US5536490A
Expired / Lapsed
US
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Contrast agents
Assignee: GE Healthcare AS
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Filing: 1992-03-28
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Granted: 1996-07-16
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Expires: 2012-03-28
Abstract
Abstract PCT No. PCT/EP92/00715 Sec. 371 Date Oct. 29, 1993 Sec. 102(e) Date Oct. 29, 1993 PCT Filed Mar. 28, 1992 PCT Pub. No. WO92/17212 PCT Pub. Date Oct. 15, 1992.The invention relates to diagnostic ultrasound contrast agents comprising vesicles comprising an amphiphilic phospholipid material capable of formation of gas-containing vesicles wherein the vesicles contain gas which comprises sulphur hexafluoride. The contrast agents and vesicles exhibit good stability in vivo upon administration and may if desired incorporate biodegradable linkages so as to possess particularly desired levels of biodegradability.
Inventors
- 👤 Jo Klaveness
- 👤 Hanno Priebe
- 👤 Pal Rongved
- 👤 Lars Stubberud
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-03 05:19
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223
Claims Analysis
Total Claims: 44
Claim 1
Independent Claim
20 words
A diagnostic ultrasound contrast agent comprising stabilized microbubbles of gaseous sulphur hexafluoride encapsulated by non-proteinaceous crosslinked or polymerized amphiphilic moieties.
Claim 2
Dependent Claim
20 words
A diagnostic ultrasound contrast agent comprising stabilized microbubbles of gaseous sulphur hexafluoride encapsulated by non-proteinaceous crosslinked or polymerized amphiphilic moieties.
Claim 3
Dependent Claim
24 words
A method of enhancing ultrasound images of a vascular system comprising administering to said system a diagnostic ultrasound contrast agent according to claim 1.
Claim 4
Dependent Claim
19 words
Microbubbles comprising an amphiphilic phospholipid material capable of formation of gas-containing microbubbles, said microbubbles containing gas comprising sulphur hexafluoride.
Claim 5
Dependent Claim
19 words
Microbubbles comprising an amphiphilic phospholipid material capable of formation of gas-containing microbubbles, said microbubbles containing gas comprising sulphur hexafluoride.
Claim 6
Dependent Claim
26 words
Microbubbles as claimed in claim 3 wherein said phospholipid material comprises hydrophilic groups selected from the group consisting of choline, ethanolamine, serine, glycerol, pentoses and hexoses.
Claim 7
Dependent Claim
16 words
Microbubbles as claimed in claim 4 wherein said phospholipid material comprises a lecithin or derivative thereof.
Claim 8
Dependent Claim
10 words
An aqueous dispersion comprising microbubbles as claimed in claim 3.
Claim 9
Dependent Claim
10 words
An aqueous dispersion comprising microbubbles as claimed in claim 4.
Claim 10
Dependent Claim
10 words
An aqueous dispersion comprising microbubbles as claimed in claim 5.
Claim 11
Dependent Claim
14 words
Microbubbles as claimed in claim 3 wherein said phospholipid material is crosslinked or polymerized.
Claim 12
Dependent Claim
35 words
Microbubbles as claimed in claim 9 wherein said crosslinked or polymerized phospholipid material contains biodegradable linkages selected from the group consisting of amide, imide, imine, ester, anhydride, acetal, carbamate, carbonate, carbonate ester and disulphide groups.
Claim 13
Dependent Claim
17 words
Microbubbles as claimed in claim 10 wherein said crosslinked or polymerized phospholipid material contains biodegradable amide linkages.
Claim 14
Dependent Claim
14 words
Microbubbles as claimed in claim 10 wherein said phospholipid material contains biodegradable crosslinking groups.
Claim 15
Dependent Claim
90 words
Microbubbles as claimed in claim 12 wherein said biodegradable crosslinking groups include units of formula --(Y).sub.n.CO.O.C(R.sup.1 R.sup.2).O.CO.(Z).sub.n -- where Y and Z, which may be the same or different, are --O--, --S-- or --NR 3 --; R 1 and R 2 , which may be the same or different, are hydrogen atoms or carbon-attached monovalent organic groups or together represent a carbon-attached divalent organic group; R 3 is a hydrogen atom or an organic group; and the symbols n, which may be the same or different, are zero or 1.
Claim 16
Dependent Claim
15 words
Microbubbles as claimed in claim 9 obtained from polymerizable phospholipid material containing unsaturated lipophilic chains.
Claim 17
Dependent Claim
25 words
Microbubbles as claimed in claim 14 wherein said unsaturated lipophilic chains are oleyl or linoleyl groups or contain diacetylene groupings or acryloyl or methacryloyl groupings.
Claim 18
Dependent Claim
17 words
Microbubbles as claimed in claim 9 which are crosslinked between the hydrophilic parts of the phospholipid moieties.
Claim 19
Dependent Claim
17 words
Microbubbles as claimed in claim 3 which comprise sulphur hexafluoride stabilized by monolayers of said phospholipid material.
Claim 20
Dependent Claim
20 words
Microbubbles as claimed in claim 9 which comprise sulphur hexafluoride stabilized by monolayers of said crosslinked or polymerized phospholipid material.
Claim 21
Dependent Claim
13 words
Microbubbles as claimed in claim 3 having an average size of 0.1-10 μm.
Claim 22
Dependent Claim
13 words
Microbubbles as claimed in claim 19 having an average size of 1-7 μm.
Claim 23
Dependent Claim
13 words
Microbubbles as claimed in claim 9 having an average size of 0.1-10 μm.
Claim 24
Dependent Claim
13 words
Microbubbles as claimed in claim 21 having an average size of 1-7 μm.
Claim 25
Dependent Claim
20 words
Microbubbles as claimed in claim 9 wherein the crosslinked or polymerized phospholipid material comprises phospholipid material reacted with preformed polymer.
Claim 26
Dependent Claim
10 words
An aqueous dispersion comprising microbubbles as claimed in claim 9.
Claim 27
Dependent Claim
12 words
A diagnostic ultrasound contrast agent comprising microbubbles as claimed in claim 9.
Claim 28
Dependent Claim
18 words
A contrast agent as claimed in claim 25 having a half-life in vivo of 1 to 48 hours.
Claim 29
Dependent Claim
18 words
A contrast agent as claimed in claim 26 having a half-life in vivo of 1 to 12 hours.
Claim 30
Dependent Claim
17 words
A contrast agent as claimed in claim 25 wherein said microbubbles are dispersed in an aqueous carrier.
Claim 31
Dependent Claim
30 words
A process for the preparation of a contrast agent which comprises generating microbubbles comprising amphiphilic phospholipid material capable of formation of gas-containing microbubbles, said microbubbles containing gas comprising sulphur hexafluoride.
Claim 32
Dependent Claim
30 words
A process for the preparation of a contrast agent which comprises generating microbubbles comprising amphiphilic phospholipid material capable of formation of gas-containing microbubbles, said microbubbles containing gas comprising sulphur hexafluoride.
Claim 33
Dependent Claim
32 words
A process as claimed in claim 29 which comprises shaking or sonicating an amphiphilie-containing mixture comprising a phospholipid in the presence of sulphur hexafluoride to generate a fluid dispersion of said microbubbles.
Claim 34
Dependent Claim
24 words
A process as claimed in claim 30 wherein an aqueous amphiphile-containing mixture comprising a phospholipid is used to generate an aqueous dispersion of microbubbles.
Claim 35
Dependent Claim
16 words
A process as claimed in claim 30 wherein the contrast agent is isolated by freeze drying.
Claim 36
Dependent Claim
32 words
A process for the preparation of a contrast agent which comprises crosslinking or polymerizing microbubbles comprising amphiphilic phospholipid material capable of formation of gas-containing microbubbles, said microbubbles containing gas comprising sulphur hexafluoride.
Claim 37
Dependent Claim
32 words
A process for the preparation of a contrast agent which comprises crosslinking or polymerizing microbubbles comprising amphiphilic phospholipid material capable of formation of gas-containing microbubbles, said microbubbles containing gas comprising sulphur hexafluoride.
Claim 38
Dependent Claim
21 words
A process as claimed in claim 33 wherein crosslinking or polymerization is effected between the hydrophilic parts of the phospholipid material.
Claim 39
Dependent Claim
20 words
A process as claimed in claim 33 wherein crosslinking or polymerization is effected by self condensation of the phospholipid material.
Claim 40
Dependent Claim
17 words
A process as claimed in claim 33 wherein the phospholipid material is reacted with a preformed polymer.
Claim 41
Dependent Claim
16 words
A process as claimed in claim 33 wherein the contrast agent is isolated by freeze drying.
Claim 42
Dependent Claim
10 words
A contrast agent prepared by the process of claim 29.
Claim 43
Dependent Claim
24 words
A method of enhancing ultrasound images of a vascular system comprising administering to said system a diagnostic ultrasound contrast agent according to claim 25.
Claim 44
Dependent Claim
24 words
A method of enhancing ultrasound images of a vascular system comprising administering to said system a diagnostic ultrasound contrast agent according to claim 38.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-07-16 | 2000-01-15 | 2000-07-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-07-16 | 2004-01-15 | 2004-07-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-07-16 | 2008-01-15 | 2008-07-16 | $7700.00 | Window Closed / Lapsed |