[关键词]
[摘要]
目的 对制备的猫爪草提取物离子敏感型原位凝胶(RTRE-ISG)进行肺部滞留性、安全性及局部药物浓度的评价。方法 以海藻酸钠作为辅料,猫爪草提取物(70%乙醇)作为溶剂,在室温下磁力搅拌使其充分溶胀,制备得到RTRE-ISG。大鼠通过气管介入给药后,测定肺部灌洗液中的炎症因子和致纤维化因子水平,筛选出相对安全的处方;再采用Cy5.5作为荧光染料,借助小动物活体成像系统对RTRE-ISG肺部滞留性进行评价;最后运用改良肺泡灌洗技术,对大鼠肺部进行灌洗,测定局部药物浓度。结果 1%海藻酸钠RTRE-ISG在肺部安全性较好,荧光活体成像技术显示其可在肺部滞留120~144 h,肺部局部药物浓度的测定显示1%海藻酸钠RTRE-ISG在5 h释放达到峰值为5.24μg/mL,144 h药物浓度为0.08μg/mL。结论 RTRE-ISG在肺部可滞留120 h以上,可为中药治疗肺结核提供一种新型的缓释制剂。
[Key word]
[Abstract]
Objective To evaluate the pulmonary retention, safety, and local drug concentration of Ranuncoli Ternati Radix extracts-ion sensitive in situ gels(RTRE-ISG). Methods Sodium alginate as excipient, RTRE(70% ethanol) as solvent, it was swollen at room temperature using magnetic stirring to prepare RTRE-ISG which was administered via endotracheal tube to rats, The levels of inflammatory cytokines and fibrosis factors were detected in BALF to screen the relative safe priscription. Then using CY5.5 as fluorescent dye, the pulmonary retention of RTRE-ISG was evaluated with the aid of the small animal in vivo imaging system. In the end, the lung lavage was performed by using the improved alveolar lavage technique and the local drug concentration was determined. Results The safety of RTRE-ISG prepared by 1% sodium alginate was better, the retention time in lung was 120-144 h revealed by fluorescence in vivo imaging system. The results showed that the release of drug reached to a peak of 5.24μg/mL in 5 h after administration and 0.08μg/mL in 144 h after administration. Conclusion RTRE-ISG was good safety with the retention time in lung more than 120 h, which is a nevol sustained preparation of Chinese materia medica for the treatment of pulmonary tuberculosis.
[中图分类号]
[基金项目]
青海大学中青年基金项目(2012-QYY-1)