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Claims for Patent: 6,773,696

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Claims for Patent: 6,773,696

Title: Contrast agent comprising low density microspheres
Abstract:Low density microspheres, methods for preparing same, and use of same as contrast agents are described. The microspheres have a void having a volume that comprises at least about 75% of the total volume of the microspheres, and which contains a gas or the vapor of a volatile liquid selected from the group consisting of aliphatic hydrocarbons, chlorofluorocarbons, tetraalkyl silanes and perfluorocarbons.
Inventor(s): Unger; Evan C. (Tucson, AZ)
Assignee: Bristol-Myers Squibb Medical Imaging, Inc. (Princeton, NJ)
Application Number:10/280,844
Patent Claims: 1. A contrast agent comprising an aqueous suspension of low density microspheres, said low density microspheres having a void containing a gas or the vapor of a volatile liquid selected from the group consisting of aliphatic hydrocarbons, chlorofluorocarbons, tetraalkyl silanes and perfluorocarbons, wherein said void has a volume that comprises at least about 75% of the volume of the microsphere and wherein said contrast agent is suitable for administration to a patient either orally, rectally, or by injection.

2. A contrast agent according to claim 1, wherein said microspheres comprise a biocompatible polymer.

3. A contrast agent according to claim 2 wherein said polymer comprises a synthetic polymer or copolymer prepared from the group of monomers consisting of acrylic acid, methacrylic acid, ethyleneimine, crotonic acid, acrylamide, ethyl acrylate, methyl methacrylate, 2-hydroxyethyl methacrylate, lactic acid, glycolic acid, .epsilon.-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichiorhydrin, hydroxyalkylacrylates, siloxane, dimethylsiloxane, ethylene oxide, ethylene glycol, hydroxyalkyl-methacrylates, N-substituted acrylamides, N-substituted methacrylamides, N-vinyl-2-pyrrolidone, 2,4-pentadiene-1-ol, vinyl acetate, acrylonitrile, styrene, p-amino-styrene, p-amino-benzyl-styrene, sodium styrene sulfonate, sodium 2-sulfoxyethyl methacrylate, vinyl pyridine, aminoethyl methacrylates, 2-methacryloyloxy-trimethylammonium chloride, N,N'-methylenebisacrylamide, ethylene glycol dimethacrylates, 2,2'-(p-phenylenedioxy)-diethyl dimethacrylate, divinylbenzene, triallylamine, and methylenebis-(4-phenyl-isocyanate).

4. A contrast agent according to claim 3 wherein said microspheres comprise synthetic polymers or copolymers prepared from the group of monomers consisting of acrylic acid, methacrylic acid, ethyleneimine, crotonic acid, acrylamide, ethyl acrylate, methyl methacrylate, 2-hydroxyethyl methacrylate, lactic acid, glycolic acid, .epsilon.-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichiorhydrin, hydroxyalkylacrylates, siloxane, dimethylsiloxane, ethylene oxide, ethylene glycol, hydroxyalkyl-methacrylates, N-substituted acrylamides, N-substituted methacrylamides, N-vinyl-2-pyrrolidone, 2,4-pentadiene-1-ol, vinyl acetate, acrylonitrile, styrene, p-amino-styrene, p-amino-benzyl-styrene, sodium styrene sulfonate, sodium 2-sulfoxyethylmethacrylate, vinyl pyridine, aminoethyl methacrylates, and 2-methacryloyloxy-trimethylammonium chloride.

5. A contrast agent according to claim 1 wherein said microspheres comprise biocompatible synthetic polymers or copolymers selected from the group consisting of polyacrylic acid, polyethyleneimine, polymethacrylic acid, polymethylmethacrylate, polysiloxane, polydimethylsiloxane, polylactic acid, poly(.epsilon.-caprolactone), epoxy resin, poly(ethylene oxide), poly(ethylene glycol), polyamide, polyvinylidene-polyacrylonitrile, polyvinylidene-poly-acrylonitrile-polymethylmethacrylate, and polystyrene-polyacrylonitrile.

6. A contrast agent according to claim 1 wherein said microspheres are prepared by a heat expansion process.

7. A contrast agent according to claim 1 wherein said microspheres are gas-filled.

8. A contrast agent according to claim 7 wherein said gas in said gas-filled microspheres is selected from the group consisting of carbon dioxide, oxygen, nitrogen, xenon, argon, neon, and helium.

9. A contrast agent according to claim 1 wherein said microspheres are filled with the vapor of a perfluorocarbon.

10. A contrast agent according to claim 9 where said perfluorocarbon has between 1 and about 9 carbon atoms and between 4 and about 20 fluorine atoms.

11. A contrast agent according to claim 10 wherein said perfluorocarbon has between 1 and 4 carbon atoms and between 4 and 10 fluorine atoms.

12. A contrast agent according to claim 10 wherein said perfluorocarbon has between 4 and, about 9 carbon atoms and between 10 and about 20 fluorine atoms.

13. A contrast agent according to claim 10 wherein said perfluorocarbon is C.sub.4 F.sub.10.

14. A contrast agent according to claim 1, further comprising a thickening or suspending agent.
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