Patent US5556610A successfully refreshed from Google Patents.
US5556610A
Expired / Lapsed
US
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Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method
Assignee: Bracco Suisse SA
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Filing: 1994-11-30
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Granted: 1996-09-17
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Expires: 2014-11-30
Abstract
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 0.15 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.
Inventors
- 👤 Feng Yan
- 👤 Michel Schneider
- 👤 Jean Brochot
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 18:06
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/225; A61K49/223
Claims Analysis
Total Claims: 31
Claim 1
Independent Claim
97 words
An injectable ultrasound contrast medium comprising biocompatible at body temperature gaseous substances which when in suspension in an aqueous carrier liquid containing usual surfactants, additives and stabilisers provide contrast agents for ultrasound echography, wherein the medium is a mixture of gases (A) and (B) in which, at least one of the gases (B), present in an amount of between 0.5-41% by vol., has a molecular weight greater than 80 daltons and its solubility in water is below 0.0283 ml of gas per ml of water measured under standard conditions, the balance of the mixture being gas A.
Claim 2
Dependent Claim
97 words
An injectable ultrasound contrast medium comprising biocompatible at body temperature gaseous substances which when in suspension in an aqueous carrier liquid containing usual surfactants, additives and stabilisers provide contrast agents for ultrasound echography, wherein the medium is a mixture of gases (A) and (B) in which, at least one of the gases (B), present in an amount of between 0.5-41% by vol., has a molecular weight greater than 80 daltons and its solubility in water is below 0.0283 ml of gas per ml of water measured under standard conditions, the balance of the mixture being gas A.
Claim 3
Dependent Claim
15 words
The ultrasound contrast medium of claim 1, wherein gas (B) is a fluorine-containing biocompatible gas.
Claim 4
Dependent Claim
71 words
The ultrasound contrast medium of claim 2, wherein the fluorine-containing gas is selected from the group consisting of SF 6 , CF 4 , C 2 F 6 , C 2 F 8 , C 3 F 6 , C 3 F 8 , C 4 F 6 , C 4 F 8 , C 4 F 10 , C 5 F 10 , C 5 F 12 and mixtures thereof.
Claim 5
Dependent Claim
17 words
The ultrasound contrast medium of claim 3, wherein the fluorine-containing gas is sulfur hexafluoride or octafluoro cyclobutane.
Claim 6
Dependent Claim
25 words
The ultrasound contrast medium of claim 1, wherein gas A is selected from the group consisting of air, oxygen, nitrogen, carbon dioxide and mixtures thereof.
Claim 7
Dependent Claim
89 words
An injectable ultrasound contrast agent comprising of a suspension of gas filled microbubbles or microballoons in a physiologically acceptable aqueous carrier comprising usual surfactants, additives and stabilisers, wherein the gas is 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 vol. 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.
Claim 8
Dependent Claim
89 words
An injectable ultrasound contrast agent comprising of a suspension of gas filled microbubbles or microballoons in a physiologically acceptable aqueous carrier comprising usual surfactants, additives and stabilisers, wherein the gas is 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 vol. 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.
Claim 9
Dependent Claim
15 words
The ultrasound contrast agent of claim 6, wherein gas (B) is a fluorine-containing biocompatible gas.
Claim 10
Dependent Claim
71 words
The ultrasound contrast agent of claim 7, wherein the fluorine-containing gas is selected from the group consisting of SF 6 , CF 4 , C 2 F 6 , C 2 F 8 , C 3 F 6 , C 3 F 8 , C 4 F 6 , C 4 F 8 , C 4 F 10 , C 5 F 10 , C 5 F 12 and mixtures thereof.
Claim 11
Dependent Claim
25 words
The ultrasound contrast agent of claim 6, wherein gas A is selected from the group consisting of air, oxygen, nitrogen, carbon dioxide or mixtures thereof.
Claim 12
Dependent Claim
27 words
The ultrasound contrast agent of claim 6, wherein the surfactants comprise at least one film forming surfactant present in laminar and/or lamellar form and, optionally, hydrophilic stabilizers.
Claim 13
Dependent Claim
15 words
The ultrasound contrast agent of claim 10, wherein the film forming surfactant is a phospholipid.
Claim 14
Dependent Claim
29 words
The ultrasound contrast agent of claim 11, wherein the phospholipid is selected from the group consisting of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, cardiolipin, sphingomyelin and mixtures thereof.
Claim 15
Dependent Claim
24 words
The ultrasound contrast agent of claim 11, wherein in addition to the phospholipid the aqueous carrier comprises copolymers of polyoxyethylene and polyoxypropylene, and glycerol.
Claim 16
Dependent Claim
21 words
The ultrasound contrast agent of claim 6, wherein the surfactants are soy bean oil, a polyethylene oxide sorbitan ester, or sorbitol.
Claim 17
Dependent Claim
84 words
A dry formulation comprising surfactants, additives and stabilisers stored under a mixture of substances which at the body temperature are biocompatible gases, at least one of which is a fluorine-containing 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 fluorine-containing gas being present in the mixture in an amount between 0.5-41% by vol., the balance 59-99.5% by vol. being air, oxygen, nitrogen, carbon dioxide or mixtures thereof.
Claim 18
Dependent Claim
84 words
A dry formulation comprising surfactants, additives and stabilisers stored under a mixture of substances which at the body temperature are biocompatible gases, at least one of which is a fluorine-containing 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 fluorine-containing gas being present in the mixture in an amount between 0.5-41% by vol., the balance 59-99.5% by vol. being air, oxygen, nitrogen, carbon dioxide or mixtures thereof.
Claim 19
Dependent Claim
132 words
A two component kit comprising, as the first component, a dry formulation of surfactants, additives and stabilisers stored under a mixture of substances which at body temperature are gases and, 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, in which at least one of the gases in the mixture is a fluorine-containing biocompatible gas whose molecular weight is greater than 80 daltons and whose solubility in water is below 0.0283 ml of gas per ml of water at standard conditions, wherein the gas is fluorine-containing biocompatible gas and is present in the mixture in an amount of between 0.5-41% by vol., the balance being air, oxygen, nitrogen, carbon dioxide or mixtures thereof.
Claim 20
Dependent Claim
132 words
A two component kit comprising, as the first component, a dry formulation of surfactants, additives and stabilisers stored under a mixture of substances which at body temperature are gases and, 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, in which at least one of the gases in the mixture is a fluorine-containing biocompatible gas whose molecular weight is greater than 80 daltons and whose solubility in water is below 0.0283 ml of gas per ml of water at standard conditions, wherein the gas is fluorine-containing biocompatible gas and is present in the mixture in an amount of between 0.5-41% by vol., the balance being air, oxygen, nitrogen, carbon dioxide or mixtures thereof.
Claim 21
Dependent Claim
71 words
The two component kit of claim 16, wherein the fluorine-containing gas is selected from the group consisting of SF 6 , CF 4 , C 2 F 6 , C 2 F 8 , C 3 F 6 , C 3 F 8 , C 4 F 6 , C 4 F 8 , C 4 F 10 , C 5 F 10 , C 5 F 12 and mixtures thereof.
Claim 22
Independent Claim
115 words
A method of imaging organs in a living body, said method comprising the steps of: (1) administering to said body an ultrasound contrast agent comprising of a suspension of gas filled microbubbles or microballoons in a physiologically acceptable aqueous carrier comprising surfactants, additives and stabilizers, wherein the gas is 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 vol. 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; and (2) subjecting said body to ultrasound therapy.
Claim 23
Independent Claim
115 words
A method of imaging organs in a living body, said method comprising the steps of: (1) administering to said body an ultrasound contrast agent comprising of a suspension of gas filled microbubbles or microballoons in a physiologically acceptable aqueous carrier comprising surfactants, additives and stabilizers, wherein the gas is 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 vol. 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; and (2) subjecting said body to ultrasound therapy.
Claim 24
Dependent Claim
13 words
The method of claim 18, wherein gas (B) is a fluorine-containing biocompatible gas.
Claim 25
Dependent Claim
69 words
The method of claim 19, wherein the fluorine-containing gas is selected from the group consisting of SF 6 , CF 4 , C 2 F 6 , C 2 F 8 , C 3 F 6 , C 3 F 8 , C 4 F 6 , C 4 F 8 , C 4 F 10 , C 5 F 10 , C 5 F 12 and mixtures thereof.
Claim 26
Dependent Claim
23 words
The method of claim 18 wherein gas A is selected from the group consisting of air, oxygen, nitrogen, carbon dioxide and mixtures thereof.
Claim 27
Dependent Claim
25 words
The method of claim 18, wherein the surfactants comprise at least one film forming surfactant present in laminar or lamellar form and, optionally, hydrophilic stabilizers.
Claim 28
Dependent Claim
13 words
The method of claim 22, wherein the film forming surfactant is a phospholipid.
Claim 29
Dependent Claim
27 words
The method of claim 23, wherein the phospholipid is selected from the group consisting of phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, cardiolipin, sphingomyelin and mixtures thereof.
Claim 30
Dependent Claim
22 words
The method of claim 23, wherein in addition to the phospholipid the aqueous carrier comprises copolymers of polyoxyethylene and polyoxypropylene, and glycerol.
Claim 31
Dependent Claim
19 words
The method of claim 18, wherein the surfactants are soy bean oil, a polyethylene oxide sorbitan ester, or sorbitol.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-09-17 | 2000-03-18 | 2000-09-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-09-17 | 2004-03-18 | 2004-09-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-09-17 | 2008-03-18 | 2008-09-17 | $7700.00 | Window Closed / Lapsed |