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Details for Patent: 5,595,725

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Details for Patent: 5,595,725

Title: Diagnostic media
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.
Inventor(s): Gries; Heinz (Berlin, DE), Rosenberg; Douwe (Berlin, DE), Weinmann; Hanns-Joachim (Berlin, DE), Speck; Ulrich (Berlin, DE), M utzel; Wolfgang (Berlin, DE), Hoyer; Georg-Alexander (Berlin, DE), Pfeiffer, deceased; Heinrich (late of Berlin, DE), Renneke; Franz-Josef (Berlin, DE)
Assignee: Schering Aktiengesellschaft (Berlin, DE)
Filing Date:Oct 28, 1994
Application Number:08/330,954
Claims:1. A method of imaging body tissue in a patient, comprising subjecting the patient to NMR tomography and 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 tissue undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to affect such relaxation times, of a paramagnetic, physiologically compatible chelate complex of an ion of a lanthanide element of atomic numbers 58-70 or of a transition metal of atomic numbers 21-29, 42, or 44, wherein said chelate complex is coupled by a chemical reaction to a biomolecule, said biomolecule being effective to transport said chelate complex to a specific site in said patient; and a pharmaceutically acceptable carrier.

2. A method of enhancing NMR imageability of a patient comprising administering to the patient an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion wherein said chelate complex is covalently bound to a biomolecule effective to transport said chelate complex to a specific site in said patient.

3. A method of enhancing NMR imageability of a patient comprising administering to the patient an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion wherein said chelate complex is coupled by a chemical reaction to a biomolecule effective to transport said chelate complex to a specific site in said patient.

4. A method of enhancing NMR imageability of a patient comprising administering to the patient an amount, effective to enhance NMR image contrast, of a physiologically acceptable chelate complex of a paramagnetic ion having as a ligand a complexing agent containing organic nitrogen, phosphorous, oxygen or sulfur, and wherein said chelate complex is covalently bound to a biomolecule effective to transport said chelate complex to a specific site in said patient.

5. A method of enhancing NMR imageability of a patient comprising administering to the patient an amount, effective to enhance NMR image contrast, of a physiologically acceptable chelate complex of a paramagnetic ion having as a ligand a complexing agent containing organic nitrogen, phosphorous, oxygen or sulfur, and wherein said chelate complex is coupled by a chemical reaction to a biomolecule effective to transport said chelate complex to a specific site in said patient.

6. A method of conducting NMR imaging comprising NMR imaging a patient to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, wherein said chelate complex is covalently bound to a biomolecule, effective to transport said chelate complex to a specific site in said patient, and whereby an NMR image of an enhanced contrast is obtained.

7. A method of conducting NMR imaging comprising NMR imaging a patient to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, wherein said chelate complex is coupled by a chemical reaction to a biomolecule, effective to transport said chelate complex to a specific site in said patient, and whereby an NMR image of an enhanced contrast is obtained.

8. A method of conducting NMR imaging comprising NMR imaging a patient to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion having as a ligand a complexing agent containing organic nitrogen, phosphorous, oxygen or sulfur, wherein said chelate complex is covalently bound to a biomolecule effective to transport said chelate complex to a specific site in said patient, and whereby an NMR image of enhanced contrast is obtained.

9. A method of conducting NMR imaging comprising NMR imaging a patient to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion having as a ligand a complexing agent containing organic nitrogen, phosphorous, oxygen or sulfur, wherein said chelate complex is coupled by a chemical reaction to a biomolecule effective to transport said chelate complex to a specific site in said patient, and whereby an NMR image of enhanced contrast is obtained.

10. A method of enhancing an NMR image, comprising obtaining an enhanced NMR image by NMR imaging a human to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, said chelate complex being covalently bound to a biomolecule effective to transport said chelate complex to a specific site in said patient.

11. A method of enhancing an NMR image, comprising obtaining an enhanced NMR image by NMR imaging a human to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, said chelate complex being coupled by a chemical reaction to a biomolecule effective to transport said chelate complex to a specific site in said patient.

12. A method of enhancing an NMR image, comprising obtaining an enhanced NMR image by NMR imaging a human to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, said chelate complex being covalently bound to a biomolecule.

13. A method of enhancing an NMR image, comprising obtaining an enhanced NMR image by NMR imaging a human to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, said chelate complex being coupled by a chemical reaction to a biomolecule.

14. A method of enhancing an NMR image, comprising obtaining an enhanced NMR image by NMR imaging a human to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, said chelate complex being covalently bound to a biomolecule effective to change the pharmacokinetics of said chelate complex with respect to its transport to a specific site in said patient.

15. A method of enhancing an NMR image, comprising obtaining an enhanced NMR image by NMR imaging a human to whom there has been administered an amount, effective to enhance NMR image contrast, of a physiologically compatible chelate complex of a paramagnetic ion, said chelate complex being coupled by a chemical reaction to a biomolecule effective to change the pharmacokinetics of said chelate complex with respect to its transport to a specific site in said patient.

16. A method of imaging body tissue in a patient, comprising subjecting the patient to NMR tomography and 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 tissue undergoing NMR diagnosis, whereby image contrast is enhanced, said agent comprising an amount, effective to affect such relaxation times, of a paramagnetic, physiologically compatible chelate complex of an ion of a lanthanide element of atomic numbers 58-70 or of a transition metal of atomic numbers 21-29, 42, or 44, wherein said chelate complex is covalently bound to a biomolecule effective to transport said chelate complex to a specific site in said patient; and a pharmaceutically acceptable carrier.

17. A method of claim 1,

wherein said ion is manganese, iron or gadolinium.

18. A method of claim 1 wherein the paramagnetic ion is Mn (II).

19. A method of claim 1, wherein the paramagnetic ion is iron.

20. A method of claim 1, 16, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, wherein the paramagnetic ion is chelated by an aminopolycarboxylic acid.

21. A method of claim 1, wherein no free acid or free base groups are present in the chelate complex.

22. A method of claim 1, wherein a free acid or a free base group is present in the chelate complex.

23. A method of claim 1, wherein a free acid or a free base group of the chelate complex is in the form of a salt thereof with an inorganic or organic base or acid.

24. A method of claim 1, wherein the paramagnetic ion is chelated by a cyclic chelating agent.

25. A method of claim 1, wherein said chelate complex is both a salt of said paramagnetic ion and the chelate complexing agent thereof, and also a salt with an inorganic or organic base or acid.

26. A method of claim 1, wherein said chelate complex is only a salt of said paramagnetic ion and the chelate complexing agent thereof and not also a salt of an inorganic or organic base or acid.

27. A method of claim 19, wherein the paramagnetic ion is Fe(II).

28. A method of claim 1, wherein the patient is a human.

29. A method of claim 1, wherein the chelate complex is nonionic.

30. A method according to claim 1, 16, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, wherein said biomolecule is an immunoglobulin.

31. A method according to claim 1, wherein said biomolecule is a hormone.

32. A method according to claim 1, 16, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, wherein said biomolecule is a protein.

33. A method according to claim 1, 16, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11, wherein said biomolecule is a peptide.

34. A method according to claim 1, 16, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11, wherein said biomolecule is a lipid.

35. A method of claim 1, wherein said paramagnetic ion is an element of atomic numbers 58-70.

36. A method according to claim 1, wherein said paramagnetic ion is an element of atomic numbers 21-29, 42 or 44.

37. A method according to claim 1, 16, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, wherein said biomolecule is a biopolymer.

38. A method of claim 1, 16, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11, wherein the paramagnetic ion is Gd(III).
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