US4770183A
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US
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Biologically degradable superparamagnetic particles for use as nuclear magnetic resonance imaging agents
Assignee: Amag Pharmaceuticals Inc
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Filing: 1986-07-03
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Granted: 1988-09-13
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Expires: 2006-07-03
Abstract
Abstract This invention relates to an improved method for obtaining the in vivo MNR image of an organ or tissue of an animal or human subject. More specifically, this invention relates to the use of small (about 10 to about 5,000 angstroms in diameter) biodegradable superparamagnetic metal oxide particles for use as imaging agents. The particles, which may be uncoated or surrounded by a stable polymeric coating, can be mixed with a physiologically acceptable medium to form a uniform dispersoid which can be administered to the subject by a variety of routes. Once administered, the particles collect in the target organ or tissue where they will remain for a time sufficiently long for an image to be obtained, but are ultimately metabolized or cleared within about 7 days.
Inventors
- 👤 Ernest V. Groman
- 👤 Lee Josephson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 15:54
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/06; A61K49/18; A61K49/1818; A61K49/1821; A61K49/1824; A61K49/1827; A61K49/1851; A61K49/1863; A61K49/1866; A61K49/1869; B; B82; B82Y; B82Y5/00; C; C08; C08G; C08G18/00; C08G18/06; C08G18/08; C08G18/16; C08G18/18; C08G18/1808; C08G18/1816; C08G18/1825; C08G18/20; C08G18/2009; C08G18/2036; C08G18/22; C08G18/24; C08G18/244; C08G18/246; C08G18/26; C08J; C08J9/00; C08J9/04; C08J9/12; C08J9/14; C08J9/143; C08J9/144; G; G01; G01R; G01R33/00; G01R33/20; G01R33/44; G01R33/48; G01R33/54; G01R33/56; G01R33/5601; C08G2101/00; C08J2375/00; C08J2375/04
Claims Analysis
Total Claims: 27
Claim 1
Independent Claim
142 words
An improved method for obtaining an in vivo NMR image or an organ or tissue of an animal or human subject, wherein the improvement comprises administering to such a subject as a contrast agent to enhance such NMR image an effective amount of a dispersoid which comprises uncoated, biodegradable superparamagnetic metal oxide particles dispersed in a physiologically acceptable carrier, an individual particle (i) comprising one or more biodegradable metal oxide crystals, each crystal about 10 to about 500 angstroms in diameter; (ii) having an overall means diameter of about 10 angstroms to about 5000 angstroms as measured on a Coulter particle size analyzer; and (iii) further characterized as having a retention time in said organ or tissue sufficiently long to permit an image to be obtained and being ultimately biodegraded in said organ or tissue within a period of about 7 days.
Claim 2
Dependent Claim
142 words
An improved method for obtaining an in vivo NMR image or an organ or tissue of an animal or human subject, wherein the improvement comprises administering to such a subject as a contrast agent to enhance such NMR image an effective amount of a dispersoid which comprises uncoated, biodegradable superparamagnetic metal oxide particles dispersed in a physiologically acceptable carrier, an individual particle (i) comprising one or more biodegradable metal oxide crystals, each crystal about 10 to about 500 angstroms in diameter; (ii) having an overall means diameter of about 10 angstroms to about 5000 angstroms as measured on a Coulter particle size analyzer; and (iii) further characterized as having a retention time in said organ or tissue sufficiently long to permit an image to be obtained and being ultimately biodegraded in said organ or tissue within a period of about 7 days.
Claim 3
Dependent Claim
161 words
An improved method for obtaining an in vivo NMR image of an organ or tissue of an animal or human subject, wherein the improvememt comprises administering to such a subject as a contrast agent to enhance such NMR image an effective amount of a dispersoid which comprises coated, biodegradable superparamagnetic metal oxide particles dispersed in a physiologically acceptable carrier, an individual particle (i) comprising a superparamagnetic metal oxide core generally surrounded by a biodegradable polymeric coat, each core comprising one or more biodegradable metal oxide crystals, each crystal about 10 to about 500 angstroms in diameter; (ii) having an overll mean diameter, inclusive of the polymeric coat, of about 10 to about 5000 angstroms as measured on a Coulter particle size analyzer; an (iii) further characterized as having a retention time in said organ or tissue sufficiently long to permit an image to be obtained and being ultimately biodegraded in said organ or tissue within a period of about 7 days.
Claim 4
Dependent Claim
161 words
An improved method for obtaining an in vivo NMR image of an organ or tissue of an animal or human subject, wherein the improvememt comprises administering to such a subject as a contrast agent to enhance such NMR image an effective amount of a dispersoid which comprises coated, biodegradable superparamagnetic metal oxide particles dispersed in a physiologically acceptable carrier, an individual particle (i) comprising a superparamagnetic metal oxide core generally surrounded by a biodegradable polymeric coat, each core comprising one or more biodegradable metal oxide crystals, each crystal about 10 to about 500 angstroms in diameter; (ii) having an overll mean diameter, inclusive of the polymeric coat, of about 10 to about 5000 angstroms as measured on a Coulter particle size analyzer; an (iii) further characterized as having a retention time in said organ or tissue sufficiently long to permit an image to be obtained and being ultimately biodegraded in said organ or tissue within a period of about 7 days.
Claim 5
Dependent Claim
67 words
The method of claim 1 or 2 wherein the superparamagetic metal oxide particle is an iron oxide particle (i) comprising crystals of about 50 to about 500 angstroms in diameter; (ii) having a surface area greater than about 75 m 2 /gram; (iii) having a magnetic saturation between about 5 and about 50 EMU/gram of iron oxide; and (iv) possessing a magnetic squareness of less than 0.1.
Claim 6
Dependent Claim
21 words
The method of claim 2 wherein the polymeric coat is selected from the group consisting of carbohydrates, proteins, and composites thereof.
Claim 7
Dependent Claim
12 words
The method of claim 2 wherein the polymeric coat consists of albumin.
Claim 8
Dependent Claim
22 words
The method of claim 5 wherein the albumin is selected from the group consisting of human serum albumin and bovine serum albumin.
Claim 9
Dependent Claim
21 words
The method of claim 2 wherein the polymeric coat consists of dextran having a molecular weight between 5,000 and 250,000 daltons.
Claim 10
Dependent Claim
36 words
The method of claim 7 wherein the dextran is selected from the group consisting of dextran of 9,000 MW, dextran of 17,900 MW, dextran of 35,600 MW, dextran of 71,000 MW and dextran of 249,000 MW.
Claim 11
Dependent Claim
18 words
The method of claim 1 or 2 wherein said dispersoid is administered to the subject by intravascular injection.
Claim 12
Dependent Claim
30 words
The method of claim 1 or 2 wherein said dispersoid is administered to the subject by a method selected from the group consisting of oral administration, intubation, and by enema.
Claim 13
Dependent Claim
22 words
The method of claim 9 wherein the physiologically acceptable carrier is selected from the group consisting of normal saline and distilled water.
Claim 14
Dependent Claim
13 words
The method of claim 10 wherein said physiologically acceptable carrier is distilled water.
Claim 15
Dependent Claim
32 words
The method of claim 1 or 2 wherein the superparamagnetic metal oxide particles are administered at a dosage of up to about 250 mg per Kilogram of body weight of the subject.
Claim 16
Dependent Claim
19 words
The method of claim 1 or 2 wherein the organ or tissue imaged is part of the reticuloendothelial system.
Claim 17
Dependent Claim
12 words
The method of claim 14 wherein the organ imaged is a liver.
Claim 18
Dependent Claim
12 words
The method of claim 14 wherein the organ imaged is a spleen.
Claim 19
Dependent Claim
12 words
The method of claim 14 wherein the tissue imaged is bone marrow.
Claim 20
Dependent Claim
16 words
The method of claim 14 wherein the organ or tissue imaged is lymph or lymph nodes.
Claim 21
Dependent Claim
14 words
The method of claim 1 or 2 wherein the tissue imaged is neural tissue.
Claim 22
Dependent Claim
14 words
The method of claim 1 or 2 wherein the organ imaged is a lung.
Claim 23
Dependent Claim
19 words
The method of claim 1 or 2 wherein the organ or tissue imaged is part of the gastrointestinal tract.
Claim 24
Dependent Claim
12 words
The method of claim 21 wherein the organ imaged is an esophagus.
Claim 25
Dependent Claim
12 words
The method of claim 21 wherein the organ imaged is a stomach.
Claim 26
Dependent Claim
13 words
The method of claim 21 wherein the organ imaged is a small intestine.
Claim 27
Dependent Claim
13 words
The method of claim 21 wherein the organ imaged is a large intestine.
References Cited (Backward Citations)
US27240A
Cited
AT45026B
Cited
GB748024A
Cited
US2820740A
Cited
US2862920A
Cited
US2971916A
Cited
US3190837A
Cited
US3275514A
Cited
US3100202A
Cited
US3093545A
Cited
US3228881A
Cited
US3234209A
Cited
US3480555A
Cited
US4001288A
Cited
US3474777A
Cited
US3531413A
Cited
US3832457A
Cited
USRE27240E
Cited
US3870645A
Cited
US3700595A
Cited
US3843540A
Cited
US3928581A
Cited
US4101435A
Cited
US4019994A
Cited
US4025448A
Cited
US4136683A
Cited
US4269826A
Cited
WO1978000005A1
Cited
US4357259A
Cited
US4230685A
Cited
US4345588A
Cited
US4247406A
Cited
US4356098A
Cited
US4331654A
Cited
FR2508802A1
Cited
US4501726A
Cited
US4452773A
Cited
WO1983003920A1
Cited
WO1984002643A1
Cited
GB2138612A
Cited
US4615879A
Cited
WO1985002772A1
Cited
WO1985004330A1
Cited
EP0160552A2
Cited
EP0184899A1
Cited
EP0186947A1
Cited
DE3443252A1
Cited
DE3443251A1
Cited
US4656026A
Cited
US4637929A
Cited
US4675173A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-09-13 | 1992-03-14 | 1992-09-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-09-13 | 1996-03-14 | 1996-09-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-09-13 | 2000-03-14 | 2000-09-13 | $7700.00 | Window Closed / Lapsed |