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Gadolinium chelate as well as preparation method and application thereof

A chelate and polymer technology, applied in the field of biomedical materials, can solve problems such as nephrotoxicity, achieve excellent water solubility, shorten imaging time, and achieve rapid imaging effects

Active Publication Date: 2021-06-11
SUZHOU ZHECI PHARM TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004]Both linear and macrocyclic gadolinium-based contrast agents cause trace gadolinium deposits in the brain and other tissues, and high doses of gadolinium-based contrast agents are used in clinical scans to Enhances the contrast between normal and diseased tissue, which may pose potential risks such as nephrotoxicity in certain patient populations

Method used

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  • Gadolinium chelate as well as preparation method and application thereof
  • Gadolinium chelate as well as preparation method and application thereof
  • Gadolinium chelate as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Preparation of Gadolinium Chelate (Gd-PAA)

[0080] Configure 40mL of polyacrylic acid (M w =2000) solution, the polymer solution was heated to reflux at 100°C. Immediately, 0.8 mL of gadolinium nitrate solution with a concentration of 125 mM was added to the reaction system, and the reaction was continued for 60 minutes at 100° C. under magnetic stirring. After the solution was cooled to room temperature, it was purified by membrane dialysis, and the final product was labeled as Gd-PAA.

[0081] Characterization and performance tests were performed on the samples provided in Example 1. The recovery rate of gadolinium calculated for the sample prepared in Example 1 is higher than 90%, indicating that the chelating effect is good and the raw material utilization rate is high. The sample prepared in Example 1, the commercially available contrast agent Magnevist, Gadavist and gadolinium nitrate solution were respectively prepared at least 5 kinds of aqueous solutions wi...

Embodiment 2

[0091] Preparation of Gadolinium Chelate (Gd-PASP)

[0092] Configure 40mL of polyaspartic acid (M w =2000) solution, the polymer solution was heated to reflux at 100°C. Immediately, 0.8 mL of gadolinium nitrate solution with a concentration of 125 mM was added to the reaction system, and the reaction was continued for 60 minutes at 100° C. under magnetic stirring. After the solution was cooled to room temperature, it was purified by membrane dialysis, and the final product was labeled as Gd-PASP.

[0093] Characterization and performance tests were performed on the samples provided in Example 2. The gadolinium recovery rate of the sample prepared in Example 2 is higher than 90%, and the raw material utilization rate is high. The sample prepared in Example 2 is prepared at least 5 kinds of aqueous solutions with different concentrations, and the in vitro imaging is carried out in a 3.0T clinical MRI system and a 7.0T MRI system respectively, and the longitudinal relaxation ...

Embodiment 3

[0100] Preparation of Gadolinium Chelate (Gd-HPMA)

[0101] It is 4.0mg / mL polymaleic acid (M w =2000) solution, the polymer solution was heated to reflux at 100°C. Immediately, 0.8 mL of gadolinium nitrate solution with a concentration of 125 mM was added to the reaction system, and the reaction was continued for 60 minutes at 100° C. under magnetic stirring. After the solution was cooled to room temperature, it was purified by membrane dialysis, and the finally obtained product was labeled as Gd-HPMA.

[0102] Characterization and performance tests were performed on the samples provided in Example 3. The sample prepared in Example 3 has a higher recovery rate of gadolinium and a higher utilization rate of raw materials. The sample prepared in Example 3 is prepared into at least 5 different concentrations of aqueous solutions, and the in vitro imaging is carried out by a 3.0T clinical MRI system and its longitudinal relaxation time and transverse relaxation time (T 1 ,T ...

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Abstract

The invention discloses a gadolinium chelate as well as a preparation method and application thereof. The gadolinium chelate is a complex formed by gadolinium ions and macromolecules through chelation, the macromolecules comprise a copolymer or a mixture of any one or more than two of a carboxylic acid-containing high-molecular polymer, an amino-containing high-molecular polymer, a hydroxyl-containing high-molecular polymer, a polyester high-molecular polymer, a polyether high-molecular polymer, a polyamide high-molecular polymer, protein, polypeptide and polysaccharide. The gadolinium ions and macromolecules form the gadolinium chelate through chelation, the gadolinium chelate is a water-soluble macromolecular drug, the longitudinal relaxation rate r1 can be increased, the r2 / r1 ratio can be reduced, the water solubility is good, the stability is high, meanwhile, a good imaging effect can be presented in a short time, and the MRI time is shortened.

Description

technical field [0001] The invention relates to the technical field of biomedical materials, in particular to a gadolinium chelate and its preparation method and application. Background technique [0002] Magnetic resonance imaging (MRI) can detect tiny or specific lesions sensitively, reducing the missed or misdiagnosed rate. MRI contrast agents, as a chemical agent that can improve the quality of MRI images, have become an important supplement to MRI examinations. T 1 (longitudinal relaxation time) and T 2 (Transverse relaxation time) is an important tissue characteristic parameter of MRI. When the paramagnetic substances (such as gadolinium, iron, manganese, etc.) in the sample are close to the hydrogen atoms in the resonance, they can effectively change the magnetic field where the protons are located and shorten the tissue relaxation. time T 1 , T 2 , so that the signal in the image enhancement area is enhanced, and the tissue signal-to-noise ratio (ΔSNR) is improv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F8/42C08F20/06C08F22/02C08F16/06C08F20/20C08F20/56C08B37/04C08B37/08C08G63/91C08G65/328C08G69/48C08G73/02C08H1/00A61K49/12A61K49/14
CPCC08F8/42C08G69/48C08G73/0206C08G63/912C08G65/328C08H1/00C08B37/003C08B37/0084A61K49/12A61K49/126A61K49/14C08F20/06C08F22/02C08F16/06C08F20/20C08F20/56C08G69/10C08L77/04C08L33/02C08L79/02C08L33/12C08L71/00C08L33/26C08G63/685C08G63/52C08G63/68C08G63/06A61K49/146A61K49/128A61K49/143C08L5/04C08L5/08C08K3/08
Inventor 沈折玉卢玉蝶
Owner SUZHOU ZHECI PHARM TECH CO LTD
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