目的 制备温度敏感型盐酸小檗碱眼用原位凝胶。方法 以泊洛沙姆407和188为温敏材料,采用搅拌子法测定溶液-凝胶相转变温度优化处方;采用高效液相色谱法测定盐酸小檗碱。结果 温度敏感型原位凝胶的胶凝温度随泊洛沙姆407浓度增大而降低,随泊洛沙姆188浓度增加先升高后降低,模拟泪液的稀释可使胶凝温度升高,建立了泪液稀释后相变温度与泊洛沙姆浓度的拟合方程,经Design-Expert软件优化盐酸小檗碱温敏型眼用原位凝胶的处方为25%泊洛沙姆407和4.19%泊洛沙姆188;优化处方在29.7℃为自由流动的液体,泪液稀释后在34.5℃能够发生相变形成凝胶。结论 该眼用温度敏感凝胶符合眼部应用要求,体现出良好的眼部应用前景。

Objective To prepare a thermosensitive in situ gel system containing berberine hydrochl-ride for ocular use.Methods The in situ thermosensitive gel system of herherine hydrochloride was prepared by Poloxamer 407(P407) and Poloxamer 188(P188) as thermosensitive materials,the formulation was optimized by determining solutiorrgelation conversion temperature by using stirring method The content of herherine hydrochloride was determined by HPLC.Results The gelation temperature of in situ thermosensitive gel containing berberine hydrochloride formulations lowered as the P407 concentration increased,as the P188 concentration increased gradually the gelation temperature initially increased to maximum and then decreased.The gelation temperature all increased after simulated tear fluid(STF) dilution.The fitted equation was established for the gelation temperature with the concentration of Poloxamer solutions after diluted by STF.An optimized formulation by Design-Expert software was freely flowing liquid at 29.7 ℃ and convert to a firm gel at 34.5 ℃ after STF diluted.Conclusion In situ thermosensitve gel system complies with the requirement for ophthalmic application and shows great potential in ocular application.

山东省高等学校科技计划项目(J09LF76)