| 摘要 |
1. A process for the preparation of a contrast agent comprising the steps: a) dispersing gas in an aqueous medium containing a membrane-forming lipid to form a lipid-stabilised gas microbubble dispersion; b) lyophilising said dispersion in the presence of a cryoprotectant and/or lyoprotectant to yield a dried product, containing a matrix from said cryoprotectant and/or lyoprotectant, containing gasfilled substantially spherical cavities or vacuoles surrounded by layers of membrane-forming lipid material; c) reconstituting said dried product in an aqueous injectable carrier liquid. 2. A process according to claim 1, wherein the gas employed in step a) is sulphur hexafluoride or a fluorinated low molecular weight hydrocarbon. 3. A process according to claim 1 or 2, wherein the lipid-containing aqueous medium employed in step a) further contains one or more additives selected from alcohols and polyols. 4. A process according to any of claims 1 to 3, wherein the membrane-forming lipid consists essentially of phospholipid and predominantly comprises molecules which individually have an overall net charge. 5. A process according to any of claims 1 to 4, wherein the lipid-stabilised dispersion formed in step a) is washed prior to being lyophilised in step b) and microbubbles are size fractionized. 6. A process according to any of claims 1 to 5, wherein said cryoprotectant and/or lyoprotectant is a physiologically tolerated sugar. 7. A dried product capable to generate microbubbles, reconstituting said dried product in an aqueous injectable carrier liquid, containing a matrix from said cryoprotectant and/or lyoprotectant, containing gasfilled substantially spherical cavities or vacuoles surrounded by layers of membrane-forming lipid material. 8. A dried product according to claim 7, wherein said cryoprotectant and/or lyoprotectant is a physiologically tolerated sugar. 9. A dried product according to claim 7, wherein the membrane-forming lipid consists essentially of phospholipid and predominantly comprises molecules which individually have an overall net charge. 10. A dried product according to claim 9, wherein substantially phospholipid and predominantly comprises molecules which individually have an overall net charge. 11. A dried product according to claim 10, wherein one or more phosphatidylserines constitute at least 70% of the phospholipid. 12. A dried product according to any of claims 7 to 11, wherein gas contains is sulphur hexafluoride or a fluorinated low molecular weight hydrocarbon. 13. A dried product according to claim 11, wherein said cryoprotectant and/or lyoprotectant is saccharose, and the gas is perfluorobutane. 14. A dried product according to claim 13, wherein a contrast agent composition comprising as a first component a dried product and as a second component an injectable aqueous carrier liquid, said first and second components being contained respectively within first and second chambers of dual chamber storage means. |
