Chelate Patents (Class 514/836)
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Patent number: 5458869Abstract: The invention relates to the use as contrast enhancing agents in medical imaging, especially X-ray imaging, of multinuclear complexes, i.e. complexes, such as those of W2O2 (u2O)2, in which the complexed entity comprises at least two contrast enhancing atoms.Type: GrantFiled: November 24, 1992Date of Patent: October 17, 1995Assignee: Nycomed Salutar Inc.Inventors: Arne Berg, Torsten Almen, Klaus D. Krautwurst, Sook-Hui Kim, Pal Rongved, Jo Klaveness, Harald Dugstad
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Patent number: 5449508Abstract: Methods of providing an image of the gastrointestinal region of a patient and diagnosing the presence of any tumorous tissue in that region using contrast media comprising a combination of at least one polyphosphorylated aliphatic or polyphosphorylated alicyclic compound and at least one paramagnetic ion, wherein the aliphatic and alicyclic compounds comprise at least five carbon atoms, is described. Also described are diagnostic kits for gastrointestinal imaging which include the subject contrast media.Type: GrantFiled: February 17, 1994Date of Patent: September 12, 1995Inventor: Evan C. Unger
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Patent number: 5439668Abstract: Heterocyclic chelating agents and salts thereof of formula I: ##STR1## wherein X represents a bond, O or S, or a group CHR.sup.1 or NR.sup.3, each R.sup.1 represents H, a group OR.sup.3 or NR.sup.3 R.sup.3, or an alkyl or alkoxyalkyl group optionally substituted by a hydroxyl group or by a group NR.sup.3 R.sup.3 or CON.sup.3 R.sup.3 ;each R.sup.2 represents H, or an alkyl or alkoxy group optionally substituted by a hydroxyl or aloxy group;each R.sup.3 represents H, an optionally hydroxylated alkyl group or a group CH.sub.2 Y;Y represents a group COZ, CON(OH)R.sup.4, POZ.sub.2 or SO.sub.2 Z; Z represents a group OR.sup.4, NR.sup.4 R.sup.4 or ##STR2## where each R.sup.11 is H, a hydroxyl group or an optionally hydroxylated alkyl group, s is 0, 1 or 2, and W is CHR.sup.11, NR.sup.11 or an oxygen atom; andeach R.sup.4 represents H, or an optionally mono- or poly-hydroxylated alkyl, alkoxyalkyl or polyalkoxyalkyl group;with the provisos that where s is O then W is CHR.sup.Type: GrantFiled: May 2, 1994Date of Patent: August 8, 1995Assignee: Nycomed Imaging ASInventors: Torsten Almen, Arne Berg, Harald Dugstad, Jo Klaveness, Klaus D. Krautwurst, Pal Rongved
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Patent number: 5429814Abstract: The invention relates to a method of using molecular sieve-enclosed paramagnetic ions as image brightening or image contrast agents. In particular, zeolite enclosed trivalent gadolinium is useful in MRI studies of the entire gastrointestinal tract, providing excellent images. Zeolite-enclosed gadolinium complexes may be conveniently administered in oral preparations without side effects of diarrhea. Other transition metal ions, including divalent manganese may be enclosed in any suitable molecular sieve which has ion exchange properties sufficient to exchange the selected metal. The exchanged paramagnetic metal ion may be a free ion within the zeolite framework or ligated with a chelator. Alternatively, a paramagnetic metal ion may be included as part of the molecular sieve framework.Type: GrantFiled: May 27, 1993Date of Patent: July 4, 1995Assignee: Board of Regents, The University of Texas SystemInventors: Stuart W. Young, Kenneth J. Balkus, Jr., A. Dean Sherry
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Patent number: 5422095Abstract: There is disclosed an imaging agent for diagnosis comprising a compound composed of a polynuclear type compound of the formula I or II: ##STR1## wherein each X is a hydrogen atom or a bifunctional ligand, at least one of them are bifunctional ligand and m or n is an integer of 1 to 6, and at least one metal ion being coordinated with at least one bifunctional ligand moiety, said metal ion being selected from the group consisting of metal ions having the atomic number of 21-29, 31, 32, 37-39, 42-44, 49 and 56-83.Type: GrantFiled: April 4, 1994Date of Patent: June 6, 1995Assignee: Nihon Medi-Physics Co., Ltd.Inventors: Yuji Hashiguchi, Kumiko Iwai, Shigemi Seri, Susumu Kondo, Makoto Azuma
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Patent number: 5419893Abstract: There are provided chelating agents particularly useful for the preparation of diagnostic and therapeutic agents for magnetic resonance imaging, scintigraphy, ultrasound imaging, radiotherapy and heavy metal detoxification, said agents being compounds of formula IX--CHR.sub.1 NZ--(CHR.sub.1).sub.n --A--(CHR.sub.1).sub.m --NZ--CHR.sub.1 --X (I)(wherein each of the groups Z is a group --CHR.sub.1 X or the groups Z together are a group --(CHR.sub.1).sub.q --A'--(CHR.sub.1).sub.r --, where A' is an oxygen or sulphur atom or a group --N--Y;A is a group --N--Y or A--(CHR.sub.1).sub.m -- represents a carbon-nitrogen bond or, when the groups Z together are a group --(CHR.sub.1).sub.q --A'--(CHR.sub.1).sub.r --, A may also represent an oxygen or sulphur atom;each Y, which may be the same or different, is a group --(CHR.sub.1).sub.p --N(CHR.sub.1 X).sub.2 or a group --CHR.sub.1 X;each X, which may be the same or different, is a carboxyl group or a derivative thereof or a group R.sub.1 ;each R.sub.Type: GrantFiled: January 19, 1993Date of Patent: May 30, 1995Assignee: Nycomed Imaging ASInventors: Arne Berg, Torsten Almen, Jo Klaveness, Pal Rongved, Terje Thomassen
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Patent number: 5417960Abstract: The subject of the invention is nitrogen-containing cyclic ligands and metal complexes formed by these ligands, the uses of these complexes as magnetic resonance imaging (MRI) agents, as X-ray contrast agents and as chemical shift reagents in vivo.Type: GrantFiled: February 3, 1994Date of Patent: May 23, 1995Assignee: Guerbet S.A.Inventors: Nichel Schaefer, Didier Doucet, Bruno Bonnemain, Dominique Meyer, Dominique Paris
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Patent number: 5416078Abstract: The invention relates to fluid resuscitation of the human or animal body by administration of deferoxamine (DFO) and a water-soluble biopolymer.The DFO and the biopolymer are preferably bonded together.The biopolymer may be a polysaccharide or a protein.The DFO and the biopolymer are preferably formulated as an aqueous solution suitable for oral administration.The fluid resuscitation may be effected for ameliorating systemic oxidant injury occurring during ischemia and subsequent reperfusion.The fluid resuscitation may be indicated in treatment of burn injury, lung injury caused by inhalation of hot and/or toxic substances, such as smoke derived from combustion, hemorrhagic shock and other types of trauma.Type: GrantFiled: November 25, 1992Date of Patent: May 16, 1995Assignee: Biomedical Frontiers, Inc.Inventors: Bo E. Hedlund, Philip E. Hallaway
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Patent number: 5407660Abstract: Nuclear magnetic resonance (NMR) imaging of body organs and tissues is enhanced by administering to a living animal body a diagnostic composition comprising a diagnostically effective amount of a substantially nontoxic paramagnetic image altering agent containing a chelate of a paramagnetic element such as magnesium, gadolinium or iron, carried by a liposome. The chelate is carried by or within or outside the external surface of the liposome in such a manner that after arrival at or delivery to the desired organ or tissue site, the paramagnetic image altering agent is released in a diagnostically useful fashion.Type: GrantFiled: November 12, 1993Date of Patent: April 18, 1995Assignee: Mallinckrodt Medical, Inc.Inventors: Mark E. Bosworth, Ronald M. Hopkins
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Patent number: 5405601Abstract: The present invention provides new and structurally diverse compositions for diagnostic imaging comprising compounds of the general formula: ##STR1## wherein A is N or CR.sub.1, R.sub.1 is hydrogen, C.sub.1 -C.sub.8 alkyl, or C.sub.6 -C.sub.10 aryl, where the alkyl or aryl group may be optionally substituted with one or more hydroxy, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 hydroxyalkyl, C.sub.1 -C.sub.8 alkoxy, C.sub.6 -C.sub.10 aryl, C.sub.6 -C.sub.10 hydroxyaryl, C.sub.6 -C.sub.10 aryloxy, --CO.sub.2 R.sub.2, --CONR.sub.3 R.sub.4, or NR.sub.3 R.sub.4 ; D is O, --O(CH.sub.2).sub.2 O--, --O(CH.sub.2).sub.3 O--, or NR.sub.5 ; E is O, --O(CH.sub.2).sub.2 O--, --O(CH.sub.2).sub.3 O-- or NR.sub.6 ; F is O, --O(CH.sub.2).sub.2 O--, --O(CH.sub.2).sub.3 O-- or NR.sub.7 ; R.sub.2 -R.sub.7 are as defined within; g, h, i, j, k and m may be the same or different and are an integer from one to about six; X is --CO.sub.2 H, --PO.sub.3 H.sub.2, --SO.sub.3 H or --CONHOH.Type: GrantFiled: July 2, 1993Date of Patent: April 11, 1995Assignee: Mallinckrodt Medical Inc.Inventors: T. Jeffrey Dunn, Dennis A. Moore, Muthanadar Periasamy, Milorad M. Rogic, Rebecca A. Wallace, David H. White, Steven R. Woulfe
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Patent number: 5403574Abstract: The present invention relates to methods for detecting the multidrug resistance phenotype in vivo and in vitro. The invention particularly relates to methods of diagnosing the multidrug resistance phenotype by imaging, particularly scintigraphic imaging, in solid tumors in vivo or in tumors and biopsies in vitro. The methods of the present invention allow the diagnosis of multidrug-resistant tumor and other multidrug-resistant phenotypes without invasive surgical methods. The present invention is also directed to methods of treating multidrug resistant tumors with novel agents that bind to P-glycoprotein. The novel compounds of the present invention are co-administered with a chemotherapeutic agent in order to enhance accumulation of the drug.Type: GrantFiled: June 26, 1992Date of Patent: April 4, 1995Assignee: Brigham and Women's HospitalInventor: David R. Piwnica-Worms
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Patent number: 5403576Abstract: Hybrid agents for enhancing in vivo diagnostic imaging of body organs and tissues, and methods of preparing and using the same.Type: GrantFiled: February 4, 1994Date of Patent: April 4, 1995Assignee: Mallinckrodt Medical, Inc.Inventors: Youlin Lin, Muthanadar P. Periasamy, Donald R. VanDeripe, William P. Cacheris
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Patent number: 5401492Abstract: This invention is directed to a magnetic resonance imaging composition for imaging of an organ rich in mitochondria comprising particles of a substantially insoluble manganese compound. In a preferred embodiment, the organ rich in mitochondria is the liver. In a further preferred embodiment, the particles are substantially nonmagnetic. In another preferred embodiment, the particles have a particle size of less than about 10 microns.In a still further preferred embodiment, the insoluble manganese compound is a manganese salt. The manganese compound is preferably selected from the group consisting of manganese phosphate, manganese carbonate and manganese 8-hydroxy quinolate.In another preferred embodiment, the composition of the present invention further comprises a surfactant.Type: GrantFiled: December 17, 1992Date of Patent: March 28, 1995Assignee: Sterling Winthrop, Inc.Inventors: Kenneth E. Kellar, Piotr H. Karpinski, Elaine Liversidge, Wolfgang H. H. Gunther, Gregory L. McIntire, Barbara Van Orman
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Patent number: 5399340Abstract: Complex compounds of general Formula I ##STR1## wherein X is a hydrogen atom and/or a metal ion equivalent of at least one element of atomic numbers 21-29, 42, 44 or 58-70, with at least two of the substituents X representing a metal ion equivalent, andR.sup.1, R.sup.2, R.sup.3, R.sup.4, Y and n are defined herein, as well as their salts with organic and/or inorganic bases, are valuable compounds for organ-specific NMR diagnostics.Type: GrantFiled: April 20, 1993Date of Patent: March 21, 1995Assignee: Schering AktiengesellschaftInventors: Bernd Raduchel, Heribert Schmitt-Willich, Heinz Gries, Gabriele Schuhmann-Giampieri, Hubert Vogler, Jurgen Conrad
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Patent number: 5382421Abstract: A method is provided utilizing contrast agents which provide increased diagnostic information in the magnetic resonance image of the hepatobiliary system and alimentary tract, especially the small intestine. Novel contrast agents which are N-carboxylated desferrioxamine B complexes with metal ions are provided.Type: GrantFiled: September 17, 1993Date of Patent: January 17, 1995Assignee: The Regents of the University of CaliforniaInventors: David L. White, Barry L. Engelstad, Kurt Muetterties
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Patent number: 5380515Abstract: Polyphosphonate ligands containing three or more phosphonate groups, combined with paramagnetic metal cations and administered in the form of pharmacologically acceptable salts, are useful as MRI contrast enhancement agents, which tend to localize in bone tissue without being conjugated to bone-specific biomolecules. Triazacyclononanes and tetraazacyclododecanes, with dihydroxyphosphorylmethyl or dihydroxyphosphorylethyl groups, optionally substituted at the methyl or ethyl bridges with alkyl, aryl, hydroxyl or amino groups, are particularly preferred.Type: GrantFiled: July 22, 1993Date of Patent: January 10, 1995Assignee: Concat, Ltd.Inventors: Harry S. Winchell, Joseph Y. Klein, Elliot D. Simhon, Rosa L. Cyjon, Ofer Klein, Haim Zaklad
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Patent number: 5370860Abstract: The present invention relates to contrast enhancing agents, conjugates thereof, pharmaceutical compositions thereof, and methods for diagnostic analysis, particularly NMR image analysis using these agents. The contrast enhancing agents are chelates of paramagnetic, ferromagnetic or diamagnetic metal ion(s) complexed with new lipophilic complexing acids related to polyaminopolycarboxylic acids.Type: GrantFiled: July 29, 1993Date of Patent: December 6, 1994Assignee: Research Corporation Technologies, Inc.Inventors: Gabriel A. Elgavish, Sung K. Kim
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Patent number: 5362475Abstract: A diagnostic medium contains at least one physiologically well tolerated complex salt comprising an anion of a complexing acid and one or more Gadolinium ions and, optionally, one or more physiologically biocompatible cation or cations of an inorganic and/or organic base or amino acid, optionally, with additives customary in galenic formulations, dissolved or suspended in an aqueous medium.Type: GrantFiled: July 10, 1992Date of Patent: November 8, 1994Assignee: Schering AktiengesellschaftInventors: Heinz Gries, Douwe Rosenberg, Hanns-Joachim Weinmann, Ulrich Speck, Wolfgang Mutzel, Georg-Alexander Hoyer, Heinrich Pfeiffer, deceased, Franz-Josef Renneke
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Patent number: 5362754Abstract: Disclosed are pharmaceutical compositions of a mixture of minocycline and EDTA (M-EDTA) and methods of using the compositions in maintaining the patency of a catheter port. Methods for inhibiting the formation of polysaccharide-rich glycocalyx (such as the glycocalyx of staphylococcal organisms) are also provided using an M-EDTA solution. The M-EDTA solution may also be used to pretreat a medical device to prevent adherence of infectious organisms, such as S. epidermidis and S. aureus. The compositions destroy and prevent the formation of polysaccharide-rich glycocalyx. Methods for treating infections of S. epidermidis and S. aureus where glycocalyx formation are provided with an M-EDTA solution. The minocycline and EDTA solutions are included together within a pharmacologically acceptable carrier solution, such as saline.Type: GrantFiled: November 12, 1992Date of Patent: November 8, 1994Assignee: Univ. of TX MD Anderson Cancer CenterInventors: Issam Raad, Robert J. Sherertz
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Patent number: 5362476Abstract: The present invention relates to a new polyazamacrocyclic compound or a salt thereof and its uses as a tissue specific chelator. The compound has the formula ##STR1## where x is 2, 3 or a combination of p 2(s) and q 3(s) where p+q=y;y is 4;R is ( CH.sub.2).sub.z P(=0)OR.sup.1 OR.sup.2 ;R.sup.1 is H or CH.sub.3 ;R.sup.2 is C.sub.n H.sub.1+2n ;n is 4 to 6;z is 1 to 3.M is a heavy metal ion.These compounds may be used for magnetic resonance imaging.Type: GrantFiled: July 31, 1992Date of Patent: November 8, 1994Assignees: Board of Regents, The University of Texas System, Dow Chemical CompanyInventors: A. Dean Sherry, Garry E. Kiefer
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Patent number: 5358704Abstract: Novel compounds of the formula ##STR1## and metal chelates of the compounds are useful particularly for MRI of the hepatobiliary system.Type: GrantFiled: September 30, 1993Date of Patent: October 25, 1994Assignee: Bristol-Myers SquibbInventors: Jean F. Desreux, Michael F. Tweedle, Peter C. Ratsep, Thomas R. Wagler, Edmund R. Marinelli
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Patent number: 5358702Abstract: A contrast medium useful for diagnostic imaging is provided. The contrast medium comprises gel particles, preferably of less than about 90.mu. in mean diameter, the gel particles comprising at least one polymer entrapping at least one contrast enhancing metal.Type: GrantFiled: May 14, 1993Date of Patent: October 25, 1994Inventor: Evan C. Unger
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Patent number: 5352438Abstract: Cosmetic or pharmaceutical composition containing a dismutase superoxide (DSO) in combination with a phosphonic acid derivative used as metal chelating agent. These compositions are used in topical administration, in particular in the fight against skin aging and in the protection of the skin against radiation exposure.Type: GrantFiled: January 26, 1993Date of Patent: October 4, 1994Assignee: L'OrealInventors: Quang L. N'Guyen, Jean-Baptiste Galey
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Patent number: 5352431Abstract: There is disclosed an imaging agent for diagnosis comprising a compound composed of a polynuclear type compound of the formula I or II: ##STR1## wherein each X is a hydrogen atom or a bifunctional ligand, at least one of them are bifunctional ligand and m or n is an integer or 1 to 6, and at least one metal ion being coordinated with at least one bifunctional ligand moiety, said metal ion being selected from the group consisting of metal ions having the atomic number of 21-29, 31, 32, 37-39, 42-44, 49 and 56-83.Type: GrantFiled: September 13, 1993Date of Patent: October 4, 1994Assignee: Nihon Medi-Physics Co., Ltd.Inventors: Yuji Hashiguchi, Kumiko Iwai, Shigemi Seri, Susumu Kondo, Makoto Azuma
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Patent number: 5350770Abstract: A therapeutic process for treating septic shock comprising the administration of a polyhydroxy-substituted benzamide or phenylacetamide derivative to a human suffering from, or in danger of contracting, septic shock.Type: GrantFiled: July 28, 1992Date of Patent: September 27, 1994Inventors: Howard L. Elford, Bartholomeus van't Riet
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Patent number: 5334371Abstract: The macrocyclic compounds of the following formula I and IV, defined herein and their salts with inorganic and/or organic bases, amino acids or amino acid amides are valuable diagnostic and therapeutic agents.Type: GrantFiled: July 6, 1992Date of Patent: August 2, 1994Assignee: Schering AktiengesellschaftInventors: Heinz Gries, Bernd Raduchel, Johannes Platzek, Hanns-Joachim Weinmann, Wolf-Rudiger Press, Ulrich Speck
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Patent number: 5330743Abstract: A contrast enhancing agent for magnetic resonance images having a chelating agent, which can be bound to metals having at least one unpaired electron. Examples of such chelating agents include 3,6,9-tris(carboxymethyl)-1, 11-bis(dimethylamine)-3,6,9-triazaundecane; 3,6,9-tris(carboxymethyl)-1, 11-bis(diethanolamino) 3,6,9-triazaundecane; 3,6,9-tris(carboxymethyl)-1, 11-bis(tris(hydroymethyl) aminomethane)-3,6,9-triazaundecane; 3,6-bis(carboxymethyl-1,8-bis(N-carboxymethylglucosamino)-3,6-diazoctane; DTPA-bis(galactosamide), DTPA-Bis(glucosamide), DTPA-Bis(pyridoxamide), and poly-(DTPA-ethylenediamide).Type: GrantFiled: November 12, 1992Date of Patent: July 19, 1994Assignee: Magnetic Research, Inc.Inventors: Wendell A. Gibby, N. Rao Puttagunta
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Patent number: 5320826Abstract: Methods of providing an image of the gastrointestinal region of a patient and diagnosing the presence of any tumorous tissue in that region using contrast media comprising a combination of at least one polyphosphorylated aliphatic or polyphosphorylated alicyclic compound and at least one paramagnetic ion, wherein the aliphatic and alicyclic compounds comprise at least five carbon atoms, is described. Also described are diagnostic kits for gastrointestinal imaging which include the subject contrast media.Type: GrantFiled: April 10, 1992Date of Patent: June 14, 1994Inventor: Evan C. Unger
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Patent number: 5316756Abstract: Compounds of the general formula I: ##STR1## R.sup.1 signifies a COOX group or the group ##STR2## R.sup.2 and R.sup.3 are the same or different and signify a hydrogen atom, a lower straight- or branched-chain, hydrocarbon radical, a phenyl or benzyl group or either R.sup.2 or R.sup.3 signifies the group ##STR3## or R.sup.2 or R.sup.3 together signify a trimethylene or tetramethylene radical, R.sup.4 represents a straight- or branched-chain mono- or poly-hydroxyalkyl radical, R.sup.5 represents a hydrocarbon atom, a lower straight- or branched-chain, optionally mono- or poly-hydroxylated, hydrocarbon radical, Q signifies an oxygen or sulfur atom or the group ##STR4## wherein j signifies the numbers 1 to 4 and R.sup.Type: GrantFiled: April 13, 1990Date of Patent: May 31, 1994Assignee: Schering AktiengesellschaftInventors: Heinz Gries, Franz-Josef Renneke, Hanns-Joachim Weinmann
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Patent number: 5314681Abstract: The invention relates to a modification of electron spin resonance enhanced magnetic resonance imaging (ESREMRI) in which two magnetically responsive materials (contrast agents) are introduced into the sample being investigated, one contrast agent serving as an ESREMRI free induction decay signal enhancing agent and the other as enhancement suppressing agent. In this way, image contrast may be enhanced further for regions in which the suppressing agent distributes poorly or not at all or which the suppressing agent reaches at a later time than the enhancing agent.Type: GrantFiled: March 22, 1993Date of Patent: May 24, 1994Assignee: Nycomed Innovation ABInventors: Ib Leunbach, Klaes Golman, Jo Klaveness
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Patent number: 5314680Abstract: Novel magnetic resonance imaging agents comprise complexes of paramagnetic ions with hydrazide derivatives of polyaminocarboxylic acid chelating agents. These novel imaging agents are characterized by excellent NMR image-contrasting properties and by high solubilities in physiological solutions.A novel method of performing an NMR diagnostic procedure involves administering to a warm-blooded animal an effective amount of a complex as described above and then exposing the warm-blooded animal to an NMR imaging procedure, thereby imaging at least a portion of the body of the warm-blooded animal.Type: GrantFiled: May 4, 1993Date of Patent: May 24, 1994Assignee: Mallinckrodt Medical, Inc.Inventors: Raghavan Rajagopalan, Rebecca A. Wallace, Muthunadar P. Periasamy
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Patent number: 5312617Abstract: Novel complexes of paramagnetic ions and compounds bearing long acyl chains have been synthesized as magnetic resonance imaging contrast agents. These novel liposoluble contrast agents may be administered alone, or with lipids, suspending agents or other additives. The lipids may be in the form of liposomes, micelles or lipid emulsions. The contrast agents of the invention have particular use in magnetic resonance imaging of the liver, blood pool and reticuloendothelial system.Type: GrantFiled: May 22, 1992Date of Patent: May 17, 1994Inventors: Evan C. Unger, DeKang Shen
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Patent number: 5277897Abstract: The invention relates to compositions that comprise (1) lipophilic cationic organometallic complexes, particularly hexakis(2-methoxyisobutylisonitrile)technetium(I) complex, and (2) an agent that decreases the intramembrane potential of a living cell. Agents which decrease the intramembrane potential of a living cell include the lipophilic anions, especially tetraphenylborate anion. The invention also relates to methods in which the compositions are administered in vivo and in vitro when it is desirable to obtain enhanced cellular accumulation of lipophilic cationic organometallic complexes. The compositions and methods are useful for diagnosis and treatment, pSTATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY-SPONSORED RESEARCH AND DEVELOPMENTPart of the work performed during development of this invention utilized U.S. Government funds. The U.S. Government has certain rights in this invention.Type: GrantFiled: September 17, 1992Date of Patent: January 11, 1994Assignee: Brigham and Women's HospitalInventors: David R. Piwnica-Worms, James F. Kronauge
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Clay enclosed transition and rare earth metal ions as contrast agents for the gastrointestinal tract
Patent number: 5277896Abstract: The invention relates to compositions and methods of using clay-enclosed paramagnetic ions as image brightening or image contrast agents. In particular, T.sub.1 relaxivity measurements on Hectorite and mortmorillonite clay-enclosed trivalent gadolinium suggest improved imaging over zeolite-enclosed paramagnetic species. Clay-enclosed gadolinium complexes are amenable to convenient administration in oral preparations and are readily formulated in stable aqueous suspensions. Other transition metal ions, including divalent manganese, may be enclosed in the clay structures, either as free metals or in the forms of chelated complexes. Alternatively, improved relaxivities are envisioned for clays incorporating a paramagnetic metal ion as part of the framework structure.Type: GrantFiled: June 15, 1992Date of Patent: January 11, 1994Assignee: Board of Reagents, The University of Texas SystemInventor: Kenneth J. Balkus, Jr. -
Patent number: 5277895Abstract: Tetraazacyclododecane compounds of general formula I ##STR1## in which E and Q are defined herein and their salts with inorganic and/or organic bases, amino acids or amino acid amides are valuable pharmaceutical agents.Type: GrantFiled: November 8, 1991Date of Patent: January 11, 1994Assignee: Schering AktiengesellschaftInventors: Johannes Platzek, Heinz Gries, Hanns-Joachim Weinmann, Wolf-Rudiger Press, Hubert Vogler
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Patent number: 5271924Abstract: There is disclosed an imaging agent for diagnosis comprising a compound composed of a polynuclear type compound of the formula I or II: ##STR1## wherein each X is a hydrogen atom or a bifunctional ligand, at least one of them are bifunctional ligand and m or n is an integer of 1 to 6, and at least one metal ion being coordinated with at least one bifunctional ligand moiety, said metal ion being selected from the group consisting of metal ions having the atomic number of 21-29, 31, 32, 37-39, 42-44, 49 and 56-83.Type: GrantFiled: September 29, 1992Date of Patent: December 21, 1993Assignee: Nihon Medi-Physics Co., Ltd.Inventors: Yuji Hashiguchi, Kumiko Iwai, Shigemi Seri, Susumu Kondo, Makoto Azuma
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Patent number: 5272142Type: GrantFiled: May 7, 1992Date of Patent: December 21, 1993Assignee: Board of Regents, The University of Texas SystemInventors: Jonathan L. Sessler, Gregory W. Hemmi, Toshiaki Murai
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Patent number: 5271929Abstract: There is disclosed a nuclear magnetic resonance imaging agent comprising a complex compound composed of (a) a dialdehyde-saccharide having a molecular weight of from 500 to 10,000, at least one of the constituent monosaccharides of which is oxidation-cleaved, (b) at least one complexing agent which is chemically coupled to an aldehyde group of the dialdehyde-saccharide and (c) a paramagnetic metal ion which is chemically coupled to the complexing agent.Type: GrantFiled: July 8, 1992Date of Patent: December 21, 1993Assignee: Nihon Medi-Physics Co., Ltd.Inventors: Yuji Hashiguchi, Kumiko Iwai, Shigemi Seri, Susumu Kondo, Makoto Azuma
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Patent number: 5268165Abstract: Compositions comprising a covalently bounded adduct of deferoxamine, ferric iron and polymer for image enhancement in magnetic resonance (MR) imaging are provided. A pharmaceutical composition comprising the adduct and method of using the composition in magnetic resonance imaging are also disclosed.Type: GrantFiled: August 7, 1992Date of Patent: December 7, 1993Assignee: Biomedical Frontiers, Inc.Inventors: Bo E. Hedlund, Philip E. Hallaway
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Patent number: 5256399Abstract: The present invention involves a novel tripyrrole dimethine-derived "expanded porphyrin" (texaphyrin), the synthesis of such compounds, their analogs or derivatives and their uses. These expanded porphyrin-like macrocycles are efficient chelators of divalent and trivalent metal ions. Metal complexes of these compounds are active as photosensitizers for the generation of singlet oxygen and thus potentially for inactivation or destruction of human immunodeficiency virus (HIV-1), mononuclear or other cells infected with such virus and tumor cells as well. A variety of texaphyrin derivatives have been produced and many more are readily obtainable. Various metal (e.g., transition, main group, and lanthanide) complexes with the texaphyrin and texaphyrin derivatives of the present invention have unusual water solubility and stability which render them particularly useful. These metallotexaphyrin complexes have optical properties making them unique as compared to existing porphyrin-like or other macrocycles.Type: GrantFiled: May 7, 1992Date of Patent: October 26, 1993Assignee: Board of Regents, The University of Texas SystemInventors: Jonathan L. Sessler, Gregory W. Hemmi, Toshiaki Murai
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Patent number: 5246696Abstract: Substantially nontoxic manganese or gadolinium complexes of compounds of the formula: ##STR1## wherein n and m=1, 2, 3 or 4, y=1, 2 or 3, and x is selected from the group consisting of S, CHOH and CHSH, are useful for enhancing magnetic resonance images of body organs and tissues. Illustrative manganese and gadolinium complexes of such compounds include disodium [[(2-hydroxytrimethylene)dinitrilo]tetraaceto]manganese(II) and sodium [[(2-hydroxytrimethylene)dinitrilo]tetraaceto)gadolinium(III).Type: GrantFiled: July 10, 1992Date of Patent: September 21, 1993Assignee: Mallinckrodt Medical, Inc.Inventor: Richard T. Dean
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Patent number: 5242683Abstract: There is provided a contrast medium comprising a physiologically tolerable paramagnetic metal species containing substance together with a water soluble iodinated X-ray contrast agent. The contrast medium can be used for both X-ray and magnetic resonance imaging of the gastro-intestinal tract but overcomes or greatly reduces the side effects experienced by mannitol-containing prior art contrast media.Type: GrantFiled: December 10, 1991Date of Patent: September 7, 1993Assignee: Nycomed Imaging ASInventor: Jo Klaveness
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Patent number: 5242681Abstract: The present invention relates to contrast enhancing agents, conjugates thereof, pharmaceutical compositions thereof, and methods for diagnostic analysis, particularly NMR image analysis using these agents. The contrast enhancing agents are chelates of paramagnetic, ferromagnetic or diamagnetic metal ion(s) complexed with new lipophilic complexing acids related to polyaminopolycarboxylic acids.Type: GrantFiled: August 4, 1992Date of Patent: September 7, 1993Assignee: Research Corporation Technologies, Inc.Inventors: Gabriel A. Elgavish, Sung K. Kim
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Patent number: 5236695Abstract: Polyphosphonate ligands containing three or more phosphonate groups, combined with paramagnetic metal cations and administered in the form of pharmacologically acceptable salts, are useful as MRI contrast enhancement agents, which tend to localize in bone tissue without being conjugated to bone-specific biomolecules. Triazacyclononanes and tetraazacyclododecanes, with dihydroxyphosphorylmethyl or dihydroxyphosphorylethyl groups, optionally substituted at the methyl or ethyl bridges with alkyl, aryl, hydroxyl or amino groups, are particularly preferred.Type: GrantFiled: September 11, 1991Date of Patent: August 17, 1993Assignee: Concat, Ltd.Inventors: Harry S. Winchell, Joseph Y. Klein, Elliot D. Simhon, Rosa L. Cyjon, Ofer Klein, Haim Zaklad
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Patent number: 5230883Abstract: Improved methods of selectively localizing, imaging and/or treating tumors, which have a net negative charge, employ novel compositions containing non-immunogenic complexes having a net positive charge in a sterile solution. The complexes contain polylysine, a linking agent bound to less than all of the lysyl groups of the polylysine, and an imaging agent or a chemotherapeutic agent which is also bound to the linking agent.Type: GrantFiled: January 27, 1992Date of Patent: July 27, 1993Assignee: Wisconsin Alumni Research FoundationInventors: Steven Kornguth, Patrick Turski, H. Ian Robins, Robert J. Nickles
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Patent number: 5219553Abstract: Magnetic resonance imaging contrast media used to affect the relaxation times of atoms in body tissues undergoing NMR diagnosis are disclosed. Such media comprise (1) a paramagnetic, physiologically compatible complex of (a) a chelant consisting of a N-carboxy methylated tetraazacyclododecane, and (b) a paramagnetic ion of a lanthanide element of atomic numbers 59-70, or of a transition metal of atomic numbers 21-29, 42 or 44, or a physiologically compatible salt of such a complex, and (2) a toxicity-reducing amount of labile calcium ions. The labile calcium ions can be derived from a source other than a salt of said chelant, e.g. an inorganic or organic calcium salt. NMR image-enhancing compositions comprising NMR image-enhancing effective amounts of said contrast media and pharmaceutically acceptable diluents are also disclosed.Type: GrantFiled: August 9, 1991Date of Patent: June 15, 1993Assignee: Salutar, Inc.Inventors: Karl F. Kraft, Steven C. Quay, Scott M. Rocklage, Dilip Worah
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Patent number: 5217998Abstract: A method for scavenging free iron or aluminum in fluids such as physiological fluids involves a provision in such fluids of a soluble polymer substrate having chelator immobilized thereon. According to the invention preferred such compounds comprise polysaccharides or proteins having a deferoxamine moiety thereon. Such a compound can be used for the treatment of iron overload, as well as to inhibit cell damage from oxidation/reduction reactions. In one embodiment, cell damage during reperfusion is inhibited, through provision of the chelating moiety at the site of reperfusion.Type: GrantFiled: June 17, 1991Date of Patent: June 8, 1993Assignee: Biomedical Frontiers, Inc.Inventors: Bo E. Hedlund, Philip E. Hallaway, Samuel S. Panter, John W. Eaton
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Patent number: 5217706Abstract: Novel magnetic resonance imaging agents comprise complexes of paramagnetic ions with hydrazide derivatives of polyaminocarboxylic acid chelating agents. These novel imaging agents are characterized by excellent NMR image-contrasting properties and by high solubilities in physiological solutions.A novel method of performing an NMR diagnostic procedure involves administering to a warm-blooded animal an effective amount of a complex as described above and then exposing the warm-blooded animal to an NMR imaging procedure, thereby imaging at least a portion of the body of the warm-blooded animal.Type: GrantFiled: June 3, 1992Date of Patent: June 8, 1993Assignee: Mallinckrodt Medical, Inc.Inventors: Raghavan Rajagopalan, Rebecca A. Wallace, Muthunadar P. Periasamy
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Patent number: 5213788Abstract: Improved compositions and methods for selective access to tumor regions (or other regions of abnormal endothelial properties). This capability provides powerful contrast-enhancement agents for nuclear magnetic resonance imaging. A polyatomic complex which includes intramolecular ferromagnetic coupling between metal atoms is associated with a polymer or microsphere carrier matrix which will bind to endothelial determinants. A solution containing this carrier complex is injected into a human (or other) body to be imaged. The carrier complex will preferentially extravasate at locations where the blood vessel walls have increased porosity or microvascular surface changes, and especially at tumor sites. Thus, the changes in relaxation time induced by the presence of the carrier complex will provide a high-gain marker for magnetic resonance imaging.Type: GrantFiled: April 4, 1991Date of Patent: May 25, 1993Inventor: David F. Ranney
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Patent number: 5204085Abstract: Paramagnetic chelates, as for example, Gadolinium diethylenetriaminepentaacetic acid (DTPA), manganese, ethylenediaminetetraacetic acid (EDTA), and others used as X-ray contrast agents are more toxic acutely when injected in high concentration or at rapid rates. The use of effective amounts of calcium in the form of, calcium chloride, calcium gluconate, or balanced salt solutions substantially reduces this toxicity without the need to add additional ligand.Type: GrantFiled: November 18, 1991Date of Patent: April 20, 1993Assignee: Mallinckrodt Medical, Inc.Inventor: Donald R. VanDeripe