Application of advanced extraction technology and equipment in traditional Chinese medicine production

Chinese herbal medicines contain complex ingredients, both active ingredients and ineffective and harmful ingredients. In order to improve the therapeutic effect of traditional Chinese medicine, it is necessary to extract the active ingredients, remove the ineffective ingredients and toxic ingredients. Therefore, Chinese medicine extraction is a key link in the production of traditional Chinese medicine. At present, the commonly used extraction methods include boiling method, reflux method, impregnation method, and percolation method. However, these extraction methods have the advantages of easily destroying active ingredients, long production cycle, many production processes, low extraction rate, complicated process, and products. Low purity, easy to residue harmful substances and other shortcomings. In the past 10 years, many new technologies and new processes have emerged in the extraction of traditional Chinese medicines, such as supercritical extraction, ultrasonic extraction, microwave extraction, etc. The application of these new technologies and new techniques has improved the quality and extraction yield of traditional Chinese medicine extracts. To improve production efficiency and speed up the pace of modernization of Chinese medicine and international integration. This paper tries to make a comparative analysis of the application of these new technologies, new processes and equipment in the production of traditional Chinese medicine.



1 Supercritical fluid extraction technology and equipment

1.1 Introduction to supercritical fluid extraction technology

Supercritical fluid extraction (SCFE) is a new technology for extracting and separating the active constituents of traditional Chinese medicines by supercritical fluid (SCF) instead of conventional organic solvents. The principle is to use fluids in a certain area under supercritical conditions. It has abnormal phase equilibrium behavior and transfer performance with the components to be separated in Chinese herbal medicines, and the solubility of the components varies within a certain range with changes in pressure and temperature, and the components are dissolved under a certain supercritical state. When the temperature and pressure are changed, the component is released at a certain temperature and pressure (still in a supercritical state) to facilitate collection. Supercritical fluid extraction is a new type of separation technology. It uses the mass transfer characteristics of high density, low viscosity and large diffusion coefficient in the supercritical state to achieve the purpose of extraction and separation. By using this SCF as a solvent, components to be separated can be extracted from various liquid or solid materials.

CO2 is generally used as a supercritical fluid because CO2 is a very common gas, non-toxic and tasteless, non-flammable and explosive, and inexpensive, safe and efficient. When the temperature is higher than the critical temperature Tc=31.3 °C and the pressure is higher than the critical pressure Pc=7.2 MPa, the properties change, the density is close to the liquid, the viscosity is close to the gas, and the diffusion coefficient is 100 times that of the liquid. Has amazing solvency. It can dissolve a variety of substances, and change the temperature and pressure to change the solubility of CO2 to achieve the purpose of extracting the active ingredients.

1.2 Application of supercritical extraction technology in the production of traditional Chinese medicine

Supercritical extraction technology has been widely used: (1) extraction of higher fatty acids (EPA, DHA, dehydroascorbic acid, etc.) from fish oil; (2) extraction of higher fatty acids (γ-linolenic acid, etc.) from plants or bacteria; (3) Extraction of medicinal ingredients (alkaloids, flavonoids, fat-soluble vitamins, strontium, etc.); (4) extraction of perfume ingredients (animal spices, plant spices, etc.); (5) cosmetic raw materials (cosmetic effect agents, surfaces) Extraction of active agents, fatty acid esters, etc.; (6) removal of nicotine from tobacco.

Supercritical extraction technology has now been applied to the mass extraction of some Chinese herbal medicines. Some Chinese herbal medicines that have adopted supercritical extraction technology in China, such as: magnolol and honokiol, ginkgo flavonoids and ginkgolides, artemisinin, garlic oil, shikimic acid, ganoderma lucidum spore oil, sea buckthorn seed oil, tomato red , soy lecithin, soy isoflavones, β-carotene (spirulina), cassia twig, Ophiopogon and the like.

For example, sea buckthorn oil is extracted from seabuckthorn seeds. Currently, supercritical extraction technology has been widely used in the Netherlands to extract sea buckthorn oil from seabuckthorn seeds, and several manufacturers have formed an annual production capacity of more than 20 tons of sea buckthorn oil. CO2 is used as the extraction medium, and the process conditions are: temperature 35-55 ° C, pressure 25.0-30.0 MPa. For example, Qinghai Kangpude Bio-Pharmaceutical Co., Ltd. used the TH321-400×3 supercritical CO2 extraction device produced by Wenzhou Zhongzhong Pharmaceutical Machinery Equipment Factory for the extraction and production of seabuckthorn oil, and achieved good results.

However, the application of supercritical extraction technology also has its limitations. Supercritical fluid extraction technology is difficult to extract and separate polar substances, and is not suitable for the extraction of traditional Chinese medicine compounds.

1.3 Production of supercritical CO2 extraction unit

At present, the domestically produced Zui large supercritical extraction device has reached the specification of 3 000 L. With the development and application of supercritical extraction technology, some enterprises in China have specialized in the development and production of supercritical extraction devices. According to the production capacity of domestic supercritical extraction device manufacturers, it can basically be divided into two categories of 24 L or less and 24 L or more. The supercritical extraction device below 24 L is mainly produced by some enterprises with limited R&D strength and production capacity. Many domestic enterprises have the production capacity of supercritical extraction devices below 24 L, and the products can fully meet the customer's process requirements. The products produced are basically the same, and the products are mainly used for pilot and small batch production. There are only a few companies with more than 24 L supercritical extraction devices that can be designed and manufactured in China. Because they are high-pressure vessels, manufacturers must have three types of pressure vessel manufacturing qualifications. Therefore, many domestic enterprises only design and assemble high-pressure vessels. It is by outsiders. At present, domestic enterprises producing industrialized supercritical extraction devices include Wenzhou Zhongjiu Machinery Equipment Factory, Guizhou Wujiang Electromechanical Equipment Co., Ltd., and Guangzhou Meichen High-tech Separation Technology Co., Ltd.



2 Ultrasonic extraction technology and equipment

2.1 Introduction to ultrasonic extraction technology

Ultrasound is a high frequency mechanical wave. Ultrasonic technology is one of the high-tech based on the disciplines of physics, mechanical vibration, electronics, materials, etc. It is an application technology that changes the state of objects or physical properties by ultrasonic energy. In the national economic construction, it has special potential ability to improve product quality, reduce production costs, prevent environmental pollution, and improve production efficiency. The application of ultrasonic vibration in the extraction of Chinese herbal medicine is a new technology developed in China in recent years.

Theoretical basis of ultrasonic extraction: According to the special effects of ultrasonication, such as cavitation, pulverization and agitation, the ultrasonic wave propagates in the liquid medium to produce a special "cavitation effect". The "cavitation effect" continuously produces numerous internal pressures reaching thousands of atmospheres. Air pockets, and constantly "blasting" to produce a powerful microscopic shock wave on the Chinese herbal medicine, which destroys the cells of the botanical material, so that the solvent penetrates into the cells of the medicine, so that the chemical components in the medicine are dissolved in the solvent. By separating and purifying the desired chemical components, the extraction of the active components of the plants is accelerated.

A large number of experiments in China have shown that ultrasonic extraction can shorten the time and increase the rate of presentation of active ingredients. It is suitable for the extraction of active ingredients of Chinese herbal medicines and can change the traditional Chinese medicine pharmaceutical extraction process. Compared with the boiled and alcohol precipitation process, ultrasonic extraction has the following outstanding features:

(1) The extraction temperature is low. Ultrasonic enhanced extraction is generally carried out at a water temperature of 40 to 50 °C without destroying some of the active ingredients of Chinese herbal medicines which are thermally unstable, easily hydrolyzed or oxidized;

(2) Atmospheric pressure extraction, good safety, easy operation and convenient maintenance;

(3) High extraction efficiency. Ultrasonic enhanced extraction for 30 ~ 50 min can get good extraction rate, extraction time is only 1/4 or less of boiled, alcohol precipitation method. The extraction is sufficient, and the extraction amount is more than twice that of the conventional method;

(4) A wide range of applications. Ultrasonic extraction can be used for most of the various Chinese herbal ingredients. Ultrasonic extraction has little to do with the nature of the solvent and target extract (such as polarity). Therefore, there are many types of extraction solvents to choose from and a wide range of target extracts;

(5) Reduce energy consumption. Since the ultrasonic extraction does not require heating or the heating temperature is low, the extraction time is short, so the energy consumption is greatly reduced;

(6) The raw material of the medicinal material is processed in a large amount, which can be increased several times, and the impurities are small, and the active ingredient is easy to be separated and purified;

(7) The extraction process has low cost and comprehensive economic benefits.

2.2 Ultrasonic extraction technology and equipment application

At present, ultrasonic Chinese medicine extraction devices mainly have the following three forms:

(1) using a polygonal transducer, the ultrasonic vibrator is welded in the transducer, and the ultrasonic wave is emitted from the inside of the transducer along the radial direction;

(2) Round bar type new radial ultrasonic transducer, ultrasonic waves can be emitted in the 360° direction;

(3) The continuous spiral conveying ultrasonic extraction unit is adopted, and the ultrasonic vibrator is fixed on the outer wall of the extractor, and is emitted from the outside to the inside, so that continuous automatic extraction and production can be realized.

Among the above three methods, (1) and (2) are the ultrasonic transducers placed in the tank along the axis of the extraction tank, which can only be produced intermittently. (3) is a brand new continuous extraction device. Automatic extraction of countercurrent or downstream flow, automatic feeding, automatic slagging, automatic filtration is a method worthy of research and promotion.

At present, ultrasonic extraction technology has been applied to the extraction production of traditional Chinese medicines such as honeysuckle, tea polyphenols and medlar.



3 microwave extraction technology and equipment

3.1 Introduction to Microwave Extraction Technology

Microwave energy is a form of energy that acts on many substances consisting of polar molecules during transmission. Microwave electromagnetic fields cause instantaneous polarization of molecules of matter. When using microwave energy with a frequency of 2 450 MHz for extraction, the molecules of the solute or solvent do the polarity change motion at a rate of 2.45 billion times/s, thereby generating mutual friction and collision between molecules, and promoting the molecular active portion ( The polar part) is better contacted and reacted, while rapidly generating a large amount of heat energy, causing the cells to rupture, allowing the cell fluid to overflow and diffuse into the solvent.

The microwave radiation process is a high-frequency electromagnetic wave that penetrates the extraction medium and reaches the internal fiber bundle and the glandular system of the material. Due to the absorption of microwave energy, the internal temperature of the cells rises rapidly, causing the internal pressure of the cells to exceed the capacity of the cell wall to expand and the cells to rupture. The active components in the cells are free to flow out, and are taken up and dissolved at a lower temperature. The extracted material is obtained by further filtration and separation.

Microwave-assisted extraction technology relies mainly on the characteristics of microwave heating to extract or separate substances. Microwave-assisted extraction studies have shown that microwave radiation-induced extraction technology has the characteristics of high selectivity, short operating time, low solvent consumption and high yield of active ingredients. It has been applied to the extraction of organic pollutants, traditional Chinese medicines and natural compounds. Biological active ingredient extraction and other aspects. Microwave heating is internal heating, which can enrich the active ingredients in the medicinal materials after microwave irradiation. Compared with the conventional extraction process, it has the following characteristics:

(1) Conventional thermal extraction is carried out from the outside to the inside by means of heat conduction, heat radiation, etc., while microwave-assisted extraction is simultaneous heating inside and outside. There is no high-temperature heat source, eliminating the thermal gradient, thereby greatly improving the extraction quality and effectively protecting the active ingredients in the Chinese herbal medicine;

(2) Since the microwave can be heated by penetration, the extraction time is greatly saved;

(3) Microwave energy has extraordinary extraction ability. The same raw materials need to be cleaned two or three times by conventional methods, and can be cleaned in one time under microwave field, which greatly simplifies the process flow;

(4) Microwave extraction has no thermal inertia, easy to control, all parameters can be digitized, and the pharmaceutical modernization level is in line;

(5) The microwave extract has high purity, can be extracted by water, extracted by alcohol, and extracted by fat, and is widely used;

(6) The amount of solvent is small (50% to 90% less than conventional methods).

3.2 Microwave extraction technology and equipment application

At present, in the field of traditional Chinese medicine and pharmacy, microwave extraction has been used in the leaching production of some Chinese herbal medicines, such as puerarin, glycosides, and ginkgo. This new extraction technology has advantages over conventional production processes in terms of extraction speed, extraction efficiency and extraction quality.

Although microwave extraction technology has many of the above advantages, it is not widely used in the extraction of traditional Chinese medicines. It is mainly used for small tests and pilot tests. The laboratory has obtained a lot of results, which proves that the microwave extraction technology of traditional Chinese medicines has higher Practical value.

Microwave extraction equipment mainly has the following structures:

(1) Pipeline microwave extraction equipment: mainly composed of microwave source, microwave action chamber, conveying pipeline and storage tank;

(2) Tank type microwave extraction equipment: mainly consists of a tank body, a microwave action chamber, a stirrer, a feeding port, a liquid adding port, a microwave source, a discharging port and a liquid outlet.

Domestic colleges and universities and research institutions mostly use the microwave extraction equipment of category (2).



4 Comparison of three advanced extraction techniques in traditional Chinese medicine

Supercritical CO2 extraction, ultrasonic extraction, and microwave extraction techniques have significant superior performance compared with conventional Chinese medicine extraction processes.

4.1 Comparison of supercritical CO2 extraction techniques

Supercritical CO2 extraction method Compared with the traditional extraction method, Zui has the advantage of being able to extract and separate under normal temperature conditions, accurately extracting the required effective components, and retaining almost all active ingredients in the product, without organic solvents. Residue, the product purity is very high, the operation is simple, the speed is fast, the energy is saved, and the various process parameters are easy to control. Due to the low extraction temperature and the system being sealed, a large amount of volatile components which are unstable to heat and easy to oxidize can be stored, which provides an advanced method for the extraction and separation of volatile components of traditional Chinese medicine. Supercritical CO2 extraction can be used to extract active ingredients from many plants that have not been chemically extracted in the past. The supercritical CO2 extraction device can realize PLC automatic control and automatically control the process parameters such as temperature and pressure to realize automatic production. The promotion and application of this technology will accelerate the process of modernization of Chinese medicine and have broad prospects for development.

The supercritical CO2 extraction process has higher requirements on the production equipment and a large one-time investment. However, the high selectivity, high yield and low toxicity of the process in the extraction of traditional Chinese medicine are unmatched by all other extraction methods, and thus the supercritical CO2 extraction technology has become the first choice for various advanced Chinese medicine extraction techniques.

4.2 Comparison of ultrasonic extraction techniques

Ultrasonic extraction technology has the advantages of simple equipment, convenient operation and low investment. Compared with the conventional extraction method, the extraction time is short, the productivity is high, and no heating is required. It mainly uses the "cavitation" of mechanical waves for extraction production, which can realize continuous automatic extraction production, and thus has certain application. However, the ultrasonic extraction technology needs further research on device amplification to form a certain data model, so as to further promote the application.

Although the ultrasonic extraction technology has many advantages compared with the conventional Chinese medicine extraction production, at present, there are not many domestic ultrasonic extraction techniques applied to the traditional Chinese medicine extraction batch production. The time and intensity of ultrasonic ultrasound action requires a series of experiments to determine, and there are many problems with amplification. Some Chinese herbal medicines use ultrasonic to enhance the extraction of active ingredients, and also extract unwanted or harmful ingredients. At the same time, due to the relatively high noise of the ultrasonic generator, it is necessary to pay attention to protection, so there are certain limitations in industrial applications.

4.3 Comparison of microwave extraction techniques

The microwave extraction technology utilizes microwave to simultaneously extract heat from the inside and outside of Chinese herbal medicine to achieve the purpose of extracting effective components. It has the characteristics of low extraction temperature, high extraction efficiency, simple process and low equipment investment. One of the focuses of the popularization and application of microwave extraction technology is that the microwave leakage of microwave extraction equipment may cause harm to the human body. At present, the microwave leakage standard manufactured by professional industrial microwave machinery equipment manufacturers is controlled below 1 mW/cm2 according to national regulations. Regardless of pipeline or tank microwave extraction equipment, the sealing performance is strong, and all can meet the microwave leakage standard requirements.

The shortcoming of microwave extraction technology is that it is difficult to realize automated production, and it can not be online with other instruments. The design of microwave extraction device needs further research and discussion. At the same time, microwave extraction technology and equipment are rarely reported in the large-scale production of traditional Chinese medicine extraction.



5 Conclusion

This paper introduces the supercritical fluid extraction, ultrasonic extraction, microwave extraction technology and equipment used in the extraction of traditional Chinese medicine, and analyzes the application scope and application prospects of the above three extraction techniques. Through analysis, it can be concluded that supercritical CO2 extraction technology has become the first choice for various advanced Chinese medicine extraction technologies.

(Author: Wenzhou Chengdong Medicine Machine Co., Ltd., Wang Chengdong, Yang Hua Tang, Ji Xiao)

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