聚乙二醇修饰人参皂苷Rg1与原人参三醇的制备及其在胃中稳定性

目的:对人参皂苷Rg1与原人参三醇进行聚乙二醇修饰和表征,并考察PEG修饰前后人参皂苷Rg1在胃中的稳定性,比较修饰前后的变化。方法:选择单甲氧基聚乙二醇2000为原料,经过与丁二酸酐的催化酯化反应活化为单甲氧基聚乙二醇2000-琥珀酸单酯后,再分别与人参皂苷Rg1和原人参三醇分子耦联,并采用核磁共振等方法来表征合成产物;以大鼠为实验动物,采用UPLC方法分析样品,分别考察人参皂苷Rg1与PEG-Rg1在离体胃中的稳定性情况,并对修饰前后的变化进行比较。结果:成功合成了原人参三醇与人参皂苷Rg1的聚乙二醇修饰产物,产率分别为16.2%和17.5%;人参皂苷Rg1在胃中容易降解,2 h时降解73.2%,PEG-Rg1在2 h时仅降解18.2%,稳定性提高。结论:成功合成了人参皂苷Rg1与原人参三醇的聚乙二醇修饰产物。修饰之后可以大大提高人参皂苷Rg1在胃中的稳定性。

Preparation of PEGylated Ginsenoside Rg1 and Protopanaxatriol and its Stability in Stomach

Objective: To study the stability of Ginsenoside Rg1 and compare the changes of Ginsenoside Rg1 before and after PEGylation.Methods: Polyethylene Glycol Monomethyl Ether 2000(mPEG2000) was activated by catalyzed esterification reaction with succinic anhydride.Then the activated mPEG2000 was coupled to ginsenoside Rg1 and protopanaxatrio separately,the synthetic products were characterized by NMR method ect.The gastrointestinal stability of the ginsenoside Rg1 and PEGylated ginsenoside Rg1 were detected by UPLC analysis and the changes were compared before and after PEGylation.Results: The PEGylated products of ginsenoside Rg1 and protopanaxatrio were successfully synthetized and the rates were 16.2% and 17.5% respectively;the ginsenoside Rg1 was easier to be degraded in stomach,which was 73.2% in 2h,while the degradation of PEG-Rg1 was 18.2% in 2h,with higher stability.Conclusion: PEGylated ginsenoside Rg1 and protopanaxtriol are successfully synthetized,and the stability of ginsenoside Rg1 has improved greatly by PEGylation.