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US5547656A Expired / Lapsed US ⏱️ 0.0 years remaining

Low density microspheres and their use as contrast agents for computed tomography, and in other applications

Assignee: ImaRx Therapeutics Inc
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Filing: 1995-05-24
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Granted: 1996-08-20
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Expires: 2015-05-24
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Abstract

Abstract Substantially homogeneous aqueous suspensions of low density microspheres are presented as contrast media for imaging the gastrointestinal tract and other body cavities using computed tomography. In one embodiment, the low density microspheres are gas-filled. With computed tomography, the contrast media serve to change the relative density of certain areas within the gastrointestinal tract and other body cavities, and improve the overall diagnostic efficacy of this imaging method.

Inventors

  • 👤 Evan C. Unger

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 16:42
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/04; A61K49/0409; A61K49/0414; A61K49/0419; A61P; A61P9/00; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/31504; Y10T428/31855; Y10T428/31859; Y10T428/31862

Claims Analysis

Total Claims: 71
Claim 1
Independent Claim 49 words
A contrast medium for computed tomography imaging of the gastrointestinal region or other body cavities comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon.
Claim 2
Dependent Claim 49 words
A contrast medium for computed tomography imaging of the gastrointestinal region or other body cavities comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon.
Claim 3
Dependent Claim 89 words
A contrast medium according to claim 1 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, ε-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, 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).
Claim 4
Dependent Claim 79 words
A contrast medium according to claim 2 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, ε-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, 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.
Claim 5
Dependent Claim 43 words
A contrast medium according to claim 1 wherein said microspheres comprise synthetic polymers or copolymers selected from the group consisting of polyacrylic acid, polyethyleneimine, polymethacrylic acid, polymethylmethacrylate, polysiloxane, polydimethylsiloxane, polylactic acid, poly(ε-capro-lactone), epoxy resin, poly(ethylene oxide), poly(ethylene glycol), polyamide, polyvinylidene-polyacrylonitrile, polyvinylidene-polyacrylonitrile-polymethylmethacrylate, and polystyrene-polyacrylonitrile.
Claim 6
Dependent Claim 13 words
A contrast medium according to claim 1 wherein said microspheres comprise polyvinylidene-polyacrylonitrile copolymer.
Claim 7
Dependent Claim 17 words
A contrast medium according to claim 1 wherein the microspheres are prepared by a heat expansion process.
Claim 8
Dependent Claim 14 words
A contrast medium according to claim 1 wherein said microspheres comprise a polyoxypropylene-polyoxyethylene copolymer.
Claim 9
Dependent Claim 36 words
A contrast medium according to claim 1 wherein said perfluorocarbon gas is selected from the group consisting of perfluorocarbons having between 1 and about 9 carbon atoms and between about 4 and about 20 fluorine atoms.
Claim 10
Dependent Claim 33 words
A contrast medium according to claim 8 wherein said perfluorocarbon gas is selected from the group consisting of perfluorocarbons having less than about 4 carbon atoms and less than about 10 fluorine atoms.
Claim 11
Dependent Claim 17 words
A contrast medium according to claim 8 wherein said perfluorocarbon gas is C 3 F 8 .
Claim 12
Dependent Claim 17 words
A contrast medium according to claim 8 wherein said perfluorocarbon gas is C 4 F 10 .
Claim 13
Dependent Claim 17 words
A contrast medium according to claim 8 wherein said perfluorocarbon gas is C 5 F 12 .
Claim 14
Dependent Claim 17 words
A contrast medium according to claim 8 wherein said perfluorocarbon gas is C 6 F 14 .
Claim 15
Dependent Claim 14 words
A contrast medium according to claim 1 further comprising a thickening or suspending agent.
Claim 16
Dependent Claim 25 words
A contrast medium according to claim 14 wherein said thickening or suspending agent is selected from the group consisting of cellulose, carboxymethylcellulose, methylcellulose, and methylhydroxycellulose.
Claim 17
Dependent Claim 15 words
A contrast medium according to claim 15 wherein said thickening or suspending agent is methylcellulose.
Claim 18
Dependent Claim 21 words
A contrast medium according to claim 1 further comprising a compound selected from the group antacids, antiflatulents, antifoaming agents, and surfactants.
Claim 19
Dependent Claim 25 words
A contrast medium according to claim 17 wherein said compound selected from the group of antacids, antiflatulents, antifoaming agents, and surfactants, comprises a polymeric siloxane.
Claim 20
Dependent Claim 13 words
A contrast medium according to claim 18 wherein said polymeric siloxane is dimethylpolysiloxane.
Claim 21
Dependent Claim 12 words
A contrast medium according to claim 19 wherein said dimethylpolysiloxane is simethicone.
Claim 22
Dependent Claim 34 words
A contrast medium according to claim 1 wherein said microspheres comprise a polyoxypropylene-polyoxyethylene copolymer, and said perfluorocarbon gas comprises C 5 F 12 , and wherein said contrast medium further comprises methylcellulose and simethicone.
Claim 23
Dependent Claim 40 words
A contrast medium for diagnostic imaging comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon.
Claim 24
Dependent Claim 40 words
A contrast medium for diagnostic imaging comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon.
Claim 25
Dependent Claim 89 words
A contrast medium according to claim 22 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, ε-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, 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).
Claim 26
Dependent Claim 79 words
A contrast medium according to claim 23 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, ε-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, 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.
Claim 27
Dependent Claim 43 words
A contrast medium according to claim 22 wherein said microspheres comprise synthetic polymers or copolymers selected from the group consisting of polyacrylic acid, polyethyleneimine, polymethacrylic acid, polymethylmethacrylate, polysiloxane, polydimethylsiloxane, polylactic acid, poly(ε-capro-lactone), epoxy resin, poly(ethylene oxide), poly(ethylene glycol), polyamide, polyvinylidene-polyacrylonitrile, polyvinylidene-polyacrylonitrile-polymethylmethacrylate, and polystyrene-polyacrylonitrile.
Claim 28
Dependent Claim 14 words
A contrast medium according to claim 22 wherein said microspheres comprise a polyvinylidene-polyacrylonitrile copolymer.
Claim 29
Dependent Claim 14 words
A contrast medium according to claim 22 wherein said microspheres comprise a polyoxypropylene-polyoxyethylene copolymer.
Claim 30
Dependent Claim 17 words
A contrast medium according to claim 22 wherein said microspheres are prepared by a heat expansion process.
Claim 31
Dependent Claim 36 words
A contrast medium according to claim 22 wherein said perfluorocarbon gas is selected from the group consisting of perfluorocarbons having between 1 and about 9 carbon atoms and between about 4 and about 20 fluorine atoms.
Claim 32
Dependent Claim 33 words
A contrast medium according to claim 29 wherein said perfluorocarbon gas is selected from the group consisting of perfluorocarbons having less than about 4 carbon atoms and less than about 10 fluorine atoms.
Claim 33
Dependent Claim 17 words
A contrast medium according to claim 29 wherein said perfluorocarbon gas is C 3 F 8 .
Claim 34
Dependent Claim 17 words
A contrast medium according to claim 29 wherein said perfluorocarbon gas is C 4 F 10 .
Claim 35
Dependent Claim 17 words
A contrast medium according to claim 29 wherein said perfluorocarbon gas is C 5 F 12 .
Claim 36
Dependent Claim 17 words
A contrast medium according to claim 29 wherein said perfluorocarbon gas is C 6 F 14 .
Claim 37
Dependent Claim 14 words
A contrast medium according to claim 22 further comprising a thickening or suspending agent.
Claim 38
Dependent Claim 25 words
A contrast medium according to claim 35 wherein said thickening or suspending agent is selected from the group consisting of cellulose, carboxymethylcellulose, methylcellulose, and methylhydroxycellulose.
Claim 39
Dependent Claim 15 words
A contrast medium according to claim 36 wherein said thickening or suspending agent is methylcellulose.
Claim 40
Dependent Claim 21 words
A contrast medium according to claim 22 further comprising a compound selected from the group antacids, antiflatulents, antifoaming agents, and surfactants.
Claim 41
Dependent Claim 24 words
A contrast medium according to claim 38 wherein said compound selected from the group antacids, antiflatulents, antifoaming agents, and surfactants, comprises a polymeric siloxane.
Claim 42
Dependent Claim 13 words
A contrast medium according to claim 39 wherein said polymeric siloxane is dimethylpolysiloxane.
Claim 43
Dependent Claim 12 words
A contrast medium according to claim 40 wherein said dimethylpolysiloxane is simethicone.
Claim 44
Dependent Claim 34 words
A contrast medium according to claim 22 wherein said microspheres comprise a polyoxypropylene-polyoxyethylene copolymer, and said perfluorocarbon gas comprises C 5 F 12 , and wherein said contrast medium further comprises methylcellulose and simethicone.
Claim 45
Dependent Claim 33 words
A substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon.
Claim 46
Dependent Claim 33 words
A substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon.
Claim 47
Dependent Claim 91 words
An aqueous suspension of microspheres according to claim 43 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, ε-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, 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).
Claim 48
Dependent Claim 82 words
An aqueous suspension of microspheres according to claim 44 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, ε-caprolactone, acrolein, cyanoacrylate, bisphenol A, epichlorhydrin, 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.
Claim 49
Dependent Claim 45 words
An aqueous suspension of microspheres according to claim 43 wherein said microspheres comprise synthetic polymers or copolymers selected from the group consisting of polyacrylic acid, polyethyleneimine, polymethacrylic acid, polymethylmethacrylate, polysiloxane, polydimethylsiloxane, polylactic acid, poly(ε-capro-lactone), epoxy resin, poly(ethylene oxide), poly(ethylene glycol), polyamide, polyvinylidene-polyacrylonitrile, polyvinylidene-polyacrylonitrile-polymethylmethacrylate, and polystyrene-polyacrylonitrile.
Claim 50
Dependent Claim 16 words
An aqueous suspension of microspheres according to claim 43 wherein said microspheres comprise a polyvinylidene-polyacrylonitrile copolymer.
Claim 51
Dependent Claim 16 words
An aqueous suspension of microspheres according to claim 43 wherein said microspheres comprise a polyoxypropylene-polyoxyethylene copolymer.
Claim 52
Dependent Claim 19 words
An aqueous suspension of microspheres according to claim 43 wherein said microspheres are prepared by a heat expansion process.
Claim 53
Dependent Claim 38 words
An aqueous suspension of microspheres according to claim 43 wherein said perfluorocarbon gas is selected from the group consisting of perfluorocarbons having between 1 and about 9 carbon atoms and between about 4 and about 20 fluorine atoms.
Claim 54
Dependent Claim 35 words
An aqueous suspension of microspheres according to claim 50 wherein said perfluorocarbon gas is selected from the group consisting of perfluorocarbons having less than about 4 carbon atoms and less than about 10 fluorine atoms.
Claim 55
Dependent Claim 19 words
An aqueous suspension of microspheres according to claim 50 wherein said perfluorocarbon gas is C 3 F 8 .
Claim 56
Dependent Claim 19 words
An aqueous suspension of microspheres according to claim 50 wherein said perfluorocarbon gas is C 4 F 10 .
Claim 57
Dependent Claim 19 words
An aqueous suspension of microspheres according to claim 50 wherein said perfluorocarbon gas is C 5 F 12 .
Claim 58
Dependent Claim 19 words
An aqueous suspension of microspheres according to claim 50 wherein said perfluorocarbon gas is C 6 F 14 .
Claim 59
Dependent Claim 34 words
An aqueous suspension according to claim 43 wherein said microspheres comprise a polyoxypropylene-polyoxyethylene copolymer, and said perfluorocarbon gas comprises C 5 F 12 , and wherein said aqueous suspension further comprises methylcellulose and simethicone.
Claim 60
Dependent Claim 53 words
A kit for computed tomography imaging of the gastrointestinal region or other body cavities of a patient comprising low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, in combination with a thickening or suspending agent.
Claim 61
Dependent Claim 53 words
A kit for computed tomography imaging of the gastrointestinal region or other body cavities of a patient comprising low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, in combination with a thickening or suspending agent.
Claim 62
Dependent Claim 44 words
A kit for diagnostic imaging of a patient comprising low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, in combination with a thickening or suspending agent.
Claim 63
Dependent Claim 44 words
A kit for diagnostic imaging of a patient comprising low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, in combination with a thickening or suspending agent.
Claim 64
Independent Claim 81 words
A method of providing an image of the gastrointestinal region and other body cavities of a patient comprising (a) administering to the patient a contrast medium comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, and (b) scanning the patient using computed tomography imaging to obtain visible images of the gastrointestinal region or other body cavities.
Claim 65
Independent Claim 81 words
A method of providing an image of the gastrointestinal region and other body cavities of a patient comprising (a) administering to the patient a contrast medium comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, and (b) scanning the patient using computed tomography imaging to obtain visible images of the gastrointestinal region or other body cavities.
Claim 66
Independent Claim 73 words
A method of providing an image of a region of a patient comprising (a) administering to the patient a contrast medium comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, and (b) scanning the patient using diagnostic imaging to obtain visible images of the region of a patient.
Claim 67
Independent Claim 73 words
A method of providing an image of a region of a patient comprising (a) administering to the patient a contrast medium comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, and (b) scanning the patient using diagnostic imaging to obtain visible images of the region of a patient.
Claim 68
Independent Claim 83 words
A method for diagnosing the presence of diseased tissue in the gastrointestinal region or other body cavities of a patient comprising (a) administering to the patient a contrast medium comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, and (b) scanning the patient using computed tomography imaging to obtain visible images of any diseased tissue in the patient.
Claim 69
Independent Claim 83 words
A method for diagnosing the presence of diseased tissue in the gastrointestinal region or other body cavities of a patient comprising (a) administering to the patient a contrast medium comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, and (b) scanning the patient using computed tomography imaging to obtain visible images of any diseased tissue in the patient.
Claim 70
Independent Claim 74 words
A method for diagnosing the presence of diseased tissue in a patient comprising (a) administering to the patient a contrast medium comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, and (b) scanning the patient using diagnostic imaging to obtain visible images of any diseased tissue in the patient.
Claim 71
Independent Claim 74 words
A method for diagnosing the presence of diseased tissue in a patient comprising (a) administering to the patient a contrast medium comprising a substantially homogeneous aqueous suspension of low density gas-filled microspheres having an internal void volume of at least about 75% of the total volume of the microsphere, wherein said gas comprises a perfluorocarbon, and (b) scanning the patient using diagnostic imaging to obtain visible images of any diseased tissue in the patient.

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