Bokser L, Schally A V
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Endocrinology. 1988 Oct;123(4):1735-9. doi: 10.1210/endo-123-4-1735.
Recently, we have developed a long-acting delivery system for our somatostatin (SS) analog RC-160 based on injectable microcapsules in poly-(D,L-lactide-coglycolide). We studied the capacity of this formulation to repeatedly block the GH secretion induced by administration of GRF-(1-29)NH2 (GRF) on different days. Male rats anesthetized with pentobarbital were injected iv with 2.5 micrograms/kg BW GRF-(1-29)NH2 or saline. Five minutes later, blood samples were taken for GH measurement, and the animals were injected im with RC-160 microcapsules at a dose calculated to release 25 micrograms/day of the analog for 7 days or with the vehicle. The GRF stimuli were repeated 48 h, 96 h, and 8 days after administration of SS analog in microcapsules. GRF administration increased GH levels at the four times tested (P less than 0.01) in the control group injected with vehicle, while RC-160 microcapsules inhibited the GH response for more than 96 h (P less than 0.01). The GH levels augmented by pentobarbital were also decreased by the RC-160 microcapsules (P less than 0.01). Animals treated with microcapsules showed smaller increases in their body weight than untreated rats (P less than 0.05). We also investigated the effect of RC-160 microcapsules on hyperprolactinemic female rats implanted with pituitary glands under the kidney capsules. High PRL levels in rats bearing pituitary grafts showed a significant decrease when measured 4 days after the administration of RC-160 microcapsules. These results demonstrate the efficacy of the long-acting delivery system of the SS analog RC-160 and suggest the possible clinical usefulness of this formulation for lowering GH and PRL levels.
最近，我们基于聚（D，L-丙交酯-共乙交酯）中的可注射微胶囊，为我们的生长抑素（SS）类似物RC-160开发了一种长效递送系统。我们研究了该制剂在不同日期反复阻断由注射生长激素释放因子（GRF）-（1-29）NH₂（GRF）诱导的生长激素（GH）分泌的能力。用戊巴比妥麻醉的雄性大鼠静脉注射2.5微克/千克体重的GRF-（1-29）NH₂或生理盐水。五分钟后，采集血样进行GH测量，然后给动物肌肉注射RC-160微胶囊，剂量按计算可在7天内每天释放25微克该类似物，或注射赋形剂。在微胶囊中给予SS类似物后48小时、96小时和8天重复进行GRF刺激。在注射赋形剂的对照组中，在四次测试时注射GRF均使GH水平升高（P<0.01），而RC-160微胶囊抑制GH反应超过96小时（P<0.01）。RC-160微胶囊也降低了由戊巴比妥引起升高的GH水平（P<0.01）。用微胶囊处理的动物体重增加幅度小于未处理的大鼠（P<0.05）。我们还研究了RC-160微胶囊对肾被膜下植入垂体的高催乳素血症雌性大鼠的影响。在给予RC-160微胶囊4天后测量，垂体移植大鼠的高催乳素水平显著降低。这些结果证明了SS类似物RC-160长效递送系统的有效性，并表明该制剂在降低GH和催乳素水平方面可能具有临床应用价值。
