Study On Evaluation Of Safety And Pharmacolynamics Of Berberine Analogues

The mode of action of berberine,which is a protoberine alkaloid,was studied in bacteria and has hypolipidemic pharmacological activity,such as lowering blood sugar.C8 position of berberine to replace long-chain alkyl derivatives 8-Octyl berberine,8—16—alkyl berberine which is a series of derivatives screened the activity of two new compounds,in vitro antibacterial experiments,significantly higher than the activity of berberine,another hypolipidemic and hypoglycemic activity also was significantly higher than that of berberine.Is highly promising antimicrobial,hypolipidemic and hypoglycemic medicinal value,such as the new compounds. Indicates that with further development into the treatment of hypoglycemic drugs to lower blood pressure and good prospects.Pharmacokinetics of 8-Octyl berberine and 8-16-alkyl berberine in rabbits plasma were studied by the method of High Performance Liquid Chromatography,and acute toxicity test,sperm shape abnormality test and mouse bone marrow micronucleus test of its security evaluation.The results showed that:1.Studied of the pharmacokinetic of 8-Octyl berberine and 8-16-alkyl berberine in rabbits plasma.As a result,the standard curve range of 8-Octyl berberine was 0.013-2.525μtg/ml.The regression equation in rabbits was A=4.2650+ 17.5689C（n=6）,r=0.9998,The 8-16-alkyl berberine in rabbits are A=0.4708+25.5397（n=6）,r=0.994.Used in this experiment pretreatment of biological samples in research methods and HPLC rabbits administered 8-Octyl-berberine and 8 -16-alkyl berberine pharmacokinetics after the process of biological samples in a high recovery rate of pre-treatment methods,chromatographic separation selectivity.This method offers the accuracy,precision,high sensitivity,specificity and linear range of quantitative drug analysis which is suitable for the study of pahrmacikinetics.2.Rabbits were fed with drugs,HPLC determination of the rabbits at different time points in plasma 8-Octyl berberine and 8-16 alkyl berberine concentration,the data will be used MCPKP pharmacokinetic analysis software,to derive the relevant pharmacokinetics parameters.Drug in rabbits after gavage,8-Octyl berberine plasma drug concentration-time data in line with the absorption of a two-compartment open model.Showed that 8-Octyl berberine and 8-the concentration of 8-16 alkyl berberine absorption in the body for faster performance,broad distribution,the elimination of slow.3.This experiment on 8-Octyl berberine and 8-16 alkyl berberine toxicological safety evaluation. The results showed that 8-Octyl berberine LD₅₀lethal dose for half of the 534.3 mg/kg·bw,8-16 alkyl berberine LD₅₀lethal dose for half of the 761.3 mg/kg.bw,are low toxicity,light degree of accumulation of toxicity;mouse sperm abnormality test and bone marrow cell micronucleus test were negative.Description of 8-Octyl berberine and 8-16 alkyl berberine toxicological evaluation of the safety of the preliminary view that it is safe and reliable.