Polymer nanoparticle composite and composition for mri imaging including same

Patent metadata

Field	Value
Publication number	US-2016206759-A1
Application number	US-201414913903-A
Country	US
Kind code	A1
Filing date	Aug 22, 2014
Priority date	Aug 23, 2013
Publication date	Jul 21, 2016
Grant date	—

Abstract

The present invention provides a safe polymer nanoparticle composite with few side effects, and an MRI contrast agent incorporating said polymer nanoparticle composite. The polymer nanoparticle composite is capable of specifically accumulating on a tumor tissue to selectively extract the tissue, exhibiting high contrast even when used in small amounts, and enabling imaging over prolonged periods of time. This polymer nanoparticle composite is characterized by containing a block copolymer that includes a non-charged hydrophilic polymer chain segment and an anionic polymer chain segment, and MnCaP.

First claim

1 . A polymer nanoparticle composite comprising: a block copolymer comprising a non-charged hydrophilic polymer chain segment and an anionic polymer chain segment; and MnCaP.

2 . The composite according to claim 1 , wherein the anionic polymer chain segment is a polypeptide having an anionic group on the side chain.

3 . The composite according to claim 1 or 2 , wherein the non-charged hydrophilic polymer chain segment is derived from a hydrophilic polymer selected from the group consisting of polyethylene glycol, poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), poly(2-isopropyl-2-oxazoline), polyacrylamide, polymethacrylamide, polyvinyl alcohol, poly(hydroxyethyl acrylate) and poly(hydroxyethyl methacrylate).

4 . The composite according to claim 1 , wherein the anionic polymer chain segment is derived from an anionic polymer selected from the group consisting of poly(glutamic acid), poly(aspartic acid), poly(acrylic acid), poly(methacrylic acid) and poly(malic acid).

5 . The composite according to claim 1 , which has a configuration in which MnCaP is incorporated into a nanoparticulate particle that is formed with the block copolymer having the non-charged hydrophilic polymer chain segment as a shell part and the anionic polymer chain segment as a core part.

6 . The composite according to claim 1 , wherein the block copolymer is represented by General Formula (1-a) or (2-a) below.

[In Formulae (1-a) and (2-a), R 1 represents a hydrogen atom or an unsubstituted or substituted, linear or branched C 1-12 alkyl group, L 1 and L 2 represent a linking group, R 2 each independently represents a methylene group or an ethylene group, R 3 each independently represents a hydrogen atom, a protective group of an amino group, a hydrophobic group or a polymerizable group, R 4 represents a hydroxyl group or an initiator residue, R 5 each independently represents a hydrogen atom or an alkali metal ion, m represents an integer of 5-20,000, and n represents an integer of 2-5,000].

7 . The composite according to claim 1 , whose average dispersed particle diameter in an aqueous medium is 30 nm-150 nm as measured by a dynamic light scattering method.

8 . The composite according to claim 1 , wherein the polymer nanoparticle composite releases an Mn 2+ ion under a low pH condition.

9 . An MRI contrast composition comprising the composite according to claim 1 .

10 . The composition according to claim 9 , which is used for detecting a tumor.

11 . The composition according to claim 10 , wherein the tumor is a primary tumor or a metastatic tumor.

12 . The composition according to any one of claims 9 - 11 , which is used for assessing grade of malignancy of a tumor.

13 . An MRI contrast method comprising a step of administering the composite according to claim 1 to a body of a test animal.

14 . The method according to claim 13 , which is used for detecting a tumor.

15 . The method according to claim 14 , wherein the tumor is a primary tumor or a metastatic tumor.

16 . The method according to any one of claims 13 - 15 , which is used for assessing grade of malignancy of a tumor.

17 . A MRI contrast kit comprising the composite according to claim 1 .

18 . The kit according to claim 17 , which is used for detecting a tumor.

19 . The kit according to claim 18 , wherein the tumor is a primary tumor or a metastatic tumor.

20 . The kit according to any one of claims 17 - 19 , which is used for assessing grade of malignancy of a tumor.

Assignees

• Univ Tokyo

Inventors

• Kataoka Kazunori
• Nishiyama Nobuhiro
• Cabral Horacio
• Mi Peng
• Kishimura Akihiro
• Miura Yutaka
• Aoki Ichio
• Kokuryo Daisuke
• Saga Tsuneo

Classifications

• A61K49/128 Primary

  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

• A61K49/1818

  particles, e.g. uncoated or non-functionalised microparticles or nanoparticles · CPC title

• A61K49/1824

  coated or functionalised nanoparticles (liposomes A61K49/1812; nanoemulsions A61K49/1806; micelles A61K49/1809) · CPC title

• A61K49/1872 Primary

  coated or functionalised with a polyamino acid, e.g. polylysine, polyglutamic acid · CPC title

• C08K3/32

  Phosphorus-containing compounds · CPC title