CN1778327B - Drug dripping pills for the treatment of cardiovascular diseases - Google Patents

Abstract

A Chinese medicine in the form of dripping pill for treating coronary heart disease is prepared from Chuan-xiong rhizome, notoginseng and dalbergia wood oil is prepared through extracting the liquid extract from Chuan-xiong rhizome and notoginseng in water or alcohol, clarifying, ultrafiltering, concentrating, adding dalbergia wood oil or storax and preparing dripping pill.

Description

Drug dripping pills for the treatment of cardiovascular diseases

technical field

The invention relates to a traditional Chinese medicine prepared by an ultrafiltration process. Specifically, the invention relates to a traditional Chinese medicine dripping pill prepared by an ultrafiltration process.

Background technique

Membrane separation technology (Membrane Separation Technique) is a new high-efficiency separation technology, which has been internationally recognized as the most promising high-tech production technology from the end of the 20th century to the middle of the 21st century. Ultrafiltration (UF) technology is a membrane separation technology whose basic principle is to use the selective screening performance of membrane pores to separate, purify and concentrate substances. The ultrafiltration method uses an anisotropic membrane (that is, an asymmetric membrane) made of polymer materials as the filter medium. Under normal temperature conditions, relying on a certain pressure and flow rate, the solution flows through the membrane surface, forcing low molecular weight substances to permeate. Through the membrane, the polymer substances are intercepted.

Because the ultrafiltration method is a physical method, it has the characteristics of no need for repeated heating, no "phase state" change, less possibility of destroying active ingredients than other general methods, and short process flow, so it is applied to the research of extracting active ingredients of traditional Chinese medicine It is becoming more and more active, and some products have moved from laboratory research to industrial production. Wang Shiling and others in the PLA 304 Hospital used ultrafiltration to extract the active ingredient baicalin in Scutellaria baicalensis. The results showed that the ultrafiltration method was better than the conventional method in terms of yield and purity. And once ultrafiltration can meet the requirement of injection, no further refinement is needed, the process is simple, and the production cycle can be shortened by 1 to 2 times (Wang Shiling, Zheng Dianbao "Preliminary investigation of extracting baicalin by ultrafiltration", Chinese patent medicine research, 1988 (3 ): 5). Wang Shiling and others have further studied the optimal process conditions for extracting baicalin by ultrafiltration. The experimental results prove that the ultrafiltration membrane with suitable pore size (molecular weight cut-off is 6000～10000) is the best way to improve the yield and quality of baicalin. The key is to increase the temperature of the liquid medicine or reduce the concentration at the same time, and strictly control the pH value (pH=1.5 during acidification, pH=7.0 during alkali dissolution), which can significantly increase the ultrafiltration speed and obtain the best output effect (Wang Shiling, "Ultrafiltration A study on the process of extracting baicalin at one time", Chinese patent medicine, 1994, 16 (3): 2). Xu Jinlin et al. used ultrafiltration (polysulfone membrane, molecular weight cut-off 6000) in the preparation of phytic acid, and the yield of phytic acid It is 86.4%, 12.6% higher than the conventional phytate method, and the phytic acid obtained by the ultrafiltration method almost does not contain inorganic phosphorus, and the appearance is transparent and almost colorless (Xu Jinlin, Xu Jie, Wang Yuanjin "Research on the Preparation of Phytic Acid by Membrane Separation Technology" , Chinese Journal of Pharmaceutical Industry, 1994, 25 (4): 150). He Changsheng and other applications of ultrafiltration technology to separate and refine stevioside, using ultra-thin plate ultrafilter and cellulose acetate membrane (CA membrane) with a molecular weight cut-off of 10000 ) field experiments on stevioside purification, the process flow is reasonable and feasible. The performance of the ultrafilter is stable, the decolorization performance of the membrane and the effect of removing impurities are good, and it can better solve the precipitation and potting that often occur in the production of stevioside. Foaming problem (He Changsheng, Wang Bingnan, Zhu Shanshan "Research on the application of stevioside ultrafiltration", Water Treatment Technology, 1994, 20(2): 89). Huang Ziqiang used ultrafiltration membranes (molecular weight cut-offs of 4000 and 10000 Compared with the bleaching method, recrystallization method, alcohol ether precipitation method and basic salt precipitation method that are mostly used in China, the ultrafiltration process is simple, efficient, and low in cost. Oils, pigments, sugars and other highly hydrophilic impurities in the water can achieve the desired effect (Huang Ziqiang, "Preliminary Study on the Purification of Camellia Camellia Saponin by Ultrafiltration Membrane Method", Water Treatment Technology, 1995, 21(2): 99). Guo Liwei from Nanjing University of Traditional Chinese Medicine compared and studied the effects of water-alcohol method and ultrafiltration method on the clarification of Cornus officinalis preparations on the ingredients contained in the preparations. The ultrafiltration membrane has no obvious effect on loganin (molecular weight is 384), but the membrane with a molecular weight cut-off of 1000 makes loganin lose about 50% Right (Guo Liwei, Peng Guoping, Pan Yang, etc. "Comparative research on refining traditional Chinese medicine preparations containing Cornus officinalis by water-alcohol method and membrane separation method", Chinese Patent Medicine, 1999, 21 (2): 59). Wang Chengzhang et al. Sulfone membrane, molecular weight cut-off 30000) and polyamide resin adsorption and elution method are used to separate and purify the ethanol extract of Ginkgo biloba leaves. After detection by high performance liquid chromatography (HPLC), the content of glycosides in Ginkgo biloba is about 45%, and the yield is 0.5% %～0.7%, compared with conventional steam distillation method, organic solvent extraction method is superior, and can reduce waste water discharge in ultrafiltration process, protect environment, reduce production cost, improve economic benefit (Wang Chengzhang etc. " ultrafiltration is in purifying ginkgo The application of lutein glycosides", Forestry Science and Technology Communication, 1997, (2): 21).

Although the application of ultrafiltration technology in the production of traditional Chinese medicine preparations has its unique advantages, the extent of its application is still very limited. The reason is that there are still the following problems:

(1) The composition of Chinese herbal medicine is complex, especially in many compound preparations, the active ingredients have not been fully understood, so it needs to be thoroughly studied before applying ultrafiltration technology to Chinese herbal medicine preparations. For example, due to the complexity of the components, it is impossible to apply ultrafiltration to the production of most traditional Chinese medicine preparations before a large number of pharmacological and clinical research tests are conducted to fully evaluate the effect of ultrafiltration on the efficacy of each component in traditional Chinese medicine preparations.

(2) There are few types of membrane materials, the membrane pore size distribution is wide, and the performance is not stable. The ultrafiltration membrane materials used in the production of traditional Chinese medicine preparations include cellulose acetate, polyacrylonitrile, polysulfone, sulfonated polysulfone, polysulfone amide, etc. According to its affinity to water, it can be roughly divided into two categories: hydrophobic membrane materials and hydrophilic membrane materials. Hydrophilic membrane materials such as cellulose acetate and sulfonated polysulfone have less adsorption of solutes and a smaller molecular weight cut-off, but poor thermal stability, mechanical strength, chemical resistance, and bacterial erosion resistance are usually not high; polysulfone and other hydrophobic Membrane material has high mechanical strength, high temperature resistance, solvent resistance, and biodegradation resistance, but because the molecular chain contains a large number of hydrophobic genes or chain links, and has a lot of electrostatic charges, the membrane has a low water permeability and low anti-pollution ability .

(3) Membrane fouling is the biggest obstacle preventing ultrafiltration technology from laboratory research to industrial application. In the ultrafiltration process of traditional Chinese medicine preparations, if the pretreatment effect of the liquid medicine is not good, the membrane surface will be easily polluted and the membrane pores will be blocked, which will reduce the permeation flux, that is, the productivity, or even fail to work normally, reduce the production efficiency, and increase the cost, resulting in membrane shortened service life.

(4) The selection method of membrane modules has not been established yet, and the operating parameters of ultrafiltration still need to be optimized. There are many factors that affect the effect of ultrafiltration, including the selection of membrane components, the determination of process parameters and the cleaning method of the ultrafilter after use. Therefore, the ultrafiltration equipment and operating technology suitable for ultrafiltration of traditional Chinese medicine systems need further research.

After long-term and unremitting efforts, the inventor determined the appropriate process operating conditions by analyzing a large number of experimental data, and provided a specific solution for the industrial production of the drug of the present invention by ultrafiltration.

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 achieved through the following technical steps: using Rhizoma Chuanxiong, Panax notoginseng and Dalbergia oil as raw materials, it is prepared 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; add balsamic oil, mix evenly with auxiliary materials, and make a drop pill preparation.

The weight percent of above-mentioned crude drug is: Rhizoma Chuanxiong 20%～97%, Panax notoginseng 2%～79%, balm oil 0.2%～3%; Be preferably Chuanxiong 63.0%%～94%, Radix notoginseng 4.0%～35.0%. Sesame oil 0.5%-2.0%; more preferably Chuanxiong 75.2%-90%, Panax notoginseng 9%-23.5%, and balm oil 0.5%-1.3%. The sum of the percentages by weight of Rhizoma Chuanxiong, Panax notoginseng and balm oil is 100%.

The above-mentioned raw material balm oil can be replaced by styrax, that is, the above-mentioned raw material can be 20%-97% of Chuanxiong, 2%-79% of Sanqi, 0.2%-3% of Styrax; preferably 63.0%-94% of Chuanxiong and 4.0% of Panax notoginseng %～35.0%, Styrax 0.5%～2.0%; more preferably Chuanxiong 75.2%～90%, Panax notoginseng 9%～23.5%, Styrax 0.5%～1.3%. The sum of the weight percentages of Chuanxiong, Sanqi and Styrax 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, backwashing time is 1min-10min. Or several sets of normal ultrafiltration and split out a part of the filtrate to backflush the ultrafiltration membrane of another set or several sets of components, and exchange after a period of time, usually working for 10-20min, and backflushing for 30sec-3min.

(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 balsamic oil or styrax and auxiliary materials, the material is heated, moved into the dropping tank of the dropping pill machine, and the medicinal liquid is dropped into low-temperature liquid paraffin , remove the liquid paraffin, and choose pills.

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

Experimental example The present invention medicine treats the clinical observation of coronary heart disease angina pectoris

1 Materials and methods

1.1 General information: Select patients who meet the WHO diagnostic criteria for stable angina pectoris, have a history of typical exertional angina pectoris for at least 3 months, have angina pectoris attacks ≥ 5 times a week, and can relieve symptoms by rest or sublingual nitroglycerin as observation objects. 300 patients, including 220 males and 80 females, aged 48 to 80 years, with an average age of 59.2 years, and a course of disease of 1 to 4.5 years, including 52 cases of old myocardial infarction, 48 cases of hypertension, and hyperlipidemia 40 cases, 38 cases of diabetes mellitus.

1.2 Observation method: 300 patients were randomly divided into a treatment group of 160 cases and a control group of 140 cases by random double-blind method. Stop taking other anti-anginal drugs two weeks before treatment, and stop using lipid-lowering drugs for those with hyperlipidemia. The treatment group is given medicine of the present invention, each 10, every day 3 times; Control group's Xiaoxintong, each 10mg, every day 3 times. The course of treatment was 8 weeks. All patients had hematuria routine, blood lipid, liver and kidney function, electrocardiogram and dynamic electrocardiogram examination before treatment, after one month of treatment and after the course of treatment. During the medication period, the number of angina attacks, blood pressure, heart rate, and side effects were recorded every week.

1.3 Efficacy Judgment Criteria:

1.3.1 Symptoms of angina pectoris: after the course of treatment, angina pectoris completely disappears or the number of attacks is reduced by more than 90% before treatment, which is markedly effective. It is effective if the frequency of reduction is more than 50% before treatment, but less than 90%. If the symptoms of angina pectoris are not reduced or the number of reductions is less than 50% of the total number before treatment, it is invalid.

1.3.2 Improvement of ECG: ①Significant effect: ECG returns to "approximately normal" or reaches normal. ②Effective: the S-T segment is lowered, and it rises above 0.05mV after treatment, but it does not reach the normal level, and the inverted T wave in the main lead becomes shallow (up to 25%) or the T wave changes from flat to upright, atrioventricular or intraatrial conduction resistance stagnation improver. ③ Invalid: The electrocardiogram is basically the same as before treatment. ④ Aggravation: S-T segment decreased by more than 0.05mV compared with before treatment. The inverted T wave in the main lead is deepened (up to 25%) or the upright T wave is flat, and the flat T wave becomes inverted, and ectopic heart rhythm, atrioventricular block or indoor conduction block occurs.

2 results

2.1 Curative effect of angina symptoms: see Table 1.

Table 1 Comparison of curative effect of angina pectoris symptoms in two groups

As can be seen from Table 1, two groups of comparison total effective rate differences are not significant (P＞0.05), but the treatment group marked rate reaches 69.4%, and matched group is 51.0%, two groups have significant difference (P＜0.05), show that the present invention Drugs are better than Painol.

2.2 Comparison of curative effect of electrocardiogram: see Table 2.

Table 2 Analysis of curative effect of electrocardiogram in two groups

It can be seen from Table 2 that the effective rate of electrocardiogram in the treatment group was 20%, and the total effective rate was 62.5%. The effective rate of the control group was 11.42%, and the total effective rate was 39.99%. There was a significant difference between the groups at P<0.05 through statistical processing, indicating that the drug of the present invention is better than Xiaoxintong in improving myocardial ischemic electrocardiogram. During the course of treatment and after the course of treatment, no exacerbation cases were found in the S-T segment and T wave of electrocardiogram in the two groups, and no ectopic heart rhythm, atrioventricular or indoor conduction block was found.

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 45.0g Chuanxiong, 14.0g Panax notoginseng, and 0.8g balsamic oil.

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.

Concentrate the ultrafiltrate to obtain an extract with a relative density of 1.35 to 1.39 (55°C). Take the extract, add balsamic oil, mix evenly with polyethylene glycol-6000 18g, heat to a temperature of 85°C, and After 20-120 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.

Embodiment two

The raw materials are 55.8g of Rhizoma Chuanxiong, 3.4g of Panax notoginseng, and 0.8g of balsamic oil.

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 Rhizoma Chuanxiong extract . 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, add balsamic oil, mix evenly with polyethylene glycol-6000 20g, heat to a temperature of 85°C, and after 20-120 minutes, move to a dripping tank of a dripping machine with a tank temperature of 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, notoginseng 23.2g, and balsamic oil 0.8g.

The Rhizoma Chuanxiong and Sanqi were extracted with 70% ethanol to obtain the ethanol extract of Rhizoma Chuanxiong and Sanqi, which was centrifuged at a high speed to obtain the supernatant. 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, add balm oil, mix evenly with polyethylene glycol-6000 20g, heat to a temperature of 60°C, and after 20 to 120 minutes of compounding, move to a dripping tank with a tank temperature of 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 50.0 grams of Rhizoma Chuanxiong, 9.4 grams of Panax notoginseng, and 0.6 grams of balsamic oil.

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 1.32-1.40 (55° C.). Take the extract, add balm oil, mix evenly with polyethylene glycol-6000 21g, heat to a temperature of 60°C, and after 20 to 120 minutes of compounding, move to a dripping tank with a tank temperature of 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 29.0 grams of Rhizoma Chuanxiong, 30.6 grams of Panax notoginseng, and 0.6 grams of balsamic oil.

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 Go and combine the filtrates. The filtrate is ultrafiltered with a polysulfone membrane with a molecular weight cut-off of 80,000, and the filtration method adopts dead-end filtration. The operating conditions of the ultrafiltration process are: the pressure of the ultrafiltration inlet is 0.5Mpa, and the ultrafiltration outlet is 0.5Mpa. The inlet pressure is 0.25kPa lower than the liquid inlet pressure. The initial ultrafiltration adopts a lower pressure, and then slowly increases the pressure; in the ultrafiltration process, adopts periodic pressure fluctuations, 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, and the flow velocity fluctuation difference is 2.0m/s. Nitrogen is intermittently fed into the ultrafiltration system to form a gas-liquid pulse flow The period is 2 hours 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 backwashing pressure is 2.5MPa, the backwashing period is 1.5h, and the backwashing time is 10min. When the ultrafiltration components are connected in parallel to use alternate backflushing, one or several sets of them perform normal ultrafiltration and part of the filtrate To recoil the ultrafiltration membrane of another set or several sets of components, exchange after a period of time, work for 20 minutes, and recoil for 3 minutes. The chemical cleaning cycle is 2 months, and the chemical cleaning agent is 0.5% to 4.0% sodium hydroxide, The mixed solution of 1.5% sodium hydroxide and 2% sodium hypochlorite, the pH value is 10-12, and the cleaning working pressure is 1.0MPa. After cleaning with chemical cleaning agent, rinse with water until nearly neutral.

Concentrating the ultrafiltrate to obtain an extract with a relative density of 1.32-1.40 (55° C.). Take the extract, add balm oil, mix evenly with polyethylene glycol-6000 20g, heat to a temperature of 60°C, and after 20 to 120 minutes of compounding, move to a dripping tank with a tank temperature of 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 21.0 grams of Rhizoma Chuanxiong, 38.0 grams of Panax notoginseng, and 0.4 grams of balsamic oil.

Put coarsely crushed Rhizoma Chuanxiong and Panax notoginseng into the extraction tank, add 0.89g sodium bicarbonate, 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, decoct for 1 hours, filtered, the filter residue was discarded, and the filtrates were combined. 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.

Concentrating the ultrafiltrate to obtain an extract with a relative density of 1.32-1.40 (55° C.). Take the extract, add balsamic oil, mix evenly with polyethylene glycol-6000 18g, heat to a temperature of 85°C, and after 20-120 minutes, move to a dripping tank of a dripping machine with a tank temperature of 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 seven

The raw materials are Chuanxiong 55.8g, Panax notoginseng 3.4g and Styrax 0.8g.

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 is ultrafiltered with a cellulose diacetate membrane with a molecular weight cut-off of 6000, 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 0.1Mpa, and the pressure of the liquid outlet of the ultrafiltration is 0.5kPa lower than the pressure of the liquid inlet. The initial ultrafiltration adopts a lower pressure, and then slowly increases the pressure ;During the ultrafiltration process, 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 flow, the flow rate fluctuation difference is 1.0m/s, nitrogen is intermittently fed into the ultrafiltration system to form a gas-liquid pulse flow, and the cycle is 0.5h for one time, each time for 1 minute. The temperature of the feed liquid is 15°C. When it 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 filter components are connected in parallel and use the method of alternate backflushing, one or several sets of them perform normal ultrafiltration and part of the filtrate is flowed out to backwash the ultrafiltration membranes of the other set or several sets of components, and the exchange is carried out after a period of time. 10min, backwash 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 cleaning agent, rinse with water to near neutral.

Concentrating the ultrafiltrate to obtain an extract with a relative density of 1.35-1.39 (55° C.). Take the extract and Styrax, mix it evenly with 18g of polyethylene glycol-6000, heat it to a temperature of 85°C, and after 20-120 minutes, move it to the dropping tank of the 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 eight

The raw materials are Chuanxiong 59.3g, Panax notoginseng 6.38g and Styrax 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 Rhizoma Chuanxiong extract . 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, microfiltration was performed with a ceramic membrane, and the filtrate was collected. 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 Styrax, mix it evenly with 20g of polyethylene glycol-6000, heat it to a temperature of 85°C, and after 20-120 minutes, 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 nine

The raw materials are 36.0g of Chuanxiong, 23.2g of Sanqi and 0.8g of Styrax.

Extract Chuanxiong and Panax notoginseng with 70% ethanol to obtain the ethanol extract of Chuanxiong and Panax notoginseng, centrifuge the extract at high speed and separate the supernatant. The liquid is ultrafiltered with a polysulfone membrane with a molecular weight cut-off of 50,000, filtered The 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. The initial ultrafiltration uses a lower pressure, and then Slowly increase the pressure; in the process of ultrafiltration, periodic pressure fluctuations are used, 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 pulsations in the membrane channel flow or unsteady flow, the flow rate fluctuation difference is 2.0m/s, nitrogen is fed intermittently in the ultrafiltration system to form a gas-liquid pulse flow, and the cycle is 2h for one time, each time for 1 minute. The temperature of the feed liquid is 40°C, when When the raw liquid of the 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, backwash 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, and the pH value is 10 to 12. The cleaning working pressure is 1.0MPa. After cleaning with chemical cleaning agent, rinse with water to near neutral.

Concentrating the ultrafiltrate to obtain an extract with a relative density of 1.35-1.39 (55° C.). Take the extract and Styrax, mix them 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 ten

The raw materials are 41.1 grams of Rhizoma Chuanxiong, 8.0 grams of Panax notoginseng, and 0.46 grams of storax.

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 Styrax, mix it evenly with 21g of polyethylene glycol-6000, heat it to a temperature of 60°C, and after 20-120 minutes, move it to the dripping tank of the dropping pill machine with the tank temperature 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 Eleven

29.0 grams of Ligusticum Chuanxiong, 30.6 grams of Panax notoginseng, and 0.6 grams of storax are used as raw materials.

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 Go and combine the filtrates. The filtrate is ultrafiltered with a polysulfone membrane with a molecular weight cut-off of 80,000, and the filtration method adopts dead-end filtration. The operating conditions of the ultrafiltration process are: the pressure of the ultrafiltration inlet is 0.5Mpa, and the ultrafiltration outlet is 0.5Mpa. The inlet pressure is 0.25kPa lower than the liquid inlet pressure. The initial ultrafiltration adopts a lower pressure, and then slowly increases the pressure; in the ultrafiltration process, adopts periodic pressure fluctuations, 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, and the flow velocity fluctuation difference is 2.0m/s. Nitrogen is intermittently fed into the ultrafiltration system to form a gas-liquid pulse flow The period is 2 hours 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 backwashing pressure is 2.5MPa, the backwashing period is 1.5h, and the backwashing time is 10min. When the ultrafiltration components are connected in parallel to use alternate backflushing, one or several sets of them perform normal ultrafiltration and part of the filtrate To recoil the ultrafiltration membrane of another set or several sets of components, exchange after a period of time, work for 20 minutes, and recoil for 3 minutes. The chemical cleaning cycle is 2 months, and the chemical cleaning agent is 0.5% to 4.0% sodium hydroxide, The mixed solution of 1.5% sodium hydroxide and 2% sodium hypochlorite, the pH value is 10-12, and the cleaning working pressure is 1.0MPa. After cleaning with chemical cleaning agent, 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 Styrax, mix them evenly 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 12

21.0 grams of Rhizoma Chuanxiong, 38.0 grams of Panax notoginseng, and 0.4 grams of Styrax are used as raw materials.

Put coarsely crushed Rhizoma Chuanxiong and Panax notoginseng into the extraction tank, add 0.89g sodium bicarbonate, 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, decoct for 1 hours, filtered, the filter residue was discarded, and the filtrates were combined. 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 flow or unstable flow in the membrane channel. The flow rate fluctuation difference 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 of them 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 Styrax, mix it with polyethylene glycol-6000 18g, 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 (13)

1. Chinese medicine dripping pills for the treatment of coronary heart disease, it is that crude drug is made with Rhizoma Chuanxiong, Radix Notoginseng and Styrax perhaps with Rhizoma Chuanxiong, Radix Notoginseng and Lignum Dalbergiae Odoriferae oil, it is characterized in that the processing step of its preparation is:

(1) with Rhizoma Chuanxiong, panax mixed or make water extract or alcohol extract separately;

(2) described extracting solution being carried out predefecation handles;

(3) further described extracting solution is carried out hyperfiltration treatment;

(4) ultrafiltrate is concentrated, with gained extractum and Lignum Dalbergiae Odoriferae oil or Styrax and adjuvant mixed even after, make drop pill; The weight percent proportioning of described crude drug is:

Rhizoma Chuanxiong 20%～97%,

Radix Notoginseng 2%～79%,

Lignum Dalbergiae Odoriferae oil or Styrax 0.2%～3%.

2. Chinese medicine dripping pills according to claim 1 is characterized in that the percentage by weight of described raw material is:

Rhizoma Chuanxiong 63.0%～94%,

Radix Notoginseng 4.0%～35.0%,

Lignum Dalbergiae Odoriferae oil or Styrax 0.5%～2.0%.

3. Chinese medicine dripping pills according to claim 2 is characterized in that the percentage by weight of described raw material is:

Rhizoma Chuanxiong 75.2%～90%,

Radix Notoginseng 9%～23.5%,

Lignum Dalbergiae Odoriferae oil or Styrax 0.5%～1.3%.

4. according to the described arbitrary Chinese medicine dripping pills of claim 1～3, it is characterized in that described alcohol extract is to be selected from the following lower alcohol or the extracting solution of its mixture: methanol, ethanol, normal propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutanol.

5. according to the described arbitrary Chinese medicine dripping pills of claim 1～3, its feature is an ethanol extract at described alcohol extract.

6. according to the described arbitrary Chinese medicine dripping pills of claim 1～3, what its feature obtained in described step (1) is the ethanol extract that Rhizoma Chuanxiong and panax mixed are made.

7. according to the described arbitrary Chinese medicine dripping pills of claim 1～3, what its feature obtained in described step (1) is the aqueous extract that Rhizoma Chuanxiong and panax mixed are made.

8. according to the described arbitrary Chinese medicine dripping pills of claim 1～3, its feature in described step (1) is: the Rhizoma Chuanxiong of the coarse pulverization of learning from else's experience, pseudo-ginseng add an amount of sodium bicarbonate to extraction pot, decoct with water secondary, filter, filtering residue discards, merging filtrate gets extracting solution.

9. according to the described arbitrary Chinese medicine dripping pills of claim 1～3, it is characterized in that described predefecation is treated to coarse filtration-adsorption clarification, adsorption clarification-high speed centrifugation, coarse filtration-microfiltration or coarse filtration-precipitate with ethanol.

10. according to the described arbitrary Chinese medicine dripping pills of claim 1～3, it is characterized in that the used ultrafilter membrane of described hyperfiltration treatment is selected from: the cellulose diacetate film, three cellulose acetate membrane, the cyanoethyl cellulose film, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, the sulfonated polyether sulfone film, the polysulfonamides film, phenolphthalein side group polyarylsulfone (PAS) film, polyvinylidene fluoride film, polyacrylonitrile film, polyimide film, cellulose membrane, methyl methacrylate-acrylonitrile copolymer film, polyacrylonitrile/cellulose diacetate blend film, the dynamically ultrafilter membrane that forms, and the Modified Membrane of above-mentioned film; The molecular cut off of its ultrafilter membrane is 6000～80000.

11. Chinese medicine dripping pills according to claim 10, it is characterized in that described ultrafilter membrane is selected from: cellulose diacetate film, three cellulose acetate membrane, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, sulfonated polyether sulfone film, polysulfonamides film, polyvinylidene fluoride film, polyacrylonitrile film; The molecular cut off of its ultrafilter membrane is 10000～70000.

12., it is characterized in that the operating procedure condition of described hyperfiltration treatment is as follows according to the described arbitrary Chinese medicine dripping pills of claim 1～3:

The inlet pressure of ultrafiltration is 0.1～0.5MPa, and the liquid outlet pressure ratio inlet pressure of ultrafiltration hangs down 0.25～0.5kPa; Feed temperature is 15～50 ℃; The pH value of feed liquid is controlled at 5～9; When feed liquid stock solution is concentrated 1/15～1/5, add water or dilute alcohol solution ultrafiltration 1～2 time again.

13. Chinese medicine dripping pills according to claim 12 is characterized in that, in the process of described ultrafiltration separately or unite the following method that adopts: periodic pressure fluctuation, periodically flow fluctuation, feed noble gas off and on; Wherein the pressure wave moment of periodic pressure fluctuation is 0.1～0.2Mpa, and periodically the flow speed wave moment of flow fluctuation is 1.0～2.0 meter per seconds, feeds noble gas off and on and be ventilation in 0.5 hour～2 hours once, each 1 minute.