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Polymer nanoparticle magnetic resonance contrast agent and preparing method thereof

A magnetic resonance contrast agent and nanoparticle technology, which can be used in pharmaceutical formulations, preparations for in vivo tests, etc., can solve problems such as non-characteristics, blood supply characteristics of lesions, and failure to achieve ideal early diagnosis of liver cancer, and increase local Concentration, improve curative effect, reduce the effect of toxic and side effects

Inactive Publication Date: 2011-04-20
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0002] In clinical magnetic resonance imaging (Magnetic Resonance Imaging, MRI), the application of ordinary contrast agents for dynamic enhancement can improve the accuracy of liver cancer diagnosis. Currently, the clinically used contrast agents are small molecule contrast agents, such as gadopentetate glutenium injection (trade name : Ma Genweixian), which is based on the blood vessel density in nodules or masses, reflecting the blood supply characteristics of the lesion, not characteristic, and the early diagnosis of liver cancer has not achieved the desired effect

Method used

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  • Polymer nanoparticle magnetic resonance contrast agent and preparing method thereof
  • Polymer nanoparticle magnetic resonance contrast agent and preparing method thereof
  • Polymer nanoparticle magnetic resonance contrast agent and preparing method thereof

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Effect test

Embodiment 1

[0040] The preparation method of polymer nanoparticle magnetic resonance contrast agent:

[0041] (1) Synthesis of diethylenetriaminepentaacetic acid (DTPA) cyclic anhydride

[0042] React 0.1 mol of diethylenetriaminepentaacetic acid with 0.5 mol of acetic anhydride in 0.7 mol of anhydrous pyridine at 65°C for 24 hours, then filter, wash the solid with anhydrous ether, and dry it in vacuo to obtain a white solid diethylene triamine Aminopentaacetic acid cyclic anhydride;

[0043] (2) Synthesis of diethylenetriaminepentaacetic acid-polyethylene glycol-polylactic acid copolymer (PLA-PEG-DTPA)

[0044] ①PLA-PEG-NH 2 The synthesis of block copolymers adopts an anionic ring-opening polymerization method. Under an argon atmosphere, KHMDS is used as an initiator to initiate ring-opening polymerization of ethylene oxide and lactide in THF at 25°C, and then add acetic acid Terminate the reaction, and add hydrochloric acid to remove the protecting group, use 9mol of ethylene oxide, ...

Embodiment 2

[0051] Preparation of polymer nanoparticle magnetic resonance contrast agent:

[0052] (1) Synthesis of diethylenetriaminepentaacetic acid (DTPA) cyclic anhydride

[0053] React 0.1 mol of diethylenetriaminepentaacetic acid with 0.5 mol of acetic anhydride in 0.7 mol of anhydrous pyridine at 65°C for 24 hours, then filter, wash the solid with anhydrous ether, and dry it in vacuo to obtain a white solid diethylene triamine Aminopentaacetic acid cyclic anhydride;

[0054] (2) Synthesis of diethylenetriaminepentaacetic acid-polyethylene glycol-polylactic acid copolymer (PLA-PEG-DTPA)

[0055] ①PLA-PEG-NH 2 The synthesis of block copolymers adopts an anionic ring-opening polymerization method. Under an argon atmosphere, KHMDS is used as an initiator to initiate ring-opening polymerization of ethylene oxide and lactide in THF at 25°C, and then add acetic acid Terminate the reaction, and add hydrochloric acid to remove the protecting group, use 9mol of ethylene oxide, 0.1mol of i...

Embodiment 3

[0062] In vitro characterization of PLA-PEG-DTPA-Gd nanoparticles of the present invention:

[0063] 1.Gd 3+ Content Determination: It is measured by high-frequency inductively coupled plasma emission spectrometry.

[0064] 2. The results of in vitro imaging of nanoparticles show that PLA-PEG-DTPA-Gd nanoparticles have a significant enhanced imaging function,

[0065] See figure 2 .

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Abstract

The invention discloses a polymer nanoparticle magnetic resonance contrast agent which is prepared by the chelation of diethylenetriamine pentaacetic acid-polyethyleneglycol-polylactic acid polymer nanoparticle and gadolinium chloride GdCl3. The structural formula is showed as right, wherein m and n are integers. The molecular weight of the diethylenetriamine pentaacetic acid-polyethyleneglycol-polylactic acid polymer nanoparticle is from 10000 to 50000. The polymer nanoparticle magnetic resonance contrast agent has obvious development increase function, realizes targeting development by the property of PLA-PEG-DTPA-Gd nanoparticle, is a passive targeting administration system, and has the characteristics of specificity, selectivity, obvious biological effect, and the like. Taking the PLA-PEG nanoparticle as a carrier of DTPA-Gd, the contrast agent increases the local concentration of medicine on liver, enhances the curative effect, reduces toxic and side effect and achieves the purpose of targeting development.

Description

technical field [0001] The invention relates to a magnetic resonance contrast agent, in particular to a polymer targeting nanoparticle contrast agent capable of specifically developing the liver in magnetic resonance imaging and a preparation method thereof. Background technique [0002] In clinical magnetic resonance imaging (Magnetic Resonance Imaging, MRI), the application of common contrast agents for dynamic enhancement can improve the accuracy of liver cancer diagnosis. Currently, the clinically used contrast agents are small molecule contrast agents, such as gadopentetate glutenium injection (trade name : Ma Genweixian), it is based on the blood vessel density in the nodule or mass, reflecting the blood supply characteristics of the lesion, not characteristic, and the early diagnosis of liver cancer has not achieved the desired effect. Contents of the invention [0003] The purpose of the present invention is to overcome the deficiencies of the prior art and provide...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/12
Inventor 张娜陈智金鲁在君马春红于德新
Owner SHANDONG UNIV
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