Watanabe Y, Matsumoto Y, Kawamoto K, Yazawa S, Matsumoto M
Department of Pharmaceutics, Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Chem Pharm Bull (Tokyo). 1992 Nov;40(11):3100-4. doi: 10.1248/cpb.40.3100.
The absorption of insulin (from porcine pancreas) in rabbits after the nasal administration of aqueous preparations containing insulin and five kinds of cyclodextrins (CyDs) in phosphate buffer solution at pH 7.0 was investigated. Without CyD, the insulin and glucose levels in plasma were unchanged, whereas a marked increase in the plasma levels of insulin and a decrease in glucose concentrations were observed following the simultaneous administration of insulin and CyD such as alpha- and heptakis (2,6-di-O-methyl)-beta-CyD (DM-beta-CyD). The largest enhancing effect on the nasal absorption of insulin was obtained by DM-beta-CyD. To evaluate the duration of the absorption-enhancing effect of CyDs, preadministration (administration of CyD 0.5, 6, 12 and 24 h before insulin administration) was performed. The area under plasma concentration-time curve (AUC) and Cmax of insulin significantly decreased with the preadministration of DM-beta-CyD 6, 12 and 24 h before nasal administration. The absorption-enhancing effect disappeared 24h after the preadministration. These findings demonstrate that CyDs enhance the nasal absorption of insulin, and the recovery of the membrane transport barrier function in nasal mucosa is achieved, at the latest, 24 h after the administration of CyDs.
研究了在pH 7.0的磷酸盐缓冲溶液中，将含有胰岛素和五种环糊精（CyDs）的水性制剂经鼻给药后，家兔对（来自猪胰腺的）胰岛素的吸收情况。在无环糊精的情况下，血浆中的胰岛素和葡萄糖水平未发生变化，而在同时给予胰岛素和α-环糊精及七（2,6-二-O-甲基）-β-环糊精（DM-β-CyD）等环糊精后，观察到血浆中胰岛素水平显著升高，葡萄糖浓度降低。DM-β-CyD对胰岛素经鼻吸收的增强作用最大。为评估环糊精吸收增强作用的持续时间，进行了预给药（在给予胰岛素前0.5、6、12和24小时给予环糊精）。在经鼻给药前6、12和24小时预给予DM-β-CyD后，胰岛素的血浆浓度-时间曲线下面积（AUC）和Cmax显著降低。预给药24小时后，吸收增强作用消失。这些结果表明，环糊精可增强胰岛素的经鼻吸收，并且在给予环糊精后最迟24小时可实现鼻黏膜膜转运屏障功能的恢复。
