Mixed gas microbubble compositions
First Claim
1. An injectable ultrasound contrast medium comprising:
- (a) biocompatible at body temperature gaseous substances which, when in suspension in an aqueous carrier liquid containing surfactants, additives, and stabilizers, provide contrast agents for ultrasound echocardiography, wherein;
(b) the medium is a mixture which contains a modifier gas A and the balance of the mixture is an osmotic agent gas B;
(c) the ratio of gas A to gas B is 200;
1 to 3;
2 by volume; and
(d) gas B has a water solubility of not more than about 0.5 mM at 25°
C. and one atmosphere and an average molecular weight at least about 4 times that of gas A.
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Accused Products
Abstract
A microbubble preparation formed of a plurality of microbubbles comprising a first gas and a second gas surrounded by a membrane such as a surfactant, wherein the first gas and the second gas are present in a molar ratio of from about 1:100 to about 1000:1, and wherein the first gas has a vapor pressure of at least about (760−x) mm Hg at 37° C., where x is the vapor pressure of the second gas at 37° C., and wherein the vapor pressure of each of the first and second gases is greater than about 75 mm Hg at 37° C.; also disclosed are methods for preparing microbubble compositions, including compositions that rapidly shrink from a first average diameter to a second average diameter less than about 75% of the first average diameter and are stabilized at the second average diameter; kits for preparing microbubbles; and methods for using such microbubbles as ultrasound contrast agents.
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Citations
26 Claims
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1. An injectable ultrasound contrast medium comprising:
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(a) biocompatible at body temperature gaseous substances which, when in suspension in an aqueous carrier liquid containing surfactants, additives, and stabilizers, provide contrast agents for ultrasound echocardiography, wherein;
(b) the medium is a mixture which contains a modifier gas A and the balance of the mixture is an osmotic agent gas B;
(c) the ratio of gas A to gas B is 200;
1 to 3;
2 by volume; and
(d) gas B has a water solubility of not more than about 0.5 mM at 25°
C. and one atmosphere and an average molecular weight at least about 4 times that of gas A.- View Dependent Claims (3, 4, 5)
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2. An injectable ultrasound contrast medium comprising:
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(a) biocompatible at body temperature gaseous substances which, when in suspension in an aqueous carrier liquid containing surfactants, additives, and stabilizers, provide contrast agents for ultrasound echocardiography, wherein;
(b) the medium is a mixture which contains a modifier gas A and the balance of the mixture is an osmotic agent gas B;
(c) the ratio of gas A to gas B is 738;
22 to 3;
2 by volume; and
(d) gas B is selected from the group consisting of fluorocarbons, CCl2F2, CHClF2, N(C2F5)3, N(C3F7)3, and mixtures thereof. - View Dependent Claims (6)
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7. An injectable ultrasound contrast agent comprising:
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(a) a suspension of gas filled microbubbles or microballoons in a physiologically acceptable aqueous carrier comprising surfactants, additives, and stabilizers, wherein;
(b) the gas is a gas mixture containing a biocompatible gas A and the balance of the mixture is a biocompatible gas B;
(c) the ratio of gas A to gas B is 200;
1 to 3;
2 by volume; and
(d) gas B has a water solubility of not more than about 0.5 mM at 25°
C. and one atmosphere and an average molecular weight at least about 4 times that of gas A.- View Dependent Claims (9, 10, 11, 12, 13, 14)
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8. An injectable ultrasound contrast agent comprising:
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(a) a suspension of gas filled microbubbles or microballoons in a physiologically acceptable aqueous carrier comprising surfactants, additives, and stabilizers, wherein;
(b) the gas is a gas mixture containing a biocompatible gas A and the balance of the mixture is a biocompatible gas B;
(c) the ratio of gas A to gas B is 738;
22 to 3;
2 by volume; and
(d) gas B is selected from the group consisting of fluorocarbons, CCl2F2, CHClF2, N(C2F5)3, N(C3F7)3, and mixtures thereof.
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15. A dry formulation comprising:
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(a) surfactants, additives, and stabilizers stored under a mixture of substances which at body temperature are biocompatible gases, wherein;
(b) at least one of the biocompatible gases is a fluorine-containing gas having a water solubility of not more than about 0.5 mM at 25°
C. and one atmosphere and an average molecular weight at least about 4 times that of air, oxygen, nitrogen, carbon dioxide or mixtures thereof;
(c) the balance is air, oxygen, nitrogen, carbon dioxide, or mixtures thereof; and
(d) the ratio of said air, oxygen, nitrogen, carbon dioxide, or mixtures thereof to said fluorine-containing gas is 200;
1 to 3;
2 by volume.
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16. A dry formulation comprising:
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(a) surfactants, additives, and stabilizers stored under a mixture of substances which at body temperature are biocompatible gases, wherein;
(b) at least one of the biocompatible gases is a fluorocarbon gas;
(c) the balance is air, oxygen, nitrogen, carbon dioxide, or mixtures thereof; and
(d) the ratio of said air, oxygen, nitrogen, carbon dioxide, or mixtures thereof to said fluorine-containing gas is 738;
22 to 3;
2 by volume.
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17. A two component kit comprising:
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(a) as the first component, a dry formulation of surfactants, additives, and stabilizers stored under a mixture of substances which at body temperature are gases; and
,(b) as the second component, a physiologically acceptable carrier liquid which, when admixed with the first component, provides, as a suspension of the two components, an ultrasound contrast agent, wherein;
(c) at least one of the gases in the mixture is a gas having a water solubility of not more than about 0.5 mM at 25°
C. and one atmosphere and an average molecular weight of at least about 4 times that of air, oxygen, nitrogen, carbon dioxide, or mixtures thereof;
(d) the balance is air, oxygen, nitrogen, carbon dioxide, or mixtures thereof; and
(e) the ratio of said air, oxygen, nitrogen, carbon dioxide, or mixtures thereof to said gas having a water solubility of not more than about 0.5 mM at 25°
C. and one atmosphere and an average molecular weight of at least about 4 times that of air, oxygen, nitrogen, carbon dioxide, or mixtures thereof is 200;
1 to 3;
2 by volume.
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18. A two component kit comprising:
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(a) as the first component, a dry formulation of surfactants, additives, and stabilizers stored under a mixture of substances which at body temperature are gases; and
,(b) as the second component, a physiologically acceptable carrier liquid which, when admixed with the first component, provides, as a suspension of the two components, an ultrasound contrast agent wherein;
(c) at least one of the gases in the mixture is a fluorocarbon biocompatible gas;
(d) the balance is air, oxygen, nitrogen, carbon dioxide, or mixtures thereof; and
(e) the ratio of said air, oxygen, nitrogen, carbon dioxide, or mixtures thereof to said gas having a water solubility of not more than about 0.5 mM at 25 °
C. and one atmosphere and an average molecular weight of at least about 4 times that of air, oxygen, nitrogen, carbon dioxide, or mixtures thereof is 200;
1 to 3;
2 by volume.- View Dependent Claims (19)
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20. A method of imaging organs in a living body, said method comprising the steps of:
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(1) administering to said body an ultrasound contrast agent comprising a suspension of gas filled microbubbles or microballoons in a physiologically acceptable aqueous carrier comprising surfactants, additives, and stabilizers, wherein;
(a) the gas is a gas mixture containing a biocompatible gas A and a biocompatible gas B;
(b) gas B has a water solubility of not more than about 0.5 mM at 25° and
one atmosphere and an average molecular weight at least about 4 times that of gas A, and(c) the ratio of gas A to gas B is 200;
1 to 3;
2 by volume; and
(2) subjecting said body to ultrasound therapy. - View Dependent Claims (26)
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21. A method of imaging organs in a living body, said method comprising the steps of:
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(1) administering to said body an ultrasound contrast agent comprising a suspension of gas filled microbubbles or microballoons in a physiologically acceptable aqueous carrier comprising surfactants, additives, and stabilizers, wherein;
(a) the gas is a gas mixture containing a biocompatible gas A and a biocompatible gas B;
(b) gas B is a fluorocarbon; and
(c) the ratio of gas A to gas B is 738;
22 to 3;
2 by volume; and
(2) subjecting said body to ultrasound therapy. - View Dependent Claims (22, 23, 24, 25)
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Specification