Preparation method of folic acid receptor-targeted ultrasound-enhanced nano-microbubbles

A technology of contrast-enhanced ultrasound and folic acid receptors, applied in the field of medical drugs, to achieve good biocompatibility, no in vitro toxicity, and good stability

Active Publication Date: 2017-08-11
NINGBO FIRST HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] After searching, there is no literature report on the construction of folic acid receptor-mediated targeted nano-ultrasound contrast agent using the principle of self-assembly of ordered supramolecular films layer by layer

Method used

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  • Preparation method of folic acid receptor-targeted ultrasound-enhanced nano-microbubbles
  • Preparation method of folic acid receptor-targeted ultrasound-enhanced nano-microbubbles
  • Preparation method of folic acid receptor-targeted ultrasound-enhanced nano-microbubbles

Examples

Experimental program
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Effect test

Embodiment 1

[0046] Example 1, preparation of folate receptor-mediated targeted ultrasound contrast-enhanced nano-microbubble core template nanoemulsion. Weigh 0.1125g glycerol (2.25% (w / v)) as an isotonic agent and co-emulsifier, and emulsifier 0.12g refined egg yolk lecithin (2.4%, w / v) and 0.03g poloxamer 188 ( 0.6%, w / v) and stabilizer 0.01g oleic acid (0.2%, w / v) were vortex mixed in 4ml ultrapure water to form a suspension, and the prepared suspension was placed at 37°C and incubated for 1h to prepare Form an emulsion, then add 100 μl perfluorooctyl bromide drop by drop under vortex mixing, dilute to 5ml with ultrapure water, put it into a 15ml Corning centrifuge tube, and quickly use the machine for ultrasound, the temperature is controlled at 20-30°C, and the temperature is controlled at 20-30°C, % Ultrasound intensity for 10 minutes, start the ultrasound for 10 seconds, and pause for 10 seconds to obtain a liquid fluorocarbon core template nanoemulsion. After the obtained liquid f...

Embodiment 2

[0049] Example 2, (1) Prepare folate receptor-mediated targeting ultrasound contrast-enhanced nano-microbubble core template nanoemulsion. Weigh 0.1125g glycerol (2.25% (w / v)) as an isotonic agent and co-emulsifier, and emulsifier 0.12g refined egg yolk lecithin (2.4%, w / v) and 0.04g poloxamer 188 ( 0.8%, w / v) and stabilizer 0.0125g oleic acid (0.25%, w / v) were vortex mixed in 4ml ultrapure water to form a suspension, and the prepared suspension was placed at 37°C and incubated for 1h to prepare Form an emulsion, then add 100 μl perfluorooctylbromide dropwise under vortex mixing, dilute to 5ml with ultrapure water, put it into a 15ml Corning centrifuge tube, and quickly put it on the machine for ultrasound, the temperature is controlled at 20-30 % Ultrasound intensity for 10 minutes, start the ultrasound for 10 seconds, and pause for 10 seconds to obtain a liquid fluorocarbon core template nanoemulsion. After the obtained liquid fluorocarbon core template nanoemulsion is dilut...

Embodiment 3

[0052]In Example 3, a folate receptor-mediated targeted ultrasound contrast-enhanced nano-microbubble core template nanoemulsion was prepared. Weigh 0.125g glycerol (2.5% (w / v)) as an isotonic agent and co-emulsifier, and emulsifier 0.11g refined egg yolk lecithin (2.2%, w / v) and 0.04g poloxamer 188 ( 0.8%, w / v) and stabilizer 0.0075g oleic acid (0.15%, w / v) were vortex mixed in 4ml ultrapure water to form a suspension, and the prepared suspension was placed at 37°C and incubated for 1h to prepare Form an emulsion, then add 125 μl perfluorooctyl bromide drop by drop under vortex mixing, dilute to 5ml with ultrapure water, put it into a 15ml Corning centrifuge tube, and quickly put it on the machine for ultrasound, the temperature is controlled at 20-30 % ultrasonic intensity for 10 minutes, ultrasonic start 15s, pause 15s, the liquid fluorocarbon core template nanoemulsion was prepared, the obtained liquid fluorocarbon core template nanoemulsion was diluted 10 times with 1ml o...

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Abstract

A method for preparing folic acid receptor-targeted ultrasound contrast-enhanced nano-microbubbles, the nano-microbubbles are composed of a core template and a shell, characterized in that the core template is a liquid fluorocarbon nanoemulsifier, and the shell is a folic acid-linked branched PEGylated chitosan derivatives. Compared with the prior art, the present invention has the advantages that the nano-microbubbles obtained with the liquid fluorocarbon nano-emulsifier as the core template and the folic acid-grafted pegylated chitosan derivative as the shell have better stability, It has the advantages of no in vitro toxicity, good biocompatibility for intravenous injection, and high specific binding force.

Description

technical field [0001] The invention relates to a preparation method of targeted nano-microbubbles, which can be accurately positioned to tumor cells with high expression of folic acid receptors through passive and active targeting effects, and can be taken up by tumor cells, thereby realizing the tumor The invention relates to specific ultrasonic molecular imaging of cells, belonging to the field of medical medicine. Background technique [0002] Ultrasound examination is an important means of clinical diagnosis of tumors due to its advantages of non-invasive, non-radiation, convenient operation, low price, and low requirements for equipment and space. Contrast-enhanced ultrasound has been proved to be effective in the detection and qualitative diagnosis of tumors in many years of clinical application. Significance. Contrast-enhanced ultrasound is superior to conventional contrast, and has more advantages than CT and MRI. Safe and efficient ultrasound contrast agent is th...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22
Inventor 王涌胡岳韩宝三张盛敏刘雅辉
Owner NINGBO FIRST HOSPITAL
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