Okada H, Heya T, Ogawa Y, Toguchi H, Shimamoto T
Pharmaceutics Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Pharm Res. 1991 May;8(5):584-7. doi: 10.1023/a:1015844421319.
Once-a-month injectable microspheres of leuprolide acetate prepared with copoly(DL-lactic/glycolic acid) using an in-water drying method were assessed for duration of the analogue release and pharmacological effects in rats after a single or repeated injection. The periodic challenge test revealed that a single injection of the microspheres caused a dramatic and persistent suppression of the ability of the pituitary-gonadal system to secrete gonadotropin and testosterone for over 5 weeks. The complete recovery of these functions was observed 10 weeks after the injection. The repeated injection of the microspheres at intervals of 2 or 4 weeks achieved persistent suppression of steroidogenesis after an initial transient flare-up and beneficially avoided the "acute-on-chronic response." This depot formulation is expected to assure patient compliance and produce stronger therapeutic effects than the daily solution.
采用水相干燥法制备的聚（DL-乳酸/乙醇酸）醋酸亮丙瑞林每月注射一次的微球，在单次或重复注射后，对大鼠体内类似物的释放持续时间和药理作用进行了评估。周期性激发试验表明，单次注射微球可导致垂体-性腺系统分泌促性腺激素和睾酮的能力受到显著且持久的抑制，持续时间超过5周。注射10周后观察到这些功能完全恢复。每隔2周或4周重复注射微球，在最初短暂的激增后实现了对类固醇生成的持续抑制，并有利地避免了“急性-on-慢性反应”。这种长效制剂有望确保患者的依从性，并产生比每日溶液更强的治疗效果。
