Application of Supercritical Extraction Technology in Extraction and Separation of Traditional Chinese Medicine

I. SITUATION OF CHINESE MEDICINE INDUSTRIALIZATION AND SIGNIFICANCE OF USING NEW TECHNOLOGY

Traditional Chinese medicine (TCM) is a traditional medicine in China. It has a long history to prevent and treat diseases with TCM. As the toxic and side effects of chemical drugs are gradually recognized and a new drug needs huge investment, the treatment of common and difficult diseases threatening human health by western medicine and Western medicine is far from meeting the clinical needs, therefore, a fever of traditional Chinese medicine has been set off all over the world. Facing the rapid development of science and technology, especially the pharmaceutical industry, the increasing frequency of international academic exchanges in medicine and the increasingly fierce competition in the pharmaceutical market, it has become the consensus of Chinese medicine practitioners to realize the modernization of traditional Chinese medicine in line with the international standards. From the reform and opening up to the 15th National Congress of the Communist Party of China, China has made clear the strategic direction and thinking of the development of traditional Chinese medicine, and put forward the strategic main objective of “promoting industry through science and education”. The development of traditional Chinese medicine has taken a great step forward. In the production of traditional Chinese medicine, the situation of barrel boiling, pot steaming and tablet, spoon and cylinder production equipment ownership has been greatly improved, and stainless steel multi-functional extraction tank, external circulation evaporator, multi-effect evaporator, fluidized dryer and other equipment have emerged. The dosage forms of Chinese patent medicines have also been greatly developed, from pills, powder, plaster and Dan to granules, tablets, capsules and oral liquids. And a small amount of powder injection and other dosage forms. The output value of traditional Chinese medicine has increased fivefold since 1979, accounting for more than 30% of the output value of the pharmaceutical industry. However, it is still difficult for Chinese patent medicines to be registered, legally sold and used abroad. At present, China accounts for only about 1% of the world trade in natural medicines, which is very incompatible with the status of the main producer of natural medicines. The main reasons are the low level of modern industrial engineering technology and the backward modernization of preparation technology and dosage form; the lack of scientific and strict process operation parameters in many aspects of production process not only leads to high consumption and low efficiency, but also to the loss of effective ingredients, unstable curative effect, inconvenient dosage, poor appearance and color of products, and unstable internal quality. At the same time, there is a lack of systematic quantitative indicators, and most products lack intrinsic quality standards that are basically consistent with the efficacy; many compound preparations are still difficult to understand the material basis of their role. The situation of “pills, powder, ointment and Dan are hard to distinguish among immortals” has not changed fundamentally. In order to change this situation, let the Western medical circles accept traditional Chinese medicine and enhance its competitive position in the international market, the main way is to take the theory of traditional Chinese medicine as a guide and adopt advanced technology to realize the modernization of traditional Chinese medicine. The focus of modernization of traditional Chinese medicine products can be simply described in eight words, namely “effective, small, safe and controllable”. In fact, it covers a wide range of issues, and the problems to be solved are more complex. But the first key problem is to modernize the extraction and separation process and preparation process, standardize and standardize the quality control. For this reason, many medical experts have repeatedly proposed to use advanced technologies such as supercritical fluid technology, molecular distillation technology, membrane separation technology, freeze-drying technology, microwave radiation-induced extraction technology, sustained and controlled release preparation technology, various advanced chromatographic, spectral analysis and so on to carry out the research, development and industrialization of traditional Chinese medicine. At the end of March 1998, more than 60 experts and scholars from more than 20 units in China and Hong Kong gathered at Xiamen University to discuss the modernization of traditional Chinese medicine, especially the important basic scientific issues in the complex system of traditional Chinese medicine. At the same time, supercritical fluid technology, molecular distillation technology and liquid chromatography-mass spectrometry (LC-MS) were also put forward.

Supercritical CO2 extraction technology, molecular distillation technology and high gravity field technology are three new extraction and separation technologies in the world at present. The application of these technologies in the extraction, separation and purification of traditional Chinese medicine is of great significance to the modernization of traditional Chinese medicine.

After two years of efforts, Tradematt has been fully equipped to produce supercritical test machine 1L-20. At the same time, the development, design and production of large-scale supercritical units from 100L to 1000L have been completed. Tradematt took the lead in manufacturing large-scale automated supercritical units nationwide, thus realizing remote monitoring and computer management of supercritical units, and has been installed in Qingdao. As a big country of traditional Chinese medicine in the world, China should play an important role in promoting the modernization of traditional Chinese medicine and the industrialization of its achievements with the approaching of China’s entry into WTO, so that China’s resource advantages can be transformed into economic advantages, and the important measures of modernization of traditional Chinese medicine can be realized.

  1. Application of Supercritical CO2 Fluid Extraction Technology in Extraction and Separation of Traditional Chinese Medicine

Supercritical Fluid (SF or SCF) refers to the high density fluid at supercritical temperature (Tc) and critical pressure (Pc). Supercritical fluids have the dual characteristics of gas and liquid. Their viscosities are similar to gases, but their diffusion coefficients are much larger than liquids, and their densities are similar to liquids. Supercritical Fluid Extraction (SFE) is a process in which substances are dissolved and separated by supercritical fluids. Its basic principle is that the critical temperature (Tc) and the critical pressure (Pc) of CO2 are 31.05 and 7.38 MPa, respectively. When above this critical point, CO2 has both gas and liquid characteristics. It is similar to gas, its viscosity is similar to gas, and it is similar to liquid, its density is similar to liquid, but its diffusion coefficient is much larger than that of liquid. It is an excellent solvent, which can dissolve many substances through the interaction and diffusion between molecules. At the same time, in the region slightly higher than the critical point, the pressure changes slightly, that is to say, the density changes greatly, and the solubility changes greatly. Therefore, supercritical CO2 can dissolve substances from the matrix to form supercritical CO2 loading phase, then reduce the pressure of carrier gas or raise the temperature, and the solubility of supercritical CO2 decreases. These substances are precipitated (resolved) and separated from CO2, so as to achieve the purpose of extraction and separation. Due to the different solubility of different substances in CO2 or the different solubility of the same substance at different pressures and temperatures, the extraction and separation process has high selectivity.

  1. Supercritical CO2 Fluid Extraction Technology’s Advantage in the Modernization of Traditional Chinese Medicine

Compared with traditional methods of traditional Chinese medicine, supercritical CO2 extraction technology has many unique advantages in the research, development and industrialization of traditional Chinese medicine.

1.1 The extraction ability is strong and the extraction rate is high. Supercritical CO2 is used to extract the active ingredients of traditional Chinese medicine. Under the optimum technological conditions, the extracted ingredients can be almost completely extracted, thus greatly improving the yield of products and the utilization rate of resources. At the same time, with the continuous progress of supercritical CO2 extraction technology, the application of perfluoropolyether ammonium carbonate (PFPE) extends supercritical CO2 extraction to aqueous system, making it possible to extract strong polar compounds such as proteins which are difficult to extract.

1.2 The extraction capacity depends on the density of the fluid, and ultimately on the temperature and pressure. Changing one or both of them can change the solubility and selectively separate many substances in traditional Chinese medicine, thus reducing impurities and enriching the active ingredients of traditional Chinese medicine. Easy to reduce dosage and quality control, product appearance greatly improved.

1.3 Supercritical CO2 has low critical temperature and low operating temperature. It can preserve the active ingredients of traditional Chinese medicine well without destroying and secondary biochemistry. Therefore, it is especially suitable for extracting those components which are highly sensitive to heat and easy to be oxidized and decomposed.

1.4 The extraction time is fast and the production cycle is short. At the beginning of the supercritical CO2 extraction (dynamic) cycle, separation begins. Generally, components are separated and precipitated in 10 minutes, and can be completely extracted in about 2-4 hours. At the same time, it does not need to concentrate steps, even if entrainers are added, it can be removed by separation function or simply concentrate.

1.5 Supercritical CO2 extraction, easy to control the operating parameters, therefore, the effective ingredients and product quality are stable.

1.6 Supercritical CO2 can also directly extract different parts or extracts from single or compound Chinese medicines for pharmacological screening, and develop new drugs, greatly improving the screening speed of new drugs. At the same time, it can extract many substances that can not be extracted by traditional methods, and it is easier to find new components from traditional Chinese medicine, so as to discover new pharmacological properties and develop new drugs.

1.7 Supercritical CO2 also has antioxidant and sterilization effects, which is conducive to ensuring and improving product quality.

1.8 Supercritical fluid extraction (SFE) has become an efficient analytical tool for analysis or in combination with GC, IR, MS and LC. It can objectively reflect the real content of effective components in traditional Chinese medicine by applying it to the quality analysis of traditional Chinese medicine.

1.9 It has been proved by pharmacology and clinic that supercritical CO2 extraction of traditional Chinese medicine is superior in technology, stable in quality and easy to control in standard, and its pharmacological and clinical effects can be guaranteed or better.

1.10 Supercritical CO2 extraction process has the advantages of simple process, convenient operation, labor saving and a large number of organic solvents, reducing the pollution of three wastes, which undoubtedly provides a new high-tech extraction, separation, preparation and concentration method for the modernization of traditional Chinese medicine.

  1. Application and Prospect of Supercritical CO2 Fluid Extraction Technology in Extraction and Separation of Traditional Chinese Medicine and Modernization of Traditional Chinese Medicine

From the national key project of “Eighth Five-Year Plan” during the period of “Eighth Five-Year Plan” to “Ninth Five-Year Plan”, the application research and development of supercritical CO2 extraction technology in the production of Chinese herbal medicines”to undertaking a number of key projects in China (research and development of new Chinese herbal medicines by SFE technology), including extraction, separation, pharmacology, toxicology and development of new medicines, important scientific and technological achievements have been achieved: 1. Supercritical CO2 extraction technology has been proved. It can be applied in the field of traditional Chinese medicine; summarized the rules of SFE application in traditional Chinese medicine; proposed the structure types of supercritical equipment suitable for extraction of traditional Chinese medicine; summarized the advantages of supercritical CO2 extraction of traditional Chinese medicine, proved that supercritical CO2 extraction of traditional Chinese medicine is not only superior in technology, but also can maintain the pharmacological activity of traditional Chinese medicine itself; _developed a number of promising varieties. Some have been industrialized and entered the market.

According to the practice of research and development, the application of supercritical fluid extraction technology in the extraction and separation of traditional Chinese medicine and modernization of traditional Chinese medicine has great potential and visible prospects. The application of SFE in traditional Chinese medicine can be divided into the following aspects according to several typical research and development examples.

2.1 SFE and Extraction of Active Components or Intermediate Materials of Traditional Chinese Medicine

This aspect mainly refers to the extraction of monomers or effective fractions that have met the quality standards, which are often products themselves, so long as they meet the standards, they can enter the market. This is a relatively easy aspect for SFE technology to be applied in this field.

2.1.1 Supercritical Fluid Extraction of Artemisinin from Yellow Flower

Artemisinin, a sesquiterpene lactone from Artemisia annua, is the only internationally recognized antimalarial drug in China. What should belong to China, however, accounts for only 0.5% of the international market share. The traditional gasoline process has the dangers of low yield, high cost and flammability and explosion. SFE process has been used to scale up the production of artemisinin from 0.1 liter and 5 liter equipment to 25 liter and 50 liter equipment, and to industrial production of 200 liter equipment. It has been proved that the supercritical CO2 extraction process can be used for artemisinin production. The artemisinin products meet the Chinese pharmaceutical standards. Supercritical CO2 extraction process is superior to the traditional method (such as gasoline method). The product yield is increased by 1.9 times, the production cycle is shortened by about 100 hours and the cost is reduced by 447/Kg. It can save a lot of organic solvent gasoline, avoid flammable and explosive hazards, reduce three wastes pollution and greatly simplify the production process. The new process has obtained a patent certificate for invention. At the recent Symposium on the Strategic Development of Artemisinin Industrialization in China, it has been initially decided to promote this new technology in order to achieve the target of 3-5% of the international market share.

2.1.2 Supercritical CO2 Extraction of Hypericum perforatum Extract

Hypericum perforatum extract is one of the ten most popular plant extracts in the world, which is mainly used to treat depression. The extract is obtained from Forsythia perforatum by boiling or ethanol extraction, concentration and drying. Supercritical CO2 extraction process is superior to the traditional process, which meets the export standard.

2.2 SFE and Chemical Constituents of Traditional Chinese Medicine

This paper mainly refers to the application of supercritical CO2 extraction and separation technology in the study of active ingredients of traditional Chinese medicine or the systematic study of chemical constituents of traditional Chinese medicine, that is, the category of phytochemistry. It is the basis of new drug research. The study of Phytochemistry by supercritical CO2 extraction technology can greatly simplify the extraction and separation steps, extract and separate some components which can not be obtained by traditional solvent method, and save a lot of organic solvents.

Studies on the Chemical Constituents of Taxanes in Taxus chinensis

The extraction and separation of taxanes in Taxus chinensis is difficult for traditional phytochemical separation to obtain pure monomers. The steps are complicated. After many times of extraction and concentration of raw materials, organic solvents are extracted many times, and then column chromatography is carried out. In this process, a variety of toxic organic solvents, such as chloroform or dichloromethane, are used. The chemical constituents of Taxus yunnensis were studied by supercritical CO2 extraction technology. The crude extract obtained by supercritical CO2 extraction for 3 hours contained fewer impurities and was easy to separate into monomers. The extract only needed one silica gel column chromatography to obtain six taxanes monomers and two other monomers. They were identified by UV, IR, HNMR, CNMR and MS spectroscopy. Taxol, taxuchin A, taxinine E, taxinine J, baccatin III, 1-hydroxybaccatin I, beta-sitosterol and stearic acid-1-glycerol esters were obtained respectively. The yield was higher than that of solvent method.

Study on Chemical Constituents of Curcuma longa Oil and Extraction of Curcuma longa Oil

The yield of turmeric oil extracted by supercritical CO2 is 1.4 times that of steam, and the production cycle is only 1/3 of that of the old process. The obtained turmeric oil was separated and identified by GC/MS. The chemical composition of turmeric butter was mainly composed of 26 components, such as ginger flavonoids. The composition of turmeric butter was similar to that of water vapor. Supercritical CO2 extraction of turmeric oil has been applied in production. It is relatively simple to study the chemical constituents of volatile oil or fatty oil of traditional Chinese medicine with supercritical CO2. The chemical constituents in the oil can be identified by GC-MS-computer analysis after 1-2 hours of extraction. In the study of volatile oils such as Artemisia annua and Angelica sinensis, SFE can extract components that can not be extracted by steam distillation.

2.3 SFE and Production Process Reform and Secondary Development of Famous and Excellent Chinese Patent Medicine

Many Chinese patent medicines currently produced in China have been developed through long-term clinical practice. However, due to backward production technology, unstable quality, large dosage, poor appearance, poor efficacy, lack of controllable quality standards and other reasons, it is difficult to enter the international market. The adoption of advanced technologies such as SFE for technological reform or secondary development is a quicker way to realize the modernization of traditional Chinese medicine and an important direction.

2.3.1 Technological Reform of Extraction of Salvia Miltiorrhiza in Compound Salvia Miltiorrhiza Preparation

Tanshinone is a general term for the total ketones and other components extracted from Salvia miltiorrhiza, a plant of Labiatae family. It is the main ingredients of raw materials for the preparation of various tanshinone preparations such as Compound Danshen Tablets, Tanshinone IIA Sodium Sulfonate Injection (mainly used for cardiovascular and cerebrovascular diseases) and Tanshinone Capsules (mainly used for anti-bacterial and anti-inflammatory drugs). Tanshinone IIA is an effective ingredient for quality control prescribed in Pharmacopoeia. The main extraction methods in pharmaceutical factories are ethanol thermal reflux extraction, and then concentrated into extracts for various preparations. Because of the poor extraction ability and long time heating extraction or concentration, the loss of active ingredients is serious. The content of tanshinone IIA in the extract is often about 0.15%-1%. When tanshinone IIA is made into the preparation, it is often not detected or the content is too small. The pharmacopoeia standard is difficult to reach. In recent years, the country canceled the production approval of compound tanshinone tablets in many pharmaceutical factories, mostly because of this. Supercritical CO2 extraction was used to reform the process. From pilot-scale to pilot-scale production, it was proved that the yield was higher than that of the old process, the production cycle was shorter, the active ingredient tanshinone IIA was highly concentrated with an average content of more than 20% and the maximum content of tanshinone IIA was about 80%. This process has been applied to the production of Compound Danshen preparations (such as compound Danshen tablets) in many pharmaceutical factories, and its due clinical effect has been maintained.

Technological Reform of 2.3.2 Garlic Injection

Garlic injection is a widely used Chinese medicine preparation in clinic. The traditional production technology is steam distillation. Supercritical CO2 extraction was used to reform the process and was applied in clinic. The results show that not only the technology is superior, but also the curative effect can be improved. The total effective rate of SFE preparation for mucosal fungal infectious diseases increased by 18.42%, and for deep fungal infectious diseases, the total effective rate increased by 33.34%.

Technological Reform of 2.3.3 Bupleurum Injection

Bupleurum chinense is an umbrella plant of Bupleurum genus, which has the functions of relieving superficial symptoms, reducing fever, soothing liver and relieving depression. The main active components are volatile oil and saikosaponin. Because Chaihu injection has good antipyretic and antipyretic effects, many domestic pharmaceutical manufacturers have been using steam distillation to extract volatile oil to make Chaihu injection. Recently, it has been reported that Chaihu injection has anti-convulsive effect, low toxicity and long onset time. It may become an anti-epilepsy adjuvant. However, because of the low concentration of volatile oil in Chaihu injection, the dosage of Chaihu injection is large. However, the traditional steam distillation process has some problems, such as low oil yield, high operating temperature and easy loss of components. Bupleurum saikosaponin has obvious central inhibitory and anti-inflammatory effects. It also has specific hindrance to cholinesterase and diuretic effects. For the extraction of Bupleurum saikosaponin, the content of some saikosaponins is reduced or lost due to the high temperature and long heating time of traditional technology. Supercritical CO2 extraction technology was used to extract and separate the volatile oil and saponins of Bupleurum chinense. The technology showed great superiority. The volatile oil and saponins have better antipyretic, antiepileptic and antiepileptic pharmacodynamic effects than the traditional process.

Technological Reform of 2.3.4 Andrographis Paniculata Tablets

This variety is a pharmacopoeia variety and has a large sales volume. However, the Pharmacopoeia process is to extract it twice with 85% ethanol, then concentrate it into extract and make it into preparation. Due to the poor extraction ability and the destruction of concentration, dehydrated andrographolide in tablets can not meet the requirements of pharmacopoeia, which affects the curative effect. SFE process can greatly improve the content of active ingredients and reduce costs. It has great advantages over traditional process.

2.4 SFE and Research and Development of New Unilateral Traditional Chinese Medicine

Single Chinese medicine preparation is a part of traditional Chinese medicine preparation. SFE is still a blank in the extraction technology, pharmacological and toxicological research and new drug development of single Chinese medicine in China. In this process, we should consider not only the extraction efficiency of effective fractions, but also the pharmacological and toxicological effects.

2.4.1 Supercritical CO2 Extraction of Effective Parts of Fructus Cnidii and Pharmacodynamic Study on the Treatment of Gynecological Inflammation

Cnidium monnieri is the fruit of the umbrella plant Cnidium monnieri. Traditional Chinese medicine is mainly used for the treatment of gynecological inflammation. Supercritical CO2 extraction has the advantages of high yield of effective ingredients, short extraction time and high concentration of effective parts, but does it maintain the medicinal effect of traditional Chinese medicine? To this end, according to the requirements of new drug approval, pharmacodynamic studies on the effective parts extracted from Cnidium monnieri supercritical CO2 were carried out, and the results showed that Cnidium monnieri has supercritical CO2 effect on gynecological inflammation. It is not only superior in technology, stable in quality and easy to control, but also can maintain the therapeutic effect of traditional Chinese medicine.

Supercritical CO2 Extraction of 2.4.2 Total Sophora Flavescens Alkaloids and Study on Two New Drugs of Sophora Flavescens Alkaloids Injection

2.5 Supercritical CO2 Extraction of New Compound Chinese Medicine and Study on New Drugs

In the field of traditional Chinese medicine, it is also a blank to study the extraction technology of new Chinese medicine compound by supercritical CO2 extraction technology and to develop new Chinese medicine. Traditional Chinese medicine compound prescription is the most important part of traditional Chinese medicine, and it is also the most difficult part for Chinese medicine to be in line with international standards. Pharmaceutical professionals have made bold explorations for many years. At present, under the auspices of the competent national authorities, they have organized “the discussion of major scientific problems in the complex system of traditional Chinese medicine”. They plan to carry out cross-industry, multi-disciplinary and all-round research and development of compound traditional Chinese medicine in order to solve major scientific problems in the complex system of traditional Chinese medicine and realize the modernization of traditional Chinese medicine. Among them, supercritical fluid technology is recommended as one of the new technologies for the modernization of traditional Chinese medicine industry in the complex system of traditional Chinese medicine. For the first time, SFE technology has been applied to the research and development of traditional Chinese medicine (TCM) compound prescriptions. It has been proved that the new SFE technology can be applied to the research and development of TCM compound prescriptions.

Study on 2.5.1 Compound Xuelian Suppository

On the basis of SFE study (including pharmacodynamics) and traditional Chinese medicine theory, a traditional Chinese medicine compound was formed. In the process of studying the new compound medicine by SFE technology, we found that: (1) after mixing four kinds of traditional Chinese medicine in proportion to the prescription and comminuting them, they were put into the extraction kettle. Under the suitable SFE parameters, the active ingredients in the four kinds of traditional Chinese medicine were put forward (TLC, HPLC, GC, etc.) and the extraction effect was similar to that of single Chinese medicine. (2) The yield of effective fraction (extract) was higher than that of single extract. For example, when the four herbs were extracted separately, the yield of effective fraction was 6.96%, 2.13%, 2.51%, 4.36%, and the yield of effective fraction was 7.25%. The yield of compound extract is higher than that of single extract, which may be due to the mutual solubility of some components of traditional Chinese medicine, which promotes the extraction of other components of traditional Chinese medicine. (3) According to the traditional medication and extraction methods, the traditional extraction of this compound was carried out. It was found that the yield of this compound extract was as high as 9.7%, 0.34 times higher than that of SFE 7.25%. However, the effective ingredients were nearly 40 times lower than that of SFE. The results showed that the traditional compound had more impurities, fewer active ingredients, poor appearance color, and poor repeatability between batches. The SFE extraction of the compound had high concentration of active ingredients, fewer impurities, better appearance color and better repeatability between batches. (4) Pharmacodynamics proves that the effective part of SFE has the pharmacodynamics required by traditional Chinese medicine, and the compound has synergistic complementary effect. The new drug has basically completed the preclinical study.

2.5.2 Study on Three New Kinds of Compound Elsholtzia

2.6 SFE Technology and Quality Standard of Traditional Chinese Medicine

Quality standard is another important factor affecting the entry of traditional Chinese medicine into the international market. The use of advanced and accurate analytical methods for quality control of traditional Chinese medicine is conducive to the modernization of traditional Chinese medicine. It has been reported that the analytical supercritical CO2 fluid extraction technology has the advantages of time-saving, less sample consumption, easy control of conditions, no decomposition and no pollution of samples, especially the separation and identification of trace components from complex matrices. Therefore, the analysis of complex components of traditional Chinese medicine, especially compound Chinese medicine, is applicable. In particular, it is worth mentioning that it can be used to analyze the content of the active ingredients that may be more accurate and objective. For example, the content of artemisinin and dehydrated andrographolide in Artemisia annua and Andrographis paniculata were determined. The content of artemisinin and dehydrated andrographolide was determined by supercritical CO2 extraction as pretreatment.

  1. Concluding remarks

3.1 The new supercritical CO2 extraction technology can be used to transform the traditional Chinese medicine industry. Compared with the traditional Chinese medicine production technology, it has great superiority and market potential. This field will be the main direction of supercritical CO2 extraction technology.

3.2 The application of supercritical fluid extraction technology in traditional Chinese medicine or natural medicine should shift from the simple extraction of intermediate raw materials to the development and application of new Chinese medicines with single flavor and compound prescription, or the process reform or secondary development of various excellent Chinese patent medicines currently produced in China, as well as to coordinate with the ongoing strategic action of modernization of Chinese medicines.

3.3 SFE technology should be applied to traditional Chinese medicine, and basic research and applied research should be strengthened. Because the chemical composition of traditional Chinese medicine is complex, it can be divided into three parts: non-polarity, medium polarity and strong polarity. For the first two kinds, it can be extracted without adding or adding entrainers. However, it was once thought that supercritical CO2 could not be used to extract strong polar compounds such as proteins and polysaccharides. With the deepening of research, perfluoropolyether ammonium carbonate (PFPE) was used to form a microemulsion with good dispersion between CO2 and water. The application of supercritical CO2 was extended to aqueous system. It has been successfully used to extract strong polar biological macromolecules such as proteins, and it is used to extract traditional Chinese medicine by supercritical CO2. The water-soluble components with special activity provide a new method. This study suggests that the previously thought difficult components can be solved by strengthening similar basic application research, including the research of increasing the working pressure of domestic equipment.

3.4 Strengthen the application of analytical supercritical fluid extraction (SFE) or supercritical chromatography (SCC) in the analysis of traditional Chinese medicine, and constantly reform the traditional and classical analytical methods.

3.5 Although SFE technology faces the problem of large one-time investment in equipment in the application process, compared with traditional solvent extraction method, SFE technology will play a greater role in the strategic action of realizing modernization of traditional Chinese medicine and international integration because of its small investment in production process and many advantages.

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