口服胰岛素的胃肠道稳定性研究

Study on the stability of oral insulin in gastrointestinal tract

目的 研究胰岛素在胃肠道环境下的稳定性。方法 根据圆二色谱图选择合适浓度的胰岛素溶液;选择不同pH值的胰岛素溶液或多种酶与胰岛素配制的溶液,以HPLC和小鼠降血糖法分别测定胰岛素的含量和生物活性变化。结果 当胰岛素溶液的浓度为100μg·mL-1时,胰岛素主要以单体形式存在;在酸性和中性的溶液中,3 h内胰岛素的含量和生物活性基本不变;在几种酶的作用下,胰岛素均发生降解,含量和生物活性均随作用时间的延长而下降。结论 胃肠道存在的不同种类的蛋白酶对胰岛素的降解是胰岛素口服研究需解决的主要问题。因此为提高口服胰岛素的稳定性,增加其在小肠的吸收,应采用多种制剂手段。

OBJECTIVE: The stability of insulin in the gastrointestinal (GI) tract was investigated. METHODS: The concentration of insulin solution was chosen according to the circular dichroism spectra. Insulin was incubated with solutions which had the different pH or contained all kinds of proteolytic enzymes and then the contents and bioactivities of insulin were determined by HPLC and mice hypoglycemia, respectively. RESULTS: Insulin was monomer when the concentration of insulin solution was chosen to be 100 μg&middotmL -1. The contents and bioactivities of insulin solution were unchanged within 3 h in the acidic and neutral environment. Insulin was degraded when incubated with all kinds of proteolytic enzymes and the contents and bioactivities were reduced with the increase of the incubation time. CONCLUSION: Various proteolytic enzymes in the GI tract is the predominant barrier which the oral insulin delivery system need to overcome. Therefore, several formulation strategies should be applied in order to enhance the stability of insulin and increase the absorption.