Microbial Transformation And Other Methods In The United States Luoxi Kang With Different E That He Will Be The Application Of Two Drug Metabolism Studies

By utilizing the microbial transformation methods, the metabolisms of meloxicam and isovalertatins were studied in this article. The studies of this article were mainly aimed towards further extending the use of microbial transformation, validating the availability of microbial model and providing an ample supply of metabolites, which can be served as standards of the drug metabolism study in human. The studies included four aspects as follows: 1. Study on the metabolisms of meloxican in rat liver microsane The meloxicam was incubated by rat liver microsomes and analyzed by LC/MS~ method. A major hydroxylation metabolite was determined as the same one in human by comparison of their liquid chromatograph and mass spectrum. Although the yield was very lowly, the hydroxylation reaction was fit for enzymatic feature and can be used for further enzymatic study. 2. Study on the microbial transformation of rneloxicaii By screening microorganisms, we obtained a strain 0247-9-I from soil, which can transform meloxicam into the objective hydroxylation metabolite that is the same as the one found in human urine and rat liver microsomes. By NMR method, the metabolite was identified as 5?hydroxymethyl meloxicam. We also found that the yield was relatively high when the pH was 5.5, the substrate concentration was 0.05%(w/v), the transformation time was 6d. 3. Study on the microbial transformation of isovalertatins Isovalertatins, which are homologous complex of pseudo- oligosaccharides and used as cc-amylase inhibitor, were investigated by microbial transformation systems. It was found that many bacteria had no activity to metabolize isovalertatins in this article, only Bacillus stearothermophilus can transform isovalertatins into new compounds with structural differences. It was also found that many fungi, especially strain 2829, could hydrolyze a-i ,4-glycosidic bonds of isovalertatins from non- reducing end into homologues with lower molecular masses. The metabolic process of isovalertatins and their components was studied by the strain 2829, and the enzymatic feature was discussed. 4. Study on the metabolisms of isovalertatins by enzymatic methods The metabolisms of isovalertatins were studied by enzymatic methods. We found that the hydrolysis speed was very fast, but the enzymatic hydrolysis couldn't give us enough messages about the metabolic middle process. The microbial transformation is a good method that is suitable for drug metabolism studies in vitro.