CN1778354B - Chinese medicine dropping ball for coronary heart disease and angina cordis - Google Patents

Abstract

A Chinese medicine in the form of dripping pill for treating coronary heart disease and angina pectoris is prepared from red sage root, Chuang-xiong rhizome and borneol through extracting the liquid extract from red sage root and Chuan-xiong rhizome in water or alcohol, clarifying, ultrafiltering, concentrating, adding borneol and preparing dripping pills.

Description

A kind of traditional Chinese medicine dripping pill for treating angina pectoris of coronary heart disease

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 Increasingly active, some products have moved from laboratory research to industrial production. People's Liberation Army 304 Hospital Wang Shiling and others used ultrafiltration to extract the active ingredient baicalin in Scutellaria baicalensis. The results showed that the ultrafiltration method was superior to the conventional method in terms of yield and purity, and one ultrafiltration can meet the requirements of injections without further steps. Refined, simple process, the production cycle can be shortened by 1 to 2 times (Wang Shiling, Zheng Dianbao "A Preliminary Investigation on the Extraction of 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 selection of an ultrafiltration membrane with a suitable pore size (molecular weight cut-off is 6000-10000) is the key to improving the yield and quality of baicalin. Liquid temperature or lower concentration, strictly control the pH value (pH=1.5 during acidification, pH=7.0 during alkali dissolution), can significantly improve the ultrafiltration speed, and obtain the best output effect (Wang Shiling, "One-time extraction of baicalin by ultrafiltration Technology Research", Chinese Patent Medicine, 1994, 16(3): 2). Xu Jinlin and others used the ultrafiltration method (polysulfone membrane, molecular weight cut-off 6000) in the preparation of phytic acid, and the yield of phytic acid was 86.4%, which was 12.6% higher than the conventional phytate method, and the phytic acid obtained by the ultrafiltration method was almost It does not contain inorganic phosphorus, and its appearance is transparent and almost colorless (Xu Jinlin, Xu Jie, Wang Yuanjin "Research on Preparation of Phytic Acid by Membrane Separation Technology", China Journal of Pharmaceutical Industry, 1994, 25(4): 150). He Changsheng and others applied ultrafiltration technology to separate and refine stevioside, and used ultra-thin plate ultrafilter and cellulose acetate membrane (CA membrane) with a molecular weight cut-off of 10,000 to carry out field experiments on the purification of stevioside. 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, which can better solve the problems of precipitation and foaming during potting that often occur in the production of stevioside (He Changsheng, Wang Bingnan, Zhu Shanshan "Stevioside Application Research of Ultrafiltration", Water Treatment Technology, 1994, 20(2): 89). Huang Ziqiang used ultrafiltration membranes (polysulfone membranes with a molecular weight cut-off of 4000 and 10000) to refine camellia oleifera saponin, compared with the bleaching method, recrystallization method, alcohol ether precipitation method and alkaline salt precipitation method mostly used in China, the ultrafiltration process flow Simple, efficient, low cost, to remove grease, pigments, sugars and other highly hydrophilic impurities in the crude camellia saponin, all can achieve the expected effect (Huang Ziqiang, "Ultrafiltration membrane method refining camellia saponin preliminary research" water Process 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. Ultrafiltration membrane has no obvious effect on loganin (molecular weight is 384), but the film with molecular weight cut-off is 1000 makes loganin loss about 50% (Guo Liwei, Peng Guoping, Pan Yang et al. A Comparative Study of Chinese Medicine Preparations from Cornus officinalis", Chinese Patent Medicine, 1999, 21(2): 59). Wang Chengzhang et al. used ultrafiltration (polysulfone membrane, molecular weight cut-off 30000) and polyamide resin adsorption elution method to separate and purify the ethanol extract of Ginkgo biloba leaves, and the content of ginkgo flavonoid glycosides was detected by high performance liquid chromatography (HPLC). At about 45%, the yield is 0.5% to 0.7%, which is superior to conventional steam distillation and organic solvent extraction, and can reduce waste water discharge in the ultrafiltration process, protect the environment, reduce production costs, and improve economic benefits ( Wang Chengzhang, Yu Qing, Tan Weihong, etc. "Application of Ultrafiltration in the Purification of Ginkgo Flavonoid 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.

So far, the application of ultrafiltration technology in (compound) Danshen preparations is limited to the report that it is used to prepare Danshen injection. A kind of traditional Chinese medicine injection (Chinese People's Liberation Army Air Force Beijing Hospital Pharmacy, "Experimental Research on Preparation of Compound Chinese Medicine Injection by Ultrafiltration", Chinese Herbal Medicine, 1981, 12(12): 8-12). Hao Li of Sichuan Ya'an Pharmaceutical Factory prepared Danshen Injection by ultrafiltration (ultrafiltration membrane with a molecular weight cut-off of 20,000) (Hao Li, "Technology Improvement for Preparation of Danshen Injection by Ultrafiltration", Journal of Chengdu University of Traditional Chinese Medicine, 1996, 27( 8): 7). Wang Dan et al reported the preparation of Danshen injection by micellar ultrafiltration (Wang Dan, "Preparation of Danshen injection by micellar ultrafiltration", Chinese Patent Medicine, 2003, 25(6): 441-443). However, these reports are all derived from laboratory research, and have not proposed the feasibility of industrial production and its specific process operating conditions.

After long-term and unremitting efforts, the present inventor verified the feasibility of preparing the drug of the present invention by the ultrafiltration method by analyzing a large amount of experimental data, and determined the appropriate process operating conditions.

Contents of the invention

The purpose of the present invention is to provide a medicine for treating coronary heart disease and angina pectoris prepared by an ultrafiltration preparation process with less impurities, less active ingredient loss and low cost. It overcomes the deficiencies in the prior art and solves the industrial production ultrafiltration process conditions operability problem.

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

(1) Mix Salvia Miltiorrhiza and Radix Paeoniae Rubra or separately make water extract or alcohol extract;

(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: 20%-97% of Danshen, 2%-79% of Radix Paeoniae Rubra, 0.2%-3% of Borneol; preferably 63.0%-94% of Salvia Miltiorrhiza, 4.0%-35.0% of Radix Radix Paeoniae Alba, and 0.5% of Borneol ～2.0%; more preferably 75.2%～90% of Danshen, 9%～23.5% of Radix Paeoniae Rubra, 0.5%～1.3% of Borneolum. The sum of the percentages by weight of salvia miltiorrhiza, red peony root and borneol is 100%.

The step (1) is as follows: take coarsely crushed medicinal materials of salvia miltiorrhiza and red peony into an extraction tank, add appropriate amount of sodium bicarbonate, decoct twice with water, filter, discard the filter residue, combine the filtrates to obtain an extract.

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 dropping pill prepared by the process of the invention has a good therapeutic effect for treating angina pectoris caused by coronary heart disease.

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

1 Materials and methods

1.1 Case selection Among 100 patients with coronary heart disease and angina pectoris, there were 65 males and 35 females, 32 cases aged 35-55 years old, 68 cases aged 56-70 years old, the average age was 50.2 years old, the course of disease was 2.6 years, and 43 cases were accompanied by hypertension For example, 7 cases of type II diabetes. All patients conformed to the WTO nomenclature and criteria for the diagnosis of ischemic heart disease, including 48 cases of stable angina pectoris and 52 cases of unstable angina pectoris. They were randomly divided into treatment group and control group, 50 cases in each group, and there was no significant difference in gender, medical history and age between the two groups.

1.2 The method of consolidating medicines is not combined with the primary disease (hypertension, conventional antihypertensive drugs), diabetes (regular diet control hypoglycemic drugs). In principle, all selected cases were required to stop using other drugs for the treatment of coronary heart disease during the treatment period. The treatment group was given oral medicine of the present invention, each 10 capsules, 3 times a day, and sublingual nitroglycerin if necessary. The control group was given Compound Danshen Tablets, 3 tablets each time, 3 times a day, and sublingual nitroglycerin if necessary. The course of treatment is 4 weeks.

1.3 Observation content Inquire about clinical symptoms and adverse reactions before and after taking the medicine of the present invention. Record blood pressure, do routine 12-lead electrocardiogram, blood, urine routine, liver and kidney function tests.

1.4 Efficacy evaluation standards are evaluated in accordance with the "Guiding Principles for Clinical Research of Cardiovascular and Cerebrovascular Drugs" designated by the Pharmaceutical Administration of the Ministry of Health of the People's Republic of China. Symptom efficacy evaluation criteria: markedly effective, the same labor capacity does not cause angina pectoris attack or the number of attacks is reduced by more than 70%, and there is no chest tightness symptom in general activities; effective, the number of angina pectoris attacks and chest tightness symptoms are reduced by 50% to 70%; obvious change. ECG curative effect evaluation criteria: markedly effective, resting ECG ischemic manifestations return to normal; effective, resting ECG ischemic ST-segment decline, after treatment, the recovery is more than 1mm, but not normal, inferior wall and left chest lead inverted T wave becomes shallow Up to 1mm or more; invalid, the resting electrocardiogram is basically the same as before treatment.

2 results

2.1 See Table 1 and Table 2 for the curative effect comparison between the treatment group and the control group.

Table 1 drug treatment of the present invention angina pectoris symptom curative effect compares with matched group

Table 2 drug treatment of the present invention electrocardiogram curative effect compares with matched group

Detailed ways

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

Embodiment one

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

Extract the salvia miltiorrhiza and red peony with ethanol to obtain the ethanol extract of the salvia miltiorrhiza and red peony, 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 them evenly with 18g of polyethylene glycol-6000, heat to a temperature of 85°C, and after 20-120 minutes to make the material, move it to a dropping tank of a dripping machine whose tank temperature is kept at 85-90°C. Drop the drug solution into liquid paraffin at 7-8°C, take out the dropping pills, remove the oil, select the pills through a sieve, and make 1000 dropping pills.

Embodiment two

The raw materials are 59.3g of Danshen, 6.38g of Radix Paeoniae Rubra, and 0.34g of Borneol.

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

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

Embodiment three

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

Extracting Danshen and Radix Paeoniae Rubra with 80% ethanol to obtain ethanol extracts of Salvia Miltiorrhiza and Radix Paeoniae Rubra, centrifuging the extract at a high speed and separating 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 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 Danshen, 8.0g of Radix Paeoniae Rubra, and 0.46g of Borneol.

Put the coarsely crushed salvia miltiorrhiza and red peony 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 29.0g of Danshen, 30.6g of Radix Paeoniae Rubra, and 0.6g of Borneol.

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

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

Embodiment six

The raw materials are 21.0g of Danshen, 38.0g of Radix Paeoniae Rubra, and 0.4g of Borneol.

Take the coarsely crushed salvia miltiorrhiza and red peony herbs 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 (12)

1. Chinese medicine dripping pills for the treatment of angina pectoris, it is that crude drug is made with Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra and Borneolum Syntheticum, it is characterized in that the weight percent proportioning of described crude drug is: Radix Salviae Miltiorrhizae 20%～97%, Radix Paeoniae Rubra 2%～79%, Borneolum Syntheticum 0.2%～3%;

The processing step of its preparation is:

(1) Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra are 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 Borneolum Syntheticum and adjuvant mixed even after, make drop pill; The operating procedure condition of described hyperfiltration treatment is as follows:

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.

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

Radix Salviae Miltiorrhizae 63.0%～94%,

Radix Paeoniae Rubra 4.0%～35.0%,

Borneolum Syntheticum 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:

Radix Salviae Miltiorrhizae 75.2%～90%,

Radix Paeoniae Rubra 9%～23.5%,

Borneolum Syntheticum 0.5%～1.3%.

4. Chinese medicine dripping pills according to claim 1 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. Chinese medicine dripping pills according to claim 4, its feature is an ethanol extract at described alcohol extract.

6. what Chinese medicine dripping pills according to claim 1, its feature obtained in described step (1) is the ethanol extract that Radix Salviae Miltiorrhizae and Radix Paeoniae Rubra are mixed and made into.

7. Chinese medicine dripping pills according to claim 1 is characterized in that, what described step (1) obtained is the aqueous extract that Radix Salviae Miltiorrhizae and Radix Paeoniae Rubra are mixed and made into.

8. Chinese medicine dripping pills according to claim 1 is characterized in that, described step (1) is: the Radix Salviae Miltiorrhizae of the coarse pulverization of learning from else's experience, Radix Paeoniae Rubra medical material add an amount of sodium bicarbonate to extraction pot, decoct with water secondary, filter, and filtering residue discards, and merging filtrate gets extracting solution.

9. Chinese medicine dripping pills according to claim 1 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. Chinese medicine dripping pills according to claim 1, it is characterized in that, the used ultrafilter membrane of described hyperfiltration treatment is selected from: cellulose diacetate film, three cellulose acetate membrane, cyanoethyl cellulose film, polysulfone membrane, sulfonated polysulfone membrane, poly (ether sulfone) film, sulfonated polyether sulfone film, 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. Chinese medicine dripping pills according to claim 1 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.