彭锐等

[摘要] 目的 制备泊那替尼纳米混悬剂冻干粉，并对其冻干保护剂、载药量及稳定性进行考察。 方法 采用溶剂蒸发技术制备泊那替尼纳米混悬剂冻干粉，利用激光纳米粒度仪、透射电镜对其粒径及形态进行表征，筛选最佳冻干保护剂，利用高效液相色谱法对其载药量和稳定性进行考察。 结果 泊那替尼纳米混悬剂冻干粉复溶后平均粒径为（92.2±5.6） nm，多分散指数为0.29±0.65，且形态圆整，分布均匀；以10%乳糖为冻干保护剂制得冻干粉的性质最佳；高效液相色谱法测得泊那替尼平均载药量为（16.3±0.8）%，稳定性较好。 结论 泊那替尼纳米混悬剂冻干粉制备方法简便，有望成为泊那替尼的新型纳米给药系统。

[关键词] 泊那替尼；纳米混悬剂；冻干粉；载药量；稳定性

[中图分类号] R927.1 [文献标识码] A [文章编号] 1673-7210（2015）09（a）-0031-05

[Abstract] Objective To prepare Ponatinib Nanosuspension Lyophilized Power and investigate the cryoprotector， drug loading and stability. Methods Ponatinib Nanosuspension Lyophilized Power was prepared by solvent evaporation technology， the particle size and morphology were characterized by laser nanometer particle sizer and transmission electron microscopy （TEM）. The optimal cryoprotector was selected， the drug loading and stability of Ponatinib Nanosuspension Lyophilized Power were determined by HPLC. Results The mean diameter of redissolved Ponatinib Nanosuspension Lyophilized Power was （92.2±5.6） nm， with polydisperse index of 0.29±0.65. TEM images showed spherical shape and uniform distribution. The nanosuspension which was lyophilized with 10% lactose presented optimal properties. The mean drug loading of Ponatinib Nanosuspension Lyophilized Power determined by HPLC was （16.3±0.8）%， with a good stability. Conclusion The preparation method of Ponatinib Nanosuspension Lyophilized Power is simple， which promises to be a novel nanometer drug delivery system for injection of Ponatinib.

[Key words] Ponatinib； Nanosuspension； Lyophilized power； Drug loading； Stability

泊那替尼是酪氨酸激酶抑制剂，对费城染色体和酶蛋白激发生成的所有野生和突变形式的酪氨酸激酶均有阻断作用。对第一代和第二代酪氨酸激酶抑制剂均能产生抵抗或耐药，如伊马替尼、达沙替尼、尼莫替尼等，其中效果最显著的是对T315I基因突变型有直接的抵抗作用[1]。慢性粒细胞白血病患者，无论处于慢性期还是急性期服用泊那替尼后疗效均明显。研究发现，泊那替尼的药理作用主要是对BCR-ABL基因的抑制作用，并且作用范围广泛[2]。这一突破性的发现在很大程度上促使泊那替尼成为治疗慢性粒细胞白血病和费城染色体阳性的急性淋巴细胞白血病的一线药物。……