长效化融合蛋白药物及其药动学分析技术的研究进展

Progression of the Long-term Mechanism and Pharmacokinetics Analysis Technology of Fusion Protein Drugs

融合蛋白技术应用于生物制药行业已超过25年,其目的为改善原来天然蛋白的性质,从而具有新的理化特征和生物学功能,其中最为显著的特点是改善了小分子蛋白及多肽半衰期短的缺陷。基于该技术所诞生的融合蛋白类药物已成为当前生物药研发的热点。结合已上市融合蛋白类药物,通过与传统多肽蛋白类药物比较,重点突出融合蛋白类药物自身特点,主要从融合抗体Fc段和人血清白蛋白以延长小分子蛋白及多肽半衰期的角度对融合蛋白药物长效化策略进行评述;对融合蛋白类药物在体内的吸收、分布、代谢和排泄的显著特征进行概述;综述该类药物在体内的分析技术并指出当前分析技术的优缺点及发展方向,为长效化融合蛋白药物的设计、分析研究与开发提供依据和思路。

It has been over 25 years since the application of fusion protein in the biopharmaceutical industry. The purpose to improve the original properties of natural protein, thus a new physical and chemical characteristics and biological function, one of the most remarkable characteristic is improved the small molecular protein and polypeptide short half-life of defects. Based on the technology, the birth of the fusion-protein drugs （FPDs） is becoming a hot spot of current research and development of biological medicine. Based on the fusion protein drugs already on the market, compared with traditional protein polypeptide drugs, highlighting characteristics FPDs, mainly from the fusion antibody Fe and human serum albumin by prolonging the small molecule protein and peptide half-life, and FPDs long-term strategy was reviewed. The FPDs in vivo absorption, distribution, metabolism and excretion of the salient features are summarized. And then analyses the technology of FPDs in the body and points out the advantages and disadvantages of the current analysis technology and the development direction, and sheds light on the design, research and development of FPDs.