US5336762A
Expired / Lapsed
US
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Polychelating agents for image and spectral enhancement (and spectral shift)
Assignee: Abeona Therapeutics Inc
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Filing: 1991-01-16
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Granted: 1994-08-09
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Expires: 2011-01-16
Abstract
Abstract The present invention includes an image-enhancing agent comprising a biodegradable, water-soluble polymer, synthetic or naturally derived and having repeating hydrophilic monomeric units with amino or hydroxyl groups. This agent also includes chelating agents comprising functional groups bound to an amino or hydroxyl group of the monomeric units. These chelating agents have a formation constant for divalent or trivalent metal cations of at least about 108 at physiological temperature and pH. This image-enhancing agent is biodegradable to intermediary metabolites, excretable chelates, oligomers, monomers or combinations thereof of low toxicity. These image-enhancing agents may further comprise a paramagnetic metal ion for enhancement of the image arising from induced magnetic resonance signals. Images resulting from scanning of gamma particle emissions may be enhanced when the image-enhancing agent of the present invention comprises radioisotopic metal ions emitting gamma particles. The physical conversion of these image-enhancing agents into microspheres (or, less optimally, microaggregates) allows further internal directioning of the image-enhancing agents to organs with phagocytic capabilities. Dextran is a preferred polymer; DTPA and gadolinium are respectively preferred chelating agents and paramagnetic metal ions.
Inventors
- 👤 David F. Ranney
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-08 01:09
CPC Classifications
A; A61; A61K; A61K51/00; A61K51/12; A61K51/1241; A61K51/1255; A61K49/00; A61K49/06; A61K49/08; A61K49/085; A61K49/10; A61K49/12; A61K49/126; A61K49/128; A61K49/14; A61K49/143; A61K49/18; A61K49/1818; A61K51/02; A61K51/04; A61K51/06; A61K51/065; A61K2123/00; Y; Y10; Y10S; Y10S977/00; Y10S977/70; Y10S977/734; Y10S977/735; Y10S977/737; Y10S977/738; Y10S977/788; Y10S977/84; Y10S977/895; Y10S977/902; Y10S977/904; Y10S977/915; Y10S977/927; Y10S977/93
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
159 words
An image-enhancing agent or spectral enhancing agent comprising: a biodegradable, water-soluble polysaccharide or oligosaccharide carrier-material comprising repeating hydrophilic monomeric units having amino, quaternary ammonium, sulfate, carboxyl or hydroxyl groups; and a chelating agent comprising functional groups bound noncovalently by strong ionic interaction to an amino, quaternary ammonium, sulfate, hydroxyl or carboxyl group of the monomeric units, said chelating agent having a formation constant for divalent or trivalent metal cations at physiological temperature and pH, of at least about 10 8 ; and a paramagnetic metal ion bound to the chelating agent, usable to enhance internal images or spectra, arising from induced magnetic resonance signals; wherein the image-enhancing agent has a molecular diameter of less than about 3 nanometers, contains less than about 5% (w/w) cross-linked or microaggregated species and is biodegradable by hydrolytic or other enzymatic or physiologic mechanisms of animals or intestinal microorganisms, to intermediary metabolites, excretable chelates, polymers, oligomers, monomers or combinations thereof, all of low toxicity.
Claim 2
Dependent Claim
159 words
An image-enhancing agent or spectral enhancing agent comprising: a biodegradable, water-soluble polysaccharide or oligosaccharide carrier-material comprising repeating hydrophilic monomeric units having amino, quaternary ammonium, sulfate, carboxyl or hydroxyl groups; and a chelating agent comprising functional groups bound noncovalently by strong ionic interaction to an amino, quaternary ammonium, sulfate, hydroxyl or carboxyl group of the monomeric units, said chelating agent having a formation constant for divalent or trivalent metal cations at physiological temperature and pH, of at least about 10 8 ; and a paramagnetic metal ion bound to the chelating agent, usable to enhance internal images or spectra, arising from induced magnetic resonance signals; wherein the image-enhancing agent has a molecular diameter of less than about 3 nanometers, contains less than about 5% (w/w) cross-linked or microaggregated species and is biodegradable by hydrolytic or other enzymatic or physiologic mechanisms of animals or intestinal microorganisms, to intermediary metabolites, excretable chelates, polymers, oligomers, monomers or combinations thereof, all of low toxicity.
Claim 3
Dependent Claim
12 words
The image-enhancing agent of claim 1 wherein the chelating agent is DTPA.
Claim 4
Dependent Claim
21 words
The image-enhancing agent of claim 1 wherein the carrier-material has a molecular weight between about 1,000 daltons and about 500,000 daltons.
Claim 5
Dependent Claim
11 words
The image-enhancing agent of claim 1 wherein the carrier-material is dextran.
Claim 6
Dependent Claim
21 words
The image-enhancing agent of claim 1 wherein the carrier-material has a molecular weight between about 40,000 daltons and about 75,000 daltons.
Claim 7
Dependent Claim
13 words
The image-enhancing agent of claim 1 wherein the functional groups are carboxyl groups.
Claim 8
Dependent Claim
27 words
The image-enhancing agent of claim 1 in which the functional groups are non-covalently bound to the carrier-material by a quaternary ammonium group covalently conjugated to the carrier-material.
Claim 9
Dependent Claim
28 words
The image-enhancing agent of claim 1 in which the functional groups are non-covalently bound to the carrier-material by a sulfate group which is covalently conjugated to the carrier-material.
Claim 10
Dependent Claim
12 words
The image-enhancing agent of claim 6 wherein the chelating agent is DTPA.
Claim 11
Dependent Claim
12 words
The image-enhancing agent of claim 7 wherein the chelating agent is DTPA.
Claim 12
Dependent Claim
12 words
The image-enhancing agent of claim 8 wherein the chelating agent is DTPA.
Claim 13
Dependent Claim
24 words
The image-enhancing agent of claim 1 wherein the paramagnetic metal ion is selected from the group of elements having atomic numbers 21-29 and 57-70.
Claim 14
Dependent Claim
25 words
The image-enhancing agent of claim 1 wherein the paramagnetic metal ion is that of gadolinium, iron, nickel, copper, erbium, europium dysprosium, holmium, chromium or manganese.
Claim 15
Dependent Claim
25 words
The image-enhancing agent of claim 1 wherein the chelating agent is in a molar ratio of chelating agent/monomeric unit between about 1/5 and about 1/25.
Claim 16
Dependent Claim
15 words
The image-enhancing agent of claim 1 wherein the paramagnetic metal ion is that of gadolinium.
Claim 17
Dependent Claim
21 words
The image-enhancing agent of claim 1 wherein the chelating agent is DTPA and the paramagnetic metal ion is that of gadolinium.
Claim 18
Dependent Claim
25 words
The image-enhancing agent of claim 1 wherein the carrier-material is dextran, the paramagnetic metal ion is that of gadolinium and the chelating agent is DTPA.
Claim 19
Dependent Claim
32 words
The image-enhancing agent of claim 1 wherein the water-soluble carrier-material comprises heparin, heparan sulfate, chondroitin sulfate, dermatan sulfate, starch, carboxymethylstarch or hydroxyethylstarch individually, in combinations with each other or with DEAE dextran.
Claim 20
Dependent Claim
16 words
The image-enhancing agent of claim 18 wherein the water soluble carrier-material comprises heparin and DEAE dextran.
Claim 21
Dependent Claim
12 words
The image-enhancing agent of claim 18 wherein the chelating agent is DTPA.
Claim 22
Dependent Claim
11 words
The image-enhancing agent of claim 18 defined further as comprising gadolinium.
Claim 23
Dependent Claim
30 words
The image-enhancing agent of claim 18 wherein the water soluble carrier-material comprises DEAE-dextran and heparin and the image-enhancing agent further comprises DTPA bound to the DEAE dextran by ion-pair bonding.
Claim 24
Dependent Claim
13 words
The image-enhancing agent of claim 1 wherein the water soluble carrier-material is heparin.
Claim 25
Dependent Claim
50 words
The image-enhancing agent or spectral enhancing agent useful with external or internal magnetic resonance imaging or spectroscopy, the agent comprising a biodegradable polysaccharide or oligosaccharide carrier-material; a DTPA chelating agent non-covalently bound by strong ionic interactions to said carrier material; and a paramagnetic metal ion bound to said chelating agent.
Claim 26
Dependent Claim
50 words
The image-enhancing agent or spectral enhancing agent useful with external or internal magnetic resonance imaging or spectroscopy, the agent comprising a biodegradable polysaccharide or oligosaccharide carrier-material; a DTPA chelating agent non-covalently bound by strong ionic interactions to said carrier material; and a paramagnetic metal ion bound to said chelating agent.
Claim 27
Dependent Claim
13 words
The image-enhancing agent of claim 24 wherein the paramagnetic metal ion is gadolinium.
Claim 28
Dependent Claim
80 words
The image-enhancing agent of claim 25 in which the agent is in a completely water soluble form having a molecular diameter less than about 3 nanometers and is useful for imaging of: internal tumors, at a potency multiple of at least about 3.3 times that of Gd-DTPA when administered by an intravenous route; and body cavities and gastrointestinal tract upon direct introduction, with the exception of the stomach, due to dechelation of gadolinium at pH's of about 1 to 3.5.
Claim 29
Dependent Claim
61 words
The image-enhancing agent of claim 25 in which the agent is in a completely water soluble form of less than about 3 nanometers in molecular diameter, and clears rapidly from the blood and body, primarily by a renal route, with at least about 80% of an injected gadolinium dose clearing from the body within less than about 6 hours of injection.
Claim 30
Dependent Claim
50 words
The image-enhancing agent of claim 24 wherein the agent is in a completely water-soluble form having a molecular diameter of less than about 3 nanometers and an osmotic activity of less than about 50 mOsm per kg of agent and also less than about 28 mOsm per micromole of gadolinium.
References Cited (Backward Citations)
US4247406A
Cited
US4370476A
Cited
US4385046A
Cited
US4647447A
Cited
EP0071564A1
Cited
US4963344B1
Cited
US4963344A
Cited
US4957939A
Cited
US4452773A
Cited
US4432987A
Cited
US4731239A
Cited
GB2137612A
Cited
US4423158A
Cited
EP0124766A2
Cited
US4735796A
Cited
US4707352A
Cited
WO1985005554A1
Cited
US4659839A
Cited
EP0186947A1
Cited
US4985233A
Cited
US4986980A
Cited
EP0184899A1
Cited
US4735210A
Cited
US4770183A
Cited
US4822594A
Cited
US4832877A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1997-08-08 | 1998-02-07 | 1998-08-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-08-08 | 2002-02-07 | 2002-08-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-08-08 | 2006-02-07 | 2006-08-09 | $7700.00 | Window Closed / Lapsed |