US5558856A
Expired / Lapsed
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Microbubble-generating contrast agents for ultrasound and magnetic resonance imaging
Assignee: GE Healthcare AS
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Filing: 1993-01-08
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Granted: 1996-09-24
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Expires: 2013-01-08
Abstract
Abstract PCT No. PCT/EP93/00027 Sec. 371 Date Dec. 9, 1994 Sec. 102(e) Date Dec. 9, 1994 PCT Filed Jan. 8, 1993 PCT Pub. No. WO93/13808 PCT Pub. Date Jul. 22, 1993The present invention relates to contrast agents comprising microbubble-generating carbohydrate particles having a surfactant admixed within the microparticulate structure, with the proviso that the surfactant is not a saturated C10-20 fatty acid. The contrast agents exhibit useful levels of contrast efficiency and/or stability and may be used in diagnostic applications such as ultrasound and MR imaging.
Inventors
- 👤 Jo Klaveness
- 👤 Pal Rongved
- 👤 Lars Stubberud
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 18:17
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/06; A61K49/18; A61K49/1818; A61K49/1821; A61K49/22; A61K49/222; A61K49/223; A61K49/225
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
34 words
A contrast agent comprising microbubble-generating carbohydrate microparticles having a surfactant admixed within the microparticulate structures, wherein the contrast agent contains sulphur hexafluoride or low molecular weight fluorinated hydrocarbons optionally together with another biocompatible gas.
Claim 2
Dependent Claim
34 words
A contrast agent comprising microbubble-generating carbohydrate microparticles having a surfactant admixed within the microparticulate structures, wherein the contrast agent contains sulphur hexafluoride or low molecular weight fluorinated hydrocarbons optionally together with another biocompatible gas.
Claim 3
Dependent Claim
22 words
A contrast agent as claimed in claim 1 in which the carbohydrate is a water-soluble pentose, hexose, disaccharide, polysaccharide or sugar alcohol.
Claim 4
Dependent Claim
14 words
A contrast agent as claimed in claim 2 in which the carbohydrate is galactose.
Claim 5
Dependent Claim
61 words
A contrast agent as claimed in claim 1 in which the surfactant is selected from straight chain aliphatic carboxylic acids and salts, sorbitan esters and mono- and di-glycerides thereof; aralkanoic acids and salts thereof; steroid acids; sterols; straight chain aliphatic alcohols; phospholipids; alkali metal alkyl sulphates and sulphonated esters; polyoxyethylene-polyoxypropylene copolymers; polyoxyethylated sorbitan esters and mixtures of any of the foregoing.
Claim 6
Dependent Claim
17 words
A contrast agent as claimed in claim 1 in which the surfactant comprises a lipophilically modified carbohydrate.
Claim 7
Dependent Claim
15 words
A contrast agent as claimed in claim 1 in which the surfactant comprises carbohydrate-containing liposomes.
Claim 8
Dependent Claim
25 words
A contrast agent as claimed in claim 1 in which the surfactant is present in an amount of 0.1-2.0% w/w relative to the microparticulate carbohydrate.
Claim 9
Dependent Claim
30 words
A contrast agent as claimed in claim 1 in which the microparticles are aggregates having an aggregate size of 30-50 micrometres of microparticles having a particle size of 1-10 micrometres.
Claim 10
Dependent Claim
55 words
A process for preparing a contrast agent as claimed in claim 1 which comprises (i) either mixing solutions of the carbohydrate and surfactant and removing the solvent(s) therefrom or mixing a solution of the carbohydrate with a liposome-forming material and removing the solvent therefrom and (ii) micronising the resulting mixture to yield the desired microparticles.
Claim 11
Dependent Claim
15 words
A process as claimed in claim 9 in which the mixture is micronised by ball-milling.
Claim 12
Dependent Claim
37 words
A method of generating an enhanced diagnostic image of a human or non-human animal body comprising administering into the vascular system of said body a diagnostic image enhancing amount of a contrast agent according to claim 1.
Claim 13
Dependent Claim
39 words
A method of generating an enhanced diagnostic ultrasonic image of a human or non-human animal body comprising administering into the vascular system of said body a diagnostic ultrasonic image enhancing amount of a contrast agent according to claim 1.
Claim 14
Dependent Claim
35 words
A method of generating an enhanced magnetic resonance image of a human or non-human animal body comprising administering to said body an magnetic resonance image enhancing amount of a contrast agent according to claim 1.
Claim 15
Dependent Claim
30 words
A contrast agent as claimed in claim 1, wherein said biocompatible gas is selected from the group consisting of air, nitrogen, oxygen, hydrogen, nitrous oxide, carbon dioxide, helium and argon.
Claim 16
Dependent Claim
17 words
A contrast agent as claimed in claim 14 containing nitrogen and a low molecular weight fluorinated hydrocarbon.
Claim 17
Dependent Claim
13 words
A contrast agent as claimed in claim 15, wherein the hydrocarbon is perfluorinated.
Claim 18
Dependent Claim
16 words
A contrast agent as claimed in claim 16 in which the carbohydrate is a water-soluble polysaccharide.
Claim 19
Dependent Claim
22 words
A contrast agent as claimed in claim 16 in which the surfactant is a phospholipid, a polyoxyethylene-polyoxoypropylene copolymer or a mixture thereof.
Claim 20
Dependent Claim
14 words
A contrast agent as claimed in claim 18 wherein said phospholipid is a phosphatidylcholine.
Claim 21
Dependent Claim
15 words
A contrast agent as claimed in claim 18 wherein said polyoxyethylene-polyoxoypropylene copolymer is Pluronic F68.
Claim 22
Dependent Claim
20 words
A contrast agent as claimed in claim 14 which is non-contrast giving before use, but which becomes effective on administration.
Claim 23
Dependent Claim
20 words
A contrast agent as claimed in claim 15 which is non-contrast giving before use, but which becomes effective on administration.
Claim 24
Dependent Claim
20 words
A contrast agent as claimed in claim 16 which is non-contrast giving before use, but which becomes effective on administration.
Claim 25
Dependent Claim
20 words
A contrast agent as claimed in claim 17 which is non-contrast giving before use, but which becomes effective on administration.
Claim 26
Dependent Claim
20 words
A contrast agent as claimed in claim 18 which as non-contrast giving before use, but which becomes effective on administration.
Claim 27
Dependent Claim
20 words
A contrast agent as claimed in claim 19 which is non-contrast giving before use, but which becomes effective on administration.
Claim 28
Dependent Claim
20 words
A contrast agent as claimed in claim 20 which is non-contrast giving before use, but which becomes effective on administration.
Claim 29
Dependent Claim
21 words
A contrast agent as claimed in claim 21 which on formulation for administration generates gas microbubbles on dissolution of the carbohydrate.
Claim 30
Dependent Claim
21 words
A contrast agent as claimed in claim 22 which on formulation for administration generates gas microbubbles on dissolution of the carbohydrate.
Claim 31
Dependent Claim
21 words
A contrast agent as claimed in claim 23 which on formulation for administration generates gas microbubbles on dissolution of the carbohydrate.
Claim 32
Dependent Claim
21 words
A contrast agent as claimed in claim 24 which on formulation for administration generates gas microbubbles on dissolution of the carbohydrate.
Claim 33
Dependent Claim
21 words
A contrast agent as claimed in claim 25 which on formulation for administration generates gas microbubbles on dissolution of the carbohydrate.
Claim 34
Dependent Claim
21 words
A contrast agent as claimed in claim 26 which on formulation for administration generates gas microbubbles on dissolution of the carbohydrate.
Claim 35
Dependent Claim
21 words
A contrast agent as claimed in claim 37 which on formulation for administration generates gas microbubbles on dissolution of the carbohydrate.
Claim 36
Dependent Claim
28 words
A contrast agent comprising microbubble-generating carbohydrate microparticles having a surfactant admixed within the microparticulate structure, wherein the contrast agent contains sulphur hexafluoride or low molecular weight fluorinated hydrocarbons.
Claim 37
Dependent Claim
28 words
A contrast agent comprising microbubble-generating carbohydrate microparticles having a surfactant admixed within the microparticulate structure, wherein the contrast agent contains sulphur hexafluoride or low molecular weight fluorinated hydrocarbons.
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) | 1999-09-24 | 2000-03-25 | 2000-09-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-09-24 | 2004-03-25 | 2004-09-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-09-24 | 2008-03-25 | 2008-09-24 | $7700.00 | Window Closed / Lapsed |