高浓度吡喹酮溶液的透皮吸收及对日本血吸虫病鼠的治疗试验

 目的制备高浓度吡喹酮溶液,初步考察其透皮吸收及对日本血吸虫病鼠的试验治疗效果。方法由试验考察了高浓度吡喹酮溶液的稳定性。用紫外可见分光光度计测定了吡喹酮在指定溶媒中不同温度下的溶解度。高效液相色谱法测定透皮到家兔血液中吡喹酮的浓度。用70,150,200 g·L^-1的吡喹酮溶液对人工感染日本血吸虫病鼠进行治疗试验。结果高浓度吡喹酮溶液具有很好的稳定性。在35～40℃之间,吡喹酮在指定溶媒中的溶解度迅速提高(由284 g·L^-1猛增到456 g·L^-1)。透皮给药比灌胃给药吸收速度快,AUC及ρ_max分别为灌胃的2.1和4.0倍。高浓度吡喹酮溶液透皮给药对日本血吸虫病鼠的治疗效果良好,减虫率可达100%。结论高浓度吡喹酮溶液有望成为吡喹酮的新型透皮给药制剂。

Study on Transdermal Absorption of Praziquantel Solution at High Concentration and Its Worm-Reduction Effect on Schistosomiasis Japonicum in Mice

OBJECTIVE To prepare praziquantel solution at high concentration and to investigate its transdermal delivery and worm-reduction effect on Schistosomiasis japoricum in mice.METHODS The stability of the solution was evaluatad by experiments.The solubility of praziquantel solution at different temperature was measured by UV spectrophotometer.The praziquantel concentrations in rabbit plasma were determined by HPLC.The praziquantel solution of 70,150,200 g·L^-1,were applied to the experimental therapy of Schistosomiasis japonicum in mice.RESULTS The praziquantel solution at high concentration showed good stability.From 35 to 45 ℃, there was a great change in the solubility of praziquantel in the solvent(284 g·L^-1→456 g·L^-1).The absorption rate of transdermal delivery was faster than that of oral administration.The AUC and ρ^max of the former was as 2.1 times and 4.0 times as oral administration.The praziquantel solution reached prefect therapy efficacy with the worm-reduction of 100%. CONCLUSION The solution containing high praziquantel concentration may be a promising vehicle for the transdermal delivery of praziquantel.