【摘要】 目的　选择氮酮 (azone)和甘氨胆酸钠 (sodiumglycocholicacid ,SGC)作为促进胰岛素经鼻吸收的助渗剂 ,比较二者的助渗能力以及观察氮酮对鼻黏膜结构的影响。方法　①药代学实验 :从 2 0只日本大白兔采血 0 5ml,进行空腹血糖测定 ;然后静脉注射 4 0U/ml胰岛素 0 1ml,在注射后 5、10、15、30、6 0和 12 0min从颈动脉采血 ;之后将含有质量浓度为 0 0 4kg/L氮酮或 0 0 1kg/LSGC的 2 70U/ml胰岛素液体 10 μL滴入鼻腔 ,采血时间同前 ,用放免技术测定血中胰岛素含量 ;②氮酮对鼻黏膜结构的影响 :逐日经鼻腔给予 0 0 4kg/L氮酮制剂 ,每日 3次 ,每次 5 0 μL ,分别在点药 7d和 3个月停止点药 ,于 7d ,2个月和停药后 1和 2周每批处死 3只动物 ,取鼻中隔黏膜 ,在光学显微下观察鼻黏膜组织结构的改变。结果　通过计算得出 3组给予胰岛素后曲线下面积 (areaunderthecurve ,AUC)分别是SGC组为 :(2 98 0 2± 6 3 0 0 )mU·L-1·min-1× 10 -3 ,氮酮组为 :(5 96 92± 84 0 0 )mU·L-1·min-1×10 -3 ,静注组为 :(12 6 4 87± 14 8 0 0 )mU·L-1·min-1× 10 -3 ;SGC组的生物利用度为 2 3 5 6 % ,氮酮组为4 7 19% ,二者之间差异有显著性 (P <0 0 5 )。鼻腔长期用 0 0 4kg/L氮酮制剂后上皮细胞消失 ,黏膜下腺?更多还原

【Abstract】 Objective To distinguish the different permeation function between sodium glycocholic acid (SGC) and Azone, and study the pathological changes induced by Azone on nasal mucosa Methods Insulin was given intravenouslly at the dose of 4 0 U The blood samples were determined by radioimmunity method SGC or Azone was administered respectively via nasal route with Insulin 270U/ml Insulin nasal drops 10 μL were given to each of rabbits via nasal route The Azone 50 μL was administered via nasal route ,t i d , lasted for 1 week and 3 months Results The level of blood Insulin was as follows: (3?954 47±644 47) mU/L, AUC=(1?264 87±148 00)mU·L -1 ·min -1 ×10 -3 in i v group; (740 44±94 16)mU/L, AUC =(298 02±63)mU·L -1 ·min -1 ×10 -3 in SGC group; (908 18±201 19) mU/L, AUC=(596 92±84 00)mU·L -1 ·min -1 ×10 -3 in Azone group The bioavailability was 23 56% and 47 19% respectively The pathological changes included cilia detachment from epithelium, glandular hypertrophy and connective tissue proliferation Conclusion It was found that Azone was an excellent permeation enhancer which promoted more Insulin to be absorbed into blood stream through nasal mucosa However, Azone also damaged the nasal mucosa in the view of pathology更多还原