Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Separation of disodium isomers of gadoxetate and its application as contrast agent in mr imaging

A technology of gadoxetate disodium and isomers, which is applied in the field of nuclear resonance contrast agents, can solve the problems of large increase and deposition, and achieve the effects of high imaging efficiency, reduced risk, and short half-life

Active Publication Date: 2022-07-26
中国人民解放军总医院第八医学中心
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, studies have reported that the half-life of gadoxetate disodium in patients with renal failure will be extended to about 10 times, resulting in the deposition of gadolinium in the body and the risk of nephrogenic systemic fibrosis (NSF). It is suggested that gadoxetate disodium is not an ideal high-efficiency liver-kidney dual channel excretion contrast agent, and the reason may be related to the two types of diastereoisomers contained in gadoxetate disodium

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Separation of disodium isomers of gadoxetate and its application as contrast agent in mr imaging
  • Separation of disodium isomers of gadoxetate and its application as contrast agent in mr imaging
  • Separation of disodium isomers of gadoxetate and its application as contrast agent in mr imaging

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Example 1. Separation, purification and stability of Gd-A and Gd-B

[0041] 1. Separation and purification of two types of diastereomers (Gd-A, Gd-B)

[0042]1), set the reversed-phase liquid chromatograph (Laballiance liquid chromatography, LC) to organic phase (pure methanol): inorganic phase (ammonium bicarbonate diluent) = 15%: 85%, start after 30mins baseline balance , put 100 μl of the solution into the micro-injector, remove the bubbles in the micro-injector, and quickly inject it into the liquid chromatographic column (Allsphere ODS-2). The marked 50ml centrifuge tube is filled to the point where the Gd-A peak falls by half; when the Gd-B rising peak appears halfway, the marked 50ml centrifuge tube is used to collect it. Repeat the injection in this way to obtain a large batch of Gd-A and Gd-B. ( figure 1 ); Get separated pure Gd-A, Gd-B every time by reversed-phase high-performance liquid chromatograph (Shimadzu high-performance liquid chromatograph, HPLC) to...

Embodiment 2

[0055] Example 2. MR imaging and pharmacokinetic animal experiments of Gd-A and Gd-B (rabbit)

[0056] 1. Animal experiment: After confirming that both Gd-A and Gd-B have the effect of MRI imaging, 12 male New Zealand white rabbits were selected and raised for 2 weeks. After confirming their health, they were randomly divided into two groups, A and B. 6 animals were used for MR imaging and pharmacokinetic studies of Gd-A and Gd-B respectively (flow chart as shown in Figure 4 shown).

[0057] 1.1 The configuration of the biological sample standard solution, take a certain amount of the original solution of Promex, and dilute it to 1 / 200, 1 / 250, 1 / 300, 1 / 400, 1 / 600, 1 / 1000 of the original solution, and take 20 μl of each dilution Put the solution and 180μl rabbit plasma into a labeled 1.5ml centrifuge tube, and after mixing thoroughly, add 600μl pure methanol to each, labeled as standard rabbit blood solution 1-6, shake and mix them well with a vortex mixer. Then put it into ...

Embodiment 3

[0066] Example 3. MR imaging and pharmacokinetic animal experiments of Gd-A and Gd-B (Beagle dogs)

[0067] 1. Animal experiments

[0068] 1. Experimental animals: After the approval of the Medical Ethics Committee, 20 male adult Beagle dogs aged 2-3 years were used, weighing 10-12 kg. After 2 weeks of normal feeding, they were randomly divided into two groups A and B (n=6), fasted for 6 hours, after anesthesia and fixation, intravenous administration of Gd-A (0.05mmol / kg) in group A, Gd-B in group B Intravenous administration (0.05mmol / kg), MR scan was started simultaneously, blood samples (2ml / time) were drawn regularly through the iliac artery preset tube, and the blood drug concentration was dynamically monitored.

[0069] 2. MR scanning protocol: MRI scanning was performed with a 3.0T MRI scanner (Magnetom Skyra, Siemens Healthcare, Erlangen, Germany), animals were fasted for 6 hours before examination, ketamine (8 mg / kg body weight), diazepam (0.5 mg / kg body weight) ) ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses the separation of disodium gadoxetate isomer and its application in MR imaging contrast agent. The method for separating disodium gadoxetate isomer A includes the following steps: S1. Separating disodium gadoxetate by reverse-phase HPLC to obtain an eluent containing disodium gadoxetate isomer A; S2, Concentrating the eluent containing disodium gadoxetate isomer A to obtain a concentrated solution containing disodium gadoxetate isomer A; S3, the concentrated solution containing disodium gadoxetate isomer A is subjected to low temperature After freezing, freeze-drying was performed to obtain disodium gadoxetate isomer A in the form of white solid powder, which was stored in a vacuum glass bottle. It is found through the experiments of the present invention that Gd-A has higher imaging efficiency and shorter half-life in rabbits and dogs than Gd-B, which further reduces the risk of gadolinium deposition in vivo, so purified Gd-A has potential clinical application value.

Description

technical field [0001] The invention relates to the separation of disodium gadoxetate isomers and its application in MR imaging contrast agents, belonging to the technical field of nuclear resonance contrast agents. Background technique [0002] Gadoxetate disodium (Gd-EOB-DTPA, trade name: Pumeixian), is a liver-specific contrast agent, by adding a fat-soluble group (Gd-DTPA) on the molecular structure of gadopentetate meglumine salt EOB), its molecular structure has both hydrophilic and lipophilic properties, so it has the characteristics of dual-channel excretion of liver and kidney. Gd-EOB-DTPA can be specifically taken up into hepatocytes by organic anion transporters (OATPs) in the basolateral membrane of hepatocytes, and excreted in feces as a drug prototype through the biliary system. Gd-EOB-DTPA exists in two diastereomers, Gd-A and Gd-B, which exist in a relatively constant ratio (65%:35%) in the range of 25-120°C and pH value of 5-9. [0003] However, some studi...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07C227/34C07C229/76A61K49/10
CPCC07C227/34A61K49/106C07C229/76
Inventor 袁小东王超吴宁孙维荣
Owner 中国人民解放军总医院第八医学中心
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com