Compound immobilized enzyme used for preparing statins and preparation method of compound immobilized enzyme

Abstract

The invention belongs to the technical field of medical industry, and mainly relates to a compound immobilized enzyme used for preparing statins, as well as a preparation method and applications of the compound immobilized enzyme. The compound immobilized enzyme provided by the invention is prepared through the manner of fixing active enzyme in an immobilized enzyme carrier through the fixing manner of adsorption, covalent binding, embedding, microencapsulation or crosslinking, wherein the active enzyme is composed of ketoreductase and / or halohydrin dehalogenase, and the mass percent of the ketoreductase in the active enzyme is 0%-100%. The immobilized enzyme product is applied to the process for producing the midbody, namely, ethyl(S)-4-chloro-3-hydroxybutanoate and / or ethyl(R)-4-cyano-3-hydroxybutyate of the products including atorvastatin, rosuvastatin, pitavastatin and the like. Compared with the liquid enzyme, the compound immobilized enzyme provided by the invention has the advantages that the production cost is reduced, the labor intensity is alleviated, the utilization efficiency of enzyme is improved, the discharge of waste water, waste gas and industrial residue is reduced, and the environment is protected.

Description

technical field [0001] The invention relates to the fields of bioengineering and green pharmacy, in particular to a composite immobilized enzyme and its preparation method and application. Background technique [0002] Statins are hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which block the endogenous cholesterol synthesis rate-limiting enzyme (HMG-CoA) reductase by competitively inhibiting The metabolic pathway of intracellular valonate reduces intracellular cholesterol synthesis, thereby stimulating the increase in the number and activity of low-density lipoprotein (LDL) receptors on the surface of cell membranes (mainly liver cells) and clearing serum cholesterol increase, decrease in level. Statins can also inhibit the synthesis of apolipoprotein B-100 in the liver, thereby reducing the synthesis and secretion of triglyceride-rich AV and lipoproteins. The currently commercially available statins mainly include atorvastatin, rivastatin, and pitavasta...

AI Technical Summary

Problems solved by technology

However, due to the short time of this technology, there are many traditional catalytic reactions that have not tried to apply immobilized enzyme technology. For the application of immobilized enzyme technology in the field of medicine and chemical industry, there is a lack of sufficient practical experience, the technical feasibility, and the exploration of related parameters. still blank

[0006] In the prior art, there is no immobilized enzyme product specially used for the production of statin drugs, nor is there any composite immobilized enzyme product that is prepared by compounding and immobilizing enzymes required in the production of various statin drugs in the same carrier