Diagnostic media
AssigneeSchering Corporation
InventorsHeinz Gries, Douwe Rosenberg, Hanns-Joachim Weinmann
Life of this patent
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Abstract
A diagnostic medium contains at least one physiologically well tolerated complex salt comprising an anion of a complexing acid and one or more central ion or ions of an element with an atomic number of 21 to 29, 42, 44 or 57 to 83 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.
Claims68
A method of performing an NMR diagnostic procedure in a patient in need of the same comprising administering to the patient an effective amount of an NMR diagnostic medium and then exposing the patient to an NMR measurement step to which the diagnostic medium is responsive thereby imaging at least a portion of the patient's body, wherein the diagnostic medium comprises a physiologically compatible salt of (a) an anion of a complexing acid and (b) at least one central ion of an element with an atomic number of 21 to 29, 42, 44 or 57 to 83 chelated therewith, wherein the salt is of the formula I or II ##STR8## or
- N(CH.sub.2 X).sub.3, (II)
- wherein
- X is --COOY, --PO.sub.3 HY or --CONHOY;
- Y is a hydrogen atom, a metal ion equivalent or a physiologically biocompatible cation of an inorganic or organic base or amino acid;
- A is --CHR.sub.2 --CHR.sub.3 --, --CH.sub.2 --CH.sub.2 --(ZCH.sub.2 --CH.sub.2).sub.m --, ##STR9## each R.sub.1 is a hydrogen atom or methyl;
- R.sub.2 and R.sub.3 together represent a trimethylene group or a tetramethylene group or individually are hydrogen, C.sub.1-8 -alkyl, phenyl or benzyl,
- W is --NN--, --NHCOCH.sub.2 -- or --NHCS--;
- m is the number 1, 2 or 3
- Z is an oxygen atom, a sulfur atom, >NCH.sub.2 X, or >NCH.sub.2 CH.sub.2 OR.sub.4
- R.sub.4 is C.sub.1-8 -alkyl
- V is one of the X groups or is --CH.sub.2 OH, or --CONH(CH.sub.2).sub.n X,
- n is a number from 1 to 12;
- if R.sub.1, R.sub.2 and R.sub.3 are hydrogen atoms, both V's together are the group ##STR10## w is a number 1, 2 or 3;
- provided that at least two of the substituents Y are metal ion equivalents of an element with an atomic number of 21 to 29, 42, 44 or 57 to 83.
In a method of imaging body tissue in a patient, comprising subjecting the patient to NMR tomography, the improvement comprising, prior to performing the NMR tomography, administering to the patient an effective amount of a pharmaceutical agent for affecting the relaxation times of atoms in body tissues undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to affect such relaxation times, of a paramagnetic, physiologically compatible salt of a physiologically compatible chelate complex of an ion of a lanthanide element of atomic numbers 57-70, or of a transition metal of atomic numbers 21-29, 42, or 44;
- and a pharmaceutically acceptable carrier.
In a method of imaging body tissue in a patient, comprising subjecting the patient to NMR tomography, the improvement comprising, prior to performing the NMR tomography, administering to the patient an effective amount of a pharmaceutical agent for affecting the relaxation times of atoms in body tissues undergoing NMR diagnosis whereby image contrast is enhanced, said agent comprising an amount effective to affect such relaxation times of a paramagnetic, physiologically compatible salt of a complex of an ion and a ligand;
- and
- a pharmaceutically acceptable carrier;
- wherein the complexed ion is an ion of a lanthanide element of atomic numbers 57-70, or of a transition metal of atomic numbers 21-29, 42, or 44;
- and wherein the ligand is that of a complexing agent which
- (a) is an aminopolycarboxylic acid which is nitrilotriacetic acid, N-hydroxyethyl-N,N',N'-ethylenediaminetriacetic acid, N,N,N',N",N"-diethylenetriaminepentaacetic acid or N-hydroxyethyliminodiacetic acid;
- (b) of the formula ##STR11## wherein R.sub.1 and R.sub.1 ' are identical or different and each is hydrogen or alkyl of 1-4 carbon atoms and p is an integer of 0-4;
- or
- (c) an aminopolycarboxylic acid of the formula ##STR12## wherein m is an integer of 1 to 4,
- n is an integer of 0 to 2, and
- R.sub.5 is C.sub.4-12 -alkyl, C.sub.4-12 -alkenyl, C.sub.4-12 -cycloalkyl, C.sub.4-12 -cycloalkenyl, C.sub.7-12 -hydrocarbon aralkyl, C.sub.8-12 -hydrocarbon alkenyl, C.sub.6-12 -hydrocarbon aryl or --CH.sub.2 COOH.
In a method of imaging body tissue in a patient, comprising subjecting the patient to NMR tomography, the improvement comprising, prior to performing the NMR tomography, administering to the patient an effective amount of a pharmaceutical agent for affecting the relaxation times of atoms in body tissues undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to affect such relaxation times, of a paramagnetic, physiologically compatible salt of a complex of an ion and, as a ligand, an acyclic or cyclic complexing agent containing organic nitrogen, phosphorus, oxygen or sulfur, the complexed ion being an ion of a lanthanide element of atomic numbers 57-70, or of a transition metal of atomic numbers 21-29, 42, or 44;
- and a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.