蛋白质药物长效化技术的现状和进展

Current Status and Progress on the Techniques for Prolonging Half-life of Protein Pharmaceuticals

综述了提高蛋白质药物半衰期技术的最新进展。由于蛋白质药物在体内会被快速清除,所以患者必须频繁用药才能保持药物浓度,限制了其治疗效果。因此,延长蛋白质药物体内的半衰期并阻止其被快速清除已成为近年来的研究热点。已建立的提高蛋白质药物半衰期的技术包括化学修饰、蛋白质融合、微囊化、糖基化、抗蛋白酶突变体等,许多长效蛋白质药物已经研制成功并应用于临床治疗。阐述了这些技术的原理并通过实例比较和评价了各种技术的优点和适用范围。

The latest developments of techniques that prolong the half-life of protein drugs were reviewed. The therapeutic potential of several proteins is limited by their rapid clearance from the body, resulting in the need for frequent treatment of individuals to maintain drug levels. Several techniques including chemical modification, protein fusion, microsphere, glycosylation, and protease-resistant variants, and so on, prevent rapid degradation of such drugs and prolong their half-lives in vivo. Several successful protein drugs with prolonged half-life have already been on the market or on clinical trials. The principles, efficiencies and scopes of application of these techniques were described, compared and discussed.s