【作者】 鲍凤娟；

【导师】 苟国敬；

【作者基本信息】 宁夏医科大学 ， 药理学， 2010， 硕士

【摘要】 1“右旋糖酐-磁性LDH-氟尿嘧啶”转运模型的体内磁靶向性研究以“右旋糖酐-磁性LDH-氟尿嘧啶”超分子组装为磁靶向给药系统,研究三聚体模型在大鼠体内各组织中药物转运分布的磁靶向性。建立高效液相色谱内标法,用于测定给药后大鼠体内各组织的药物分布浓度;用紫外分光光度法、原子吸收法及等离子体发射光谱法测定给药后大鼠各组织中铁的浓度分布特征。方法学研究表明,高效液相色谱内标法回收率高、精密度好,适合模型运载和释放到动物组织中的氟尿嘧啶的定量检测;铁染色及定量分析方法能较好地评价载体铁的体内分布情况。经腹腔注射给药后,在不同部位给予磁场干预,实验结果显示,设立磁场的部位(背右侧及头部)药物浓度明显高于远离磁场部位的组织,验证了三级超分子药物转运模型的体内磁靶向性。在外磁场作用下“磁靶向LDH-氟尿嘧啶-右旋糖酐”三级复合物能在动物体特定部位浓集,表现良好的磁靶向特异性。2“右旋糖酐-磁性LDH-氟尿嘧啶”转运模型的体内缓释性研究建立给药后大鼠血浆5-Fu浓度测定的HPLC内标法,通过DAS2.0软件分析药动学实验数据,研究“右旋糖酐-磁性LDH-氟尿嘧啶”转运模型在大鼠体内的药物缓释效果。结果表明,原药组的药时曲线为单峰、二室模型,超分子转运模型组表现多峰、多房室模型过程,第一个药峰呈二室模型、其余各峰为一室模型;原药组的达峰时间为10分钟,而LDH组的首次达峰时间为6小时,是原药组的36倍;原药组5-Fu的消除半衰期为1.16小时,LDH组首峰的半衰期为3.53小时,是5-Fu原药的3.06倍。在“右旋糖酐-磁性LDH-氟尿嘧啶”转运模型下5-Fu的药代动力学行为改变,表现了良好的体内缓释作用效果。更多还原

【Abstract】 1 Study on targeted-specificity of Dextran-Magnetic LDH-Fluorouracil model in vivoWith a supermolecule model of dextran-magnetic LDH-fluorouracil as magnetic targeted drug delivery system, the magnetic targeting drug bio-distribution of this transfering model in rats was studied. A HPLC internal labeling method had been established to determine the concentration of 5-Fu in tissues. Ultraviolet spectro-photometry, flame atomic absorption spectrometer and the inductively coupled plasma were used to detect the iron concentration in tissues, and Prussian blue iron staining was employed for observing the difference of iron bio-distribution in tissues. The results shown that the established HPLC internal standard method had good recovery rate and precision, after administration via peritoneal injection, the drug concentration were significant higher in both right back and head where the magnetic field had been set up, than in other parts which were far away from the magnetic field. Drug concentration distribution shown statistical significance, and proved that the ternary composite model had an ideal magnetic targeted transfering effect. The data reported here suggest that under the influence of an external magnetic field, the Dextran-Magnetic LDH-Fluorouracil can be significantly enriched in the target area, and show good magnetic targeted-specificity.2 Study on intravital sustained-release effect of Dextran-Magnetic LDH- Fluorouracil modelWith an objective to study the sustained-release function of the transfer model of Dextran-Magnetic LDH-Fluorouracil in rats, the HPLC internal standard method had been established to test the plasma concentrations of 5-Fu in rats after administration, and the pharmacokinetic experimental data were analysed with the software of DAS 2.0. The results demonstrated that the concentration-time curve of fluorouracil group shown single peak with a two-compartment model, but that of the LDH group shown multi-peak with a multi-compartment model, in which the 1st peak shown two-compartment model, while others shown single compartment model. The fluorouracil group presented drug peak at 10 minutes, but LDH group presented the 1st drug peak at 6h which was 36 times of that of fluorouracil group; the half time of fluorouracil group was 1.16h, but that of LDH group was 3.53h which was 3.06 times of that of fluorouracil group. The data reported here suggest that Dextran-Magnetic LDH-Fluorouracil transfer model can change pharmacokinetic action of 5-Fu after injection into animals, and will show good intravital sustained-release effect in vivo.更多还原