Tumor-targeted T1-T2 double nuclear magnetic resonance imaging contrast agent and preparation method and application thereof

A nuclear magnetic resonance imaging, T1-T2 technology, applied in preparations for in vivo tests, pharmaceutical formulas, emulsion delivery, etc.

Active Publication Date: 2015-07-08
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The present invention has mild reaction conditions, simple operation process, and is easy to separate and purify; the Fe prepared by the present inventio

Method used

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  • Tumor-targeted T1-T2 double nuclear magnetic resonance imaging contrast agent and preparation method and application thereof
  • Tumor-targeted T1-T2 double nuclear magnetic resonance imaging contrast agent and preparation method and application thereof
  • Tumor-targeted T1-T2 double nuclear magnetic resonance imaging contrast agent and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0063] This embodiment adopts the following steps to prepare T 1 -T 2 Dual MRI contrast agents:

[0064] (1) Dissolve 0.5 g of HA in 50 mL 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; wherein, the molecular formula of HA used is as follows:

[0065]

[0066] Among them, n=17~290,

[0067] (2) Take 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;

[0068] (3) Inject solution B into reaction system A in step (1), slowly add 15 mL of ammonia water with a mass fraction of 27% dropwise until pH = 10; reflux at high temperature for 40 minutes to obtain reaction system C;

[0069] (4) After the reaction system C in step (3) is cooled to room temperature, all the reaction solution is transferred to a dialysis bag, and after dialysis with deionized...

Embodiment 2

[0083] This embodiment adopts the following steps to prepare T 1 -T 2 Dual MRI contrast agents:

[0084] (1) Dissolve 0.25g of HA in 50mL of deionized water, place it in a three-necked flask, pass nitrogen to the reaction system for 20 minutes, and raise the temperature of the oil bath to 80°C to obtain reaction system A; wherein, the molecular formula of HA used is as follows:

[0085]

[0086] Among them, n=17~290,

[0087] (2) Take 0.1459g of FeCl 3 ·6H 2 O with 0.0804g FeCl 2 4H 2 O was dissolved in 2 mL of 1M hydrochloric acid solution to obtain solution B;

[0088] (3) Inject solution B into reaction system A in step (1), slowly add 15 mL of ammonia water with a mass fraction of 25% dropwise until pH=10; reflux at high temperature for 40 minutes to obtain reaction system C;

[0089] (4) After the reaction system C in step (3) is cooled to room temperature, all the reaction solution is transferred to a dialysis bag, and after dialysis with deionized water at 20°...

Embodiment 3

[0092] This embodiment adopts the following steps to prepare T 1 -T 2 Dual MRI contrast agents:

[0093] (1) Dissolve 2 g of HA in 50 mL of deionized water and place it in a three-necked flask. The reaction system is ventilated with nitrogen for 50 minutes, and the oil bath is heated to 120° C. to obtain reaction system A; wherein, the molecular formula of HA used is as follows:

[0094]

[0095] Among them, n=17~290,

[0096] (2) Take 0.1459g of FeCl 3 ·6H 2 O with 0.0537g FeCl 2 4H 2 O was dissolved in 2 mL of 1M hydrochloric acid solution to obtain solution B;

[0097] (3) Inject solution B into reaction system A in step (1), slowly add 15 mL of ammonia water with a mass fraction of 28% dropwise until pH = 10; reflux at high temperature for 120 minutes to obtain reaction system C;

[0098] (4) After the reaction system C in step (3) is cooled to room temperature, all the reaction solution is transferred to a dialysis bag, and after dialysis with deionized water at...

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Abstract

The invention relates to a tumor-targeted T1-T2 double nuclear magnetic resonance imaging contrast agent and a preparation method and an application thereof. The contrast agent comprises hyaluronic acid-coated ferroferric oxide composite magnetic nanoparticles, wherein the molecular formula of hyaluronic acid is as shown in the specification; n is an integer of 17-290. The preparation method of the contrast agent comprises the following steps: (1) dissolving hyaluronic acid into deionized water, introducing a gas, and heating to obtain a reaction system A; (2) dissolving ferric salt and ferrous salt into a strong acid to obtain a solution B; (3) injecting the solution B into the reaction system A, adjusting the pH to be alkaline, and then refluxing at a high temperature to obtain a reaction system C; and (4) cooling a reaction system C to a room temperature, and dialyzing to obtain the contrast agent. The invention further provides an application of the contrast agent in T1 and T2 weighted imaging in in-vivo and in-vitro nuclear magnetic resonance. The contrast agent provided by the invention has superparamagnetism and outstanding T1 and T2 relaxation enhancement effects, and is suitable for being used as a T1-T2 double nuclear magnetic resonance imaging contrast agent.

Description

technical field [0001] The invention relates to the field of nuclear magnetic resonance imaging contrast agent materials, in particular to a tumor-targeted T 1 -T 2 Dual-nuclear magnetic resonance imaging contrast agent and its preparation method and application. Background technique [0002] According to the type of imaging enhancement, the currently used MRI contrast agents are divided into two categories: positive contrast agents and negative contrast agents. They respectively enhance the 1 / T of the local area 1 or 1 / T 2 Relaxation efficiency to achieve the effect of image signal enhancement to brighten or darken the picture. The commonly used negative contrast agent is iron, but many of them are unstable in nature due to large particle size, or can only be stable in the organic phase due to the limitation of the preparation method, which makes the application limited. In addition, most contrast agents only have one contrast enhancement effect, and cannot achieve two...

Claims

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Application Information

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IPC IPC(8): A61K49/18A61K49/12
Inventor 陈春英唐敬龙周会鸽徐梦真
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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