US5558857A
Expired / Lapsed
US
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Contrast agents
Assignee: GE Healthcare AS
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Filing: 1992-06-03
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Granted: 1996-09-24
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Expires: 2012-06-03
Abstract
Abstract PCT No. PCT/EP92/01327 Sec. 371 Date Dec. 23, 1993 Sec. 102(e) Date Dec. 23, 1993 PCT Filed Jun. 3, 1992 PCT Pub. No. WO92/21382 PCT Pub. Date Dec. 10, 1992This invention relates to ultrasound contrast agents in the form of microparticles comprising a biotolerable matrix (e.g. of a carbohydrate or an X-ray contrast agent) in association with a gas or a precursor therefor. The contrast agents are stabilized to enhance their in vivo stability and/or echogenicity by covalently modifying the structure of the matrix, e.g. to introduce crosslinking groups or to attach lipophilic groups and/or molecules. The covalent moieties may include biodegradable linkages to assist rapid subsequent elimination of the contrast agents from the system.
Inventors
- 👤 Jo Klaveness
- 👤 Pål Rongved
- 👤 Per Strande
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 06:47
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
50 words
Ultrasound contrast agents in the form of microparticles comprising a biotolerable matrix in association with a gas or a precursor therefor, characterised in that the microparticles are stabilised by covalent bonding of the matrix and by having lipophilic groups, lipophilic molecules, or a combination thereof, covalently attached to the microparticles.
Claim 2
Dependent Claim
50 words
Ultrasound contrast agents in the form of microparticles comprising a biotolerable matrix in association with a gas or a precursor therefor, characterised in that the microparticles are stabilised by covalent bonding of the matrix and by having lipophilic groups, lipophilic molecules, or a combination thereof, covalently attached to the microparticles.
Claim 3
Dependent Claim
16 words
Ultrasound contrast agents as claimed in claim 1 in which the biotolerable matrix is a carbohydrate.
Claim 4
Dependent Claim
14 words
Ultrasound contrast agents as claimed in claim 2 in which the carbohydrate is galactose.
Claim 5
Dependent Claim
18 words
Ultrasound contrast agents as claimed in claim 1 in which the biotolerable matrix is an X-ray contrast agent.
Claim 6
Dependent Claim
35 words
Ultrasound contrast agents as claimed in claim 1 in which the microparticles are present in the form of aggregates having an aggregate size of 30-50 micrometers of microparticles having a particle size of 5-10 micrometers.
Claim 7
Dependent Claim
18 words
Ultrasound contrast agents as claimed in claim 5 in which the said aggregates have been prepared by ball-milling.
Claim 8
Dependent Claim
25 words
Ultrasound contrast agents as claimed in claim 1 in which the microparticles are stabilised by the presence of crosslinking groupings covalently attached to the matrix.
Claim 9
Dependent Claim
42 words
Ultrasound contrast agents as claimed in claim 7 in which the crosslinking groupings contain linkages which are biodegradable in vivo, and which are selected from the group consisting of amide, imide, imine, ester, anhydride, acetal, carbamate, carbonate, carbonate ester and disulphide groups.
Claim 10
Dependent Claim
111 words
Ultrasound contrast agents in the form of microparticles comprising a biotolerable matrix in association with a gas or a precursor therefor, characterized in that the microparticles are stabilized by covalent bonding of the matrix and by the presence of crosslinking groups covalently attached to the matrix and wherein the crosslinking groups contain linkages which are biodegradable in vivo, and which have a formula (Ia): ##STR12## where m and n are each 0 or 1; R 1 and R 2 are each selected from the group consisting of hydrogen atoms, monovalent organic groups and groups of formula --O.CO.(O) m ; or R 1 and R 2 together form a divalent organic group.
Claim 11
Dependent Claim
111 words
Ultrasound contrast agents in the form of microparticles comprising a biotolerable matrix in association with a gas or a precursor therefor, characterized in that the microparticles are stabilized by covalent bonding of the matrix and by the presence of crosslinking groups covalently attached to the matrix and wherein the crosslinking groups contain linkages which are biodegradable in vivo, and which have a formula (Ia): ##STR12## where m and n are each 0 or 1; R 1 and R 2 are each selected from the group consisting of hydrogen atoms, monovalent organic groups and groups of formula --O.CO.(O) m ; or R 1 and R 2 together form a divalent organic group.
Claim 12
Dependent Claim
43 words
Ultrasound contrast agents as claimed in claim 9 in which the microparticles are stabilised by having lipophilic groups covalently attached to the microparticles wherein the lipophilic groups are derived from a fatty acid, an aralkanoic acid, or a cholesterol, poloxamer or phospholip derivative.
Claim 13
Dependent Claim
39 words
Ultrasound contrast agents as claimed in claim 10 in which the said lipophilic groups are derived from capric acid, palmitic acid, stearic acid, linolenic acid, behenic acid, docosanedioic acid, melissic acid, phenylbutyric acid, 5β-cholanic acid, bis(acryloyl)pluronic F68 or dioleylphosphatidylethanolamine.
Claim 14
Dependent Claim
72 words
Ultrasound contrast agents as claimed in claim 8 in which the crosslinking groups contain linkages which are biodegradable in vivo and which have formula (Ia): ##STR13## where m and n are each 0 or 1; R 1 and R 2 are each selected from the group consisting of hydrogen atoms, monovalent organic groups and groups of formula --O.CO.(O) m ; or R 1 and R 2 together form a divalent organic group.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 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 |