Wheaton J E, al-Raheem S N, Godfredson J A, Dorn J M, Wong E A, Vale W, Rivier J, Mowles T F, Heimer E P, Felix A M
University of Minnesota, St. Paul 55108.
J Anim Sci. 1988 Nov;66(11):2876-85. doi: 10.2527/jas1988.66112876x.
Osmotic pumps were evaluated for 7-d delivery of growth hormone-releasing factor (GRF). In Exp. 1, 12 steers weighing 253 kg received hGRF(1-29)NH2 in H2O at rates of 0, 3, 30 and 300 pmol.h-1.kg-1. Pumps were implanted s.c. on d 0 and removed at 1200 on d 7. Blood samples were drawn at 20-min intervals from 0800 to 1200 on d -1, 1, 3, 5, 7 and 9. Growth hormone levels were not altered by GRF treatment (P greater than .05). Solubility and volume limitations render hGRF(1-29)NH2 delivery via osmotic pumps problematical. Flow rate and duration of release of dimethyl sulfoxide (DMSO):H2) (1:1) from osmotic pumps incubated in vivo and in vitro were found to be consistent with manufacturer's specifications. Two hGRF(1-29) analogues, Ro23-7863 and 4SG-29, were dissolved in DMSO:H2O. In Exp. 2, six 222-kg steers had pumps implanted and blood samples were taken as in Exp. 1. Three steers received each analogue at a rate of 300 pmol.h-1.kg-1. Analogues had similar GH-releasing ability and GH levels differed (P less than 0.001) among days, being approximately fourfold higher on d 3, 5 and 7 than on d -1, 1 and 9. Residual analogue solutions retained full bioactivity after 7-d implantation, and in vitro biopotencies of Ro23-7863 and 4SG-29 were similar (Exp. 3). In Exp. 4, 15 wethers (means = 31.3 kg) received osmotic pumps delivering 0, 3, 15, 75 and 300 pmol.h-1.kg-1 Ro23-7863 in DMSO:H2O for 7 d. Lambs were bled at 0800 and 1400 from d -1 to 8. The latter two doses increased (P less than .01) mean GH levels 2.7- and 4.3-fold over those in control animals during the treatment period. Results demonstrate that increased GH secretion can be elicited in steers and wethers for 1 wk by continuous s.c. infusion of GRF analogues utilizing osmotic pumps.
对渗透泵进行了评估，以实现生长激素释放因子（GRF）的7天递送。在实验1中，12头体重253千克的阉牛以0、3、30和300皮摩尔·小时⁻¹·千克⁻¹的速率接受溶于水的人GRF(1-29)NH₂。在第0天皮下植入泵，并在第7天12:00取出。在第-1、1、3、5、7和9天，从08:00到12:00每隔20分钟采集血样。GRF处理未改变生长激素水平（P大于0.05）。溶解度和体积限制使得通过渗透泵递送hGRF(1-29)NH₂存在问题。发现体内和体外孵育的渗透泵中二甲亚砜（DMSO）:水（1:1）的流速和释放持续时间与制造商的规格一致。两种hGRF(1-29)类似物Ro23-7863和4SG-29溶于DMSO:水。在实验2中，6头体重222千克的阉牛植入泵，并按实验1的方式采集血样。3头阉牛以300皮摩尔·小时⁻¹·千克⁻¹的速率接受每种类似物。类似物具有相似的生长激素释放能力，且生长激素水平在不同天数间存在差异（P小于0.001），在第3、5和7天比在第-1、1和9天高约四倍。残留的类似物溶液在植入7天后仍保留全部生物活性，且Ro23-7863和4SG-29的体外生物效价相似（实验3）。在实验4中，15只阉羊（平均体重 = 31.3千克）接受以0、3、15、75和300皮摩尔·小时⁻¹·千克⁻¹的速率在DMSO:水中递送Ro23-7863的渗透泵，持续7天。从第-1天到第8天，每天08:00和14:00对羔羊进行采血。后两个剂量在治疗期间使平均生长激素水平比对照动物提高了2.7倍和4.3倍（P小于0.01）。结果表明，通过使用渗透泵连续皮下输注GRF类似物，可使阉牛和阉羊的生长激素分泌增加1周。
