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Stable cluster-shaped nanometer contrast agent and preparation method and use thereof

A nano-contrast agent and stability technology, applied in pharmaceutical formulations, preparations for in vivo tests, etc., can solve the problems of contrast agent use, toxicity, non-water-solubility of nanoparticles, and achieve good re-dispersion effect.

Inactive Publication Date: 2019-03-29
HEFEI UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these nanoparticles themselves are not water-soluble, and some have certain toxicity, so they cannot be directly used as contrast agents

Method used

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  • Stable cluster-shaped nanometer contrast agent and preparation method and use thereof
  • Stable cluster-shaped nanometer contrast agent and preparation method and use thereof
  • Stable cluster-shaped nanometer contrast agent and preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1: NaGdF 4 Preparation of nanoparticles

[0029] Take 3ml oleic acid, 1mmol GdCl 3 ·6H 2 O was added to a 150ml three-neck flask and stirred magnetically at 100-110°C for 30-60 minutes until a light yellow, clear and transparent solution was formed. The prepared Gd-OA precursor solution was stored in a 5ml EP tube in an oven at 25°C for later use.

[0030] Take 6ml of oleic acid and 15ml of octadecene into a 150ml three-necked flask with magnetic stirring, then add 10ml of methanol dissolved with 0.0741g of NH4F and 0.05g of NaOH, then slowly raise the temperature to 70°C and keep it warm until all the methanol is evaporated and then rise to 100°C Keep warm at ℃ for 10 minutes to evaporate water, vacuumize for 10 minutes to remove oxygen, then heat up to 280°C, quickly inject 3ml of Gd-OA and keep warm for 30 minutes, then cool down to room temperature, and the reaction product is precipitated with acetone and centrifuged before dispersing in cyclohexane.

Embodiment 2

[0031] Embodiment 2: the preparation of polymer

[0032] First, the POEGMA segment was prepared by RAFT polymerization. Add 1.2g of OEGMA (oligoethylene glycol methyl ether methacrylate), 3mg of AIBN (azobisisobutylcyanide) and 5ml of dioxane into a 50mL reaction bottle, and react at a constant temperature of 70°C for 24 hour, the product was dried in a vacuum oven to obtain POEGMA;

[0033] Add the product POEGMA, AA (acrylic acid) 1.15g, AIBN 3mg and dioxane 10ml into the reaction bottle, under the protection of nitrogen, react at a constant temperature of 75°C for 24 hours, and dry the product in a vacuum oven to obtain the polymer PAA -POEGMA.

Embodiment 3

[0034] Embodiment 3: Preparation of clustered nano-contrast agent

[0035] Usually, 4ml of NaGdF4 (5mg / ml) was dissolved in 10ml of 1,4-dioxane solution of 25mg of PAA-POEGMA, mixed and stirred at 50°C for 5h, and then the solution was naturally cooled to room temperature. Disperse the solution in 10ml centrifuge tubes, about 3ml in each tube, add 6ml of acetone to precipitate, and centrifuge at 10000rpm for 10min. Pour off the liquid to obtain a milky white precipitate, hydrate the precipitate with a total of 10ml of deionized water to obtain a white turbid liquid, spin dry and dry it in a vacuum, collect and redistribute the knot-free NaGdF4 nanoparticles in water, and you can A clustered nano-contrast agent is obtained.

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Abstract

The invention discloses a stable cluster-shaped nanometer contrast agent and a preparation method and use thereof. The stable cluster-shaped nanometer contrast agent consists of a gadolinium-based nanometer material and a polymer layer coating the whole surface or a part of surface of the gadolinium-based nanometer material, wherein the mass ratio of the gadolinium-based nanometer material to polymers is 1 to (1-10). The contrast agent disclosed by the invention has favorable water solubility and favorable stability, and has high relaxation rate.

Description

technical field [0001] The invention relates to a magnetic resonance imaging material, in particular to a stable cluster nano-contrast agent and its preparation method and application, belonging to the technical field of nano-materials and magnetic resonance imaging. Background technique [0002] At present, some nanoparticles have been used for magnetic resonance imaging in medicine, such as: Fe 2+ , Fe 3+ , Mn 2+ or Gd 3+ Wait. However, these nanoparticles themselves are not water-soluble, and some have certain toxicity, so they cannot be directly used as contrast agents. [0003] Utilizing polymeric micelles to construct electron-based nanoscale MRI contrast agents has favorable advantages because it enables the contrast agents to have high relaxation and blood circulation, which is especially beneficial for imaging of tumor regions. Furthermore, polymeric micelles can be easily introduced with various functionalities, such as targeting specificity, additional imagin...

Claims

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Application Information

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IPC IPC(8): A61K49/12
CPCA61K49/12
Inventor 何涛汪翔闫旭陆杨刘建华徐晓莉
Owner HEFEI UNIV OF TECH
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