Merkus F W, Verhoef J C, Romeijn S G, Schipper N G
Center for Bio-Pharmaceutical Sciences, Leiden University, The Netherlands.
Pharm Res. 1991 May;8(5):588-92. doi: 10.1023/a:1015896405389.
The absorption enhancing effect of alpha-, beta-, and gamma-cyclodextrin (CD), dimethyl-beta-cyclodextrin (DM beta CD), and hydroxypropyl-beta-cyclodextrin (HP beta CD) on intranasally administered insulin was investigated in rats. Coadministration of 5% (w/v) DM beta CD to the insulin solution resulted in a high bioavailability, 108.9 +/- 36.4% (mean +/- SD, n = 6), compared to i.v. administration, and a strong decrease in blood glucose levels, to 25% of their initial values. Coadministration of 5% alpha-CD gave rise to an insulin bioavailability of 27.7 +/- 11.5% (mean +/- SD, n = 6) and a decrease in blood glucose to 50% of its initial value. The rate of insulin absorption and the concomitant hypoglycemic response were delayed for the alpha-CD-containing solution as compared to the DM beta CD preparation. The other CDs, HP beta CD (5%), beta-CD (1.8%), and gamma-CD (5%), did not have significant effects on nasal insulin absorption. DM beta CD at a concentration of 5% (w/v) induces ciliostasis as measured on chicken embryo tracheal tissue in vitro, but this effect is reversible. In conclusion, DM beta CD is a potent enhancer of nasal insulin absorption in rats.
在大鼠中研究了α-、β-和γ-环糊精（CD）、二甲基-β-环糊精（DMβCD）和羟丙基-β-环糊精（HPβCD）对经鼻给药胰岛素的吸收增强作用。将5%（w/v）的DMβCD与胰岛素溶液共同给药，与静脉注射相比，产生了高生物利用度，为108.9±36.4%（平均值±标准差，n = 6），并且血糖水平大幅下降，降至初始值的25%。共同给予5%的α-CD产生了27.7±11.5%（平均值±标准差，n = 6）的胰岛素生物利用度，血糖降至初始值的50%。与含DMβCD的制剂相比，含α-CD溶液的胰岛素吸收速率和伴随的降血糖反应有所延迟。其他环糊精，5%的HPβCD、1.8%的β-CD和5%的γ-CD，对经鼻胰岛素吸收没有显著影响。浓度为5%（w/v）的DMβCD在体外鸡胚气管组织上测量时会诱导纤毛运动停滞，但这种作用是可逆的。总之，DMβCD是大鼠经鼻胰岛素吸收的有效增强剂。
