超分子方法可以稳定胰岛素,但不需要长时间的作用
Rolande Meudom1,2, Yanxian Zhang1, Michael A VandenBerg3
1Division of Endocrinology and Diabetes, Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA 94305, USA.
Acta pharmaceutica Sinica. B
|May 30, 2023
概括
改性胰岛素类似物稳定配方并减少长时间的作用,降低低血糖的风险. 这促进了超分子PEGylation,以获得更好的饮食时间胰岛素治疗.
科学领域:
- 制药科学 制药科学
- 生物化学 生物化学
- 药物运输 药物运输 药物运输
背景情况:
- 胰岛素聚合挑战了长期配方稳定性.
- 超分子PEGylation与CB[7]‒PEG稳定胰岛素,但导致长时间的作用.
- 长时间的作用限制了饮食时间的使用,增加了低血糖的风险.
研究的目的:
- 为了合成N端酸修饰的胰岛素类似物.
- 在生理学pH下降CB[7]相互作用亲和力.
- 为了减少饮食时间胰岛素应用的作用持续时间.
主要方法:
- 合成的N端酸修饰胰岛素类似物.
- 评估了与CB[7]‒PEG在不同pH值下的胰岛素模拟相互作用.
- 在鼠糖尿病模型中评估了体外和体内生物活性和作用的持续时间.
主要成果:
- 胰岛素类似物在生理pH下显示微弱/没有CB[7]‒PEG相互作用,但在降低pH下显示稳定性.
- 经过N端修饰的类似物表现出与原生胰岛素相当的生物活性.
- 在糖尿病大鼠中,配制的酸改性胰岛素的作用时间缩短.
结论:
- N-终端酸修饰减少了胰岛素与CB[7]‒PEG在生理pH的相互作用.
- 这种修改提高了配方的稳定性,同时缩短了体内作用的持续时间.
- 超分子PEGylation可以优化用于餐时间胰岛素输送,减轻低血糖风险.
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