CN1778322B - A drug for the treatment of cardiovascular disease - Google Patents

Abstract

The invention discloses a traditional Chinese medicine composition for treating cardiovascular diseases, which is prepared from Rhizoma Chuanxiong, Radix Notoginseng and Borneolum as raw materials. (2) carry out preliminary clarification treatment to described extract; (3) further carry out ultrafiltration treatment to described extract; (4) ultrafiltrate is concentrated, add borneol, according to conventional method Made into preparations.

Description

A drug for the treatment of cardiovascular disease

technical field

The invention relates to a traditional Chinese medicine composition prepared by an ultrafiltration process. Specifically, the present invention relates to a traditional Chinese medicine composition for treating cardiovascular diseases.

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.

Regarding the practical application of compound Chuanxiong tablets prepared by ultrafiltration, there are no reports in the current literature. In particular, the use of ultrafiltration for industrial production has always been a technical problem in this field.

The inventor has made unremitting efforts for a long time, and verified the feasibility of preparing compound Chuanxiong tablets by ultrafiltration by analyzing a large amount of experimental data. Specific solutions are provided.

Contents of the invention

The object of the present invention is to provide a traditional Chinese medicine for treating cardiovascular diseases with less impurities and less active ingredient loss, which overcomes the deficiencies of the prior art and solves the difficult problem of operability of industrial production ultrafiltration process conditions.

The present invention is realized through the following technical steps: using Rhizoma Chuanxiong, Radix Notoginseng and Borneolum 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, add borneol, and make a preparation according to a conventional method.

The weight percentages of the above-mentioned raw materials are: Rhizoma Chuanxiong 20%～97%, Radix Notoginseng 2%～79%, Borneol 0.2%～3%; Preferably Chuanxiong 63.0%%～94%, Radix Notoginseng 4.0%～35.0%, Borneol 0.5% %～2.0%; more preferably Chuanxiong 75.2%～90%, Panax notoginseng 9%～23.5%, Borneol 0.5%～1.3%. The sum of the percentages by weight of Rhizoma Chuanxiong, Panax notoginseng and Borneol is 100%.

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

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

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

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

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

The operating conditions of the ultrafiltration process are as follows:

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

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

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

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

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

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

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

(7) The chemical cleaning period is 0.5 months to February. 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 2 % sodium hypochlorite mixed solution, 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 extract, the preparation is then prepared in a conventional manner. For example, it can be mixed with any one or more pharmaceutical excipients such as starch, dextrin, lactose, microcrystalline cellulose, hydroxypropylmethylcellulose, polyethylene glycol, magnesium stearate, micronized silica gel, xylose Alcohol, lactitol, glucose, glycine, mannitol, glycine, etc. are mixed to form tablets, capsules, granules, oral liquids, sustained-release preparations, controlled-release preparations, gels, ointments, ointments, creams, suppositories , injections, powder injections, patches, dripping pills, suspensions, etc.

The medicine of the invention has a good therapeutic effect in treating angina pectoris of coronary heart disease.

Experimental example Clinical observation of medicament treatment of coronary heart disease angina pectoris of the present invention

General information: 248 patients with coronary heart disease and angina pectoris, including 166 males and 82 females; aged from 32 to 74 years, with an average of 56.8 years; the course of disease was 1 week to 32 years, with an average of 6.61 years; 212 cases belonged to mild to moderate angina pectoris, severe 36 cases of angina pectoris.

Diagnostic criteria: The diagnostic criteria of coronary heart disease and angina pectoris are based on WHO's "Ischemic Heart Disease Nomenclature and Diagnostic Criteria"; the diagnostic criteria of chest pain and syndrome, the diagnostic criteria of syndrome types and the degree of illness are all issued in March 1990 by the Department of Medical Affairs, State Administration of Traditional Chinese Medicine Chest obstruction and heart pain emergency diagnosis and treatment standard in the "Traditional Chinese Internal Medicine Emergency Diagnosis and Treatment Standards (Trial)" (hereinafter referred to as "standards").

treatment method

In this group of patients, 48 cases belonged to the syndrome of heart-qi deficiency, 10 cases of which had severe angina pectoris; 37 cases belonged to the syndrome of heart-yin deficiency, of which 6 cases had severe angina pectoris; 17 cases belonged to the syndrome of heart-yang deficiency, and 4 cases had severe angina pectoris; Among the 44 cases, 4 cases had severe angina pectoris; 84 cases belonged to heart-blood stagnation syndrome, 8 cases had severe angina pectoris; 18 cases belonged to Hanning Qi stagnation syndrome, 4 cases had severe angina pectoris. All cases take medicine (tablet) of the present invention, each 2, every day 3 times, serve on 4 weeks, stop using other medicines for the treatment of coronary heart disease angina pectoris during the treatment. The onset of angina pectoris and changes in electrocardiogram were observed before and after treatment. The data were tested by ^x2 .

treatment result

The curative effect on angina pectoris symptoms and electrocardiogram was evaluated according to the curative effect evaluation standard in the "standard" chest pain and heart pain emergency standard. The results are shown in Table 1 and Table 2, respectively.

Table 1 Comparison of curative effects of various types of angina pectoris after treatment

Note: X ² =20.13, P<0.01

Table 2 Comparison of curative effect of various types of electrocardiogram after treatment

Note: X ² =14.83, P<0.01

Detailed ways

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

Embodiment one:

The raw materials are 450g of Rhizoma Chuanxiong, 141g of Radix Notoginseng and 8g of Borneol.

Extract the Rhizoma Chuanxiong with ethanol to obtain the ethanol extract of Rhizoma Chuanxiong, 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 Chuanxiong extract with a relative density of 1.35-1.39 (55° C.). Crush notoginseng into fine powder, mix with Chuanxiong extract, dry and make granules. Grind the borneol finely, mix it with the above granules, press it into 1000 pieces, or coat it with sugar.

Embodiment two:

The raw materials are Chuanxiong 558g, Panax notoginseng 34g and Borneol 8g.

Rhizoma Chuanxiong and Panax notoginseng were extracted with 70% ethanol to obtain the ethanol extract of Rhizoma Chuanxiong and Panax notoginseng, and microfiltration was performed with a ceramic membrane to collect the filtrate. 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 1.35 to 1.39 (55° C.), add borneol, mix with the above extract, add 3% povidone ethanol solution to make a soft material, and pass through a 18-mesh sieve. Granules, dried at 60°C for 30-45 minutes, granulated, added with talcum powder, mixed evenly, filled in capsules, and obtained.

Embodiment three:

The raw materials are 360g of Rhizoma Chuanxiong, 232g of Radix Notoginseng, and 8g of Borneol.

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

Concentrating the ultrafiltrate to obtain Chuanxiong extract with a relative density of 1.35-1.39 (55° C.). Crush notoginseng into fine powder, mix with Chuanxiong extract, dry and make granules. Grind the borneol finely, mix it with the above granules, press it into 1000 pieces, or coat it with sugar.

Embodiment four:

The raw materials are 500 grams of Rhizoma Chuanxiong, 94 grams of Radix Notoginseng, and 8 grams of Borneol.

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

Concentrate the ultrafiltrate to obtain an extract with a relative density of 1.32-1.40 (55°C), add borneol, mix evenly, fluidize with lactose in a batch fluidized bed, dry, and make granules.

Embodiment five:

The raw materials are 290 grams of Rhizoma Chuanxiong, 306 grams of Panax notoginseng, and 6 grams of borneol.

Put the coarsely crushed Ligusticum chuanxiong and Panax notoginseng into the extraction tank, add 5 times the amount of water, decoct for 2 hours, filter, and extract the filter residue for the second time, add 4 times the amount of water, fry for 1 hour, filter, and discard the filter residue To, combine the filtrates. The filtrate was ultrafiltered with a 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 1.32-1.40 (55° C.), add borneol, add 30 g of mannitol, 5 g of calcium sodium edetate, and 5 ml of distilled water. After mixing the above components, freeze Dry, sub-package, that is.

Embodiment six:

The raw materials are 210 grams of Rhizoma Chuanxiong, 380 grams of Panax notoginseng, and 4 grams of borneol.

Put the coarsely crushed Ligusticum chuanxiong and Panax notoginseng into the extraction tank, add 5 times the amount of water, decoct for 2 hours, filter, and extract the filter residue for the second time, add 4 times the amount of water, fry for 1 hour, filter, and discard the filter residue To, combine the filtrates. The filtrate was ultrafiltered with a 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.), mixing the extract with borneol and an appropriate amount of magnesium stearate, and pressing it into tablets.

Claims (12)

1. a Chinese medicine composition for the treatment of coronary heart disease angina pectoris, is characterized in that it is prepared from by the crude drug of following percentage by weight: Chuanxiong 20%～97%, Panax notoginseng 2%～79%, Borneol 0.2% to 3%. 2. Chinese medicine composition as claimed in claim 1, is characterized in that the weight percent of described crude drug is: Chuanxiong 63.0%%～94%, Panax notoginseng 4.0%～35.0%, Borneol 0.5% ~ 2.0%. 3. Chinese medicine composition as claimed in claim 2, is characterized in that the weight percent of described crude drug is: Chuanxiong 75.2% ~ 90%, Notoginseng 9%～23.5%, Borneol 0.5% ~ 1.3%. 4. The traditional Chinese medicine composition according to any one of claims 1 to 3, characterized in that it can be prepared by the following steps: (a) Rhizoma Chuanxiong and Panax notoginseng are mixed or separately made into water extract or alcohol extract; the alcohol extract is ethanol extract; (b) carrying out preliminary clarification treatment to the extract in the step (a); (c) further carry out ultrafiltration treatment to the extract described in the preliminary clarification treatment in step (b); (d) Concentrate the ultrafiltrate, add borneol, and make a preparation according to a conventional method. 5. The Chinese medicine composition as claimed in claim 4, wherein when Rhizoma Chuanxiong is extracted separately in said step (a), the Rhizoma Chuanxiong extract obtained is the ethanol extract of Rhizoma Chuanxiong. 6. The Chinese medicine composition as claimed in claim 4, characterized in that what is obtained in the step (a) is the water extract prepared by mixing Rhizoma Chuanxiong and Radix Notoginseng. 7. The traditional Chinese medicine composition according to claim 4, characterized in that the preliminary clarification treatment is coarse filtration-adsorption clarification, adsorption clarification-high-speed centrifugation, coarse filtration-microfiltration or coarse filtration-alcohol precipitation. 8. The Chinese medicine composition as claimed in claim 4, wherein the ultrafiltration membrane used in the ultrafiltration treatment is selected from: cellulose diacetate membrane, cellulose triacetate membrane, cyanoethyl cellulose acetate membrane, polyester Sulfone membrane, sulfonated polysulfone membrane, polyethersulfone membrane, sulfonated polyethersulfone membrane, polysulfone amide membrane, polyarylsulfone membrane with phenolphthalein side group, polyvinylidene fluoride membrane, polyacrylonitrile membrane, polyimide membrane , cellulose membrane, methyl methacrylate-acrylonitrile copolymer membrane, polyacrylonitrile/cellulose diacetate blend membrane, and the modified membrane of the above membrane; the molecular weight cut-off of the ultrafiltration membrane is 6000-80000. 9. The Chinese medicine composition as claimed in claim 8, wherein said ultrafiltration membrane is selected from the group consisting of: cellulose diacetate membrane, cellulose triacetate membrane, polysulfone membrane, sulfonated polysulfone membrane, polyethersulfone membrane , Sulfonated polyethersulfone membrane, polysulfoneamide membrane, polyvinylidene fluoride membrane, polyacrylonitrile membrane; the molecular weight cut-off of the ultrafiltration membrane is 10,000-70,000. 10. The traditional Chinese medicine composition as claimed in claim 4, characterized in that the operating conditions of the ultrafiltration treatment are as follows: the pressure of the liquid inlet of the ultrafiltration is 0.1 to 0.5 MPa, and the pressure of the liquid outlet of the ultrafiltration is higher than that of the liquid inlet. The outlet pressure is 0.25-0.5kPa lower; the temperature of the feed liquid is 15-50°C; the pH value of the feed liquid is controlled at 5-9; Filter 1-2 times. 11. The traditional Chinese medicine composition as claimed in claim 10, characterized in that, in the process of the ultrafiltration, the following methods are used alone or in combination: periodic pressure fluctuations, periodic flow fluctuations, intermittently feeding inert gas; Among them, the pressure fluctuation difference of the periodic pressure fluctuation is 0.1-0.2Mpa, the flow velocity fluctuation difference of the periodic flow fluctuation is 1.0-2.0 m/s, and the inert gas is intermittently injected once every 0.5-2 hours, each time for 1 minute . 12. The traditional Chinese medicine composition as claimed in claim 4, characterized in that the preparation contains any one or more pharmaceutical excipients selected from the following: starch, dextrin, lactose, microcrystalline cellulose, hypromellose Cellulose, Polyethylene Glycol, Magnesium Stearate, Micronized Silica Gel, Xylitol, Lactitol, Glucose, Glycine, Mannitol, Glycine.