Takada Shigeyuki, Kurokawa Tomofumi, Misaki Masafumi, Taira Keiko, Yamagata Yutaka
Drug Formulation Research Laboratories, Takeda Chemical Industries, Ltd, 2-17-85, Juso-honmachi, Yodogawa-ku, Osaka 532-8686, Japan.
J Pharm Pharmacol. 2003 Jul;55(7):951-61. doi: 10.1211/0022357021323.
A new animal model to evaluate the long-term growth rate produced by a sustained-release formulation of recombinant human growth hormone (rhGH) over one month was developed and the usefulness of our microcapsule formulations was demonstrated in this model. Long-term pharmacological effects by subcutaneous injection of microcapsules for sustained release of rhGH were evaluated in hypophysectomized (Hpx) rats treated with immunosuppressive agent along with hormone supplement. Copoly(DL-lactic/glycolic)acid (PLGA) microcapsules for sustained release of rhGH, a two-week sustained-release formulation (rhGH-SR-2W) and a one-month sustained-release formulation (rhGH-SR-1M), were prepared by a solid-in-oil-in-water emulsion solvent evaporation technique. Body-weight gain, body-length gain and serum levels of rat insulin-like growth factor-I (rIGF-I) induced by subcutaneous injection of rhGH-SR were compared with those by daily injections of rhGH solution in Hpx rats for 35 days. Serum IGF-I levels in Hpx rats after the injection of rhGH-SR2W microcapsules were higher than those after daily injections of rhGH solution. Body-length gain, a new parameter, after single injection of rhGH-SR-1M microcapsules demonstrated the higher growth rate than that after daily injections of rhGH solution for 35 days. Thus, single injection of rhGH-SR microcapsules demonstrated long-term pharmacological effects greater than those by daily injections of rhGH solution in a newly developed model, immunosuppressed Hpx rats.
开发了一种新的动物模型，用于评估重组人生长激素（rhGH）缓释制剂在一个月内产生的长期生长速率，并在该模型中证明了我们微胶囊制剂的有效性。在用免疫抑制剂和激素补充剂治疗的垂体切除（Hpx）大鼠中，评估了皮下注射rhGH缓释微胶囊的长期药理作用。通过水包油包固乳液溶剂蒸发技术制备了用于rhGH缓释的聚（DL-乳酸/乙醇酸）共聚物（PLGA）微胶囊，一种两周缓释制剂（rhGH-SR-2W）和一种一个月缓释制剂（rhGH-SR-1M）。将皮下注射rhGH-SR诱导的体重增加、体长增加和大鼠胰岛素样生长因子-I（rIGF-I）血清水平与Hpx大鼠每日注射rhGH溶液35天的情况进行比较。注射rhGH-SR2W微胶囊后Hpx大鼠的血清IGF-I水平高于每日注射rhGH溶液后的水平。单次注射rhGH-SR-1M微胶囊后的体长增加（一个新参数）显示出比每日注射rhGH溶液35天更高的生长速率。因此，在新开发的免疫抑制Hpx大鼠模型中，单次注射rhGH-SR微胶囊显示出比每日注射rhGH溶液更大的长期药理作用。
