Application of Ultrafiltration in Separation and Purification of Traditional Chinese Medicine Extracts


Traditional Chinese medicine is the general name of traditional Chinese medicine. Its use is based on the theory of traditional Chinese medicine. It has a unique theoretical system and application form, which fully reflects the characteristics of traditional culture and natural resources in China. According to the Yin and Yang Dynasties, Chinese medicine uses different medicinal materials to complement each other and reconcile the yin and yang five elements to achieve therapeutic effects. Traditional Chinese medicines are derived from plants, minerals and animals, especially plant medicinal materials. The chemical composition of plant-based Chinese herbal medicines is very complex, usually containing alkaloids, amino acids, organic acids, phenols, saponins, steroids, terpenoids and proteins, mucilage, tannins, sugars, starches, cellulose, inorganic salts. Etc [1]. On the other hand, traditional Chinese medicine uses a compound in the course of use, and a compound consisting of 4 to 5 Chinese medicines may contain 300 to 500 chemical components [2]. The natural nature of traditional Chinese medicine makes its chemical composition very complicated, and the confirmation and separation and purification of its active ingredients (or effective parts) are very important for improving the quality of traditional Chinese medicine and promoting the internationalization of traditional Chinese medicine. The active ingredients of Chinese herbal medicine are mostly alkaloids, glycosides, ketones, etc. The extraction solvent is generally water and alcohol. The commonly used purification methods are alcohol precipitation method, adsorption clarification method, macroporous resin adsorption method and ultrafiltration method. During the alcohol precipitation process, a large amount of precipitation occurs, and the adsorption and embedding of the precipitate will cause the loss of the active ingredient. The adsorption of the macroporous resin is difficult to retain the complex active ingredients in the compound due to the selectivity, and the clarification agent is also present in the adsorption clarification method. Residual problem [3]. In contrast, ultrafiltration membrane separation has the advantages of mild operating conditions, low energy consumption, simple operation, short process flow, etc. At the same time, ultrafiltration can retain a certain range of components, so it has a unique role in the Chinese medicine industry and is relatively large. Application potential. Applying ultrafiltration technology to the processing of traditional Chinese medicine to replace the traditional separation method can reduce the production cost of traditional Chinese medicine, improve the quality of medicines, and promote the modernization of traditional Chinese medicine.

1 The basic principle of ultrafiltration Ultrafiltration is between nanofiltration and microfiltration, and the molecular weight of the trappable molecules ranges from 5×103 to 5×105um. There is a very thin dense layer on the working surface of the ultrafiltration membrane. The pore size of the micropores in the layer is about 2-15 nm, and the lower layer of the membrane is a loosely supported support layer with a void of >15 nm. The membrane structure allows the macromolecular solute particles to flow through the membrane surface in the liquid separation process. Due to the rapid flow of the liquid, the substances can neither enter the dense pores and cause internal clogging of the membrane, and will not stay. Surface clogging is formed on the membrane surface; while the small molecular material and solvent are driven by pressure through the micropores on the dense layer, they can smoothly pass through the lower loose support layer and enter the other side of the membrane [4]. The membrane materials of the ultrafiltration membrane are mainly cellulose and its derivatives, polycarbonate (PC), polyvinyl chloride (PVC), polyvinylidene fluoride (PVDF), polysulfone (PS), polyethersulfone (PES), Polyacrylonitrile (PAN), polyamide (PA), and the like.

The molecular weight of the ultrafiltration membrane is 5×103~5×105um, and the relative molecular weight of the active ingredients of most Chinese medicines does not exceed 1000um. The relative molecular weights of ineffective components such as starch, protein, resin and pectin are above 5×104um. . Therefore, the selection of ultrafiltration membranes with suitable molecular weight cutoff range can achieve the separation of active ingredients and impurities, and can retain the original compound characteristics of traditional Chinese medicine, and Zui exerts its efficacy to a large extent [5].

2 Ultrafiltration operation mode and its application is different from ordinary filtration. Ultrafiltration uses a porous asymmetric ultrafiltration membrane to achieve liquid-liquid separation on the surface of the membrane. The filtration method is cross-flow, that is, the feed liquid flows parallel to the membrane surface. Ultrafiltration can be divided into batch operation and continuous operation according to the operation mode.

2.1 Intermittent operation Intermittent operation is divided into two modes of operation: the full circulation of the retentate and the partial circulation of the retentate according to the circulation mode of the retentate. In the ultrafiltration process, in order to reduce the effects of concentration polarization and membrane fouling, a high feed liquid flow rate must be maintained in the membrane cell. Therefore, a large circulation of the retentate must be used to maintain a high flow rate, and in addition, the membrane permeation flux Smaller, the feed liquid also needs to be circulated multiple times on the membrane to meet the concentration requirements.

Intermittent ultrafiltration has large transmission rate, high separation efficiency, simple operation, small equipment and membrane area, and can realize rapid concentration of a small amount of raw liquid, so it is suitable for laboratory and small-scale product processing. The disadvantage of intermittent ultrafiltration is that the amount of treatment is small, while the throughput of the continuous ultrafiltration operation is large, and the residence time of the feed liquid on the membrane is short, so the concentration ratio is low, so a large membrane area is required.

2.2 Continuous operation Liang Wanqiu et al [6] compared the effects of continuous plate ultrafiltration and intermittent plate ultrafiltration in the filtration and purification of cephalosporin C fermentation broth, and found that continuous plate ultrafiltration has a small degree of membrane fouling and easy recovery of membrane flux after cleaning. The quality of the filtrate is good and the unit of the filtrate is equal.

Continuous ultrafiltration is divided into single-stage and multi-stage according to equipment technology. According to the circulation mode of the retentate, it can be divided into two types: no cycle and partial cycle. Among them, single-stage partial cycle and multi-stage partial cycle are widely used in the process. . The characteristic of single-stage continuous ultrafiltration is that the ultrafiltration process is always carried out at a high concentration, so the permeation amount and the rejection rate are both low. To overcome this disadvantage, multi-stage continuous operation is generally employed. The concentration of the circulating liquid in each stage of the multi-stage ultrafiltration is sequentially increased, and the concentrated liquid is taken out after the Zui, so that the liquid in the previous stages can be operated at a lower concentration.

3 Ultrafiltration in the purification of traditional Chinese medicine The pretreatment of the liquid is an indispensable process before the separation of the traditional Chinese medicine membrane. Since the extract of traditional Chinese medicine generally contains more solids and impurities with higher relative molecular weight, and colloids which are easy to cause membrane fouling, the direct use of ultrafiltration separation of the chemical solution may cause membrane fouling and reduce the service life of the membrane. Therefore, the stock solution must be pretreated before ultrafiltration. Commonly used pretreatment methods are: first, centrifugal separation and flocculation precipitation are used to remove suspended solids such as large solid impurities, and then microfiltration further removes bacteria, colloids and the like. Due to the high content of viscous substances such as colloids in traditional Chinese medicine ingredients, membrane fouling is more serious. Therefore, it is better to use membrane materials with better stain resistance, such as polyacrylonitrile, sulfonated polysulfone membranes, etc. [1].

3.1 The effective part (part) of traditional Chinese medicine is complex in the extraction of traditional Chinese medicine, and there are some differences in the molecular weight of each component. The ultrafiltration membrane with appropriate pore size can be used to separate these components according to molecular size by membrane screening. Guo Lijun [2] considered the scientific and technical problems of membrane separation of complex systems of traditional Chinese medicine from the aspects of separation of material basis, separation target and properties that can be used for separation, and proposed the process design principle and membrane pollution prevention of traditional Chinese medicine membrane separation technology. Ideas.

In recent years, there have been many reports on the use of ultrafiltration technology to treat common Chinese medicine extracts. Combining the new technology of ultrafiltration with traditional Chinese medicine treatment is conducive to improving the quality of traditional Chinese medicine preparations and promoting the modernization of traditional Chinese medicine. Specific research work can be divided into specific research work can be divided into specific research work can be divided into three aspects: (1) to explore the application of ultrafiltration in the extraction of active ingredients of traditional Chinese medicine [8-10]; (2) research super Process conditions for filtration in the treatment of traditional Chinese medicine extracts [11]; (3) industrialization of ultrafiltration processes and related problems [12]. Li Shuli et al [10] used a polyacrylonitrile film with a cut-off value of 10000um for seven representative Chinese medicines (danshen drink, Si Miao Yong An Tang, Huanglian Jiedu Decoction, Ginseng Shengmaiyin, Lizhong Decoction, and Astragalus Membranaceus A preliminary study on the ultrafiltration process of the liquid and water extracts of the boiled liquid system revealed that the relative fluxes of the seven systems were almost the same, while Danshen, Si Miao Yong An Tang, Huang Lian Jie Du Tang, Li Zhong The recoveries of the active ingredients in the four systems of the soup were all above 60%, which was significantly higher than the recovery after the alcohol precipitation. Li Yanni [13] purified the acid mucopolysaccharide of sea cucumber with an ultrafiltration membrane with molecular weight cutoff of 8000um, and the rejection rate reached 97.2%. Xu Zhihong et al [14] purified the ginkgo flavonoid extract (GBE) crude raw material by using sulfonated polyethersulfone (SPES) plate ultrafiltration membrane with molecular weight cut off of 10000um, and increased the content of ginkgo flavonoids from 21.3% to 39.2%.

3.2 Application of ultrafiltration technology in the preparation of traditional Chinese medicine liquid preparations The new liquid traditional Chinese medicine preparations mainly include traditional Chinese medicine injection, Chinese medicine oral liquid and traditional Chinese medicine eye drops.

Ultrafiltration technology can filter out unstable micelles, macromolecules and other impurities in the liquid, improve the clarity of liquid Chinese medicine preparations, remove heat source and tannin, and improve the safety of injection [15].

Ultrafiltration is an effective means of preparing Chinese herbal medicine injections. The ultrafiltration process is adopted to obtain a stable clearness of the injection, which is suitable for intravenous administration. In recent years, ultrafiltration has been widely used in the preparation of traditional Chinese medicine injections. Table 1 lists the application of ultrafiltration in the preparation of traditional Chinese medicine injections in recent years.

Traditional Chinese medicine oral liquid has good curative effect, quick effect and convenient drinking [12]. However, the extract of traditional Chinese medicine has a large viscosity, and a large amount of impurities such as submicron particles and flocs are difficult to be refined by sedimentation, filtration, leaching, etc., and the ultrafiltration method can effectively remove these impurities and improve the quality of the Chinese medicine oral liquid and Exterior. It should be pointed out that due to the complexity of traditional Chinese medicine, the use of ultrafiltration and the selection of ultrafiltration membranes should be selected according to the nature of the drug and the composition of the drug [21]. Table 2 lists the application of ultrafiltration technology in the preparation of some traditional Chinese medicine oral liquids.

4 Ultrafiltration technology in the treatment of traditional Chinese medicine Compared with the traditional treatment method, ultrafiltration has the advantages of mild operating conditions, low energy consumption, simple operation, short process flow, etc., but due to the complexity and diversity of traditional Chinese medicine itself. It is easy to cause contamination and blockage of the membrane surface. Membrane fouling refers to the adsorption or deposition of various particles on the surface of the membrane or pores of the membrane due to the physicochemical action of particles, colloidal ions or solute molecules in the filtered liquid and the membrane, causing the membrane pores to become clogged or smaller and The permeation flux and separation characteristics of the membrane cause irreversible changes. Membrane fouling affects membrane flux and transmission while also reducing membrane life. The degree of membrane fouling is related to membrane material, pore size, operating pressure of membrane process, concentration and nature of macromolecular solute in the system to be separated, pH of solution, ionic strength, charge composition, etc. [2]. The control of membrane fouling is an urgent problem that ultrafiltration technology needs to solve in the process of treating Chinese medicine.

At present, the prevention and control of membrane fouling is mainly considered from three aspects: (1) pre-treatment of flocculation and microfiltration of extracts before ultrafiltration to remove major membrane pollutants; (2) comprehensive adjustment of flow rate during ultrafiltration Factors such as temperature, electric field, pH, etc., to reduce the adsorption of the membrane surface, such as increasing the flow rate of the liquid on the surface of the membrane, enhancing the scouring effect, etc.; (3) cleaning and regeneration of the membrane.

Since the mechanism of membrane fouling is still unclear, on the one hand, the research on membrane fouling theory should be strengthened. On the other hand, experimental data and practical experience should be accumulated for different systems, and membrane equipment and membrane materials suitable for Chinese medicine separation should be developed to solve the membrane. The problems caused by contamination in membrane separation applications.

5 Conclusion In summary, in view of the complexity of traditional Chinese medicine ingredients and the characteristics of the active ingredient "group", ultrafiltration technology has gradually replaced the traditional Chinese medicine extract in the separation and purification of the active ingredients (effective parts) of traditional Chinese medicine due to its many advantages. It will play an increasingly important role in the modernization of Chinese medicine. Of course, modern analytical techniques and modern Chinese medicine theory also require ultrafiltration, a new method applied to traditional Chinese medicine treatment to prepare new preparations such as traditional Chinese medicine injection and Chinese medicine oral liquid. The composition and pharmacology of traditional Chinese medicine is very complicated. With the deepening of people's understanding of traditional Chinese medicine ingredients and the development of membrane technology, ultrafiltration technology will play a greater role in the modernization of traditional Chinese medicine.

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