Liver target high molecule magnetic resonance image-forming contrast medium and its synthesizing method and application

A technology of magnetic resonance imaging and synthesis method, which is applied in pharmaceutical formulations, genetic material components, preparations for in vivo experiments, etc. The effect of increasing the susceptibility and prolonging the cycle time

Inactive Publication Date: 2007-04-11
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] (1) Small molecule contrast agents are easy to leak out from the blood vessel wall and enter the interstitium because of their small molecules, so the metabolism rate in the body is fast, which is not conducive to angiography;
[0004] (2) The small molecule contrast agent cannot form an effective distribution in the body, lacks tissue selectivity, and is highly toxic to normal tissues;
[0005] (3) The small molecule contrast agent is not suitable as the shell of the gene carrier system

Method used

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  • Liver target high molecule magnetic resonance image-forming contrast medium and its synthesizing method and application
  • Liver target high molecule magnetic resonance image-forming contrast medium and its synthesizing method and application
  • Liver target high molecule magnetic resonance image-forming contrast medium and its synthesizing method and application

Examples

Experimental program
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Effect test

Embodiment 1

[0051] Example 1α, the synthesis of β-poly[(2-aminoethyl)-L-asparagine] (PI)

[0052] Add 25 grams (0.19mol) of L-aspartic acid powder and 12.5 grams of 85% phosphoric acid in a 500ml round bottom flask, mix well, and react under reduced pressure at 185°C on a rotary evaporator for 3 hours until no more water vapor is produced. until. Add 100mL of DMF and stir to dissolve the solid matter, then slowly add the obtained solution dropwise into a beaker filled with 500mL of water under stirring, to obtain a white precipitate, let it stand, pour off the supernatant, filter, and wash the solid with water until neutral. Vacuum drying at 60° C. for 24 hours yielded 17 g of powdery solid with a yield of 93%.

[0053] Dissolve the prepolymer in DMF, add N,N-dicyclohexylcarbodiimide (DCC) and condense at room temperature for 24 hours, then filter and concentrate the filtrate. The product is precipitated with distilled water, collected and dried.

[0054] Dissolve 2.5 g (26 mmol) of the...

Embodiment 2

[0055] Coupling reaction (PII) of embodiment 2 lactobionic acid and polymer PI

[0056] Weigh 2 g of lactobionic acid (5.58 mmol) and dissolve it in 40 mL of phosphate buffer solution with pH=5.7, and cool in an ice bath. Add 20mL phosphate buffer solution of 2.6g (22.3mmol) N-hydroxysuccinimide and 4.3g (22.3mmol) EDC.HCl solid, stir in ice bath for 20 minutes, add polymer PII2.9g (18.6mmol), ice After bath reaction for 1 hour, the reaction was continued at room temperature for 36 hours. After 72 hours of dialysis of the reactant mixed solution bag, the solution was concentrated under reduced pressure to dryness to obtain 4.4 g of pale yellow solid PII, with a yield of 91%.

Embodiment 3

[0057] The synthesis of embodiment 3 macromolecular ligand (PIII)

[0058] (a) Synthesis of diethylenetriaminepentaacetic acid diactive ester

[0059] Weigh 8.6g of diethylenetriaminepentaacetic anhydride (DTPAA), 6.69g of N-hydroxysuccinimide and 100mg of 4-dimethylaminopyridine (DMAP) in 100ml of DMF and stir at room temperature for 24 hours. The product was precipitated with a 1:1 ethanol-ether mixture, washed with methanol, soaked in ether overnight, and dried to obtain 10.7 g of a white powdery solid with a yield of 76%.

[0060] (b) Synthesis of diethylenetriaminepentaacetic acid monoactive ester (Tyr-DTPA-OSu) containing tyrosine residues

[0061] Weigh 6.3541g (27.4mmol) methyl tyrosine hydrochloride and dissolve it in 30mlDMF, add 4ml triethylamine, stir and react for 20 minutes, filter out the white solid produced, transfer the filtrate to the dropping funnel, and slowly add it dropwise to In 40ml of DMF solution of diethylenetriaminepentaacetic acid bisactive este...

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Abstract

The invention synthesizes a type of liver targeted, biodegradable high molecular MRI contrast medium with alpha,beta- poly [(2-aminoethyl) - L-asparagine] as fundamental chain, galactose as target gene, diethylenetriamine pentaacetic acid or L-tyrosine methyl ester derivatives as Gd3+ ligand. The contrast agent is less toxic, biocompatible, and has good relaxation rate than low molecular business contrast medium. Animal experiments showed that in liver organizations its enhancing effect is three times better than commercial and low molecular contrast medium (gadolinium sprayed acid cyelophosphate); the residence time in liver is more than 24 hours, which is 18 hours longer than low molecular business contrast medium. The feature is that Zeta potential for the contrast medium is negative and less than -10mV. We can achieve the MRI visible, the liver targeted, core-shell nanogene vector system with it as a gene vector system shell structure.

Description

technical field [0001] The invention relates to a magnetic resonance imaging contrast agent, in particular to a liver-targeting, biodegradable polymer magnetic resonance imaging contrast agent, a synthesis method and an application thereof. Background technique [0002] Magnetic resonance imaging contrast agent is a medical diagnostic reagent that is injected intravenously into the human body to assist magnetic resonance imaging. It can improve the signal-to-noise ratio of imaging, thereby facilitating the diagnosis and treatment process and reducing the rate of misdiagnosis. Today, the annual sales of contrast agents in my country is close to 100 million yuan, and about 30% of the diagnostic process requires the assistance of MRI contrast agents. At present, the MRI contrast agents used clinically are all small molecule contrast agents, such as: Magnevist, (NMG) 2 [Gd(DTPA)(H 2 O)]; Omniscan, Gd(DTPA2DMA); Prohance, Gd(HP2DO3A) and Dotarem, (NMG)[Gd(DOTA)(H 2 O)], (where...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/12A61K48/00
Inventor 余家会舒婕李建奇罗淑芳刘顺英俞磊陈群
Owner EAST CHINA NORMAL UNIV
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