The significance of applying new technology to Chinese medicine industry with supercritical extraction

I. the industrialization of traditional Chinese medicine and the significance of applying new technology

Traditional Chinese medicine (TCM) has a long history in China. As the toxic and side effects of chemical drugs are gradually recognized by people and the synthesis of a new drug requires huge investment, western medicine and western medicine for the treatment of common diseases and difficult diseases that threaten human health are far from meeting the clinical needs. Therefore, the fever of traditional Chinese medicine (TCM) has been aroused worldwide. In the face of the rapid development of science and technology, especially the pharmaceutical industry, the increasingly frequent international medical academic exchange activities and the increasingly fierce competition in the pharmaceutical market, it has become the consensus of TCM workers to realize the modernization of traditional Chinese medicine and to be in line with international practices. After the reform and opening up to the 15th national congress of the CPC, China has made clear the strategic direction and thought of the development of traditional Chinese medicine, and put forward the strategic subject goal of "scientific and educational development". In traditional Chinese medicine production VAT of boiling, steaming cauldron boil and plaque, spoon, cylinder has improved the condition of production equipment, and a multi-purpose extraction tank, stainless steel outer circulation evaporation, multiple effect evaporator, fluidized dryer and other equipment, proprietary Chinese medicine formulations have larger development, by the pill, powder, plaster, Dan agent mainly developed into granules, tablet, capsule, oral liquid, a small amount of booster injection dosage forms, etc. The value of the production of traditional Chinese medicine has quintupled since 1979, accounting for more than 30 percent of the value of the pharmaceutical industry. However, it is difficult for Chinese patent medicine to be registered, sold and used in foreign countries. China accounts for only about 1 percent of the world's trade in natural medicines, which is far from being a major producer of natural medicines. The reason is that the level of modern engineering technology is not high, and the modernization of preparation technology and dosage form is still very backward. The lack of scientific and strict process operating parameters in many aspects of the production process not only leads to high consumption and low efficiency, but also leads to effective component loss, unstable curative effect, inconvenient use of large doses, poor product appearance and color, and unstable internal quality. At the same time, there is a lack of systematic quantitative indicators, and most products lack internal quality standards with basically consistent curative effect. Many complex formulations also struggle to understand the physical basis of their effects." The condition of pill, powder, cream, Dan and immortals has not changed fundamentally. To change this situation, the western medical community should accept traditional Chinese medicine and enhance its competitive position in the international market. The emphasis of the modernization of traditional Chinese medicine products can be simply described in eight words, namely "effective, small amount, safe and controllable". In fact, it covers a wide range, and the problems to be solved are relatively complicated. However, the first and most critical problem is to extract separation technology, modernize preparation technology, and standardize and standardize quality control. For this reason, many medical experts have proposed to adopt advanced technologies such as supercritical fluid technology, molecular distillation technology, membrane separation technology, freeze-drying technology, microwave radiation-induced extraction technology, slow release formulation technology, various kinds of advanced chromatographic and spectral analysis, etc. for the research and development and industrialization of traditional Chinese medicine. In 1998 under the auspices of the relevant state departments, the end of march, from all over the country and Hong Kong more than 20 units of more than 60 experts and scholars gathered in xiamen university, probes into the traditional Chinese medicine (TCM) modernization, especially the important scientific basis of Chinese traditional medicine complex system problems, supercritical fluid technology, molecular distillation technology, liquid mass combination, etc, were also mentioned.

Supercritical CO2 extraction technology, molecular distillation technology and overweight force field technology are the three new extraction and separation technologies in the world at present.

After two years of efforts, dongyu group has been fully capable of producing 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. Dongyu group takes the lead in the national manufacturing of automatic large supercritical units, thus realizing the remote monitoring and microcomputer management of supercritical units, and has been installed in Qingdao. As a big country 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 approach of China's accession to wto.

The application of new technology of supercritical CO2 fluid extraction in the extraction and separation of traditional Chinese medicine

Supercritical Fluid (SF or SCF) is a high density Fluid in the state of Supercritical temperature (Tc) and critical pressure (Pc). Supercritical fluid has the dual characteristics of gas and liquid. Its viscosity is similar to gas, but its diffusion coefficient is much higher than liquid. Its density is similar to that of liquid. Supercritical Fluid Extraction (SFE) is the process by which a Supercritical Fluid is extracted. Its basic principle is: the CO2 critical temperature (Tc) and critical pressure (Pc) were 31.05 ℃ and 7.38 MPa, when at the critical point above, at this time of CO2 has a dual characteristic of gas and liquid at the same time. It is similar to the gas, and the viscosity is similar to the gas. Similar to the liquid, the density is similar to the liquid, but its diffusion coefficient is much larger than the liquid. It is an excellent solvent that dissolves many substances through intermolecular interaction and diffusion. At the same time, in the region slightly higher than the critical point, the pressure changes slightly, which causes a large change in its density, thus causing a large change in solubility. Therefore, supercritical CO2 can be dissolved from the matrix to form the supercritical CO2 load phase, and then reduce the pressure of the carrier gas or increase the temperature. The solubility of supercritical CO2 is reduced, and these substances are precipitated (analyzed) and separated from CO2 to achieve the purpose of extraction and separation. Due to different solubility in CO2 or different solubility of the same substance under different pressure and temperature, this extraction and separation process is highly selective.

1. Advantages of supercritical CO2 fluid extraction in the modernization of traditional Chinese medicine

Compared with traditional Chinese medicine, the supercritical CO2 extraction technique has many unique advantages.

1. 1. Strong extraction capability and high extraction rate. The effective components of traditional Chinese medicine were extracted with supercritical CO2. Under the optimal process conditions, the extracted components could be extracted almost completely, thus greatly improving the product yield and resource utilization. At the same time, with the continuous progress of supercritical CO2 extraction technology, the application of perfluoropolyether ammonium carbonate (PFPE) extended supercritical CO2 extraction to aqueous solution system, making it possible to extract supercritical CO2 extraction of strong polar compounds such as proteins.

1. 2. The extraction capacity depends on the density of fluid, and ultimately depends on temperature and pressure. Changing one or both of them can change the solubility. It is convenient to reduce dosage and quality control, and the appearance of the product is greatly improved.

1. 3 with low critical temperature of supercritical CO2 and low operating temperature, the effective components of traditional Chinese medicine can be well preserved without damage or sub-biochemistry. Therefore, it is especially suitable for the extraction of ingredients with strong thermal sensitivity and easy oxidative decomposition and destruction.

1. Fast extraction time and short production cycle. As soon as the supercritical CO2 extraction (dynamic) cycle begins, the separation begins. Generally, the extraction can be separated and separated within 10 minutes, and the extraction can be completed within 2 to 4 hours. At the same time, it does not require a concentration step, even if the entrainer is added, it can be removed by a separation function or simply concentrated.

1. 5. Supercritical CO2 extraction, operating parameters are easy to control, therefore, effective components and product quality are stable.

1. 6 supercritical CO2 can also directly extract different parts from single or compound Chinese medicine or extract extracts directly for pharmacological screening and development of new drugs, which greatly improves the screening speed of new drugs. At the same time, it can extract many substances not mentioned by traditional methods, and it is easier to find new ingredients 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. Supercritical fluid extraction is used in analysis or in combination with GC, IR, MS, LC, etc., and becomes an efficient analytical method. It can be used in the quality analysis of traditional Chinese medicine to objectively reflect the true content of the active ingredients in traditional Chinese medicine.

1. It has been proved by pharmacology and clinical practice that the extraction of traditional Chinese medicine by supercritical CO2 is not only superior in process, stable in quality and easy to control in standard, but also reliable or better in pharmacology and clinical effect.

1. 10. Supercritical CO2 extraction process is simple, easy to operate, labor saving and large amount of organic solvent and reducing waste pollution, which undoubtedly provides a new method of extraction, separation, preparation and concentration for the modernization of traditional Chinese medicine.

2. Application method and prospect of supercritical CO2 fluid extraction technology in the extraction and separation of traditional Chinese medicine and the modernization of traditional Chinese medicine

From during the "eighth five-year" national "eighth five-year project" supercritical CO2 extraction technology in the application of Chinese herbal medicine production research and development "to" five-year "period to undertake a number of key projects of China (SFE technology research and development) of new drug of TCM, including the extraction separation of pharmacology and toxicology research and new drug research and development research, has made important scientific and technological achievements: (1) proved that the supercritical CO2 extraction technology can be applied to field of traditional Chinese medicine (TCM); The regularity of application of SFE in traditional Chinese medicine was summarized by new technology. Bai put forward the type of supercritical equipment structure suitable for Chinese medicine extraction. The advantages of traditional Chinese medicine extraction with supercritical CO2 were summarized, and it was proved that the extraction of traditional Chinese medicine with supercritical CO2 was not only technically superior, but also could maintain the pharmacological activity of traditional Chinese medicine itself. Through research and development of a number of species with good prospects, some have industrialized, to the market.

According to the research and development practice, the supercritical fluid extraction technology is applied to the extraction and separation of traditional Chinese medicine and the modernization of traditional Chinese medicine. The application of SFE in traditional Chinese medicine, combined with several typical research and development examples, can be divided into the following aspects.

2. Extraction of SFE with active ingredients or intermediate raw materials

This aspect mainly refers to the extraction of monomers or effective parts with quality standards, which are often products themselves and can enter the market as long as the standards are met. This is one of the easier aspects of the application of SFE in this field.

2. 1. A new process for extraction of Artemisinin from yellow flowers by supercritical fluid extraction. Artemisinin, a compound of sesquiterpene lactone from Artemisia annua, is the only internationally recognized anti-malaria drug in China. Yet China accounts for just 0.5% of the international market. Traditional method of gas high yield and low cost, such as inflammable and explosive dangerous, by SFE process, from the test in 0.1, 5 litres equipment to 25, 50 litres pilot amplification equipment, has been to industrialized production of 200 l equipment that supercritical CO2 extraction technology can be used in the production of artemisinin, artesunate products in China pharmaceutical standards. The supercritical CO2 extraction process is superior to the traditional method (such as the 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, which can save a lot of organic solvent gasoline, avoid the risk of inflammable and explosive, reduce the waste pollution and greatly simplify the production process. The new process has obtained the invention patent certificate. At the recent conference on the industrial development strategy of China's artemisinin achievements, a preliminary decision has been made to promote the new process to achieve the goal of taking 3-5% of the international market share.

2. 1. The supercritical CO2 extraction of the extract of forsythia is one of the ten most popular plant extracts in the world. The extract is obtained by boiling, concentrating and drying through water or alcohol extraction. Supercritical CO2 extraction technology is adopted to achieve the export standard, which is superior to the traditional process.

2. Study on the chemical constituents of SFE and traditional Chinese medicine

Here mainly refers to the application of supercritical CO2 extraction separation technology to the study of the effective components of traditional Chinese medicine or the systematic study of the chemical components of traditional Chinese medicine, namely the category of phytochemistry. It is the basis of new drug research. The study of phytochemistry using supercritical CO2 extraction technology can greatly simplify the extraction and separation steps, extract and separate some ingredients that cannot be obtained by traditional solvent method, and save a lot of organic solvents.

2. 2. 1 research fields to chemical composition of taxanes in component extraction and separation of taxanes in taxus chinensis, traditional plant chemical separation is tasted is difficult to get a monomer, step is relatively cumbersome, raw material after many times extraction enrichment, organic solvent extraction for many times, many times to column chromatography, the process, want to use a variety of toxic organic solvents, such as chloroform or dichloromethane, etc. We use supercritical CO2 extraction technology of Taxus yunnanensis (Taxus yunnensis) to study the chemical composition of crude extract obtained by supercritical CO2 extraction of 3 hours with impurity is less, more easily isolated monomers, the extract with a silica gel column chromatography to get six monomer and 2 other taxanes, UV, IR, HNMR and CNMR and MS spectral analysis and chemical identification, They are taxol (taxol),taxuchin A,taxinine E,taxinine J,baccatin III,1-hydroxybaccatin I, acid-glutenol and stearic acid-1-glycerin, the yield is higher than the solvent method.

2. 2. 2. Study on oil chemical composition of Curcuma longa and extraction of turmeric oil from supercritical CO2 extraction. The obtained turmeric oil was separated and identified by GC/MS, and its chemical composition was mainly composed of 26 components, including curcumin, which was similar to that of water vapor. The supercritical CO2 extraction of turmeric oil has been applied in production. The study on chemical components of essential oil or fat oil using supercritical CO2 is relatively simple. As long as the oil is extracted within 1-2 hours, the chemical components in the oil can be identified by direct gc-ms-computer combined technical analysis. In the study of artemisia annul l. and angelica sinensis, SFE could extract components that could not be extracted by steam distillation.

2. Production process reform and secondary development of SFE and proprietary Chinese patent medicine

Many Chinese patent medicines produced in our country are developed through long-term clinical practice. However, it is difficult to enter the international market due to the backward production process, unstable quality, large dosage, poor appearance color, inadequate efficacy and lack of controllable quality standards. Adopting advanced technology such as SFE for technological reform or secondary development is a relatively quick way to realize the modernization of traditional Chinese medicine and an important direction.