Optimum formulation for sustained-release insulin.
Optimum formulation for sustained-release insulin.
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DOI：
10.1016/j.ijpharm.2003.10.027
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发表时间：
2004-03
影响因子：
5.8
通讯作者：
M. Takenaga;Y. Yamaguchi;A. Kitagawa;Y. Ogawa;S. Kawai;Y. Mizushima;R. Igarashi
中科院分区：
文献类型：
--
作者：
M. Takenaga;Y. Yamaguchi;A. Kitagawa;Y. Ogawa;S. Kawai;Y. Mizushima;R. Igarashi
我们的目的是制备一个最佳的处方，用于缓释制剂的胰岛素使用可生物降解的聚合物组成的共聚（d，l-乳酸/乙醇酸）（PLGA）（L/G比：50/50）。将含3%胰岛素的各种PLGA微囊（250 U/kg）单次皮下注射给链脲佐菌素诱导的糖尿病大鼠，并监测血浆胰岛素水平。获得了以下结果。(1)甘油和水是制备可重现注射制剂的合适添加剂。(2)锌化合物的添加是必不可少的，以减少胰岛素的快速释放和六倍摩尔过量的ZnO胰岛素是可取的。(3)胰岛素颗粒大小顺序为人胰岛素>冻干人胰岛素>无锌人胰岛素。无锌胰岛素在控制快速释放方面与冻干胰岛素相似，因此较小的粒度是必需的。(4)微囊的大小也影响胰岛素的释放。对于较大的微囊（约30μm），存在逐渐释放和显著的胰岛素释放第二相，而较小的微囊不允许持续释放。微胶囊尺寸的一些变化有助于更恒定和持续的释放。(5)基于体内胰岛素释放曲线，PLGA的合适分子量为6000左右。从该制剂中提取的胰岛素的生物活性与正常胰岛素的生物活性相似。这些实验使我们能够制备理想的缓释胰岛素制剂。
Our aim was to prepare an optimum formulation for a sustained-release preparation of insulin using biodegradable polymer composed of co-poly(d,l-lactic/glycolic) acids (PLGA)(L/G ratio: 50/50). Various kinds of PLGA microcapsules containing 3% insulin were administered subcutaneously (250U/kg) as a single dose to rats with streptozotocin-induced diabetes, and plasma insulin levels were monitored. The following results were obtained. (1) Glycerin and water were suitable additives to prepare a reproducible injectable formulation. (2) Addition of zinc compounds was essential to diminish rapid insulin release and six-fold molar excess of ZnO to insulin was desirable. (3) The size of insulin particles showed the following order: human insulin>lyophilized human insulin>Zn-free human insulin. Zn-free insulin was similar to lyophilized insulin with respect to control of rapid release, so a smaller particle size was essential. (4) The size of the microcapsules also affected the release of insulin. With larger microcapsules (∼30μm), there was gradual release and a significant second phase of insulin release, while smaller microcapsules did not allow sustained release. Some variation in microcapsule size contributed to more constant and sustained release. (5) Based on the insulin release profile in vivo, a suitable molecular weight for PLGA was around 6000. The biological activity of insulin extracted from the formulation was similar to that of normal insulin. These experiments allowed us to prepare a desirable sustained-release insulin formulation.