公开(公告)号：EP0660724B1

公开(公告)日：1998-07-01

申请号：EP93919497.3

申请日：1993-09-03

申请人： NYCOMED IMAGING AS

发明人： KLAVENESS, Jo ,  RONGVED, P l ,  JOHANSEN, John Henrik ,  FOSS, Per Antonius ,  HOGSET, Anders ,  HVOSLEF, Anne Marie

IPC分类号： A61K49/00

CPC分类号： A61K49/1821 ,  A61K49/18 ,  A61K49/223

摘要： Proteinaceous gas- or gas precursor-containing microbubble contrast agents, e.g. for use in ultrasound and/or MR imaging, in which the protein matrix is crosslinked by reaction with a bifunctional aldehyde (e.g. a dialdehyde such as glutaraldehyde or an α,β-unsaturated aldehyde such as acrolein) in an aqueous medium at substantially neutral pH exhibit improved in vivo and storage stabilities, particularly if the matrix is also reacted with a Schiff's base reducing agent such as a borohydride. Modification of the size distribution of such crosslinked proteinaceous gas-containing contrast agents, e.g. to reduce the mean size of the microbubbles, further enhances their stability and permits preparation of novel contrast agents having a particularly narrow microbubble size distribution.