摘 要
糖尿病作为一种全球性慢性疾病，其发病率逐年上升，传统胰岛素注射给药方式存在诸多不便与患者顺应性差的问题，开发新型口服胰岛素制剂具有重要意义。本研究旨在研制一种新型口服胰岛素制剂并对其药效进行评价。通过构建特殊载体保护胰岛素免受胃肠道酶破坏，并促进其跨膜吸收，以微丸为载体负载胰岛素，采用流化床包衣技术制备制剂。在体外模拟胃肠液环境中考察制剂的稳定性、释放度等性质；体内实验选择健康大鼠和糖尿病模型大鼠，检测给药后不同时间点血糖变化情况以及血液中胰岛素浓度。结果显示该新型口服胰岛素制剂在酸性和弱碱性环境下均能保持稳定，可在肠道内缓慢释放胰岛素，大鼠口服给药后血糖水平显著降低且与注射胰岛素效果相近，血液中可检测到有效浓度的胰岛素。本研究创新性地解决了胰岛素口服生物利用度低的难题，为糖尿病患者提供了一种潜在的有效且便捷的治疗手段，推动了口服胰岛素制剂的研发进程，在药物剂型改进方面有着重要贡献。
关键词：口服胰岛素制剂；糖尿病治疗；胰岛素递送系统；微丸载体；流化床包衣技术
Abstract
Diabetes mellitus, as a global chronic disease, has seen an increasing incidence rate annually. Traditional insulin injection therapy poses numerous inconveniences and poor patient compliance. Therefore, developing a novel oral insulin formulation is of significant importance. This study aims to develop a new oral insulin formulation and evaluate its pharmacological efficacy. A special carrier was constructed to protect insulin from enzymatic degradation in the gastrointestinal tract and promote its transmembrane absorption. Insulin-loaded microspheres were prepared using fluidized bed coating technology. The stability and release characteristics of the formulation were investigated in simulated gastric and intestinal fluid environments in vitro. In vivo experiments were conducted on healthy rats and diabetic rat models to monitor changes in blood glucose levels and insulin concentrations at different time points post-administration. Results demonstrated that the novel oral insulin formulation maintained stability in both acidic and weakly alkaline conditions, allowing for sustained insulin release in the intestine. Oral administration in rats led to a significant reduction in blood glucose levels comparable to insulin injection, with detectable effective concentrations of insulin in the bloodstream. This study innovatively addresses the challenge of low oral bioavailability of insulin, offering a potentially effective and convenient therapeutic option for diabetes patients, thereby advancing the development of oral insulin formulations and contributing significantly to drug dosage form improvements.
Keywords：Oral Insulin Formulation；Diabetes Treatment；Insulin Delivery System；Microsphere Carrier；Fluidized Bed Coating Technology
目 录
摘 要 I
Abstract II
引 言 1
第一章 新型口服胰岛素制剂的开发背景 2
1.1 糖尿病治疗现状分析 2
1.2 口服胰岛素研发意义 2
1.3 国内外研究进展综述 3
第二章 新型口服胰岛素制剂的设计与制备 4
2.1 制剂设计原理探讨 4
2.2 关键辅料的选择研究 4
2.3 制备工艺优化方案 5
第三章 新型口服胰岛素制剂的体外评价 6
3.1 稳定性测试方法 6
3.2 吸收机制研究 6
3.3 释放特性分析 7
第四章 新型口服胰岛素制剂的体内药效评价 8
4.1 动物模型建立 8
4.2 药代动力学研究 8
4.3 药效学评价指标 9
结 论 10
参考文献 11
致 谢 12
