Iron oxide nanocapsules, method of manufacturing the same, and MRI contrast agent using the same

Patent metadata

Field	Value
Publication number	US-9757482-B2
Application number	US-201113819525-A
Country	US
Kind code	B2
Filing date	Aug 30, 2011
Priority date	Aug 30, 2010
Publication date	Sep 12, 2017
Grant date	Sep 12, 2017

Abstract

Provided are iron oxide nanocapsules for an MRI contrast agent having high contrast, in which a plurality of iron oxide nanoparticles having a hydrophobic ligand attached thereto are encapsulated in an encapsulation material including a biodegradable polymer and a surfactant, and which satisfy Relations 1, 2, 3, 4 and 5 below. Also a method of manufacturing the iron oxide nanocapsules is provided.

5≦100* D μ (IO)/ C ω (IO)  [Relation 1]

2.5≦100* D μ (Cap)/ C ω (Cap)  [Relation 2]

0.5 wt %≦ F (IO)≦50 wt %  [Relation 3]

1 nm≦ D μ (IO)≦25 nm  [Relation 4]

50 nm≦ D μ (Cap)≦200 nm  [Relation 5]

First claim

The invention claimed is:

1. Iron oxide nanocapsules, in which a plurality of iron oxide nanoparticles having an oleate ligand attached thereto are encapsulated in an encapsulation material including a biodegradable polymer and a surfactant, and which satisfy Relations 1, 2, 3, 4 and 5 below:
10≦100* D m (IO)/ C v (IO)  Relation 1

2.5≦100* D m (Cap)/ C v (Cap)  Relation 2

7 wt %≦ F (IO)≦35 wt %  Relation 3

1 nm≦ D m (IO)≦25 nm  Relation 4

50 nm≦ D m (Cap)≦200 nm  Relation 5

in which:
in Relation 1, D m (IO) is an average size of iron oxide nanoparticles, and C v (IO) is a standard deviation in size distribution of iron oxide nanoparticles, and
in Relation 2, D m (Cap) is an average size of iron oxide nanocapsules, and C v (Cap) is a standard deviation in size distribution of iron oxide nanocapsules, and
in Relation 3, F(IO) is encapsulation efficiency which refers wt % of iron oxide nanoparticles encapsulated in the iron oxide nanocapsules, and
in Relation 4, D m (IO) is defined as in Relation 1, and
in Relation 5, D m (Cap) is defined as in Relation 2.

2. The iron oxide nanocapsules of claim 1 , which further satisfy Relation 7 below:
5≦100* D m (Cap)/ C v (Cap)  Relation 7

in which, D m (Cap) and C v (Cap) are defined as in Relation 2.

3. The iron oxide nanocapsules of claim 1 , which are manufactured by mixing a dispersion solution of iron oxide nanoparticles comprising 0.1˜20 wt % of iron oxide nanoparticles dispersed in an organic solvent and 0.1˜20 wt % of a biodegradable polymer dissolved therein with an aqueous surfactant solution and performing emulsification, thus preparing an emulsion, and adding water to the emulsion.

4. The iron oxide nanocapsules of claim 1 , wherein the biodegradable polymer is one or more biodegradable polymers selected from polylactide, polyglycolide, and poly(lactide-co-glycolide).

5. The iron oxide nanocapsules of claim 4 , wherein the surfactant is one or more surfactants selected from sodium lauryl sulfate, polyvinylalcohol, poloxamer, polysorbate, alkyldiphenyloxide disulfonate.

6. The iron oxide nanocapsules of claim 1 , wherein the biodegradable polymer has a molecular weight of 1,000˜250,000 g/mol.

7. An MRI (Magnetic Resonance Imaging) T2 contrast agent, comprising the iron oxide nanocapsules of claim 1 .

8. An MRI T2 liver-specific contrast agent, comprising the iron oxide nanocapsules of claim 1 .

9. The iron oxide nanocapsules of claim 1 , wherein the surfactant is one or more surfactants selected from sodium lauryl sulfate, polyvinylalcohol, poloxamer, polysorbate, alkyldiphenyloxide disulfonate.

Assignees

• Jeon Bong-Sik
• Kim Eung Gyu
• Kwon Eun Byul
• Park Ju Young
• Myeong Wan Jae
• Hanwha Chemical Corp

Inventors

• Jeon Bong-Sik
• Kim Eung Gyu
• Kwon Eun Byul
• Park Ju Young
• Myeong Wan Jae

Classifications

• A61K49/1893 Primary

  Molecular sieves · CPC title

• A61K49/1857

  the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA · CPC title

• A61K49/1824 Primary

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

• A61K49/1887

  Agglomerates, clusters, i.e. more than one (super)(para)magnetic microparticle or nanoparticle are aggregated or entrapped in the same maxtrix · CPC title

• A61K49/1827

  having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle · CPC title