Carbon dioxide is a very common gas, but too much carbon dioxide will cause "greenhouse effect", so it is of great significance to make full use of carbon dioxide. The traditional carbon dioxide utilization technology is mainly used to produce dry ice (for fire fighting) or as a food additive. At present, efforts are being made at home and abroad to develop a new CO2 utilization technology-CO2 supercritical extraction technology. This technology can be used to produce high value-added products and extract substances that could not be extracted by chemical methods in the past, and it is cheap, non-toxic, safe and efficient. Suitable for chemical, pharmaceutical, food and other industries.
When the temperature is higher than the critical temperature Tc=3 1.26℃ and the pressure is higher than the critical pressure Pc=7.2MPa, the properties of carbon dioxide will change. Its density is close to liquid, its viscosity is close to gas, and its diffusion coefficient is 100 times that of liquid, so it has amazing solubility. It can dissolve a variety of substances and then extract effective components, which has broad application prospects.
Traditional methods for extracting effective components from substances, such as steam distillation, vacuum distillation, solvent extraction, etc. The process is complex, the product purity is low, and harmful substances are easy to remain. Supercritical fluid extraction (SFE) is a new separation technology successfully developed by using the excellent mass transfer characteristics of fluid such as high density, low viscosity and large diffusion coefficient in supercritical state. It has the advantages of high extraction rate, good product purity, simple process and low energy consumption. CO2- SFE technology can store a large number of volatile components which are unstable to heat and easy to be oxidized because of its low temperature and closed system, which provides the most advanced method for the extraction and separation of volatile components in traditional Chinese medicine. Supercritical CO2 extraction can extract effective components from many plants, but these components could not be extracted by chemical methods in the past. This technology can be applied to tobacco, spices, food and other aspects besides chemical and pharmaceutical industries. For example, in food, it can be used to remove caffeine from coffee and tea, and garlic, germ oil, sea buckthorn oil, vegetable oil, opium, atropine, ginseng, ginkgo biloba and yew can be extracted. It can be seen that this technology has a broad development prospect in the future.
1. Basic principle of supercritical fluid extraction
Definition of (1) supercritical fluid
Any substance has three phases-gas, liquid and solid. The point where the three-phase equilibrium exists is called the three-phase point. The point at which liquid and gas are in equilibrium is called the critical point. The temperature and pressure at the critical point are called critical pressure. The critical points of different substances require different pressures and temperatures.
SCF in supercritical fluid (SCF) technology refers to fluids whose temperature and pressure are higher than the critical point, such as carbon dioxide, ammonia, ethylene, propane, propylene and water. Above the critical temperature and pressure, the state close to the critical point is called supercritical state. In supercritical state, the properties of gas phase and liquid phase are very similar and cannot be separated, so it is called SCF.
Carbon dioxide is the most widely studied supercritical fluid at present, and it is the most commonly used because of its advantages of non-toxicity, non-combustion, non-reaction with most substances and low price. In supercritical state, CO2 fluid has dual characteristics of gas phase and liquid phase, with high diffusion coefficient and low viscosity equivalent to gas, density similar to liquid and good substance solubility. Its density is very sensitive to the change of temperature and pressure, and it is directly proportional to solubility in a certain pressure range, so the solubility of substances can be changed by controlling temperature and pressure.
(2) The basic principle of supercritical fluid extraction.
The process of supercritical fluid extraction separation is based on the relationship between the solubility of supercritical fluid and its density, that is, the influence of pressure and temperature on the solubility of supercritical fluid. When gas is in supercritical state, it becomes a single phase between liquid and gas, its density is close to that of liquid, its viscosity is higher than that of gas but obviously lower than that of liquid, and its diffusion coefficient is 10 ~ 100 times that of liquid. Therefore, the material has good permeability and strong solubility, and some components can be extracted from the material.
In the supercritical state, the supercritical fluid contacts with the substance to be separated, so that it can selectively extract components with polarity, boiling point and molecular weight in turn. Moreover, in the closed system, the density and dielectric constant of supercritical fluid increase with the increase of pressure, and the polarity increases. Components with different polarities can be extracted step by step through programmed pressurization. Of course, it is impossible to obtain a single extract corresponding to each pressure range, but the mixed components with the best ratio can be obtained by controlling the conditions, and then the supercritical fluid can be converted into ordinary gas by heating under reduced pressure, so that the extracted substances can be completely or basically separated automatically, thus achieving the purpose of separation and purification, and combining the two processes of extraction and separation into one, which is the basic principle of supercritical fluid extraction and separation.
Solubility of supercritical CO2
In supercritical state, the solubility of CO2 in different solutes is very different, which is closely related to the polarity, boiling point and molecular weight of solutes. Generally speaking, it follows the following rules:
Lipophilic and low-boiling components, such as volatile oil, hydrocarbons and esters, can be extracted at low pressure (1 04pa).
2. The more polar groups a compound has, the more difficult it is to extract.
3. The higher the molecular weight of the compound, the more difficult it is to extract.
Characteristics of supercritical CO2
Supercritical CO2 has become the most commonly used extractant at present, and it has the following characteristics:
The critical temperature of 1.CO2 is 3 1. 1℃, and the critical pressure is 7.2MPa, so the critical conditions are easy to reach.
2.CO2 is chemically inert, colorless, tasteless, nontoxic and safe.
3. The price is cheap, the purity is high, and it is easy to obtain.
Therefore, CO2 is especially suitable for the extraction of effective components from natural products.
Second, the characteristics of supercritical fluid extraction
1. Extraction and separation are integrated. When the CO2 supercritical fluid filled with dissolved substances flows through the separator, CO2 and the extract quickly become two phases (gas-liquid separation) due to the pressure drop, and are separated immediately, so there is no phase change process of the material, and there is no need to recover the solvent, so the operation is convenient; Not only is the extraction efficiency high, but also the energy consumption is low and the cost is saved.
2. Both pressure and temperature can be used as parameters to adjust the extraction process. Near the critical point, slight changes in temperature and pressure will cause significant changes in CO2 density, thus causing changes in the solubility of substances to be extracted. The purpose of extraction can be achieved by controlling temperature or pressure. The pressure is fixed, and substances can be separated by changing the temperature; Otherwise, fixing the temperature and reducing the pressure to separate the extract; Therefore, the process flow is short and the time consumption is low. It has no pollution to the environment, and the extract can be recycled, thus realizing the green production process.
3. The extraction temperature is low, the critical temperature of CO2 is 3 1.265℃, and the critical pressure is 7. 18MPa, which can effectively prevent the oxidation and escape of heat-sensitive components, completely retain the biological activity, and extract substances with high boiling point, low volatility and easy pyrolysis below its boiling point.
4. The critical CO2 fluid is usually a non-toxic gas. After being separated from the extracted components, there is no solvent residue at all, which effectively avoids the toxic solvent residue under the traditional extraction conditions. At the same time, it also avoids the toxicity to human body and the pollution to the environment during the extraction process, and 100% is pure natural.
5. The polarity of supercritical fluid can be changed. Under certain temperature conditions, substances with different polarities can be extracted by changing pressure or adding appropriate entrainer, and the selection range is wide.
Third, the application of supercritical fluid extraction technology
(1). Application of supercritical fluid technology in the development of domestic natural drugs
At present, the resources that can be used for CO2 supercritical extraction technology at home and abroad are: Taxus chinensis, Astragalus membranaceus, ginseng leaves, hemp, Swertia japonica, Artemisia annua, Ginkgo biloba, Fritillaria cirrhosa, eucalyptus leaves, roses, camphor leaves, jasmine, Chinese prickly ash, star anise, osmanthus fragrans, ginger, garlic, Chinese prickly ash, dried tangerine peel, hops, Miscanthus, citronella and so on.
In supercritical fluid technology, supercritical fluid extraction (SFE) is closely related to the modernization of natural medicines. The extraction of nonpolar and moderately polar components by SFE can overcome the sample loss and environmental pollution caused by solvent recovery in traditional extraction methods, and is especially suitable for the extraction of volatile compounds with unstable temperature. For more polar compounds, polar entrainers, such as ethanol and methyl ethanol, can be added to change the extraction range and improve the extraction rate.
(2). Advantages of Supercritical CO2 Extraction Technology in the Development of Traditional Chinese Medicine
Compared with traditional Chinese medicine extraction methods, supercritical CO2 extraction technology has many unique advantages in the research and development and industrialization of Chinese medicine:
1, and the critical temperature of carbon dioxide is 3 1.2℃, which can well preserve the effective components of traditional Chinese medicine from destruction or secondary biochemistry, and is especially suitable for the extraction of those components that are sensitive to heat and easy to be oxidized and decomposed.
2. The solubility of a fluid is related to its density. Small changes in temperature and pressure will cause great changes in fluid density, thus affecting its solubility. Therefore, by adjusting the operating pressure and temperature, impurities can be reduced, the effective components of traditional Chinese medicine can be highly enriched, the appearance of the product can be greatly improved, the extraction efficiency is high, and there is no solvent residue.
3. According to the theory of syndrome differentiation and treatment of traditional Chinese medicine, the effective components in the compound prescription of traditional Chinese medicine restrict each other and play a synergistic role. Supercritical carbon dioxide extraction is not a simple purification of a certain component, but a selective separation of effective components, which is more conducive to giving play to the advantages of traditional Chinese medicine compound.
4. Supercritical CO2 can also directly extract different parts from single or compound Chinese medicines or directly extract extracts for pharmacological screening, thus developing new drugs and greatly improving the screening speed of new drugs. At the same time, many substances that cannot be extracted by traditional methods can be extracted, and it is easier to find new components from traditional Chinese medicine, thus discovering new pharmacological characteristics and developing new drugs.
5. Carbon dioxide is non-toxic, non-flammable, non-explosive, low in viscosity, low in surface tension and low in boiling point, and it is not easy to cause environmental pollution.
6. By directly combining with gas chromatography, infrared spectroscopy, mass spectrometry and liquid chromatography. It can objectively reflect the concentration of effective components in the extract and realize the integration of traditional Chinese medicine extraction and quality analysis.
7. The extraction time is fast and the production cycle is short. Separation begins as soon as the supercritical CO2 extraction (dynamic) cycle begins. General extraction 10 minutes later, the components can be separated and extracted completely in about 24 hours. At the same time, there is no need for concentration and other steps, even if the entrainer is added, it can be removed by separation or simply concentrated.
8. Supercritical CO2 extraction, the operating parameters are easy to control, therefore, the effective components and product quality are stable.
9. Pharmacology and clinic have proved that supercritical CO2 extraction of traditional Chinese medicine is not only superior in process, stable in quality and easy to control, but also can ensure its pharmacological and clinical effects.
10. The supercritical CO2 extraction process is simple and easy to operate, which saves labor and a lot of organic solvents, reduces the pollution of three wastes, and undoubtedly provides a new high-tech method for the modernization of traditional Chinese medicine.
In addition, RESS process and gas process in supercritical fluid crystallization technology can prepare ultrafine particles with uniform particle size, so as to prepare controlled-release pellets and other dosage forms, which can be used to prepare new dosage forms of traditional Chinese medicine.
Supercritical extraction technology has obvious advantages in the extraction of effective components of traditional Chinese medicine, and is also widely used in food, chemical industry, bioengineering and other fields.
(3) Application of supercritical fluid technology in other fields.
Application of 1. in food
At present, supercritical carbon dioxide can be used to extract oil from sunflower seeds, safflower seeds, peanuts, wheat germ and cocoa beans. The recovery rate of this method is higher than that of traditional pressing method, and there is no solvent separation problem of solvent method.
2. Application in medicine and health care products
In the production of antibiotics, traditional methods often use organic solvents such as acetone and methanol, but it is difficult to completely remove the solvents without deterioration. If SCFE rules are adopted, it can fully meet the requirements.
In addition, ginkgo flavone extracted from ginkgo biloba leaves by SCFE method, polyunsaturated fatty acids (DHA and EPA) extracted from fish viscera and bones, seabuckthorn oil extracted from seabuckthorn seeds and lecithin extracted from egg yolk have unique curative effects on cardiovascular and cerebrovascular diseases.
3. Extraction of natural spices and essences
Extracting spices by SCFE method can not only effectively extract aromatic components, but also improve product purity and maintain its natural fragrance, such as extracting flower essence from osmanthus fragrans, jasmine, chrysanthemum, plum blossom, orchid and rose, extracting spices from pepper, cinnamon and mint, and extracting essential oil from celery seed, ginger, turnip seed, fennel, Amomum villosum, star anise and cumin. Hop is an indispensable additive in beer brewing, which has unique aroma, umami taste and bitter taste. Hop extract produced by traditional methods contains no or only a small amount of essential oil, which destroys the flavor of beer and the residual organic solvent is harmful to human body. Supercritical extraction technology has opened up a broad prospect for the production of hops extract.
4. Application in chemical industry
In the United States, supercritical technology is also used to prepare liquid fuel. Using toluene as extractant, the extraction was carried out at PC = 100 atm and TC = 400-440℃. Under the diffusion of SCF solvent molecules, the deep thermal decomposition of coal organic matter is promoted, and 1/3 organic matter can be transformed into liquid products. In addition, chemical products such as sulfur can be extracted from coal.
Recently, the United States has successfully developed a new acetic acid manufacturing process, which uses supercritical carbon dioxide as reactant and extractant. Russia and Germany also use SCFE to deasphalt.
In addition, supercritical extraction can also be used to extract tea polyphenols from tea; Extracting ginkgo flavone and lactone; Extract osmanthus essence and rice sugar oil.
Fourth, the prospect of supercritical fluid extraction technology
Traditional Chinese medicine is a traditional medicine in China, and it has a long history to prevent and treat diseases with traditional Chinese medicine. Because the toxic and side effects of chemicals are gradually recognized by people, the synthesis of a new drug requires huge investment, and the treatment of common and difficult diseases that threaten human health by western medicine is far from meeting the clinical needs. Therefore, the world has set off a fever of traditional Chinese medicine.
As a natural medicine, Chinese medicine has a long history of application in China. The output once again ranks first in the world. However, according to the current world drug trade, China only accounts for about 18%. The main reason is that the technical level of industrial modernization project is not high, and the modernization level of preparation technology and dosage form is still very backward. Therefore, in order to change this situation, it is necessary to modernize the extraction and separation process and preparation process. Standardization and standardization of quality control. Facing the rapid development of science and technology, especially the pharmaceutical industry, international medical academic exchanges are increasingly frequent, and the competition in the pharmaceutical market is increasingly fierce. Realizing the modernization of Chinese medicine and connecting with the international community has become the knowledge of Chinese medicine practitioners.
In modern society, the situation of cooking in vats, cooking in cauldrons and mastering utensils such as plaques, spoons and jars has been greatly improved, and then stainless steel multifunctional extraction tanks, external circulation evaporation, multi-effect evaporators and fluidized dryers have appeared, and the dosage forms of Chinese patent medicines have also developed greatly, from pills, powders, ointments and pills to granules, tablets, capsules, oral liquids and a small amount of powder injections. However, it is still difficult to register, legally sell and use Chinese patent medicines abroad. Judging from the current global trade volume of natural medicines, China only accounts for about l%, which is out of proportion to the status of a big country producing natural medicines. The main reason is that the level of modern industrial engineering technology is not high, and the modernization of preparation technology and dosage form is still very backward; The lack of scientific and strict technological operation parameters in many links in the production process not only leads to high consumption and low efficiency, but also leads to the loss of effective ingredients, unstable curative effect, inconvenience in taking large doses, poor appearance color of products 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 the same curative effect; Many compound preparations are still difficult to understand the material basis of their actions. "Pills, powders, ointments, elixirs and immortals are indistinguishable" has not fundamentally changed. In order to change this situation, let the western medical community accept Chinese medicine and enhance the competitive position of Chinese medicine in the international market, the main way is to realize the modernization of Chinese medicine under the guidance of Chinese medicine theory and advanced technology. The key point of modernization of traditional Chinese medicine products can be simply described in eight words, that is, "effective, small in quantity, safe and controllable". In fact, it involves a wide range and the problems to be solved are very complicated, but the most critical problems are the modernization of extraction and separation technology and preparation technology, and the standardization and standardization of quality control. For this reason, many medical experts have put forward many advanced technologies such as supercritical fluid technology, membrane separation technology, freeze-drying technology, microwave radiation-induced extraction technology, sustained-release preparation technology, and various advanced chromatography and spectral analysis to carry out the research and development and industrialization of traditional Chinese medicine.
The modernization of traditional Chinese medicine production and the scientification of quality standards are the keys to the development and internationalization of traditional Chinese medicine. The research and development of traditional Chinese medicine must follow the principles of "three effects" (quick-acting, high-efficiency and long-lasting), "three small" (small dosage, small side effects and low toxicity) and "five convenience" (convenient for production, transportation, storage, carrying and use). So we must choose some modern drugs. It is especially suitable for substances unstable in damp and heat, and has no solvent residue, no environmental pollution caused by recycled solvent, fast extraction speed and shortened production cycle. Undoubtedly, it is a high-tech that can not only improve the yield and product purity, but also reduce the cost. However, because the extractants used in this method are all fat-soluble, the extraction yield of effective components with large polarity or molecular weight (generally greater than 500) is poor, and efforts must be made to select suitable entrainers in the future. Of course, it has been reported abroad that the application of perfluoropolyether ammonium carbonate can extend SFE method to water-soluble system. In recent years, SFE technology, combined with high-tech analytical instruments such as chromatography, mass spectrometry and high-pressure liquid chromatography, has become an effective separation and analysis method, which can effectively and quickly analyze drug components. Some traditional Chinese medicine preparations can formulate controllable indexes that can guide the production operation and reflect the internal quality uniformity, effectiveness, stability and reproducibility of the products, and implement scientific quality standardization.
At present, SFE is mainly used to extract the effective components in natural medicines, mostly used to extract the pure natural components in single medicine. We believe that SFE extraction technology should also be studied and new drugs should be developed for some compound preparations of ancient Chinese patent medicines with a long history of application in China, as well as polysaccharide components with strong pharmacological activities and participating in life function activities in many traditional Chinese medicines, which is also the only way to make traditional Chinese medicine in line with international standards and realize the modernization of traditional Chinese medicine.
In supercritical fluid technology, supercritical fluid extraction technology has been widely studied, developed and applied. Because of its own characteristics, it is widely used in food, spices and other fields at home and abroad. China is rich in natural resources, and supercritical extraction technology has great promotion value. Some mountainous areas with underdeveloped transportation are rich in specialty resources, especially Chinese herbal medicines. The treatment of these medicinal materials requires considerable equipment and is inconvenient to transport. If CO2 supercritical extraction equipment can be established in these mountainous areas, it can be used to extract the most useful essence of traditional Chinese medicine, which not only reduces a lot of transportation costs, but also greatly enhances the important added value.
At present, in the field of traditional Chinese medicine, most foreign or domestic companies have reported on the research, development and application of SFE technology, but they lack systematicness, and most of them only stay in the extraction of effective components or intermediates of traditional Chinese medicine, which is only one aspect of traditional Chinese medicine. The research and development of traditional Chinese medicine is special, that is, it must have pharmacological and clinical effects. Therefore, SFE technology must be combined with pharmacological clinical research when it is used in traditional Chinese medicine. Only when the process is superior and the pharmacological clinical effect is guaranteed or better can the vitality or potential of SFE technology in this field be truly reflected.