Wang W
Biotechnology, Bayer Corporation, 800 Dwight Way, Berkeley, CA 94701, USA.
Int J Pharm. 1999 Aug 20;185(2):129-88. doi: 10.1016/s0378-5173(99)00152-0.
One of the most challenging tasks in the development of protein pharmaceuticals is to deal with physical and chemical instabilities of proteins. Protein instability is one of the major reasons why protein pharmaceuticals are administered traditionally through injection rather than taken orally like most small chemical drugs. Protein pharmaceuticals usually have to be stored under cold conditions or freeze-dried to achieve an acceptable shelf life. To understand and maximize the stability of protein pharmaceuticals or any other usable proteins such as catalytic enzymes, many studies have been conducted, especially in the past two decades. These studies have covered many areas such as protein folding and unfolding/denaturation, mechanisms of chemical and physical instabilities of proteins, and various means of stabilizing proteins in aqueous or solid state and under various processing conditions such as freeze-thawing and drying. This article reviews these investigations and achievements in recent years and discusses the basic behavior of proteins, their instabilities, and stabilization in aqueous state in relation to the development of liquid protein pharmaceuticals.
蛋白质药物研发中最具挑战性的任务之一是应对蛋白质的物理和化学不稳定性。蛋白质不稳定性是蛋白质药物传统上通过注射给药而非像大多数小分子化学药物那样口服的主要原因之一。蛋白质药物通常必须在低温条件下储存或冻干以达到可接受的保质期。为了理解并最大化蛋白质药物或任何其他可用蛋白质（如催化酶）的稳定性，人们进行了许多研究，尤其是在过去二十年。这些研究涵盖了许多领域，如蛋白质折叠与去折叠/变性、蛋白质化学和物理不稳定性的机制，以及在水溶液或固态中、在诸如冻融和干燥等各种加工条件下稳定蛋白质的各种方法。本文综述了近年来的这些研究和成果，并讨论了与液体蛋白质药物研发相关的蛋白质基本行为、其不稳定性以及在水溶液状态下的稳定化。
