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由于基因重组技术的发展,药用蛋白质制剂的商品化生产已成为现实。近来已有150多种重组蛋白质制剂在进行Ⅰ期或Ⅰ期以上的临床试验,有12种已获美国FDA的批准。然而,由于蛋白质的理化性质,使其在纯化、分离、贮存和销售时存在独有的困难。本文将从分子水平来认识蛋白质的稳定性,以解决其众多的制剂问题。蛋白质的降解途径可分为二种类型,即化学不稳定性和物理不稳定性。前者系指蛋白质通过成键或断键生成新的化合物;而物理稳定性则不涉及蛋白质的共价键变异,而是指蛋白质变成更高级的结构(二级或更高),包括变性、表面吸附、凝聚和沉淀。以下介绍这些不稳定过程以及延迟和抑制这些不稳定性的方法,以提高蛋白质的稳定性。
Due to the development of genetic recombination technology, the commercial production of medicinal protein preparations has become a reality. More than 150 recombinant protein preparations have recently undergone Phase I or Phase I clinical trials and 12 have been approved by the U.S. FDA. However, due to the physicochemical properties of proteins, there are unique difficulties in purification, isolation, storage and marketing. This article will recognize the stability of the protein at the molecular level to solve its numerous formulation problems. Protein degradation pathways can be divided into two types, namely chemical instability and physical instability. The former refers to the formation of new compounds by bonding or breaking of proteins. The physical stability does not involve the covalent variation of proteins, but the protein becomes more advanced structure (level 2 or higher), including denaturation, Surface adsorption, aggregation and precipitation. The following describes these unstable processes as well as ways to delay and inhibit these instabilities to improve protein stability.