Microbubble-based contrast agents with crosslinked and reduced proteinaceous shells

US5718884A · kind A · utility

Assignee

• NYCOMED IMAGING AS · NO

Inventors

• Jo Klaveness · Oslo, NO
• Pal Rongved · Oslo, NO
• John Henrik Johansen · Oslo, NO
• Per Antonius Foss · Oslo, NO
• Anders H.o slashed.gset · Oslo, NO
• Anne Marie Hvoslef · Sandnes, NO

Key dates

• Filing date: May 4, 1995
• Grant date: Feb 17, 1998
• Expiry date: May 4, 2015

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K49/223
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention pertains to proteinaceous gas- or gas precursor-containing microbubble contrast agents 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 .alpha.,.beta.-unsaturated aldehyde such as acrolein) in an aqueous medium at substantially neutral pH. The contrast agents 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.