Preparation Of Artemisinin Solid Dispersion And Chrysosplenetin,Influences The Resistant Of Artemisinin

The preparation technology of Artemisinin solid dispersions(ART SDs)was studied and the process parameters were determined in this experiment.A preliminary exposition indicates that the mechanism of artemisinin resistance of non-antimalarial component chrysosplenetin in the artemisinin industrial waste,which is mediated by the transporter.It implies an important foundation for finding artemisinin resistant small molecule inhibitors.A UV spectrophotometric method was established to determine the content of artemisinin solid dispersions,and the paddle method was used to determine its dissolution.The solvent method was chosen as the preparation method of artemisinin solid dispersions.Based on dissolution as the evaluation index,this paper studied influence of the single-factor screening of the carrier types,drug-carrier ratio,agitating time,solvent dosaget on the solid dispersions of dissolution and determines the best preparation technology.Artemisinin,soy lecithin,PVPk30,PEG6000,physical mixture,solid dispersions were characterized by a combination of differential scanning calorimetry(DSC)and infrared spectroscopy(IR).Final formulation: artemisini-soy lecithinPVPk30=1:1:7,20 mLof absolute ethanol solvent,stirred for 30 min,and dried at 50 ? for 24 h.The phase identification for solid dispersions shows that the hydrogen bond produced in drug and carrier,and novel amorphous status formed by using.Using blood transmission of plasmodium berghei,establish the artemisinin sensitive and resistant mice model,investigate the antimalarial activity of mice in different drug treatment groups of artemisinin,artemisinin solid dispersions,artemisinin solid dispersions and acetone layer,chrysosplenetin,artemisininsolid dispersions and chrysosplenetin(1:2)were given to the mice.RT-qPCR was used to investigate the expression level of MRP(1?2?4?5)/ABCC1 ? ABCC2 ? ABCC4 ? ABCC5 mRNA.The parasitism rate of artemisinin in the resistant mice model was higher than that of the sensitive mice,but the inhibition rate was lower than that of the sensitive group;There was no antimalarial activity in the sensitive animal models,but the parasitism rate of the resistant mice was significantly reduced and the inhibition rate increased significantly.Artemisinin for seven consecutive days can significantly increase MRP2/ABCC2 mRNA expression,chrysosplenetin alone group and combination group can significantly reversed by the artemisinin induced increase of MRP2 gene expression level.In this experiment,We find a simple preparation process of Artemisinin solid dispersions(ART SDs),which significantly improves the dissolution rate of artemisinin and solves the problem of poor water solubility of artemisinin.Discover the significant down-regulation of MRP2/ABCC2 mRNA expression level by chrysosplenetin is one of the important mechanisms to reverse artemisinin resistance.