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卵泡刺激素(FSH)是一种促进女性卵泡发育和成熟、男性精子正常发生的重要糖蛋白激素。常用FSH药物半衰期相对较短,体内代谢和消除迅速,患者一般需要每天1次或2次皮下注射,才能维持FSH血药浓度在卵巢刺激的阈值水平以上。长效FSH的开发有利于增强生物活性和患者的依从性,减缓患者的精神压力和用药不当。目前用于长效FSH分子设计的技术手段包括在FSH亚基末端融合绒毛膜促性腺激素β亚基的羧端肽(CTP),或引进新的糖基化位点序列,或创建由CTP或糖基化连接序列连接而成的FSHβ和α亚基单链融合蛋白,或创建FSH与IgG1的Fc片段的融合蛋白等。基于各种重组FSH分子优良的药动学和药效学特性,体内半衰期长、生物活性高的新型FSH药物一定会在将来临床应用中发挥重要作用。
Follicle stimulating hormone (FSH) is an important glycoprotein hormone that promotes the development and maturation of female follicles and the normal occurrence of male sperm. Commonly used FSH drugs have a relatively short half-life and rapid in vivo metabolism and elimination. Patients generally require 1 or 2 subcutaneous injections daily to maintain FSH plasma levels above the threshold for ovarian stimulation. The development of long-acting FSH is conducive to enhancing biological activity and patient compliance, relieve stress and medication in patients. Current techniques for designing long-acting FSH molecules include the fusion of the carboxy terminal peptide (CTP) of the chorionic gonadotropin beta subunit at the FSH subunit end, or the introduction of new glycosylation site sequences or the creation of a CTP- FSHβ and α subunit single-chain fusion proteins linked by glycosylation linker, or fusion proteins that create FSH and Fc fragment of IgG1. Based on the excellent pharmacokinetic and pharmacodynamic properties of various recombinant FSH molecules, novel FSH drugs with long half-life in vivo and high biological activity will play an important role in the future clinical application.