中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (16): 3019-3022.doi: 10.3969/j.issn.1673-8225.2010.16.042

• 生物材料临床实践 clinical practice of biomaterials • 上一篇    下一篇

胰岛素吸入给药降血糖的效果评价

王正梅，高桂枝，马  嫣   

  1. 南京信息工程大学环境科学与工程学院化学系，江苏省南京市  210044
  • 出版日期:2010-04-16 发布日期:2010-04-16
  • 作者简介:王正梅★，女，1970年生，江苏省淮安市人，汉族，2002年东南大学毕业，硕士，讲师，主要从事生物医学材料的研究。

Glucose-lowering effects of insulin delivered by oral inhalation in normal rats

Wang Zheng-mei, Gao Gui-zhi, Ma Yan   

  1. Department of Chemistry, School of Environmental Science and Engineering, Nanjing University of Information Science & Technology, Nanjing  210044, Jiangsu Province, China
  • Online:2010-04-16 Published:2010-04-16
  • About author:Wang Zheng-mei★, Master, Lecturer, Department of Chemistry, School of Environmental Science and Engineering, Nanjing University of Information Science & Technology, Nanjing 210044, Jiangsu Province, China Wzm199500@163.com

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摘要：

背景：口服胰岛素易被胃酸及胃肠道内的各种酶降解，难以透过胃肠道上皮细胞膜，针剂形式也至少需要36 h注射1次。近年正在不断研究各种肺部给药制剂如干粉型吸入剂、吸入气雾剂、电喷雾剂、胰岛素纳米化技术和吸收增强剂等，具有较好的应用前景。
目的：观察胰岛素溶液经正常大鼠吸入后的降血糖作用。
方法：体质量(220±30) g的健康雄性大鼠30只，随机分为7组。其中3组分别予吸入胰岛素溶液1.0，5.0，10.0 U/kg，每组4只；另3组分别给予吸入2.0 U/kg胰岛素溶液＋5%的卵磷脂、2.0 U/kg胰岛素溶液＋1%的油酸、2.0 U/kg胰岛素溶液＋1%DTPA，每组5只；剩余3只为空白对照组。分别于给药后0，30，60，120，180，240 min从大鼠尾部取血     15 μL，使用ONE TOUCHTM BASICTM PLUS 稳捷基础倍加型血糖仪测定血糖，计算不同条件下胰岛素溶液的药理生物利用度。
结果与结论：1 U/kg的胰岛素溶液经大鼠吸入后即有明显的降血糖作用, 随着剂量的增加，大鼠体内血糖下降幅度随之增大，10 U/kg的剂量降血糖最低可降至14.5%。1 U/kg的胰岛素溶液经吸入后，在不加吸收促进剂的条件下的药理生物利用度为11.5%。吸收促进剂油酸、DTPA和卵磷酯的加入均能显著地增强胰岛素溶液的降血糖作用。

关键词: 胰岛素, 吸入给药, 吸收促进剂, 降血糖作用

Abstract:

BACKGROUND: Insulin taken orally is easy to be degraded by hydrochloric acid in the gastric juice and various enzymes in the gastrointestinal tract. It is hard for oral insulin to pass through the epithelial cell membrane in the gastrointestinal tract. Insulin delivered by injection needs at least 36 hours every administration. Many pulmonary administrations of insulin have been recently studied, such as dry powder inhalation, aerosol inhalation, electron spraying, insulin nanometer technique, and absorption enhancer, with promising clinical application prospects.
OBJECTIVE: To investigate the glucose-lowering effects of insulin delivered by oral inhalation in normal rats.
METHODS: Thirty healthy male rats, weighing (220±30) g were randomly divided into seven groups: low dose insulin (1.0 U/kg,  n = 4), middle dose insulin (5.0 U/kg, n = 4), high dose insulin (10.0 U/kg, n = 4), insulin (2.0 U/kg) +5% lecithin (n = 5), insulin   (2.0 U/kg) +1% oleic acid (n = 5), insulin (2.0 U/kg) +1% diethylenetriaminepentaacetic acid (DTPA; n = 5), and blank control     (n = 3). At 0, 30, 60, 120, 180, 240 minutes after administration. 1.5 μL blood was taken from rat tails through the use of ONE TOUCHTM BASICTM PLUS blood glucose detection system for determination of blood glucose level and calculation of insulin pharmacological bioavailability under various conditions.
RESULTS AND CONCLUSION: Insulin (1U/kg) markedly decreased glucose levels immediately after inhalation. Blood glucose level decreased with increasing insulin dose. Insulin (10 U/kg) could produce a 14.5% decrease of blood glucose level. Insulin   (1 U/kg) could yield a pharmacological bioavailability of 11.5% in the absence of absorption enhancer. The concomitant administration of oleic acid, DTPA and lecithin appeared to be more effective in enhancing the pulmonary absorption of insulin, and decreasing blood glucose level.

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