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重组蛋白长效化策略 被引量:4
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作者 王珊珊 牛晓霞 +1 位作者 王颖 刘金毅 《药物生物技术》 CAS 2022年第3期291-299,共9页
相比传统小分子药物,重组蛋白药物具有高活性、高特异性和低毒性等多种独特优势,但囿于机体内蛋白水解、肾脏消除、肝脏代谢以及免疫清除等影响,往往导致重组蛋白药物的体内半衰期短,使用受限,显然,蛋白长效化处理策略对于重组蛋白药物... 相比传统小分子药物,重组蛋白药物具有高活性、高特异性和低毒性等多种独特优势,但囿于机体内蛋白水解、肾脏消除、肝脏代谢以及免疫清除等影响,往往导致重组蛋白药物的体内半衰期短,使用受限,显然,蛋白长效化处理策略对于重组蛋白药物的发展十分必要。延长半衰期的基本策略是结构改造,如置换不稳定氨基酸或转换不稳定构象来避免蛋白水解;PEG修饰是如今最成功的策略之一,它代表了增加流体动力学体积,减少肾脏清除的亲水聚合物修饰策略,其中聚合物包括了化学聚合物、多肽聚合物以及碳水化合物聚合物;Fc融合也是一种成功的长效化策略,它代表了天然长效蛋白分子机制的利用,具有广阔发展前景;而针对免疫原性的糖基化修饰不仅可以降低蛋白免疫原性,还可以改善蛋白的理化性质。文章将对一些经典和新兴的重组蛋白长效化策略如结构修饰、聚合物修饰、蛋白修饰、糖基化进行综述,并且通过实例加以说明。 展开更多
关键词 长效重组蛋白 结构修饰 化学聚合物 非结构多肽 白蛋白 fc融合 碳水化合物
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A review of existing strategies for designing long-acting parenteral formulations: Focus on underlying mechanisms, and future perspectives 被引量:11
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作者 Yujie Shi An Lu +3 位作者 Xiangyu Wang Zakia Belhadj Jiancheng Wang Qiang Zhang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2021年第8期2396-2415,共20页
The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations(LAPFs)with the aim of improving drug pharmacokinetics and therapeutic efficacy.LAPF... The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations(LAPFs)with the aim of improving drug pharmacokinetics and therapeutic efficacy.LAPFs have been proven to extend the half-life of therapeutics,as well as to improve patient adherence;consequently,this enhances the outcome of therapy positively.Over past decades,considerable progress has been made in designing effective LAPFs in both preclinical and clinical settings.Here we review the latest advances of LAPFs in preclinical and clinical stages,focusing on the strategies and underlying mechanisms for achieving long acting.Existing strategies are classified into manipulation of in vivo clearance and manipulation of drug release from delivery systems,respectively.And the current challenges and prospects of each strategy are discussed.In addition,we also briefly discuss the design principles of LAPFs and provide future perspectives of the rational design of more effective LAPFs for their further clinical translation. 展开更多
关键词 LONG-ACTING Chemical modification fc/hsa fusion Biomimetic strategies Hydrogels Nanocrystal suspensions MICRONEEDLES Implantable systems
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