A t1-t2 dual-mode ultra-high field magnetic resonance contrast agent and its preparation method and application

A magnetic resonance contrast agent, T1-T2 technology, applied in nano-magnetism, pharmaceutical formulations, preparations for in vivo tests, etc., can solve problems such as toxic side effects, interference with T1 contrast agent relaxation process, and reduction of T1 signal. Achieve high biocompatibility, good possibility of clinical transformation, and high biosafety

Active Publication Date: 2022-04-01
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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  • A t1-t2 dual-mode ultra-high field magnetic resonance contrast agent and its preparation method and application
  • A t1-t2 dual-mode ultra-high field magnetic resonance contrast agent and its preparation method and application
  • A t1-t2 dual-mode ultra-high field magnetic resonance contrast agent and its preparation method and application

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 dual-mode ultra-high-field magnetic resonance contrast agent, which comprises magnetic nanoparticles, water-soluble ligands modified on the surface and water-soluble polymers modified on the surface through chemical coupling. The contrast agent exhibits a good ultra-high-field magnetic resonance imaging effect in vivo, and can accurately and sensitively evaluate tumor vascular permeability through T1‑T2 dual-mode magnetic resonance imaging. The invention also relates to a preparation method of T1-T2 dual-mode ultra-high field magnetic resonance contrast agent and its application in the preparation of magnetic resonance nano contrast agent. The reaction conditions of the preparation method are controllable, the size of the product is uniform, the shape is good, the product has high biological safety, and has good possibility of clinical transformation.

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 Patents(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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