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A kind of imaging agent, preparation method and use

A composite imaging and fluorescence imaging technology, applied in echo/ultrasonic imaging agents, pharmaceutical formulations, preparations for in vivo tests, etc., can solve problems such as complex operation, poor solubility, and limited application

Active Publication Date: 2019-12-13
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The commonly used negative contrast agent is iron, but many of them are unstable due to their large particle size, or can only be stable in the organic phase due to the limitation of the preparation method, which limits their application.
In addition, most contrast agents only have one contrast-enhancing effect, and cannot achieve two contrast effects at the same time, which limits the accuracy of disease diagnosis
[0006] For example, although the MRI contrast agent gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) has been approved for clinical use, it causes toxicity due to the easy release of its chelated gadolinium ions, and it does not have long circulation and target directional effect, so that its application is limited; in addition, although this contrast agent has T 1 and T 2 Contrast effect at the same time, but T 1 Contrast effect is better than T 2 Contrast effect; contrast effect of negative contrast agent SPIO is opposite
[0007] CN104174037A discloses a 1 , T 2 A method for preparing a blended contrast agent with imaging function. The method uses a double-headed amphiphilic organic molecule as a template agent, and in the presence of an aromatic acid, mixes rare earth ions and VIB-VIIIB group ions in a self-autoclaved system. A blended contrast agent prepared with nanoscale particle size and better T 1 , T 2 Contrast effect; but it cannot exist in aqueous solution stably for a long time, the operation is complicated, and the cost is also high
But its poor solubility in water limits its application in many aspects

Method used

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  • A kind of imaging agent, preparation method and use
  • A kind of imaging agent, preparation method and use
  • A kind of imaging agent, preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] This embodiment adopts the following steps to prepare a multi-mode imaging agent:

[0101] (1) Preparation of CSQ-Fe

[0102] ①Dissolve 2g of CSQ with a molecular weight of 100,000Da in 50mL of deionized water and place it in a three-necked flask. The reaction system is ventilated with nitrogen for 30 minutes, and the oil bath is heated to 102°C to obtain reaction system A. The molecular formula of CSQ used is as follows:

[0103]

[0104] Among them, n=32~320,

[0105] ②Take 0.1459g of FeCl 3 ·6H 2 O with 0.0715g FeCl 2 4H 2 O was dissolved in 2 mL of hydrochloric acid solution with a concentration of 1 mol / L to obtain solution B;

[0106]③ Inject solution B into reaction system A in step (1), slowly add 15 mL of concentrated ammonia water dropwise to pH = 10; reflux at 80-120°C for 40 minutes to obtain reaction system C;

[0107] ④ After cooling the reaction system C in step (3) to room temperature, transfer all the reaction solution to a dialysis bag, and di...

Embodiment 2

[0129] This embodiment adopts the following steps to prepare a multi-mode imaging agent:

[0130] (1) Preparation of CSQ-Fe

[0131] ①Dissolve 2g of CSQ with a molecular weight of 10,000Da in 50mL of deionized water, place it in a three-necked flask, pass nitrogen gas through the reaction system for 30 minutes, and raise the temperature of the oil bath to 102°C to obtain reaction system A; among them, the molecular formula of CSQ used is as follows:

[0132]

[0133] Among them, n=32~320,

[0134] ②Take 0.1459g of FeCl 3 ·6H 2 O with 0.0715g FeCl 2 4H 2 O was dissolved in 2 mL of 1M hydrochloric acid solution to obtain solution B;

[0135] ③ Inject solution B into reaction system A in step (1), slowly add 15 mL of concentrated ammonia water dropwise to pH = 10; reflux at high temperature for 40 minutes to obtain reaction system C;

[0136] ④ After cooling the reaction system C in step (3) to room temperature, transfer all the reaction solution to a dialysis bag, and d...

Embodiment 3

[0145] This embodiment adopts the following steps to prepare a multi-mode imaging agent:

[0146] (1) Preparation of CSQ-Fe

[0147]①Dissolve 2g of CSQ with a molecular weight of 100,000Da in 50mL of deionized water, place it in a three-necked flask, pass nitrogen gas through the reaction system for 30min, and heat the oil bath to 102°C to obtain reaction system A; the molecular formula of CSQ used is as follows:

[0148]

[0149] Among them, n=32~320,

[0150] ②Take 0.1459g of FeCl 3 ·6H 2 O with 0.0715g FeCl 2 4H 2 O was dissolved in 2 mL of 1M hydrochloric acid solution to obtain solution B;

[0151] ③ Inject solution B into reaction system A in step (1), slowly add 15 mL of concentrated ammonia water dropwise to pH = 10; reflux at high temperature for 40 minutes to obtain reaction system C;

[0152] ④ After cooling the reaction system C in step (3) to room temperature, transfer all the reaction solution to a dialysis bag, and dialyze with deionized water at 20°C t...

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Abstract

The invention relates to an imaging agent. The imaging agent is characterized by comprising IR820-CSQ-Fe nanoparticles, wherein the IR820-CSQ-Fe nanoparticles comprises Fe3O4 coated with an A-X-B structure, wherein A is chitosan quaternary ammonium salt CSQadopting a structure shown as a formula (I), and n is an integer ranging from 17 to 290; B is new indocyanine green IR820 adopting a structure shown as a formula (II); X is a compound adopting a structure shown as a formula (III), and R is an alkylene group. The imaging agent has the advantages of superparamagnetism, outstanding T1 and T2 relaxation enhancement effect, photoacoustic imaging capacity, obvious fluorescence spectra, small and uniform particle size, good penetrability, avoidance of obvious cytotoxicity, good biocompatibility and better long circulation effect; a preparation method is simple, mild in condition and lower in cost; the imaging agent can be freeze-dried and stored for a long time in a solid form.

Description

technical field [0001] The invention belongs to the field of nano-imaging agents, in particular to a multi-mode imaging agent and its preparation method and application, especially to an imaging agent capable of T1 and T2 relaxation enhancement, fluorescence imaging or photoacoustic imaging for MRI imaging. In particular, it relates to an imaging agent that can be used as a tumor-targeted T1-T2 dual-nuclear magnetic resonance imaging contrast agent. Background technique [0002] At present, for major diseases, it is very limited to use only one imaging method to determine the lesion location or lesion degree, and it has become a development trend to be able to image jointly by multiple methods. [0003] The sensitivity of fluorescence imaging is particularly high, but the tissue penetration ability is relatively poor; the sensitivity of photoacoustic imaging is also high, and the penetration ability is strong, but due to the limited penetration ability of laser light, there ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00A61K49/18A61K49/12A61K49/22
CPCA61K49/0034A61K49/0093A61K49/1863A61K49/225
Inventor 陈春英周会鸽赵天鸣尚秋宇武秋池王辉罗泽浩
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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