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Thermal-enhanced polymer nano ultrasonic imaging micelle loaded with liquid fluorocarbon and preparation method thereof

An enhanced polymer technology, applied in the fields of polymer chemistry and biomedical engineering, can solve the problems of immature production process, limited echo enhancement effect, unstable surfactant activation, etc., and achieve excellent biocompatibility and degradation sexual effect

Inactive Publication Date: 2012-08-29
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, the nano-scale ultrasound contrast agents studied at home and abroad are mainly divided into three types: nano-scale liposome contrast agents, nano-scale microbubble contrast agents and nano-scale liquid fluorocarbon emulsions. , easy to be cleared, short circulation time in the body, difficult to carry out surface modification, limited effect of echo enhancement, etc.
Due to the defects of the shell material and the preparation method itself, the first two types of contrast agents have disadvantages such as wide particle size distribution range, short duration in the body, obvious rear sound attenuation, and unstable effect. Gas contrast agents are more due to Introduce gas inside tissue with possible adverse effects
Although the imaging effect of the latter type of contrast agent is better, the activation of the surfactant is very unstable, and the phenomenon of inactivation and precipitation of the contrast agent is likely to occur in the case of high dilution and high temperature in the body.

Method used

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  • Thermal-enhanced polymer nano ultrasonic imaging micelle loaded with liquid fluorocarbon and preparation method thereof
  • Thermal-enhanced polymer nano ultrasonic imaging micelle loaded with liquid fluorocarbon and preparation method thereof
  • Thermal-enhanced polymer nano ultrasonic imaging micelle loaded with liquid fluorocarbon and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] 1. Preparation of PEG-PDLLA or PEG-PCL carrier material for polymer nano-ultrasound imaging micelles:

[0032] Under the protection of argon, 0.2g of hydroxyl-terminated PEG (molecular weight 2.0~3.0Kg / mol) was vacuum-dried at around 50°C for several hours, cooled to room temperature, and then injected with 1.6~2.4g of dry lactide or -caprolactone and a small amount of stannous octoate. After vacuum drying at room temperature for 1 hour, 20 ml of anhydrous toluene was added, and refluxed at 120°C for 12 to 24 hours to polymerize. After the reaction, reprecipitate in anhydrous ether, filter and dissolve with dichloromethane, perform secondary reprecipitation in anhydrous ether, filter and vacuum dry to obtain a pure sample.

[0033] 2. Preparation of polymer nano-ultrasound imaging micelles loaded with perfluoropentane:

[0034]Co-dissolve 40mg of copolymer (PEG-PDLLA or PEG-PCL) with 0.025, 0.05, 0.1 and 0.2ml of perfluoropentane respectively in 8ml of carbon tetrachl...

Embodiment 2

[0035] Example 2 Test of particle size of polymer nano-ultrasonic imaging micelles loaded with perfluoropentane

[0036] The particle size of the obtained micelles is measured by a dynamic light scattering system, and the test results are shown in Figures 1 to 3 . figure 1 (0.025ml PFP), figure 2 (0.05ml PFP) and image 3 (0.1ml PFP) are the histograms of the dynamic light scattering particle size distribution of micelles corresponding to the PFP concentration. It can be seen that the particle size distribution of polymer nanomicelles loaded with perfluoropentane is narrow, mainly between 400 and 500 nm, which is nanoscale.

Embodiment 3

[0037] Example 3 In Vitro Ultrasonic Imaging Test of Polymer Nano-ultrasonic Imaging Micelles Loaded with Perfluoropentane

[0038] Use a 2ml syringe to fill up the prepared micellar solution for ultrasound imaging, place it in a temperature-controllable water bath with an immediate temperature of about 25°C, place the ultrasound probe into it for imaging, and record the original ultrasound imaging image and heating (i.e. After the temperature of the water bath was increased to about 35°C), the ultrasonic imaging images were taken at different times, and the gray value of the inner area of ​​the syringe was measured for comparison. see test results Figures 4 to 7 . Figures 4 to 6 Initial ultrasound imaging images of polymer nanomicelles with different PFP concentrations are shown: 0.025ml PFP ( Figure 4 ), 0.05ml PFP ( Figure 5 ) and 0.1ml PFP ( Figure 6 ). It can be seen that the polymer nanomicelles loaded with perfluoropentane have obvious imaging effect in vitro,...

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Abstract

The invention discloses a thermal-enhanced polymer nano ultrasonic imaging micelle loaded with liquid fluorocarbon and a preparation method thereof. The polymer nano ultrasonic imaging micelle loading with the liquid fluorocarbon consists of the following components in part by weight: 1 part of amphiphilic copolymer of polyethylene glycol and poly lactide or polycaprolactone, and 1 to 20 parts ofliquid fluorocarbon ultrasonic imaging reagent. The liquid fluorocarbon loaded on the polymer nano ultrasonic imaging micelle of the invention is dodecafluoropentane. The prepared micelle reaches nano grade, has narrower particle diameter distribution, has obvious in vitro ultrasonic imaging effect and heat enhancement effect, obvious imaging under the animal skins, can be expected to be further applied in vivo and onto other organ tissues and has important research value and application prospect in the diagnosis field.

Description

technical field [0001] The invention relates to the fields of polymer chemistry and biomedical engineering, in particular to a heat-enhanced polymer nano-ultrasonic imaging micelle loaded with liquid fluorocarbon and a preparation method thereof. Background technique [0002] Ultrasound is one of the most commonly used and important imaging methods. Compared with other imaging methods, it has the advantages of being economical, simple, radiation-free, repeatable for multiple inspections, and used at the bedside and during surgery. universal. [0003] The emergence and development of ultrasound contrast agents and imaging technologies have brought opportunities for ultrasound molecular imaging. At present, the commonly used ultrasound contrast agent belongs to the blood pool imaging agent. The diameter of the microbubbles of the contrast agent is similar to that of red blood cells, reaching a few microns. The acoustic impedance of the object interface is poor, resulting in ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22A61K47/34C08G63/664
Inventor 郑荣琴帅心涛李皓
Owner SUN YAT SEN UNIV