Patent US5512268A successfully refreshed from Google Patents.
US5512268A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Polymeric shells for medical imaging prepared from synthetic polymers, and methods for the use thereof
Assignee: Abraxis Bioscience LLC
•
Filing: 1995-06-06
•
Granted: 1996-04-30
•
Expires: 2015-06-06
Abstract
Abstract In accordance with the present invention, compositions comprising imaging agent(s) contained within polymeric shells are provided. Invention compositions are useful, for example, as contrast agents for magnetic resonance imaging (MRI), ultrasonography, and X-ray computer tomography. The polymeric shell diameter is typically approximately 2 microns in diameter. Consequently, these materials have organ specificity due to rapid scavenging by the reticuloendothial system (RES) or the mononuclear phagocyte (MNP) system upon intravenous injection. Furthermore, polymeric shells of the invention can be used to measure and monitor local oxygen and temperature. Exemplary contrast agents contemplated for use in the practice of the present invention include fluorinated compounds. Fluorinated compounds in general are hydrophobic and as such have limited water solubility. The invention method permits preparation of such compounds in a biocompatible form suitable for ready delivery.
Inventors
- 👤 Mark W. Grinstaff
- 👤 Neil P. Desai
- 👤 Kenneth S. Suslick
- 👤 Patrick Soon-Shiong
- 👤 Paul A. Sandford
- 👤 Noma R. Merideth
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 15:25
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223; A61K47/00; A61K47/50; A61K47/69; A61K47/6921; A61K47/6925; A61K49/06; A61K49/08; A61K49/10; A61K49/12; A61K49/126; A61K49/18; A61K49/1806; A61K49/1818; A61K49/1821; A61K49/1824; A61K49/1827; A61K49/1851; A61K49/1857; A61K49/186; A61K49/1863; A61K49/1866; A61K49/1869; Y; Y10; Y10S; Y10S436/00; Y10S436/806; Y10T; Y10T436/00; Y10T436/24
Claims Analysis
Total Claims: 38
Claim 1
Independent Claim
77 words
A composition for obtaining in vivo medical diagnostic images, said composition comprising imaging agent(s) substantially completely contained within a polymeric shell; wherein said polymeric shell comprises a biocompatible polymer which is substantially crosslinked by way of disulfide bonds, and wherein said crosslinked polymer is a synthetic polymer, wherein said polymer, prior to crosslinking, has covalently attached thereto sulfhydryl groups or disulfide groups, wherein said disulfide bonds are crosslinked directly, that is, without a crosslinking agent being used.
Claim 2
Dependent Claim
77 words
A composition for obtaining in vivo medical diagnostic images, said composition comprising imaging agent(s) substantially completely contained within a polymeric shell; wherein said polymeric shell comprises a biocompatible polymer which is substantially crosslinked by way of disulfide bonds, and wherein said crosslinked polymer is a synthetic polymer, wherein said polymer, prior to crosslinking, has covalently attached thereto sulfhydryl groups or disulfide groups, wherein said disulfide bonds are crosslinked directly, that is, without a crosslinking agent being used.
Claim 3
Dependent Claim
17 words
A composition according to claim 1 wherein said polymeric shell further comprises polyethylene glycol covalently linked thereto.
Claim 4
Dependent Claim
20 words
A composition according to claim 1 wherein said composition is useful for the in vivo determination of local oxygen concentrations.
Claim 5
Dependent Claim
16 words
A composition according to claim 1 wherein said composition is capable of undergoing a phase transition.
Claim 6
Dependent Claim
20 words
A composition according to claim 4 wherein said composition is useful for imaging as well as in vivo temperature determination.
Claim 7
Dependent Claim
106 words
A composition according to claim 1 wherein said synthetic polymers are selected from synthetic polypeptides containing sulfhydryl groups and/or disulfide groups, polyvinyl alcohol modified to contain free sulfhydryl groups and/or disulfide groups, polyhydroxyethyl methacrylate modified to contain free sulfhydryl groups and/or disulfide groups, polyacrylic acid modified to contain free sulfhydryl groups and/or disulfide groups, polyethyloxazoline modified to contain free sulfhydryl groups and/or disulfide groups, polyacrylamide modified to contain free sulfhydryl groups and/or disulfide groups, polyvinyl pyrrolidinone modified to contain free sulfhydryl groups and/or disulfide groups polyalkylene glycols modified to contain free sulfhydryl groups and/or disulfide groups, as well as mixtures of any two or more thereof.
Claim 8
Dependent Claim
19 words
A composition according to claim 1 wherein the disulfide bonds on the crosslinked polymer are formed by ultrasonic irradiation.
Claim 9
Dependent Claim
21 words
A composition according to claim 1 wherein the disulfide bonds on the crosslinked polymer are formed by reaction with free radicals.
Claim 10
Dependent Claim
23 words
A composition according to claim 1 wherein said imaging agent is selected from superparamagnetic or paramagnetic metal particles suspended in a biocompatible medium.
Claim 11
Dependent Claim
18 words
A composition according to claim 9 wherein said metal particle is iron, iron oxide, manganese or manganese oxide.
Claim 12
Dependent Claim
213 words
A composition according to claim 9 wherein said particles are suspended in a biocompatible fluorocarbon medium selected from: (a) C x F 2x+y-z A z , wherein: x=1-30, y=2; or 0 or -2, when x≧2; or -4 when x≧4, z=any whole number from 0 up to (2x+y-1), and A is selected from H, halogens other than F, --CN, --OR, wherein R is H, alkyl, fluoroalkyl, alkenyl, fluoroalkenyl, alkynyl, fluoroalkynyl, aryl, fluoroaryl, alkanoyl, fluoroalkanoyl, alkenyl, fluoroalkenoyl, alkynoyl, fluoroalkynoyl, (b) C x F 2x+y'-z A z ! a JR b-a , wherein: x, z, A and R are as defined above, y'=+1; or -1 or -3, when x≧2; or -5 when x≧4, J=0, S, N, P, Al or Si, a=1, 2, 3, or 4, and b=2 for a divalent J, or 3 for a trivalent J, or 4 for a tetravalent J, (c) A'-- (CF 2 ) x --O! c --A", wherein: x is as defined above, A' is selected from H, halogens, --CN, --OR, wherein R is H, alkyl, fluoroalkyl, alkenyl, fluoroalkenyl, alkynyl, fluoroalkynyl, aryl, fluoroaryl, alkanoyl, fluoroalkanoyl, alkenoyl, fluoroalkenoyl, alkynoyl, fluoroalkynoyl, A" is selected from H or R wherein R is as defined above, c=1-300, or ##STR2## wherein: x is as defined above, and c'=2-20, or mixtures of any two or more thereof.
Claim 13
Dependent Claim
28 words
A composition according to claim 1 wherein said magnetic resonance imaging agent is selected from gadolinium, dysprosium, or manganese metal complexes that are encapsulated within the polymeric shell.
Claim 14
Dependent Claim
20 words
A composition according to claim 1 wherein said polymeric shell containing agent therein is suspended in a biocompatible aqueous liquid.
Claim 15
Dependent Claim
42 words
A composition according to claim 13 wherein said biocompatible aqueous liquid is selected from water, buffered aqueous media, saline, buffered saline, solutions of amino acids, solutions of sugars, solutions of vitamins, solutions of carbohydrates, or combinations of any two or more thereof.
Claim 16
Dependent Claim
15 words
A composition according to claim 1 wherein said agent is contained within said shell neat.
Claim 17
Dependent Claim
21 words
A composition according to claim 1 wherein said agent within said shell is dissolved or suspended in a biocompatible dispersing agent.
Claim 18
Dependent Claim
94 words
A composition according to claim 16 wherein said biocompatible dispersing agent is selected from soybean oil, mineral oil, corn oil, rapeseed oil, coconut oil, olive oil, safflower oil, cotton seed oil, aliphatic, cycloaliphatic or aromatic hydrocarbons having 4-30 carbon atoms, aliphatic or aromatic alcohols having 2-30 carbon atoms, aliphatic or aromatic esters having 2-30 carboatoms, alkyl, aryl, or cyclic ethers having 2-30 carbon atoms, alkyl or aryl halides having 1-30 carbon atoms, optionally having more than one halogen substituent, ketones having 3-30 carbon atoms, polyalkylene glycol, or combinations of any two or more thereof.
Claim 19
Dependent Claim
21 words
A method to obtain in vivo magnetic resonance images by administering to a subject a composition as described in claim 1.
Claim 20
Dependent Claim
27 words
A method for the delivery of imaging agents to a subject, said method comprising administering to said subject an effective amount of composition according to claim 1.
Claim 21
Dependent Claim
215 words
A composition according to claim 1, wherein said imaging agent is a fluorine-containing magnetic imaging agent selected from: (a) C x F 2x+y-z A z , wherein: x=1-30, y=2; or 0 or -2, when x≧2; or -4 when x≧4, z=any whole number from 0 up to (2x+y-1), and A is selected from H, halogens other than F, --CN, --OR, wherein R is H, alkyl, fluoroalkyl, alkenyl, fluoroalkenyl, alkynyl, fluoroalkynyl, aryl, fluoroaryl, alkanoyl, fluoroalkanoyl, alkenoyl, fluoroalkenoyl, alkynoyl, fluoroalkynoyl, (b) C x F 2x+y'-z A z ! a JR b-a , wherein: x, z, A and R are as defined above, y'=+1; or -1 or -3, when x≧2; or -5 when x≧4, J=0, S, N, P, Al or Si, a=1, 2, 3, or 4, and b=2 for a divalent J, or 3 for a trivalent J, or 4 for a tetravalent J, (c) A'-- (CF 2 ) x --O! c --A", wherein: x is as defined above, A' is selected from H, halogens, --CN, --OR, wherein R is H, alkyl, fluoroalkyl, alkenyl, fluoroalkenyl, alkynyl, fluoroalkynyl, aryl, fluoroaryl, alkanoyl, fluoroalkanoyl, alkenoyl, fluoroalkenoyl, alkynoyl, fluoroalkynoyl, A" is selected from H or R, wherein R is as defined above, c=1-300, or ##STR3## wherein: x is as defined above, and c'=2-20, as well as mixtures of any two or more thereof.
Claim 22
Dependent Claim
13 words
A composition according to claim 1, wherein said images are magnetic resonance images.
Claim 23
Dependent Claim
18 words
A composition according to claim 21, wherein said imaging agent(s) are selected from ferromagnetic or superparamagnetic metal particles.
Claim 24
Dependent Claim
14 words
A composition according to claim 22, wherein said particles are dispersed in a fluorocarbon.
Claim 25
Dependent Claim
15 words
A composition according to claim 21, further comprising a positron emission tomography (PET) contrast agent.
Claim 26
Dependent Claim
14 words
A composition according to claim 24, wherein said PET contrast agent contains 18 F.
Claim 27
Dependent Claim
15 words
A composition according to claim 21, wherein said biocompatible polymer comprises an iron containing protein.
Claim 28
Dependent Claim
12 words
A composition according to claim 1, wherein said images are ultrasonic images.
Claim 29
Dependent Claim
15 words
A composition according to claim 27, wherein said imaging agent is an ultrasonic contrast agent.
Claim 30
Dependent Claim
14 words
A composition according to claim 28, wherein said ultrasonic contrast agent is a perfluorohalocarbon.
Claim 31
Dependent Claim
17 words
A composition according to claim 28, wherein said perfluorohalocarbon is selected from perfluorooctylbromide, perfluorodecalin, perfluorotripropylamine, or perfluoropentane.
Claim 32
Dependent Claim
14 words
A composition according to claim 1, wherein said images are x-ray computer tomography images.
Claim 33
Dependent Claim
13 words
A composition according to claim 31, wherein said imaging agent is a perfluorohalocarbon.
Claim 34
Dependent Claim
16 words
A composition according to claim 31, wherein said imaging agent is a brominated or iodinated fluorocarbon.
Claim 35
Dependent Claim
14 words
A composition according to claim 1, wherein said polymeric shell further comprises a fluorocarbon.
Claim 36
Dependent Claim
14 words
A composition according to claim 1, wherein said polymeric shell further comprises a ligand.
Claim 37
Dependent Claim
13 words
A composition according to claim 35, wherein said ligand is natural or synthetic.
Claim 38
Dependent Claim
22 words
A composition according to claim 36, wherein said natural ligand is selected from a sugar, carbohydrate, steroid, protein, polypeptide, neurotransmitter, or antibody.
References Cited (Backward Citations)
US4639364A
Cited
US4832941A
Cited
EP0307863A1
Cited
WO1989003603A1
Cited
US5171755A
Cited
WO1990001953A1
Cited
US4951673A
Cited
US4957656A
Cited
US5114703A
Cited
WO1991001759A1
Cited
US5116599A
Cited
WO1991015753A1
Cited
US5310540A
Cited
US5143716A
Cited
WO1992017213A1
Cited
WO1992018165A2
Cited
US5233995A
Cited
US5196183A
Cited
EP0633030A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1999-04-30 | 1999-10-30 | 2000-04-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-04-30 | 2003-10-30 | 2004-04-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-04-30 | 2007-10-30 | 2008-04-30 | $7700.00 | Window Closed / Lapsed |