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Chitosan-based MRI contrast medium and preparation method

A chitosan and contrast agent technology, applied in the field of medical clinical magnetic resonance imaging, can solve the problems of short cycle time and tissue residence time, high biological toxicity, low relaxation efficiency, etc., and achieve simple preparation method and easy biodegradation , the effect of high relaxation rate

Inactive Publication Date: 2016-07-13
SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, in application, the above-mentioned contrast agents still have short circulation time in vivo and tissue residence time, low relaxation efficiency, difficulty in reducing the carrier, high biological toxicity and Gd 3+ The defect of small load

Method used

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  • Chitosan-based MRI contrast medium and preparation method
  • Chitosan-based MRI contrast medium and preparation method
  • Chitosan-based MRI contrast medium and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1 The preparation method of the targeted MRI contrast agent based on chitosan, the specific steps are as follows:

[0037] (1) Chitosan pretreatment: Chitosan was dissolved in glacial acetic acid solution with a concentration of 0.1M, and then sodium hydroxide (NaOH) with a concentration of 0.2M was added to the above solution to obtain chitosan precipitation. The precipitate was then washed several times with water until pH = 7.0.

[0038] (2) Disperse the treated chitosan in the DMSO solution, and add the DMSO solution containing maleic anhydride dropwise into the above. After the dropwise addition, the mixed solution was reacted in an oil bath at 60°C for 8h. The product was precipitated with acetone and dried under vacuum to obtain N-maleylated chitosan (NMC).

[0039] (3) Dissolve N-maleylated chitosan completely in 0.25% sodium hydroxide solution, then add polyethyleneimine-containing aqueous solution dropwise into the above solution, and react at 60°...

Embodiment 2

[0043] Embodiment 2 measures NMC, NMC-g-PEI and NMC-g-PEI-DTPA 1 HNMR chart, including: test NMC, NMC-g-PEI and NMC-g-PEI-DTPA respectively with heavy water as solvent 1 HNMR diagram, such as figure 2 shown.

Embodiment 3

[0044] Example 3 The polymer contrast agent of the present invention and the relaxation time T of Gd-DTPA are tested on an MRI tester at 11.7T 1 and T 1 Weighted imaging, including:

[0045] Prepare above-mentioned two kinds of samples of 0.1, 0.2, 0.4, 0.8, 1.0mM respectively, after the test, take the concentration as the abscissa and the reciprocal of the relaxation time as the ordinate to carry out linear fitting to obtain the contrast agent of the present invention and Gd-DTPA Relaxation rates were 6.6mM -1 ·s -1 and 4.8mM -1 ·s -1 ( image 3 ). The relaxation rate of the contrast agent of the present invention is obviously higher than that of Gd-DPTA. Through the T of both at different concentrations 1 weighted imaging ( Figure 4 ) It can be seen that both of them tend to become brighter with the increase of the concentration, but the contrast effect of the contrast agent of the present invention is obviously brighter than that of Gd-DTPA.

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Abstract

The invention discloses a chitosan-based MRI contrast medium and a preparation method. The contrast medium comprises polyethyleneimine-grafted chitosan taken as a main body of the contrast medium and a gadolinium chelate mainly connected to side chains of polyethyleneimine-grafted chitosan. Furthermore, the contrast medium also comprises a targeting group, such as folic acid, connected to side chains of polyethyleneimine-grafted chitosan. The preparation method comprises: firstly, providing polyethyleneimine-grafted chitosan, then coupling a gadolinium chelating ligand, such as diethylene triamine pentaacetic acid to polyethyleneimine-grafted chitosan, enabling the obtained product together with Gd3+ to form the gadolinium chelate, and optionally connecting the targeting group, such as folic acid to the obtained polyethyleneimine-grafted chitosan to produce the contrast medium. The chitosan-based targeting MRI contrast medium is good in biocompatibility, is easy to biologically degrade, and has a high relaxation rate. The preparation method is simple, needs medium reaction temperature, and is easy to control.

Description

technical field [0001] The invention belongs to medical clinical magnetic resonance imaging technology, in particular to a chitosan-based targeted MRI contrast agent for magnetic resonance imaging contrast and a preparation method. Background technique [0002] Contrast agent is an imaging-enhanced contrast agent used to shorten imaging time and improve imaging contrast and clarity in medical clinical MRI. Imaging contrast, thus revealing the functional status of internal organs. In diagnostic magnetic resonance imaging, nearly 50% of examinations use MRI contrast agents. Contrast agents are mainly divided into two categories: paramagnetic agents, namely T 1 Class; ferromagnetic or superciliability contrast agent, ie T 2 kind. Among them, the small-molecule non-targeting Gd-based contrast agents that are widely used in clinical practice belong to T 1 kind. There are still some disadvantages in the application of this type of small molecule contrast agent to living orga...

Claims

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Application Information

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IPC IPC(8): A61K49/12
Inventor 裴仁军仝晓艳刘敏
Owner SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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