Cascade polymer bound complexing compounds, their complexes and conjugates, processes for their production, and pharmaceutical agents containing them

• US 20030232017A1
• Filed: 12/11/2002
• Published: 12/18/2003
• Est. Priority Date: 11/21/1989
• Status: Active Grant

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Gabriele Schuhmann-Giampieri, Hanns-Joachim Weinmann, Hans Bauer, Heinz Gries, Heribert Schmitt-Willich, Hubert Vogler, Johannes Platzek
• Inventors: Schmitt-Willich, Heribert, Platzek, Johannes, Bauer, Hans, Weinmann, Hanns-Joachim, Gries, Heinz, Schuhmann-Giampieri, Gabriele, Vogler, Hubert
• Granted Patent: US 6,855,309 B2
• Time in Patent Office: Days
• US Class Current: 424/9.322
• CPC Class Codes: A61K 49/0002 General or multifunctional contrast agents, e.g. chelated agents
• CPC Class Codes: A61K 49/04 X-ray contrast preparations
• CPC Class Codes: A61K 49/06 Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
• CPC Class Codes: A61K 49/085 conjugated systems
• CPC Class Codes: A61K 49/124 dendrimers, dendrons, hyperbranched compounds
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: A61K 51/065 conjugates with carriers being macromolecules
• CPC Class Codes: C08G 83/003 Dendrimers
• CPC Class Codes: C08G 85/00 General processes for preparing compounds provided for in this subclass
• CPC Class Codes: Y10T 436/24 Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry

Abstract

Cascade polymers, containing complex-forming ligands, optionally at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83, as well as, if desired, cations of inorganic and/or organic bases, amino acids or amino acid amides, are valuable complexing compounds and complexes for diagnostics and therapy.

Claims

1. A cascade polymer, containing complex-forming ligands, optionally at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83, as well as optionally cations of inorganic and/or organic bases, amino acids or amino acid amides.

2. A cascade polymer according to claim 1, having the structure of Formula I

3. A cascade polymer according to claim 2, wherein the complex (forming) residue K, bound to the terminal nitrogen atoms of the final generation by way of —

CH₂CO or V, is a residue of general Formulae I A, I B or I C;

4. A cascade polymer according to claim 2, wherein S is —

(CH₂)₂—

CONH—

(CH₂)₃—

or

5. A Cascade polymer according to claim 2, wherein A is a nitrogen atom,

6. A cascade polymer according to claim 2, containing at least five ions of an element of atomic numbers 21-29, 39, 42, 44 or 57-83 bound to the complexing agent K.

7. A cascade polymer according to claim 2, wherein the functional group contained in V′

is

8. A cascade polymer according to claim 2, wherein the bio- or macromolecule(s) optionally contained in V′

is/are an antibody or antibodies or antibody fragment or fragments.

9. A cascade polymer according to claim 2, wherein the bio- or macromolecule(s) optionally contained in V′

is/are a protein or proteins.

10. A cascade polymer of claim 9, wherein the protein is albumin, globulin or lectin.

11. A cascade polymer according to claim 2, wherein the bio- or macromolecule(s) optionally contained in V′

is/are a polysaccharide or polysaccharides.

12. A cascade polymer of claim 11, wherein the polysaccharide is starch, dextran or dextrin.

13. A cascade complex according to claim 2, wherein V is

14. A pharmaceutical agent comprising at least one cascade polymer complex according to claim 1 and a pharmaceutically acceptable carrier.

15. A pharmaceutical agent comprising at least one cascade polymer complex according to claim 6 and a pharmaceutically acceptable carrier.

16. A method of conducting NMR imaging comprising administering a cascade polymer of claim 6, wherein the atomic number of the metal is 21-29, 42, 44 or 58-70.

17. A method of conducting X-ray imaging comprising administering a cascade polymer of claim 6, wherein the atomic number of the metal is 21-29, 39, 42, 44 or 57-83.

18. A process for the preparation of cascade polymers according to claim 2, comprising reacting a corresponding compound of Formula I′

20. A process according to claim 18, wherein coupling of the macro- or biomolecule to the functionalized polymer complex or ligand and also (in case of coupling to the ligand) the subsequent complexing with the desired metal ion or ions is performed on a stationary phase.

19. A complex and/or complex-forming K′

of the formulae