Polymer-metal complex composite having MRI contrast ability and MRI contrasting and/or antitumor composition using the same

Patent metadata

Field	Value
Publication number	US-8961949-B2
Application number	US-200913000836-A
Country	US
Kind code	B2
Filing date	Jun 26, 2009
Priority date	Jun 26, 2008
Publication date	Feb 24, 2015
Grant date	Feb 24, 2015

Abstract

The present invention provides a polymer-metal complex composite, which comprises a block copolymer capable of serving as a constituent member of a polymeric micelle and a metal complex having MRI contrast ability, accumulates in a tumor-specific manner, achieves high image contrast even in a small amount, and has reduced side effects and a long retention time in blood.
The polymer-metal complex composite of the present invention comprises a block copolymer (A) represented by general formula (a) and a metal complex (B) having MRI contrast ability, wherein the composite comprises a structure in which a carboxyl anion of poly(carbo) in the copolymer (A) is attached to the metal complex (B) via a metal atom (M).

First claim

The invention claimed is:

1. A polymer-metal complex composite, which comprises a block represented by the following general formula (1) or (2):

wherein R 1 represents a hydrogen atom or an unsubstituted or substituted linear or branched C 1-12 alkyl group, L 1 and L 2 each represent a linker group, R 2 independently represents a methylene group or an ethylene group, R 3 independently represents a hydrogen atom, a protecting group for an amino group, a hydrophobic group or a polymerizable group, R 4 represents a hydroxyl group or an initiator residue, R 5 independently represents a hydrogen atom, an alkali metal ion, or a group represented by the following general formula (3) and/or (4):

wherein R 6 represents a metal atom or a group derived from a metal complex, and R 7 represents a group derived from a metal complex having MRI contrast ability,
provided that at least one R 5 comprises the group represented by general formula (3) in which each R 6 is independently a group derived from a metal complex having antitumor activity represented by the following formula (5-a) or (6-a):

each R 7 is independently a group represented by the following formula (7-a), (8-a), (9-a) or (10-a):

m represents an integer of 5 to 20,000, n represents an integer of 2 to 5,000, and x represents an integer of 0 to 5,000provided that x≦n.

2. The composite according to claim 1 , which is represented by the following general formula (1-a) or (2-a):

3. The composite according to claim 1 or 2 , wherein the group represented by general formula (3) is independently a group represented by the following formula (15-a), (16-a), (17-a) or (18-a):

4. The composite according to claim 1 , which when dispersed in an aqueous medium forms micellar particles.

5. The composite according to claim 4 , which has an average dispersed particle size of 10 nm to 1 μm in an aqueous medium, as measured by dynamic light scattering.

6. An MRI contrasting and antitumor composition, which comprises the composite according to claim 1 .

7. An MRI contrasting method for tumor detection, which comprises administering the composite according to claim 1 to the body of an animal subject.

8. An MRI contrasting and antitumor kit, which comprises the composite according to claim 1 .

9. The composite according to claim 1 or 2 , wherein the group represented by general formula (3) is independently a group represented by the following formula (11-a), (12-a), (13-a), or (14-a):

Assignees

• Kataoka Kazunori
• Kaida Sachiko
• Cabral Horacio
• Kumagai Michiaki
• Sekino Masaki
• Japan Science & Tech Agency

Inventors

• Kataoka Kazunori
• Kaida Sachiko
• Cabral Horacio
• Kumagai Michiaki
• Sekino Masaki

Classifications

• A61K47/60 Primary

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K47/645

  Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT · CPC title

• A61K49/146

  the peptide being a polyamino acid, e.g. poly-lysine · CPC title

• C08G83/001

  Macromolecular compounds containing organic and inorganic sequences, e.g. organic polymers grafted onto silica · CPC title

• A61K49/128

  comprising multiple complex or complex-forming groups, being either part of the linear polymeric backbone or being pending groups covalently linked to the linear polymeric backbone · CPC title