Novel liver-targeting nanometer Fe3O4MRI (Magnetic Resonance Imaging) contrast medium and preparation method

A contrast agent, fe3o4 technology, applied in the field of biomedical materials, can solve the problems of limiting the application of magnetic resonance imaging technology, short metabolism time, large surface, etc., and achieve the effects of prolonging circulation time in vivo, long circulation time, and simple preparation process

Inactive Publication Date: 2011-10-19
YANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the small size and large surface of nano-ferric oxide, it is easy to aggregate in aqueous media; it has no specificity to biological organs and tissues; it has short metabolism time in tissues and organs, etc.
These shortcomings limit the application of magnetic resonance imaging technology in the early diagnosis of tumors

Method used

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  • Novel liver-targeting nanometer Fe3O4MRI (Magnetic Resonance Imaging) contrast medium and preparation method
  • Novel liver-targeting nanometer Fe3O4MRI (Magnetic Resonance Imaging) contrast medium and preparation method
  • Novel liver-targeting nanometer Fe3O4MRI (Magnetic Resonance Imaging) contrast medium and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Preparation of Fe by Co-precipitation 3 o 4 Nanoparticles:

[0030] Weigh 2mmol FeCl 3 and 1mmol FeCl 2 In the three-neck flask, add 4ml of distilled water, and stir magnetically under the protection of nitrogen until it is completely dissolved; at room temperature, at a stirring rate of 200r / min, add 6ml of 2mol / L ammonia solution dropwise to the above solution; after the dropwise addition, Continue to stir for 0.5h; then, precipitate under the action of an external magnetic field, wash with deoxygenated water, and repeat precipitation and washing until the supernatant is neutral; freeze-dry to obtain powdery black Fe 3 o 4 particle.

Embodiment 2

[0032] Synthesis of mPEG-COOH

[0033] Reaction formula:

[0034]

[0035] synthesis:

[0036] Weigh 5g of mPEG (molecular weight: 2000) into a round bottom flask, dissolve it with 25ml of anhydrous pyridine, then add 2g of succinic anhydride, and react at 60°C for 2h. Pyridine was then distilled off under reduced pressure using a rotary evaporator at 45°C. The obtained solid was dissolved in 30ml of benzene, stirred continuously on a magnetic heating stirrer, and 40ml of n-hexane precipitant was slowly added to obtain the crude product mPEG-COOH.

[0037] The crude product was purified by dialysis for 4 days, and freeze-dried to obtain mPEG-COOH freeze-dried powder.

Embodiment 3

[0039] Preparation of Lactosylated and PEGylated Chitosan (PGC)

[0040] Weigh 1.1g lactobionic acid, 0.5g mPEG-COOH, 1g CS, add 0.1-10% EDC to dissolve in 25ml TEMED / HCl buffer solution, adjust pH=4.7, and stir magnetically for 30min. LA: CS (molar ratio) = 1: 2, mPEG-COOH: CS = 1: 25, mechanically stirred for 72 hours, and the pH value of the entire reaction system was strictly controlled. After dialysis for 4 days, the product was freeze-dried to obtain PGC. The synthesis schematic is as follows:

[0041]

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Abstract

The invention relates to a novel liver-targeting Fe3O4 nanometer particle MRI (Magnetic Resonance Imaging) contrast medium and a preparation method. In a technical scheme provided by the invention, the preparation method comprises steps of: the preparation of black powder nanometer Fe3O4 with a coprecipiation method, the preparation of mPEG (Methoxy Polyethylene Glycol)-COOH, the preparation of lactosamiated and PEGylated chitosan, and the preparation of novel liver-targeting superparamagnetism Fe3O4MRI contrast medium; and the surfaces of Fe3O4 nanometer particles of the contrast medium are modified by the lactosamiated and PEGylated chitosan. The invention is beneficial to overcoming of the defects that the nanometer ferroferric oxide is easy to aggregate in an aqueous medium due to small size and big surfaces, and has the disadvantages of no specificity to organs and tissues of organisms and short metabolism time in the tissues and the organs. The invention has the effects that thebiocompatible lactosamiated and PEGylated chitosan is used as a surface modifier and is anchored on the surfaces of the Fe3O4 nanometer particles through the adsorption and the mechanism of coordination action; and the suspension dispersedly stable MRI liver-targeting contrast medium has the advantages of small grain size, high saturation magnetic susceptibility, good biocompatibility, stability in suspension and dispersion, low toxicity, high relaxation rate, targeting effect to liver and spleen and the like.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a novel liver targeting Fe 3 o 4 Nano particle MRI contrast agent and preparation method thereof. Background technique [0002] Magnetic resonance imaging (MRI) is an effective medical imaging diagnostic technique that can be used to diagnose tumors. In clinical diagnostic imaging applications, more than 35% of diagnoses require the use of contrast agents in order to improve the signal contrast between lesion and normal tissue. Superparamagnetic nano-iron tetroxide (Fe 3 o 4 ) is a biocompatible magnetic resonance contrast agent. However, due to the small size and large surface of nano-ferric oxide, it is easy to gather in the water medium; it has no specificity to biological organs and tissues; it has short metabolism time in tissues and organs. These shortcomings limit the application of MRI technology in the early diagnosis of tumors. Contents of the inven...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/06A61K47/12
Inventor 朱爱萍骆夏丹
Owner YANGZHOU UNIV
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