Toguchi H, Ogawa Y, Okada H, Yamamoto M
Pharmaceutics Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Yakugaku Zasshi. 1991 Aug;111(8):397-409. doi: 10.1248/yakushi1947.111.8_397.
Leuprorelin (leuprolide, D-Leu6-(des-Gly10-NH2)-LH-RH ethylamide) acetate is a super-active agonist of luteinizing hormone-releasing hormone (LH-RH). We developed once-a-month injectable microcapsules of this agonist by our novel in-water drying method. This depot formulation can release the drug at an apparent zero-order rate over one month with bioerosion of copoly (lactic/glycolic acid) utilized as a wall material of the polycore microcapsules. A dramatic prolonged depression of pituitary-gonadal axis, chemical castration, was achieved by the once-a-month injection in experimental animals; it expects a reliable efficacy for treating hormone-dependent prostatic, breast cancers and endometriosis. Studies on the dosage design of this new delivery system of leuprorelin are summarized.
醋酸亮丙瑞林（亮丙瑞林，D-亮氨酸6-（去甘氨酸10-氨基）-促黄体生成素释放激素乙酰胺）是促黄体生成素释放激素（LH-RH）的超活性激动剂。我们通过新型水相干燥法研制出了这种激动剂的每月一次注射用微胶囊。这种长效制剂可以通过作为多核微胶囊壁材的聚（乳酸/乙醇酸）共聚物的生物侵蚀作用，以明显的零级速率在一个月内释放药物。通过在实验动物中每月一次注射，实现了垂体-性腺轴的显著长期抑制，即化学去势；预计其对治疗激素依赖性前列腺癌、乳腺癌和子宫内膜异位症具有可靠疗效。本文总结了关于这种亮丙瑞林新给药系统剂量设计的研究。
