Study On The Construction And Pharmacokinetics Of Toad Pastry Extract Long Cycle Nanoparticle Liposomes System

Objective: In this study,the raw drugs of toad pastry were extracted and purified,and the main pharmacodynamic components of toad pastry poison base and lipid toad poison ligand were obtained.The main pharmacodynamic groups were divided into model drugs,long circulating nano-liposomes as carriers,and modern preparation techniques were used to develop their long-circulating nano-liposomes,and the physicochemical properties,the characteristics of in vitro release and pharmacokinetics and tissue distribution of the long circulating nano-liposomes were studied to provide new ideas for exploring drug liver targeted administration,new methods and technologies.Methods: : 1.On the basis of reference to the research results of the previous scholars,the methods of methanol extraction,chloroform extraction and silica gel column chromatography were used to purify 2 effective components of toad pastry poison base and lipid toad poison ligand,and the content of pharmacodynamic components was significantly improved to enhance the therapeutic effect.2.On the basis of single factor test,the long cycle nano liposomes of toad Pastry extract were prepared by thin film dispersion-high pressure homogenization method,the encapsulation rate was selected as the main index,and the optimum preparation prescription and technology of toad pastry extract long circulation nano-liposomes were designed by star-effect surface.3.The physical and chemical properties such as the appearance,particle size,zeta potential and so on were investigated and studied by transmission electron microscope,particle size analyzer and Zeta potentiometer in the long circulation nano liposomes of the prepared toad pastry extract.4.The release characteristics of the long circulating nano liposomes of toad pastry extract in vitro were investigated by forward dynamic dialysis method.5.The pharmacokinetics and tissue distribution of toad pastry extract common liposomes and toad pastry long circulating nano-liposomes in rats were studied by using Toad Pastry extract API as control.Result:.: 1.The optimum extraction and purification process of toad pastry: the ratio of diameter to column height was 2:14,the ratio of upper sample to ADsorbent was 1:7,the ratio of eluent cyclohexane-chloroform-ketone was 4:3:3,and the total content of toad poison ligand obtained by this purification process reached 65.58%.2.The best process for the preparation of toad pastry extract long cycle nano liposomes: lecithin and toad pastry extract ratio is 7:1,lecithin and cholesterol ratio is 3.5:1,ultrasonic time is 100 MPa min,hydration temperature is 60 ℃,the carrier medium is PH 6.8 PBS buffer,high pressure homogenous machine pressure is.3.Under this process condition,the encapsulation rate of toad poison ligand with toad pastry long circulating nano-liposomes was 85.12%,and the particle size 115 nm,zeta potential was-47.28 mv.4.The cumulative release rate of toad pastry APIs measured in ph 6.8 release media was released completely at the time of H,while the cumulative release rates of the long-cycle nano-liposomes of the toad pastry extract were 79.63% and 74.45%,respectively.5.The study of Pharmacokinetics showed that the toad pastry extract raw material solution Group,Common Liposomes Group and toad pastry extract long cycle nano-liposomes group were in line with the two-chamber model,and the t1/2β of common liposomes was 3.77 times times that of the control group of Toad Pastry API solution,and the long circulating nano-liposomes t1/ 2β was 8.76 times times the control group of raw drug solution.The total amount of drugs distributed by common liposomes in liver and lung organs in tissue distribution was 1.709 times times and 1.764 times times that of the control group of toad pastry Extract API,respectively,and the total number of drugs distributed in liver and lung viscera was 2.953 times times and 2.4714 times times that of the raw drug solution Group of toad pastry extract.This study shows that the effect of long circulation nano liposomes in vivo circulation and retention is better than that of ordinary liposomes,which is beneficial to the enrichment of drugs and has a more significant targeting effect.Conclusion: 1.In this study,the optimum preparation process was optimized by combining single factor test with star point-effect surface method.2.The method of high performance liquid chromatography(HPLC)for the determination of the blood concentration of toad pastry poison base and lipid toad poison ligand is simple and reasonable,which provides the theoretical basis and support for the safe use and research and development of toad pastry and toad pastry preparations.3.Toad Pastry Extract long circulating nano-liposomes can effectively transport drugs to the liver and lung lesions,to achieve slow release and targeted treatment purposes,for the exploration of drug targeted administration and new drug research and development to provide new ideas.