Abstract: Peptide/protein drugs generally have short half-life in vivo, which limit their application. In recent years, great progress has been made in the study of protein half-life. Many techniques have been proposed and tested to extend the action time of therapeutic proteins, such as fusion with other protein genes (immunoglobulin domain or serum protein, such as albumin), and binding with polymers (PEGylation, polysialylation, hepylation, etc.). These technologies are mainly based on their long half-life and regulation of circulation mechanism to prolong the half-life of peptide/protein drugs. In this paper, the above-mentioned long-acting methods and related products were summarized and discussed, in order to provide research ideas for the long-acting research of such drugs.

Key words: long-acting, half-life, PEGylation, recombinant polypeptide, Fc fusion, glycosylation

摘要： 多肽/蛋白质类药物普遍存在体内半衰期短的问题，使其应用受到了限制。近年来，蛋白质半衰期的研究取得了很大的进展，许多技术已经被提出并测试延长治疗性蛋白的作用时间，如与其他蛋白基因融合(免疫球蛋白域或血清蛋白，如白蛋白)、与聚合物结合(PEG化修饰、聚唾液酸化、HEP化等)。这些技术主要基于本身较长的半衰期及循环机制调控以延长多肽/蛋白质类药物的半衰期。针对上述的多种长效化方式及相关产品进行了综述与讨论，以期为此类药物的长效化研究提供思路。

关键词: 长效, 半衰期, PEG修饰, 重组多肽, Fc融合, 糖基化