丁香苦苷单体与丁香苦苷 PEG－PLGA纳米粒在大鼠体内药动学比较研究

摘要

Objective:By finding the amount of syringopicroside in the rats'plasma,to make a comparative re-search between clove nucleoside monomers with anti-hepatitis B virus and nano-syringopicroside particles on pharmacokinetics subjects on rats.Methods:After injecting 40g/L of syringopicroside and syringopicroside PEG-PLGA-NPs into Wistar rats’ tail vein, find the density of the medicine in the plasma after different time points according to the HPLC rules.Use the 3p97 software to analyze and calculate the pharmacokinetic parameter.Results:The syringopicroside density appeared to be within the range of 0.01~100.30μg/L with a nice linear relation,the equation: Y =13250X +16364.Extraction recovery rate:above 85%, RSD below 5%.The pharmacokinetic parameter showed the process of clove nucleoside monomers and syringopicroside PEG-PLGA-NPs in the rats body fitted the two compartment models.The T1/2αand T1/2βin syringopicroside PEG-PLGA solutions were 1.58 times and 11.46 times relative to the syringopicroside solution.The AUC was 2.40 times the one of syringopicroside solution, while the plasma clearance of syringopicroside PEG-PLGA solution was about 0.42 times the one of syringopicroside solution.Conclusion:The experimental data from this research make a great contribution to the further study on the clinical application of syringopicroside.%目的：通过测定大鼠血浆中丁香苦苷的含量，对具有抗乙肝病毒的丁香苦苷单体和丁香苦苷PEG－PLGA纳米粒进行大鼠体内药动学比较研究。方法：Wistar大鼠尾静脉注射（40g／L）给予丁香苦苷和丁香苦苷PEG－PLGA－NPs后， HPLC法测定不同时间点测定血浆中的药物浓度，所得数据用3p97软件分析求算药动学参数。结果：丁香苦苷浓度在0．01～100．30μg／L范围内线性关系良好，回归方程为Y＝13250 X＋16364，提取回收率在85％以上、RSD低于5％。药动学参数表明丁香苦苷单体与丁香苦苷PEG－PLGA－NPs在大鼠体内过程均符合二室模型，丁香苦苷PEG－PLGA溶液的T1／2α和T1／2β是丁香苦苷溶液的1．58倍和11．46倍，AUC是丁香苦苷溶液的2．40倍，血浆清除率约为其0．42倍。结论：本实验研究数据为进一步研究丁香苦苷的临床应用提供了重要的实验数据。