Teng C L, Groves M J
Department of Pharmaceutics, College of Pharmacy, University of Illinois, Chicago 60612.
Pharm Res. 1988 Dec;5(12):776-80. doi: 10.1023/a:1015988718381.
Jack bean urease is a proteinaceous enzyme, MW approximately 489 kD, readily soluble in water but losing activity when sheared in solution at stresses as low as 2.5 Pa. There is a need for controlled-release forms of many of the new genetically engineered peptide and polypeptide drugs with high specific activities. The simplest form of controlled release would be a sterile compressed pellet of the active component inserted subdermally. However, "activity" may be lost on compaction. Urease can be regarded as a model protein which may lose activity when sheared during compaction in the dry state. Tablets of urease weighing 100 mg were compressed over a range of pressures from 60 to 1750 MPa. No relative loss of activity would be detected following compaction at pressures up to 474 MPa. Above this limiting pressure there was a 50% loss of relative activity, evidently by a compactional effect on the protein quaternary and tertiary structures. No direct relationship was observed between stress (compactional pressure) and inactivation.
刀豆脲酶是一种蛋白质酶，分子量约为489千道尔顿，易溶于水，但在溶液中受到低至2.5帕的剪切力时会失去活性。许多具有高比活性的新型基因工程肽和多肽药物都需要控释剂型。最简单的控释形式是将活性成分制成无菌压缩微丸皮下植入。然而，“活性”可能在压缩过程中丧失。脲酶可被视为一种模型蛋白，在干燥状态下压缩时可能因剪切而失去活性。将重100毫克的脲酶片剂在60至1750兆帕的压力范围内进行压缩。在高达474兆帕的压力下压缩后，未检测到活性的相对损失。高于此极限压力时，相对活性损失50%，显然是由于对蛋白质四级和三级结构的压缩作用。未观察到应力（压缩压力）与失活之间存在直接关系。
