Method for the production of medical-grade lipid-coated microbubbles, paramagnetic labeling of such microbubbles and therapeutic uses of microbubbles

Claim 1

A method for preparing an imaging about suitable for enhancement of ultrasonic imaging and magnetic resonance imaging comprising the steps of: A. obtaining a moderately hydrophobic neutral amino acid homopolymer or copolymer which is capable of readily incorporating into a lipid monolayer, and is labeled with a paramagnetic complex comprising a metal ion and organic chelating ligand; B. dissolving the labeled, hydrophobic polymer in a saline solution in an amount of about 10 mM; C. adding a surfactant mixture comprising: (a) a member selected from the group consisting of glycerol monoesters of saturated carboxylic acids containing from about 10 to about 18 carbon atoms and aliphatic alcohols containing from about 10 to about 18 carbon atoms; (b) a sterol-aromatic acid ester; (c) a member selected from the group consisting of sterols, terpenes, bile acids and alkali metal salts of bile acids; (d) a member selected from the group consisting of sterol esters of aliphatic acids containing from one to about 18 carbon atoms; sterol esters of sugar acids; esters of sugar acids and aliphatic alcohols containing from about 10 to about 18 carbon atoms, esters of sugars and aliphatic acids containing from about 10 to about 18 carbon atoms; sugar acids, saponins; and sapogenins; and (e) a member selected from the group consisting of glycerol, glycerol di or triesters of aliphatic acids containing from about 10 to about 18 carbon atoms and aliphatic alcohols containing from about 10 to about 18 carbon atoms; D. shaking said solution mechanically for from about 2 to about 10 seconds in gaseous atmosphere at room temperature, thereby forming a concentrated gas-in-liquid emulsion; and E. passing the solution obtained after step (D) through a sterile polysulfone membrane filter having an average pore diameter of about 0.40-6.0 μm.

Claim 2

A method for preparing an imaging about suitable for enhancement of ultrasonic imaging and magnetic resonance imaging comprising the steps of: A. obtaining a moderately hydrophobic neutral amino acid homopolymer or copolymer which is capable of readily incorporating into a lipid monolayer, and is labeled with a paramagnetic complex comprising a metal ion and organic chelating ligand; B. dissolving the labeled, hydrophobic polymer in a saline solution in an amount of about 10 mM; C. adding a surfactant mixture comprising: (a) a member selected from the group consisting of glycerol monoesters of saturated carboxylic acids containing from about 10 to about 18 carbon atoms and aliphatic alcohols containing from about 10 to about 18 carbon atoms; (b) a sterol-aromatic acid ester; (c) a member selected from the group consisting of sterols, terpenes, bile acids and alkali metal salts of bile acids; (d) a member selected from the group consisting of sterol esters of aliphatic acids containing from one to about 18 carbon atoms; sterol esters of sugar acids; esters of sugar acids and aliphatic alcohols containing from about 10 to about 18 carbon atoms, esters of sugars and aliphatic acids containing from about 10 to about 18 carbon atoms; sugar acids, saponins; and sapogenins; and (e) a member selected from the group consisting of glycerol, glycerol di or triesters of aliphatic acids containing from about 10 to about 18 carbon atoms and aliphatic alcohols containing from about 10 to about 18 carbon atoms; D. shaking said solution mechanically for from about 2 to about 10 seconds in gaseous atmosphere at room temperature, thereby forming a concentrated gas-in-liquid emulsion; and E. passing the solution obtained after step (D) through a sterile polysulfone membrane filter having an average pore diameter of about 0.40-6.0 μm.