Effect of additives on insulin absorption from intratracheally administered dry powders in rats.
Effect of additives on insulin absorption from intratracheally administered dry powders in rats.
复制标题
添加剂对大鼠气管内给药干粉胰岛素吸收的影响。
DOI：
10.1016/s0378-5173(01)00662-7
复制
发表时间：
2001
影响因子：
5.8
通讯作者：
K. Danjo
中科院分区：
文献类型：
--
作者：
H. Todo;H. Okamoto;K. Iida;K. Danjo
肺对大分子的摄入很有用，大分子很难从肠道吸收。在本研究中，我们使用喷雾干燥技术制备了几种胰岛素干粉制剂，以考察添加剂对胰岛素吸收的影响。胰岛素的生物利用度通过血糖水平的变化来评估。不加任何添加剂的干粉中胰岛素的生物利用度高于pH 7.4溶液中的生物利用度。胰岛素与杆菌素1.4 mg/剂或Span 85 1.0 mg/剂溶液的绝对生物利用度接近100%。添加0.42 mg/剂量杆菌肽干粉的生物利用度为1.4 mg/剂量杆菌肽溶液的20%。含0.21 mg/剂Span 85的胰岛素干粉的生物利用度低于含0.1 mg/剂Span 85的胰岛素溶液。在本研究中，杆菌肽和Span 85在干粉中不如在溶液中有效。而柠檬酸在干粉中的降糖作用比在溶液中更有效。0.1ml中含有0.19mg柠檬酸的pH5.0和pH3.0溶液的绝对生物利用度分别为43%和57%，而含0.025 mg和0.036 mg/剂量柠檬酸的干粉的绝对生物利用度分别为42%和53%。此外，干粉的降糖作用持续时间较长，在240min时仍有降血糖作用，而在溶液中的降糖作用在180min时消失。当给予含0.036 mg/剂量柠檬酸的胰岛素干粉时，支气管肺泡灌洗液中反映急性毒性的敏感指标乳酸脱氢酶活性低于生理盐水，提示柠檬酸是一种安全的添加剂。因此，柠檬酸似乎是一种安全而有效的干粉胰岛素吸收促进剂。
The lungs are useful for administration of macromolecules, which are poorly absorbed from the intestine. In the present study, we prepared several dry powder formulations of insulin using a spray drying technique to examine the effect of additives on insulin absorption. The bioavailability of insulin was estimated from the change in the plasma glucose level. The bioavailability of insulin from dry powder with no additive exceeded that obtained from pH 7.4 solution. The absolute bioavailability of insulin administered as a solution with 1.4 mg/dose of bacitracin or 1.0 mg/dose of Span 85 was almost 100%. The bioavailability of dry powder with 0.42 mg/dose of bacitracin was 20% that of the solution with 1.4 mg/dose of bacitracin. The insulin dry powder with 0.21 mg/dose of Span 85 showed a bioavailability less than that for the insulin solution with 0.1 mg/dose of Span 85. Bacitracin and Span 85 were not as effective in dry powder as in solution in the present study. While citric acid was more effective in dry powder that in solution to increase the hypoglycemic effect. The pH 5.0 and pH 3.0 solutions containing 0.19 mg of citric acid in 0.1 ml showed absolute bioavailabilities of 43% and 57%, respectively, while the bioavailabilities for dry powders containing 0.025 and 0.036 mg/dose citric acid were 42% and 53%, respectively. In addition, the hypoglycemic effect of dry powders continued for a longer period and remained at 240 min with the dry powders, while it disappeared at 180 min with the solutions. When the insulin dry powder containing 0.036 mg/dose of citric acid was administered, the lactate dehydrogenase activity, a sensitive indicator of acute toxicity to lung cells, in bronchoalveolar lavage was as low as that for saline administration, suggesting citric acid is a safe additive. Thus, citric acid appears to be a safe and potent absorption enhancer for insulin in dry powder.
影响因子：
56.9
作者：
Edwards, DA;Hanes, J;Langer, R
通讯作者：
Langer, R
大鼠和兔体内胰岛素的肺部生物转化。
影响因子：
6.1
作者：
Liu,FY;Kildsig,DO;Mitra,AK
通讯作者：
Mitra,AK