Okada H
Pharmaceutical Business Development (DDS Research Laboratories), Takeda Chemical Ind., Ltd., 2-17-85 Juso-honmachi, Yodogawa, Osaka 532, Japan
Adv Drug Deliv Rev. 1997 Oct 13;28(1):43-70. doi: 10.1016/s0169-409x(97)00050-1.
The biodegradable polymers poly(lactic/glycolic acid) (PLGA) and poly(lactic acid) (PLA) were used as wall materials in the preparation of microspheres (msp) containing the LH-RH superagonist leuprorelin (leuprolide) acetate. A novel W/O/W emulsion-solvent evaporation method was devised for the preparation of msp containing this water-soluble peptide. This method achieved high entrapment efficiency and sustained drug release over a long period predominantly due to polymer bioerosion. The msp are fine microcapsules with polycores containing the peptide at a high concentration and are easily injectable through a conventional fine needle. Leuprorelin msp made with PLGA(75/25)-14,000 or PLA-15,000 released the drug in a zero-order fashion, maintained constant serum drug levels and attained persistent objective suppression of the pituitary-gonadal system ('chemical castration') over 1 or 3 months after i.m. or s.c. injection into animals. These results indicate that depot formulations may be potentially useful in the therapy of endocrine diseases in humans. In this paper, studies on the formulation, drug release and pharmacological effects in animals for these leuprorelin depot formulations are reviewed.
可生物降解聚合物聚（乳酸/乙醇酸）（PLGA）和聚乳酸（PLA）被用作制备含有促黄体激素释放激素（LH-RH）超级激动剂醋酸亮丙瑞林（亮丙瑞林）的微球（msp）的壁材。设计了一种新型的水包油包水（W/O/W）乳液-溶剂蒸发法来制备含有这种水溶性肽的微球。该方法实现了高包封率，并主要由于聚合物生物侵蚀而在很长一段时间内实现药物的持续释放。这些微球是具有多核的精细微胶囊，其中含有高浓度的肽，并且易于通过传统的细针注射。用PLGA(75/25)-14,000或PLA-15,000制成的亮丙瑞林微球以零级方式释放药物，维持恒定的血清药物水平，并在肌肉注射或皮下注射给动物后1或3个月内实现对垂体-性腺系统的持续客观抑制（“化学去势”）。这些结果表明，长效制剂可能对人类内分泌疾病的治疗具有潜在用途。本文综述了这些亮丙瑞林长效制剂在制剂、药物释放和动物药理作用方面的研究。
