Cotes P M, Bartlett W A, Gaines Das R E, Flecknell P, Termeer R
J Endocrinol. 1980 Nov;87(2):303-12. doi: 10.1677/joe.0.0870303.
Different methods for administration of human growth hormone (hGH) have been examined with a view to efficient use of the limited amounts of hGH at present available for clinical use. We found that in hypophysectomized rats (1) hGH administered by continuous subcutaneous infusion induced a greater increase in body weight (referred to throughout as growth) than hGH administered by intermittent (daily) injection and (2) intermittent injections of hGH dissolved in 16% gelatin induced more growth than hGH dissolved in a glycine buffer. It was further found that (1) hGH dissolved in 16% gelatin compared with hGH dissolved in a glycine buffer induced lower maximal levels of immunoreactive plasma hGH and between 7 and 9 h after treatment higher plasma levels when injected subcutaneously in rabbits, (2) 125I-labelled hGH added as a tracer to hGH in gelatin was removed more slowly from subcutaneous injection sites in rabbits than 125I-labelled hGH given with hGH in glycine buffer and (3) changes in the ratio of hGH to gelatin had little effect on the time-course of plasma levels of hGH in the rabbit. Addition of the protease inhibitors aprotinin or 6-aminohexanoic acid, to injection of hGH in gelatin or glycine did not induce any consistent increase in plasma levels of hGH.
为了有效利用目前临床可用的有限量人生长激素(hGH),人们对其不同的给药方法进行了研究。我们发现,在垂体切除的大鼠中:(1)连续皮下输注给予hGH比间歇性(每日)注射给予hGH能使体重增加更多(以下全程称为生长);(2)溶解于16%明胶中的hGH间歇性注射比溶解于甘氨酸缓冲液中的hGH能诱导更多的生长。进一步发现:(1)与溶解于甘氨酸缓冲液中的hGH相比,溶解于16%明胶中的hGH皮下注射给兔后,诱导的免疫反应性血浆hGH最高水平较低,且在治疗后7至9小时血浆水平较高;(2)作为示踪剂添加到明胶中hGH的125I标记的hGH从兔皮下注射部位清除的速度比与甘氨酸缓冲液中hGH一起给予的125I标记的hGH慢;(3)hGH与明胶比例的变化对兔血浆hGH水平的时间进程影响很小。在明胶或甘氨酸中注射hGH时添加蛋白酶抑制剂抑肽酶或6-氨基己酸,并未导致hGH血浆水平持续升高。