目的 建立制备胸腺五肽纳米粒的方法并对其处方进行优化,为制备符合要求的压力定量吸入气雾剂奠定基础.方法 将胸腺五肽、卵磷脂、乳糖溶于叔丁醇-水的混合溶剂中,冷冻干燥,将冻干产物用异丙醇混悬,离心除去多余的卵磷脂以得到纯药物纳米粒.采用星点设计-效应面法对其中水、卵磷脂、胸腺五肽的用量进行优化,因胸腺五肽的含量受此处方影响不显著,所以只选取纳米粒的粒径、粒径分布为结果考察指标.结果 最优处方:水∶叔丁醇、卵磷脂∶叔丁醇、胸腺五肽∶水的比例分别为0.5(mL∶mL) 、213.5(mg∶mL) 、17.0(mg∶mL),即水的用量1.5 mL、卵磷脂的用量640.57 mg、胸腺五肽的用量25.57 mg、叔丁醇的用量3.0 mL.按此处方制备的纳米粒粒径在150 nm左右,多分散系数为0.1以下,含量均能保持在98％以上.结论 采用该方法制备胸腺五肽纳米粒,质量佳,重现性好,方法简便,具有良好的应用前景.%Objective A noveJ bottom-up process was developed to produce nanoparticles containing thymopentin and the formulation was optimized to produce desirable nanoparticles for development of pressed metered dose inhaler ( pMDI) of thymopentin( TP-5 ). Methods A solution of TP-5 , lecithin and lactose in tert-butyl alcohol( TBA )/ water co-solvent system was freeze-dried to generate nanoparticles and residual lecithin was washed off in lyophilizate through eentrifugation. Formulation parameters such as lecithin content in organic phase,water content in TB A/water co-solvent, and TP-5 content in water were optimized with the central composite design-response surface methodology. As the retained content of TP-5 in nanoparticles did not significantly vary with the above formulation parameters, only particle size and size distribution of TP-5 nanoparticles was taken as response parameters. Results The ratios of water to TBA, lecithin to TBA and TP-5 to water in the optimum formulation were separately 0.5(mL: mL) ,213. 5 (mg: ml,) ,17.0(mg: mL) ,by which TP-5 nanoparticles with about 150 nm of the mean particle size and 0. 1 of polydispersity index(PI) and the retained content of TP-5 above 98% were gained. Conclusion The novel bottom-up process was demonstrated to produce TP-5 nanoparticles with process simplicity and convenience, good reprodueibility as well as high-product quality.
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