Nasal absorption enhancement of insulin by sodium deoxycholate in combination with cyclodextrins  

脱氧胆酸钠-环糊精联用促进鼻对胰岛素的吸收(英文)

作　　者：张奕[1] 蒋新国[1] 姚洁 

机构地区：[1]复旦大学药学院药剂学研究室,上海中国200032

出　　处：《Acta Pharmacologica Sinica》2001年第11期1051-1056,共6页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China,No 39770883

摘　　要：AIM: To evaluate the nasal absorption enhancement of insulin by sodium deoxycholate (SDC) in combination with cyclodextrins ( CD ). METHODS: The concentration of glucose in blood was measured. Scanning electron microscopy technique was used to investigate the effect of enhancers on the nasal muco-cilia, The effect of SDC in combination with CD on the leucine aminopeptidase (LAP) activity in the nasal mucosa was observed. RESULTS: Intranasal administration of insulin (4 U/kg) along with 0. 75 % SDC/β-CD at a molar ratio of 1:2 slowly decreased the blood glucose levels of rats. The minimal blood glucose level was (72.6 ± 2.1) % of baseline, and which was lasted for 3 h. Though the decrement of blood glucose in 0.75 % SDC/β-CD (1:2) treated group was less than that in 0. 75 % SDC treated group, there was no significant difference between the two groups in AOCo-t values ( P > 0. 05). SDC (0.01 %) solution did not have any absorption prompting effect. Scanning electron microscopy investigation showed that 0.75 % SDC/β-CD (1:2) solution had no marked damage on rat nasal mucosa 4 h after nasal administration, while 0. 01 % SDC still had some damage on the rat nasal mucosa. The inhibitory effect of SDC on the LAP activity was decreased from 89.2 % to 69.2 % , 71.5 % , 60.4 % , and 61. 3 % in 0.75 % SDC/β-CD (1:1), 0.75 % SDC/β-CD (1:2), 0.75 % SDC/DM-β-CD (1:1), and 0.75 % SDC/DM-β-CD (1:2) treated group, respectively. CONCLUSION: Combining β-CD with SDClowered the serious nasal ciliotoxicity of SDC and had a marked absorption promoting effect, which was not due to low concentration of SDC but was related with the inhibition of LAP activity.目的:评价β-环糊精(β-CD)或二甲基-β-环糊精与脱氧胆酸钠(SDC)联用对胰岛素的吸收促进作用。方法:通过胰岛素降血糖作用来反映其吸收效果;用扫描电镜观察单次给药后的鼻纤毛毒性;测定亮氨酰氨肽酶的活性。结果:0.75％ SDC/β-CD(1:2)联用时,鼻腔给予胰岛素产生的降血糖作用相对缓慢而持久,血糖最低值为初始的(72.6±2.1)％,血糖-时间曲线在1至4h内较平稳。虽然与0.75％ SDC组比较,两组的最低血糖水平有显著性差异,但血糖-时间曲线上面积AOC_(0-t)值无显著性差异(P>0.05)。扫描电镜结果显示大鼠鼻腔给药4h后粘膜纤毛无明显改变。0.01％ SDC促吸收能力很弱,但仍有纤毛毒性。SDC与β-环糊精或二甲基-β-环糊精联用后,亮氨酰氨肽酶的活性抑制率由89.2％下降至60％-70％。结论:β-环糊精与SDC联用后,降低了SDC的纤毛毒性,但仍保留了较强的胰岛素吸收促进作用。这种促进作用并不是由于SDC浓度的降低,而是与亮氨酰氨肽酶的活性被抑制有关。

关 键 词：deoxycholic acid cyclodextrins INSULIN ABSORPTION nasal mucosa leucyl aminopeptidase 

分 类 号：R96[医药卫生—药理学]