Preparation and properties of an alpha-1-protease inhibitor concentrate with high specific activity

Background and Objectives Because the current demand for alpha-1-protease i nhibitor A1PI) exceeds the available supply, we aimed to develop a process for purification of A1PI from plasma which would achieve the highest possib le degree of purity, specific activity and yield. Introduction Materials and Methods A1PI was purified from Cohn fraction IV-1,4 using eth anol precipitation and Q-Sepharose chromatography. Ceramic hydroxyapatite c hromatography was used as a final purification step. Two independent virus- inactivation procedures (chemical and vapour heating) were applied. Results The resulting A1PI had an unprecedented high specific activity. In addition, the process led to the discovery of a new isoform of A1PI in isoe lectric focusing gels. Conclusion The high specific activity of the A1PI preparation achieved with this process should allow a reduction of the A1PI total protein load neces sary to achieve clinically relevant effects.