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Magnetic resonance contrast agent using human endogenous protein as chelating agent and preparation thereof

A technology of magnetic resonance contrast agent and endogenous protein, which is applied in nuclear magnetic resonance/magnetic resonance imaging contrast agent, preparations for in vivo experiments, pharmaceutical formulations, etc. Poor scalability, narrow imaging time window, etc., to achieve the effect of easy mass preparation, good biocompatibility and relaxation stability, and long blood half-life

Inactive Publication Date: 2018-04-24
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, small-molecule Magnevist (Gd-DTPA) is widely used as the most common positive contrast agent in clinical magnetic resonance imaging, but it also has many limitations, such as the relaxation rate of Gd-DTPA small-molecule contrast agent. Low, narrow imaging time window (easy metabolism, short circulation time in vivo), potential toxicity (kidney fibrosis), poor targeting, poor multifunctional expansion ability, etc.

Method used

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  • Magnetic resonance contrast agent using human endogenous protein as chelating agent and preparation thereof
  • Magnetic resonance contrast agent using human endogenous protein as chelating agent and preparation thereof
  • Magnetic resonance contrast agent using human endogenous protein as chelating agent and preparation thereof

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Embodiment 1

[0036] like figure 1 As shown, the preparation method of a magnetic resonance contrast agent using human endogenous protein as a chelating agent comprises the following steps:

[0037] 1) Weigh 290 mg (about 0.01 mmol) of glutathione transferase (GST) powder, dissolve it in 2.0 mL of ultrapure water, and stir on a 37°C water bath stirrer;

[0038] 2) Add 2.0 mL of 50 mg / mL trisodium citrate dihydrate aqueous solution into the above GST protein solution, the final concentration of trisodium citrate dihydrate aqueous solution is 25 mg / mL, and continue stirring;

[0039] 3) Measure the aqueous solution of gadolinium nitrate according to the molar ratio of protein and paramagnetic metal ion being 1:4, add it dropwise to the mixed solution in 2), continue to stir and react, carry out paramagnetic ion chelation, and obtain the reaction solution;

[0040] 4) Use acetic acid-sodium acetate buffer solution to adjust the pH value of the reaction solution to 5.0;

[0041] 5) After the re...

Embodiment 2

[0045] like figure 1 As shown, the preparation method of a magnetic resonance contrast agent using human endogenous protein as a chelating agent comprises the following steps:

[0046] 1) Weigh 435 mg (about 0.015 mmol) of glutathione transferase (GST) powder, dissolve it in 3.0 mL of ultrapure water, and stir on a water bath stirrer at 37°C;

[0047] 2) Add 2.0 mL of 50 mg / mL trisodium citrate dihydrate aqueous solution to the above GST protein solution, the final concentration of trisodium citrate dihydrate aqueous solution is 20 mg / mL, and continue stirring;

[0048] 3) Measure the aqueous solution of gadolinium chloride according to the molar ratio of protein to paramagnetic metal ion being 1:8, add it dropwise to the mixed solution in 2), continue to stir and react, and perform paramagnetic ion chelation to obtain a reaction solution;

[0049] 4) Use acetic acid-sodium acetate buffer solution to adjust the pH value of the final reaction solution to 6.5;

[0050] 5) Afte...

Embodiment 3

[0055] like figure 1 As shown, the preparation method of a magnetic resonance contrast agent using human endogenous protein as a chelating agent comprises the following steps:

[0056] 1) Weigh 580 mg (about 0.02 mmol) of glutathione transferase (GST) powder, dissolve it in 4.0 mL of ultrapure water, and stir on a 37°C water bath stirrer;

[0057] 2) Add 1.0 mL of 50 mg / mL trisodium citrate dihydrate aqueous solution into the above GST protein solution, the final concentration of trisodium citrate dihydrate aqueous solution is 10 mg / mL, and continue stirring;

[0058] 3) Measure the aqueous solution of gadolinium acetate according to the molar ratio of protein and paramagnetic metal ion of 1:16, add it dropwise to the mixed solution in 2), continue to stir and react, and perform paramagnetic ion chelation to obtain a reaction solution;

[0059] 4) Use acetic acid-sodium acetate buffer solution to adjust the pH value of the final reaction solution to 7.0;

[0060] 5) After th...

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Abstract

The invention relates to a magnetic resonance contrast agent using a human endogenous protein as a chelating agent and preparation thereof. The contrast agent comprises the chelating agent and paramagnetic metal ions coordinated with the chelating agent, the chelating agent is the human endogenous protein, and the human endogenous protein includes aspartic acid and glutamic acid; during the preparation, firstly the human endogenous protein is added to water, the human endogenous protein is dissolved by stirring, and then trisodium citrate dihydrate is added and stirred evenly to obtain a mixedsolution; paramagnetic metal salt is added and stirred to coordinate the paramagnetic metal ions with the chelating agent so as to obtain a reaction solution, finally the pH of the reaction solutionis adjusted to 5.0-7.4, and then the reaction solution is separated and dried. Compared with the prior art, the contrast agent is formed by the direct chelation of the human endogenous protein and theparamagnetic metal ions, and traditional micro-molecule chelating agents are not needed; the contrast agent has simple synthesis process, mild reaction conditions and good environmental compatibility, reduces energy consumption, and is easy in mass production.

Description

technical field [0001] The invention belongs to the technical field of medical magnetic resonance contrast agents, and relates to a magnetic resonance contrast agent using human endogenous protein as a chelating agent and its preparation. Background technique [0002] Magnetic resonance imaging (MRI) Due to the advantages of no radiation damage, multi-directional and multi-parameter imaging, high spatial resolution and soft tissue resolution, no tissue penetration limitation, and metabolic and functional imaging, it has obvious advantages in positioning, qualitative and quantitative lesions. It has become an indispensable and important auxiliary examination method for clinical diagnosis. As an important supplementary method of magnetic resonance imaging examination, magnetic resonance contrast agent can enhance the contrast between normal tissue and diseased tissue by changing the relaxation time of free water in the tissue, improve the sensitivity and image quality of magn...

Claims

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Application Information

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IPC IPC(8): A61K49/08A61K49/14
CPCA61K49/085A61K49/14
Inventor 张兵波杨维涛
Owner TONGJI UNIV
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