Hydrophilic nanoparticles surface-modified with monosaccharide phosphate or monosaccharide phosphate derivatives, its colloidal solution and use thereof

Patent metadata

Field	Value
Publication number	US-9457104-B2
Application number	US-201214236502-A
Country	US
Kind code	B2
Filing date	Aug 3, 2012
Priority date	Aug 3, 2011
Publication date	Oct 4, 2016
Grant date	Oct 4, 2016

Abstract

Disclosed are a composition including hydrophilic nanoparticles that have a monosaccharide-phosphate or a derivative thereof adhered to the surface thereof, a colloidal solution of the composition dispersed in water, and a magnetic resonance imaging contrast agent including the colloidal solution. According to the present invention, nanoparticles having biocompatibility and excellent water-dispersibility can be prepared by modifying the surface of inorganic nanoparticles. The prepared nanoparticles may be effectively used in a variety of applications including, for example, in vivo imaging applications such as an MRI contrast agent, nano-electronic convergence technologies such as a quantum dot light emitting device, biomedical applications such as hyperthermia, or the like. Moreover, compared to existing nanoparticles dispersed by a dispersion stabilizer known in the art, excellent dispersion stability and a relatively small hydrodynamic diameter may be attained.

First claim

The invention claimed is:

1. Iron oxide nanoparticles surface-modified by adhering a monosaccharide-phosphate derivative of Formula 2 on the surface of iron oxide nanoparticles

wherein X 1 is a monosaccharide, X 2 is aminoalcohol, and X 3 is OH; and
wherein a core size of the iron oxide nanoparticles ranges from 1 nm to 20 nm and a difference between a number mean hydrodynamic diameter and a core size of iron oxide nanoparticles is 6 nm or less.

2. The nanoparticles of claim 1 , wherein the aminoalcohol is one or two or more selected from a group consisting of ethanolamine, heptaminol, isoetharine, norepinephrine, propanolamine and sphingosine.

3. The nanoparticles of claim 1 , wherein the iron oxide is one or two or more selected from a group consisting of FeO, Fe 3 O 4 (magnetite), α-Fe 2 O 3 , β-Fe 2 O 3 , γ-Fe 2 O 3 (maghemite), ε-Fe 2 O 3 , Fe(OH) 2 , Fe(OH) 3 , α-FeOOH, β-FeOOH, γ-FeOOH, δ-FeOOH, Fe 5 HO 8 .4H 2 O, 5Fe 2 O 3 .9H 2 O, FeOOH.4H 2 O, Fe 8 O 8 (OH) 6 (SO).nH 2 O, Fe 3+ 16 O 16 (OH.SO 4 ) 12-13 .10-12H 2 O and a mixture of Fe 3 O 4 (magnetite) and γ-Fe 2 O 3 (maghemite).

4. The nanoparticles of claim 1 , wherein the iron oxide is one or two or more selected from a group consisting of Fe 3 O 4 (magnetite), γ-Fe 2 O 3 (maghemite) and a mixture thereof.

5. The nanoparticles of claim 1 , wherein the surface-modified iron oxide nanoparticles are obtained by contacting a solution of a monosaccharide-phosphate of Formula 1 or a monosaccharide-phosphate derivative of Formula 2 dispersed in water with iron oxide nanoparticles having a lipophilic ligand bonded to the surface thereof, and a polar solvent, to modify the surface of the iron oxide nanoparticles into a hydrophilic state.

6. A colloidal solution prepared by dispersing the nanoparticles of claim 1 in water.

7. A contrast agent including the colloidal solution of claim 6 .

8. The contrast agent of claim 7 , wherein the contrast agent is a magnetic resonance imaging (MRI) T1 contrast agent or T2 contrast agent.

9. A method for manufacturing surface-modified hydrophilic iron oxide nanoparticles, comprising contacting: a solution of a monosaccharide-phosphate derivative of Formula 2 dispersed in water; a polar organic solvent; and iron oxide nanoparticles having a lipophilic ligand bonded to the surface thereof, to modify the surface of the iron oxide nanoparticles into a hydrophilic state,

wherein X 1 is a monosaccharide, X 2 is aminoalcohol, and X 3 is OH; and
wherein a core size of the surface-modified iron oxide nanoparticles ranges from 1 nm to 20 nm and a difference between a number mean hydrodynamic diameter and a core size of the surface-modified iron oxide nanoparticles is 6 nm or less.

10. The method of claim 9 , wherein the iron oxide is one or two or more selected from a group consisting of Fe 3 O 4 (magnetite), γ-Fe 2 O 3 (maghemite) and a mixture thereof.

Assignees

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

Inventors

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

Classifications

• A61K47/26

  Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin · CPC title

• A61K9/5115 Primary

  Inorganic compounds · CPC title

• A61K9/5036

  Polysaccharides, e.g. gums, alginate; Cyclodextrin · CPC title

• A61K47/50

  the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates · CPC title

• A61K49/1845 Primary

  the small organic molecule being a carbohydrate (monosaccharides, discacharides) · CPC title