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Application of SMB Technology in Separation and Preparation of Natural Products

In recent years, with the in-depth study of SMB technology, its application field has been further expanded. The separation of single petrochemical products gradually involves the fields of fine chemicals, sugar industry, cosmetics and spices industry. Natural products are abundant in resources, diverse varieties, and strong potential active function, which has been the focus of scientific researchers. However, the components of natural products are complex and low content of active ingredients. In order to prepare products with clear ingredients, clear pharmacodynamics and controllable content of active ingredients, it is necessary to establish an effective separation process by using modern science and technology.


Separation and preparation of flavonoids

Quercetin is one of the representative flavonoids. It has many bioactivities and pharmacological effects, such as anti-free radical, anti-oxidation, anti-cancer and anti-diabetic complications. It has good effects on respiratory diseases, especially asthma and bronchitis. Zhang Lihua et al. separated Ginkgo biloba extracts by SMB twice and obtained quercetin with purity more than 90%. Glycyrrhizin is a monomer active ingredient of Glycyrrhiza flavonoids. It has many pharmacological effects such as anti-oxidation, anti-HIV and so on.


Separation and preparation of polyphenols

Resveratrol widely exists in Polygonum cuspidatum, grapes, peanuts, pine and other plants. It has the functions of anti-tumor, anti-inflammatory, anti-bacterial, anti-oxidation, anti-free radical, liver protection, cardiovascular protection and anti-myocardial ischemia. Zhang Jianchao [2] et al. used SMB with 4 columns and 3 regions to separate and prepare the Polygonum cuspidatum extracts, and obtained high purity resveratrol. The column connection method is 1-2-1, reversed-phase ODS as separation packing, 50% methanol as elution solvent, 0.1 mL/min injection flow rate, 1.0 mL/min flow rate of elution zone, 1.5 mL/min flow rate of refinement zone, 1.6 mL/min flow rate of adsorption zone and switching time is 19 min.


Separation and preparation of amino acids

L-phenylalanine is an aromatic amino acid with physiological activity. It is one of the essential amino acids that can not be synthesized naturally by human beings and animals. Phenylalanine is the intermediate of amino acid anticancer drugs such as phenylalanine, formic acid sarcomatolysin and so on. It is also the raw material for the production of adrenaline, thyroxine and aspartame. Wu Hao [3] et al. separated the conversion solution of 12 g/LL-phenylalanine enzyme through SMB. Using four-zone SMB with five chromatography columns. Each functional zone was allocated to 1-1-2-1. WH-6 styrene strong acidic cation exchange resin was used as separation packings and eluent was 0.5 mol/L ammonia water. The switching time of L-zone I was 1.8 h, that of zone II was 0.5 h, that of zone III was 7.32 h, that of zone IV was 2.44 h, that fluid rate of injection was 1 L/h, and that fluid rate of elution was 1.74 L/h.


Separation and preparation of peptide

Teicoplanin is a new glycopeptide antibiotic. Its antimicrobial spectrum and antimicrobial activity are similar to vancomycin. It is sensitive to Gram-positive bacteria such as Staphylococcus, Streptococcus, Enterococcus and most anaerobic positive bacteria. In clinic, it is mainly used for serious infections caused by sensitive bacteria such as Staphylococcus aureus and Streptococcus, such as endocarditis, osteomyelitis, sepsis, respiratory tract, urinary tract, skin and soft tissue. Lin Bingchang [4] et al. studied the separation and preparation of teicoplanin by SMB. Through single column experiment, a self-designed three-band SMB with a column diameter ф=5 cm was used to separate fillers by C18. Using 65% methanol as mobile phase, 50 mg/mL injection concentration, 5 mL/min injection flow rate, 50 mL/min elution flow rate, 21 mL/min extraction flow rate, and the switching time was 7 min. Two batches of samples were separated and prepared, and the purity of teicoplanin was more than 87%. According to the above experimental method, the SMB equipment was further enlarged, i.e. the diameter of chromatography column was enlarged from 5 cm to 10 cm; the purity of teicoplanin was 87.1% by using 12 mL/min injection flow rate, 200 mL/min elution flow rate, 132 mL/min extraction flow rate and 415s switching time.


Separation and preparation of sugar

Fructose is the sweetest natural nutritive sweetener. It has high sweetness, cold sweetness, pure and refreshing sweetness and excellent metabolic characteristics, such as insulin-independent metabolism and no excessive fluctuation of blood sugar. Fructose and glucose are isomers, belonging to hexone sugar, which is rich in Jerusalem artichoke and other Compositae plants, honey and fruit. Fructose syrup is often used as raw material to separate and prepare fructose in industry. Li Liangyu [5]et al. used simulated moving bed to separate and prepare F42 Fructose-glucose syrup. The using of chromatography packing is Ca2+ ion exchange resin. The feed flow rate is 3.0mL/min, the elution flow rate is 7.5mL/min, the circulation flow rate is 12.0mL/min, and the switching time is 400s. The purity of fructose is 95%, and the recovery rate is as high as 85%.


Conclusion

Active ingredients of natural products are one of the important sources of drugs. The preparation technology of separation and purification of active ingredients of natural products has attracted the attention of researchers all over the world. SMB technology, as an innovation in separation technology, is a real continuous preparative chromatography technology. On the one hand, SMB has the advantages of high separation efficiency, low consumption of packings and eluents, which greatly reduces the cost of separation and preparation of active ingredients; on the other hand, the flexibility of SMB separation operation is conducive to the separation of different types of compounds in natural products. At the same time, with the development of sequential SMB technology, it will play a positive role in the separation of multi-component and complex natural products.