T1-T2 bimodal ultrahigh-field magnetic resonance contrast agent as well as preparation method and application thereof

A magnetic resonance contrast agent, T1-T2 technology, applied in the direction of nano-magnetism, pharmaceutical formulations, preparations for in vivo tests, etc., can solve the problems of reducing T1 signal, interfering with the relaxation process of T1 contrast agent, toxic and side effects, etc. Achieve high biological safety, good possibility of clinical transformation, and high biocompatibility

Active Publication Date: 2021-01-29
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] One of the common design strategies for T1-T2 dual-mode contrast agents is to directly adsorb paramagnetic T1 contrast agents on the surface of T2 contrast agent SPION, but SPION has a strong T2 effect under ultra-high field and may interfere with T1 contrast. The relaxation process of the agent, thereby significantly reducing the T1 signal; at the same time, the doped paramagnetic substances usually contain Gd, Mn, Co and other elements, which have certain toxic and side effects

Method used

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  • T1-T2 bimodal ultrahigh-field magnetic resonance contrast agent as well as preparation method and application thereof
  • T1-T2 bimodal ultrahigh-field magnetic resonance contrast agent as well as preparation method and application thereof
  • T1-T2 bimodal ultrahigh-field magnetic resonance contrast agent as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Embodiment 1: Preparation of ultra-small iron oxide nanoparticles

[0045] Accurately weigh 10.8g ferric chloride hexahydrate (FeCl 3 ·6H 2 (2, 40mmol) and 36.5g sodium oleate (120mmol) were placed in a 500mL round bottom flask, and then 80mL absolute ethanol, 60mL deionized water, and 140mL n-hexane were added to the round bottom flask using a graduated cylinder, and the mixture was placed in the oil 70°C oil bath in a bath, stirring and reacting for 4 hours. After the reaction was completed, the mixture was transferred to a separatory funnel, 30 mL of distilled water was added for extraction, the lower transparent liquid was discarded, and the operation was repeated three times. After the extraction was completed, a dark liquid was obtained, which was removed by rotary evaporation, and then heated and dried under vacuum to finally obtain the iron oleate complex in the form of a waxy solid.

[0046] Accurately weigh 0.9g (1mmol) iron oleate complex and place it in a...

Embodiment 2

[0048] Example 2: Ligand Exchange of Ultra-Small Iron Oxide Nanoparticles Using Citric Acid

[0049] Take a chloroform solution containing 120mg of ultra-small iron oxide nanoparticles, add acetone to precipitate, centrifuge and redisperse the black solid in o-dichlorobenzene solution, place it in a 50mL round bottom flask, accurately weigh 0.1g of citric acid and add Add o-dichlorobenzene and N,N-dimethylformamide to the flask, so that the total volume of the liquid is 15 mL, and the volume ratio of o-dichlorobenzene and N,N-dimethylformamide is 1:1. The flask was placed in an oil bath at 100°C and stirred for 24 hours. After the reaction, cool to room temperature, add diethyl ether to precipitate, then wash the precipitate twice with diethyl ether and acetone respectively, and disperse the ultra-small iron oxide nanoparticles exchanged with citric acid ligands in deionized water for use.

Embodiment 3

[0050] Example 3: Ultra-small iron oxide nanoparticles modified with polyethylene glycol after ligand exchange

[0051] There are carboxyl groups on the surface of ultra-small iron oxide nanoparticles after citric acid ligand exchange, you can choose polyethylene glycol with modified amino groups at the end, and use the condensation reaction between carboxyl and amino groups to modify polyethylene glycol on the surface of ultra-small iron oxide particles , to obtain T1-T2 dual-mode ultra-high field contrast agent.

[0052] (1) Take 50 mg of the ultra-small iron oxide nanoparticle solution after citric acid ligand exchange and disperse it in 10 mL of deionized water, add 50 mg of polyethylene glycol-amino (Shanghai Ziqi Biological Co., Ltd.), 0.05 g of 1-(3- Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 0.06g N-hydroxysuccinimide, stirred overnight at room temperature, adjusted the pH value of the solution to 9, stirred at room temperature for 24 hours, and transferre...

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Abstract

The invention relates to a T1-T2 bimodal ultrahigh-field magnetic resonance contrast agent. The contrast agent comprises magnetic nanoparticles, a water-soluble ligand modifying the surfaces of the magnetic nanoparticles, and a water-soluble polymer modified the surfaces of the magnetic nanoparticles through chemical coupling. The contrast agent has a good ultrahigh-field magnetic resonance imaging effect in vivo, and the tumor vascular permeability can be accurately evaluated with high sensitivity through T1-T2 bimodal magnetic resonance imaging. The invention further relates to a preparationmethod of the T1-T2 bimodal ultrahigh-field magnetic resonance contrast agent and application of the contrast agent in preparation of magnetic resonance nano contrast agents. The contrast agent has the advantages of controllable reaction conditions of the preparation method, uniform product size, good morphology, high product biosafety and good clinical conversion possibility.

Description

technical field [0001] The invention relates to the synthesis of inorganic nanometer materials, in particular to a T1-T2 dual-mode ultra-high field magnetic resonance contrast agent and its preparation method and application. Background technique [0002] Among the current various diseases, the mortality rate of cardiovascular disease and tumor ranks first and second respectively. The occurrence and development of tumors and cardiovascular diseases are often accompanied by changes in the structure and function of blood vessels, such as abnormal angiogenesis in malignant tumors and vascular changes in cardiovascular and cerebrovascular diseases. Accurate diagnosis and treatment guidance of cardiovascular and cerebrovascular diseases have important clinical significance. [0003] As a non-invasive medical imaging method, magnetic resonance imaging (MRI) has great advantages in soft tissue imaging, and a variety of techniques have been developed to analyze the structure and fu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18B82Y25/00B82Y30/00B82Y40/00
CPCA61K49/1851B82Y25/00B82Y30/00B82Y40/00A61K49/186
Inventor 凌代舜李方园白瑞良汪瑾
Owner ZHEJIANG UNIV
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