US4863717A
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US
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Methods for circumventing the problem of free radial reduction associated with the use of stable nitroxide free radicals as contrast agents for magnetic reasonance imaging
Assignee: University of Oregon
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Filing: 1986-11-10
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Granted: 1989-09-05
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Expires: 2006-11-10
Abstract
Abstract Nitroxide contrast agents for MRI have a long useful life and can be administered in low concentration doses. Such agents include nitroxide-doped liposomes that encapsulate an oxidant and large molecules having surfaces covered with persistent nitroxide free radicals.
Inventors
- 👤 John F. W. Keana
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:37
CPC Classifications
C; C07; C07C; C07C291/00; C07C291/02; C07C291/04; A; A61; A61K; A61K49/00; A61K49/06; A61K49/18; A61K49/1806; A61K49/1812; A61K49/20; Y; Y10; Y10S; Y10S436/00; Y10S436/803; Y10S436/806; Y10T; Y10T436/00; Y10T436/24
Claims Analysis
Total Claims: 50
Claim 1
Independent Claim
50 words
In an MRI contrast agent which is a liposome having a bound spin label that is subject to reduction, and thus loss of contrast enhancement capability when in a reducing environment, the improvement wherein the liposome incorporates oxidizing means for oxidizing and thereby restoring spin labels that have been reduced.
Claim 2
Dependent Claim
50 words
In an MRI contrast agent which is a liposome having a bound spin label that is subject to reduction, and thus loss of contrast enhancement capability when in a reducing environment, the improvement wherein the liposome incorporates oxidizing means for oxidizing and thereby restoring spin labels that have been reduced.
Claim 3
Dependent Claim
25 words
The contrast agent of claim 1 wherein the oxidizing means comprises an amount of an oxidant substance encapsulated within a compartment defined by the liposome.
Claim 4
Dependent Claim
26 words
A contrast agent of claim 1 in which an antibody, carbohydrate, or other cell recognition targeting agent is attached to the liposome to provide specific targeting.
Claim 5
Dependent Claim
30 words
An MRI contrast agent, the agent comprising: a liposome having a bilayer shaped to define a compartment; multiple nitroxides incorporated into the bilayer; and an oxidant substance inside the compartment.
Claim 6
Dependent Claim
30 words
An MRI contrast agent, the agent comprising: a liposome having a bilayer shaped to define a compartment; multiple nitroxides incorporated into the bilayer; and an oxidant substance inside the compartment.
Claim 7
Dependent Claim
16 words
The contrast agent of claim 4 wherein the oxidant substance comprises K 3 Fe(CN) 6 .
Claim 8
Dependent Claim
26 words
A contrast agent of claim 4 in which an antibody, carbohydrate, or other cell recognition targeting agent is attached to the liposome to provide specific targeting.
Claim 9
Dependent Claim
16 words
A diagnostic preparation comprising the MRI contrast agent of claim 4 in a biocompatible carrier liquid.
Claim 10
Dependent Claim
28 words
A method for enhancing the magnetic resonance image of a target tissue, the method comprising providing, in the target tissue, an MRI contrast agent according to claim 4.
Claim 11
Dependent Claim
31 words
An MRI contrast agent comprising a molecule or assembly of molecules, the molecule or assembly having at least ten nitroxide groups positioned to contact surrounding bulk water and effect magnetic relaxation.
Claim 12
Dependent Claim
31 words
An MRI contrast agent comprising a molecule or assembly of molecules, the molecule or assembly having at least ten nitroxide groups positioned to contact surrounding bulk water and effect magnetic relaxation.
Claim 13
Dependent Claim
26 words
A contrast agent of claim 9 in which an antibody, carbohydrate, or other cell recognition targeting agent is attached to the molecule to provide specific targeting.
Claim 14
Dependent Claim
11 words
The contrast agent of claim 9 comprising a nitroxide doped liposome.
Claim 15
Dependent Claim
23 words
The contrast agent of claim 11 comprising a liposome formed from amphipathic molecules, substantially all such molecules having at least one nitroxide group.
Claim 16
Dependent Claim
19 words
The contrast agent of claim 11 comprising a liposome formed from amphipathic molecules having at least two nitroxide groups.
Claim 17
Dependent Claim
17 words
The contrast agent of claim 11 comprising a liposome formed from amphipathic molecules having three nitroxide groups.
Claim 18
Dependent Claim
41 words
The contrast agent of claim 11 wherein the liposome is made up of amphipathic molecules of which the long chains are polymerizable such that, after polymerization of the chains, rapid take-up of the liposome by the liver and spleen is inhibited.
Claim 19
Dependent Claim
38 words
The contrast agent of claim 9 comprising a liposome formed from multiple chain amphiphatic molecules attached to a polar group, each chain having a nitroxide group sufficiently near the polar group that the nitroxide can contact bulk water.
Claim 20
Dependent Claim
19 words
The contrast agent of claim 16 wherein at least one of the amphipathic molecules have more than two chains.
Claim 21
Dependent Claim
16 words
The contrast agent of claim 16 wherein the polar group has at least one nitroxide group.
Claim 22
Dependent Claim
36 words
The contrast agent of claim 16 comprising a liposome formed from cations of the formula: ##STR24## wherein R is an alkyl or aromatic group with or without hetero atoms present and with or without a nitroxide.
Claim 23
Dependent Claim
13 words
The contrast agent of claim 19 wherin R is --CH 3 or ##STR25##
Claim 24
Dependent Claim
22 words
The contrast agent of claim 9 comprising a nitroxide-doped, linear or branched polymer of a molecular weight not more than about 10,000.
Claim 25
Dependent Claim
24 words
The contrast agent of claim 21 comprising an arborol of the formula: ##STR26## wherein R is an acyl nitroxide, phosphoryl nitroxide or aromatic nitroxide.
Claim 26
Dependent Claim
16 words
A diagnostic preparation comprising the MRI contrast agent of claim 9 in a biocompatible carrier liquid.
Claim 27
Independent Claim
69 words
A method for enhancing the magnetic resonance image of a target tissue, the method comprising providing, in a target tissue, an MRI contrast agent comprising a molecule or assembly of molecules, the molecule or assembly having at least ten nitroxide groups positioned to contact surrounding bulk water and effect magnetic relaxtion, the agent being provided in an amount sufficient to enhance the magnetic resonance image of the target tissue.
Claim 28
Independent Claim
69 words
A method for enhancing the magnetic resonance image of a target tissue, the method comprising providing, in a target tissue, an MRI contrast agent comprising a molecule or assembly of molecules, the molecule or assembly having at least ten nitroxide groups positioned to contact surrounding bulk water and effect magnetic relaxtion, the agent being provided in an amount sufficient to enhance the magnetic resonance image of the target tissue.
Claim 29
Dependent Claim
25 words
The method of claim 24 in which an antibody, carbohydrate, or other cell recognition targeting agent is attached to the molecule to provide specific targeting.
Claim 30
Dependent Claim
14 words
The method of claim 24 wherein the contrast agent comprises a nitroxide doped liposome.
Claim 31
Dependent Claim
27 words
The method of claim 26 wherein the contrast agent comprises a liposome formed from amphipathic molecules, substantially all of such molecules having at least one nitroxide group.
Claim 32
Dependent Claim
22 words
The method of claim 26 wherein the contrast agent comprises a liposome formed from amphipathic molecules having at least two nitroxide groups.
Claim 33
Dependent Claim
20 words
The method of claim 26 wherein the contrast agent comprises a liposome formed from amphipathic molecules having three nitroxide groups.
Claim 34
Dependent Claim
43 words
The method of claim 26 wherein the contrast agent comprises a liposome made up of amphipathic molecules of which the long chains are polymerizable such that, after polymerization of the chains, rapid take-up of the liposome by the liver and spleen is inhibited.
Claim 35
Dependent Claim
42 words
The method of claim 26 wherein the contrast agent comprises a liposome formed from multiple double chain amphipathic molecules attached to a polar group, each chain having a nitroxide group sufficiently near the polar group that the nitroxide can contact bulk water.
Claim 36
Dependent Claim
18 words
The method of claim 31 wherein at least some of the amphipathic molecules have more than two chains.
Claim 37
Dependent Claim
15 words
The method of claim 31 wherein the polar group has at least one nitroxide group.
Claim 38
Dependent Claim
39 words
The method of claim 31 wherein the contrast agent comprises a liposome formed from cations of the formula: ##STR27## wherein R is an alkyl or aromatic group with or without hetero atoms present and with or without a nitroxide.
Claim 39
Dependent Claim
12 words
The method of claim 34 wherein R is --CH 3 or ##STR28##
Claim 40
Dependent Claim
25 words
The method of claim 24 wherein the contrast agent comprises a nitroxide-doped, linear or branched polymer of a molecular weight not more than about 10,000.
Claim 41
Dependent Claim
27 words
The method of claim 36 wherein the contrast agent comprises an arborol of the formula ##STR29## wherein R is an acyl nitroxide, phosphoryl nitroxide or aromatic nitroxide.
Claim 42
Dependent Claim
13 words
The method of claim 36 wherein the arborol is bound to a liposome.
Claim 43
Dependent Claim
25 words
The method of claim 38 in which an antibody, carbohydrate, or other cell recognition targeting agent is attached to the liposome to provide specific targeting.
Claim 44
Dependent Claim
26 words
A salt of the cation: ##STR30## wherein R is an alkyl or aromatic group with or without hetero atoms present and with or without a nitroxide.
Claim 45
Dependent Claim
26 words
A salt of the cation: ##STR30## wherein R is an alkyl or aromatic group with or without hetero atoms present and with or without a nitroxide.
Claim 46
Dependent Claim
12 words
The salt of claim 40 wherein R is --CH 3 or ##STR31##
Claim 47
Dependent Claim
11 words
A salt of claim 40 wherein the anion is a halide.
Claim 48
Dependent Claim
9 words
A liposome formed from a salt of claim 40.
Claim 49
Dependent Claim
17 words
An arborol of the formula: ##STR32## wherein R is an acyl nitroxide, phosphoryl nitroxide or aromatic nitroxide.
Claim 50
Dependent Claim
17 words
An arborol of the formula: ##STR32## wherein R is an acyl nitroxide, phosphoryl nitroxide or aromatic nitroxide.
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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) | 1992-09-04 | 1993-03-06 | 1993-09-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-09-04 | 1997-03-06 | 1997-09-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-09-04 | 2001-03-06 | 2001-09-05 | $7700.00 | Window Closed / Lapsed |