Details for Patent: 6,183,725

Title:	Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method
Abstract:	The invention relates to injectable media for ultrasonic echography in the form of microbubbles or microballoons comprising at least two biocompatible substances A and B (gaseous at the body temperature) forming a mixture which when in suspension with usual surfactants, additives and stabilisers provides useful ultrasound contrast agents. At least one of the components (B) in the mixture is a gas whose molecular weight is greater than 80 daltons and whose solubility in water is below 0.0283 ml per ml of water at standard conditions. The presence of the first component (B) in the contrast medium may vary between 0.5 and 41 volume percent. The other component (A) of the ultrasound contrast media is a gas or a mixture of gases whose molecular weight is below 80 daltons. The second component is present in a proportion of between 59-99.5% by vol., and is preferably chosen from oxygen, air, nitrogen, carbon dioxide or mixtures thereof. Gas mixtures described are found to be very effective as ultrasound contrast media. The invention also comprises a method of making the ultrasound contrast medium, the contrast agent and the ultrasound agent kit.
Inventor(s):	Yan; Feng (Carouge, CH), Schneider; Michel (Troinex, CH)
Assignee:	Bracco Research S.A. (Carouge, CH)
Filing Date:	Feb 10, 1998
Application Number:	09/021,367
Claims:	1. An injectable ultrasound contrast agent comprising a suspension of gas filled microbubbles in a physiologically acceptable aqueous carrier containing usual surfactants, additives and stabilizers, the microbubbles being bounded by a monolayer of saturated phospholipids in laminar or lamellar form, the microbubbles being filled with a gas mixture of at least two biocompatible gases A and B in which at least one gas (B) present in an amount of between 0.5-41% by volume has a molecular weight greater than 80 daltons and solubility in water below 0.0283 ml per ml of water at standard conditions, the balance of the mixture being gas A, wherein gases A and B are both gaseous at body temperature. 2. The ultrasound contrast agent of claim 1 wherein gas (B) is a fluorine-containing biocompatible gas. 3. The ultrasound contrast agent of claim 2 wherein the fluorine-containing gas is SF.sub.6. 4. The ultrasound contrast agent of claim 2 wherein the fluorine-containing biocompatible gas contains 1 to 5 carbon atoms. 5. The ultrasound contrast agent of claim 2, wherein the fluorine-containing gas is CF.sub.4. 6. The ultrasound contrast agent of claim 2, wherein the fluorine-containing gas is C.sub.2 F.sub.6. 7. The ultrasound contrast agent of claim 2, wherein the fluorine-containing gas is C.sub.3 F.sub.6. 8. The ultrasound contrast agent of claim 2, wherein the fluorine-containing gas is C.sub.3 F.sub.8. 9. The ultrasound contrast agent of claim 2, wherein the fluorine-containing gas is C.sub.4 F.sub.6. 10. The ultrasound contrast agent of claim 2, wherein the fluorine-containing gas is C.sub.4 F.sub.8. 11. The ultrasound contrast agent of claim 2, wherein the fluorine-containing gas is C.sub.4 F.sub.8. 12. The ultrasound contrast agent of claim 2, wherein the fluorine-containing gas is C.sub.5 F.sub.10. 13. The ultrasound contrast agent of claim 2, wherein the fluorine-containing gas is C.sub.5 F.sub.12. 14. The ultrasound contrast agent of claim 3, wherein gas A is air. 15. The ultrasound contrast agent of claim 1, 2 or 4, wherein gas A is oxygen. 16. The ultrasound contrast agent of claim 1, 2 or 4, wherein gas A is nitrogen. 17. The ultrasound contrast agent of claim 1, 2 or 4, wherein gas A is carbon dioxide. 18. The ultrasound contrast agent of claim 1, wherein the aqueous carrier further contains hydrophilic stabilizers. 19. The ultrasound contrast agent of claim 1, wherein the saturated phospholipid is selected from the group consisting of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidyl linositol, cardiolipin, sphingomyelin and mixtures thereof. 20. The ultrasound contrast agent of claim 1, wherein in addition to the phospholipid the aqueous carrier comprises copolymers of polyoxyethylene and polyoxypropylene, and glycerol. 21. The ultrasound contrast agent of claim 1, wherein the surfactants are soy bean oil, Tween and/or sorbitol. 22. The ultrasound contrast agent of claim 3, wherein SF.sub.6 is present in an amount of 25-41% by volume the balance being air. 23. The ultrasound contrast agent of claim 10, wherein C.sub.4 F.sub.8 is present in an amount of 10-41% by volume the balance being air. 24. The ultrasound contrast agent of claim 10, wherein C.sub.4 F.sub.8 is present in an amount of 15% by volume the balance being air. 25. The ultrasound contrast agent of claim 13, wherein C.sub.5 F.sub.12 is present in an amount of 2.9-4.5% by volume the balance being air. 26. The ultrasound contrast agent of claim 1, wherein the fluorine-containing gas is a mixture of two or more fluorine containing gases. 27. The ultrasound contrast agent of claim 26, wherein the mixture contains C.sub.4 F.sub.8. 28. The ultrasound contrast agent of claim 26, wherein the mixture contains CF.sub.4. 29. The ultrasound contrast agent of claim 26, wherein the mixture consists of 5-15% volume of C.sub.4 F.sub.8, 80% volume of air, the balance being CF.sub.4.