of 85°C, and after 20 to 120 minutes of compounding, move to a dropping tank of a dripping machine whose tank temperature is kept at 85 to 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 are Chuanxiong 59.3g, Panax notoginseng 6.38g and Borneol 0.34g.

Add 5 times the amount of water to the coarsely crushed Rhizoma Chuanxiong, 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, discard the filter residue, and combine the filtrates to obtain the extract of Salvia miltiorrhiza . Extract the notoginseng with 70% ethanol to obtain the notoginseng extract. The above-mentioned Chuanxiong 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 Chuanxiong 36.0g, Panax notoginseng 23.2g and Borneol 0.8g.

The Rhizoma Chuanxiong and Sanqi were extracted with 80% ethanol to obtain the ethanol extract of Rhizoma Chuanxiong and Sanqi, which was centrifuged at high speed and supernatant was 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 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 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 are 41.1g of Chuanxiong, 8.0g of Panax notoginseng, and 0.46g of borneol.

Put the coarsely crushed Ligusticum chuanxiong 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 dropping pill 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 are Chuanxiong 29.0g, Panax notoginseng 30.6g and Borneol 0.6g.

Put the coarsely crushed Ligusticum chuanxiong 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 Chuanxiong 21.0g, Panax notoginseng 38.0g, and Borneol 0.4g.

Take the coarsely crushed Rhizoma Chuanxiong and Panax notoginseng 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 Chinese medicine dripping pill for the treatment of coronary heart disease angina pectoris, it is made with Rhizoma Chuanxiong, Radix Notoginseng and Borneolum as raw material medicine, it is characterized in that the processing step of its preparation is: (1) Mix Rhizoma Chuanxiong 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. Chinese medicine dripping pill according to claim 1, is characterized in that the weight percentage distribution ratio of described crude drug is: Chuanxiong 20%～97%, Panax notoginseng 2%～79%, Borneol 0.2% to 3%. 3. Chinese medicine dripping pill according to claim 2, is characterized in that the weight percent of described raw material is: Chuanxiong 63.0%%～94%, Panax notoginseng 4.0%～35.0%, Borneol 0.5% ~ 2.0%. 4. Chinese medicine dripping pill according to claim 3 is characterized in that the weight percent of described raw material is: Chuanxiong 75.2% ~ 90%, Notoginseng 9%～23.5%, Borneol 0.5% ~ 1.3%. 5. according to the described Chinese medicine dripping pill of claim 1～4, it is characterized in that described ethanol extract is the extract that is selected from following lower alcohol or its mixture: methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol. 6. according to the described Chinese medicine dropping pill of claim 1～4, it is characterized in that described ethanol extract is ethanol extract. 7. The Chinese medicine dripping pill according to claims 1 to 4, characterized in that what is obtained in the step (a) is the ethanol extract prepared by mixing Rhizoma Chuanxiong and Radix Notoginseng. 8. The Chinese medicine dripping pill according to claims 1 to 4, characterized in that what is obtained in the step (a) is the water extract prepared by mixing Rhizoma Chuanxiong and Radix Notoginseng. 9. according to the described Chinese medicine dripping pill of claim 1～4, it is characterized in that described step (a) is: get through the Rhizoma Chuanxiong of coarse pulverization, Radix Notoginseng medical material to extraction tank, add appropriate amount of sodium bicarbonate, add water decoction times, filter, discard the filter residue, and combine the filtrates to obtain the extract. 10. The traditional Chinese medicine dripping pill according to claims 1-4, characterized in that the preliminary clarification treatment is adsorption clarification by coarse filtration, adsorption clarification-high-speed centrifugation, coarse filtration-microfiltration or coarse filtration-alcohol precipitation. 11. The Chinese medicine dripping pill 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 Amine membranes, cellulose membranes, methyl methacrylate-acrylonitrile copolymer membranes, polyacrylonitrile/cellulose diacetate blend membranes, dynamically formed ultrafiltration membranes, and modified membranes of the above membranes; ultrafiltration membranes thereof The molecular weight cut off is 6000~80000. 12. The Chinese medicine dripping pill according to claim 11, wherein said ultrafiltration membrane is selected from: 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 Chinese medicine dripping pill 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 ratio of the liquid outlet of the ultrafiltration is The pressure at the liquid inlet 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 The solution was ultrafiltered 1 to 2 times. 14. The Chinese medicine dripping pill according to claim 13, characterized in that, in the process of the ultrafiltration, the following methods are adopted alone or in combination: periodic pressure fluctuations, periodic flow fluctuations, intermittently feeding inert gas; Among them, 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 once every 0.5-2 hours, each time for 1 minute .