Patent US5562099A successfully refreshed from Google Patents.
US5562099A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Polymeric microparticles containing agents for imaging
Assignee: Penn State Research Foundation
•
Filing: 1994-08-18
•
Granted: 1996-10-08
•
Expires: 2014-08-18
Abstract
Abstract Compositions, methods for preparing and methods of using contrast agent-filled polymeric microparticles for imaging are disclosed. In a preferred embodiment, air-encapsulating microparticles are formed by ionotropically gelling synthetic polyelectrolytes such as poly(carboxylatophenoxy)phosphazene, poly(acrylic acid), poly(methacrylic acid) and methacrylic acid copolymers (Eudragit's) by contact with multivalent ions such as calcium ions. In the preferred embodiment, the average size of the microparticles is less than seven μm so that they are suitable for injection intravenously. The polymeric microparticles are stable to imaging and display high echogenicity, both in vitro and in vivo. Due to their in vivo stability their potential application is extended beyond vascular imaging to liver and renal diseases, fallopian tube diseases, detecting and characterizing tumor masses and tissues, and measuring peripheral blood velocity. The microparticles can optionally be linked with ligands that minimize tissue adhesion or that target the microparticles to specific regions.
Inventors
- 👤 Smadar Cohen
- 👤 Alexander K. Andrianov
- 👤 Margaret Wheatley
- 👤 Harry R. Allcock
- 👤 Robert S. Langer
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 08:18
CPC Classifications
B; B82; B82Y; B82Y5/00; A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223; A61K49/225; A61K49/226; A61K51/00; A61K51/12; A61K51/1258; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1641; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5031; B01; B01J; B01J13/00; B01J13/02; B01J13/06; B01J13/14; C; C08; C08G; C08G79/00; C08G79/02; C08G79/025; C12; C12N; C12N11/00; C12N11/02; C12N11/04; A61K2123/00; Y; Y10; Y10S; Y10S977/00; Y10S977/70; Y10S977/734; Y10S977/753
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
151 words
A method for imaging a predetermined area of a mammal in medical procedures, the method comprising the steps of: a) providing microparticles formed by dispersing or dissolving an imaging contrast agent in an aqueous solution or dispersion of an ionically crosslinkable synthetic polymer that has charged side groups, wherein the polymer is selected from the group consisting of poly(phosphazenes), poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid and methacrylic acid, copolymers of acrylic acid or methacrylic acid and polyvinyl ethers or poly(vinyl acetate), and sulfonated polystyrene, and reacting the polymer with a multivalent ion of the opposite charge to form synthetic microparticles comprising a hydrogel having the imaging contrast agent incorporated therein in an amount effective to be detectable by an imaging technique after administration to a patient, b) administering the microparticles to a mammal; and c) scanning a predetermined area of the mammal to obtain an image of the area.
Claim 2
Independent Claim
151 words
A method for imaging a predetermined area of a mammal in medical procedures, the method comprising the steps of: a) providing microparticles formed by dispersing or dissolving an imaging contrast agent in an aqueous solution or dispersion of an ionically crosslinkable synthetic polymer that has charged side groups, wherein the polymer is selected from the group consisting of poly(phosphazenes), poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid and methacrylic acid, copolymers of acrylic acid or methacrylic acid and polyvinyl ethers or poly(vinyl acetate), and sulfonated polystyrene, and reacting the polymer with a multivalent ion of the opposite charge to form synthetic microparticles comprising a hydrogel having the imaging contrast agent incorporated therein in an amount effective to be detectable by an imaging technique after administration to a patient, b) administering the microparticles to a mammal; and c) scanning a predetermined area of the mammal to obtain an image of the area.
Claim 3
Dependent Claim
17 words
The method of claim 1 wherein the diameter of the microparticles is between one and ten microns.
Claim 4
Dependent Claim
31 words
The method of claim 1 wherein the polymer is soluble prior to crosslinking in an aqueous solution selected from the group consisting of water, aqueous alcohol, and buffered aqueous salt solutions.
Claim 5
Dependent Claim
31 words
The method of claim 1 wherein the charged groups on the surface of the hydrogel are further complexed with a multivalent polyion of the opposite charge to form a semi-permeable membrane.
Claim 6
Dependent Claim
19 words
The method of claim 4 wherein the hydrogel is liquefied within the semi-permeable membrane by removing the multivalent ions.
Claim 7
Dependent Claim
34 words
The method of claim 1 wherein the multivalent ion is selected from the group consisting of calcium, copper, aluminum, magnesium, stromium, barium, tin, chromium, zinc, organic cations, dicarboxylic acids, sulfate ions and carbonate ions.
Claim 8
Dependent Claim
37 words
The method of claim 1 wherein the imaging contrast agent is gas, and the gas is entrappeal in the polymer solution or dispersion by sonication of the polymer in the presence of the gas in step (a).
Claim 9
Dependent Claim
44 words
The method of claim 1 wherein the imaging contrast agent is gas and the gas is mixed with the polymer solution or dispersion and atomized through an orifice forming droplets which are dispersed into a crosslinking solution comprising the multivalent ion in step (a).
Claim 10
Dependent Claim
44 words
The method of claim 1 wherein the contrast agent is selected from the group consisting of air, argon, nitrogen, carbon dioxide, nitrogen dioxide, methane, helium, neon, oxygen, perfluorocarbon, a gatalinium chelate, iron, magnesium, manganese, copper, chromium, a radiolabeled compound, an iodine-containing material and barium.
Claim 11
Dependent Claim
36 words
The method of claim 1 wherein step c) is conducted using an imaging technique selected from the group consisting of ultrasound, magnetic resonance imaging, computer tomography, x-ray, positron emission tomography and single photon emission computerized tomography.
Claim 12
Dependent Claim
14 words
The method of claim 10 wherein step c) is conducted using ultrasound imaging techniques.
Claim 13
Dependent Claim
29 words
The method of claim 11 wherein the contrast agent is selected from the group consisting of air, argon, nitrogen, carbon dioxide, nitrogen dioxide, methane, helium, neon, oxygen and perfluorocarbon.
Claim 14
Dependent Claim
25 words
The method of claim 1 wherein the microparticles are administered by an administration route selected from the group consisting of injection, oral administration, and inhalation.
Claim 15
Dependent Claim
24 words
The method of claim 9 wherein the iodine-containing material is selected from group consisting of diatrizoate, iothalamate, iopamidol, isohexol, ioversol, iotrol, iodixanol and ioxagalte.
References Cited (Backward Citations)
US3773919A
Cited
US4021364A
Cited
US3893980A
Cited
US4016078A
Cited
US4058001A
Cited
US5212143A
Cited
US4777154A
Cited
US4352883A
Cited
WO1980002365A1
Cited
US4276885A
Cited
US4650769A
Cited
US4442843A
Cited
US4657756A
Cited
US4681119A
Cited
US4495174A
Cited
US4440921A
Cited
US4718433A
Cited
EP0127989A2
Cited
JPS6034731A
Cited
GB2145992A
Cited
US4765973A
Cited
US4908233A
Cited
US4592755A
Cited
US4880622A
Cited
US4927761A
Cited
US5277979A
Cited
US5271881A
Cited
US5380411A
Cited
US4975280A
Cited
US4990336A
Cited
US5089272A
Cited
US4946938A
Cited
US5104947A
Cited
US5132117A
Cited
US5053451A
Cited
US5271928A
Cited
US5078994A
Cited
EP0458745B1
Cited
US5196343A
Cited
US5149543A
Cited
US5308701A
Cited
US5310540A
Cited
WO1992005788A1
Cited
US5120349A
Cited
JPH0634731A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-10-08 | 2000-04-08 | 2000-10-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-10-08 | 2004-04-08 | 2004-10-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-10-08 | 2008-04-08 | 2008-10-08 | $7700.00 | Window Closed / Lapsed |