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Novel PLGA-PEG-PLGA multipolymer microbubble ultrasound contrast agent and preparation method thereof

A technology of PLGA-PEG-PLGA and ultrasonic contrast agent, which is applied in the field of ultrasonic medical diagnosis and treatment, can solve the problems of controlling the particle size of microbubbles, the thickness of the particle size distribution envelope, and the limitations of elastic and nonlinear acoustic properties, and achieve good results. The effect of backscattering performance, simple and convenient production method, and easy operation

Inactive Publication Date: 2009-11-11
FUJIAN MEDICAL UNIV UNION HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, at present, the preparation of most microbubble ultrasound contrast agents adopts the method of mixing the film-forming material and the coated gas with acoustic vibration. and nonlinear acoustic characteristics have certain limitations

Method used

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  • Novel PLGA-PEG-PLGA multipolymer microbubble ultrasound contrast agent and preparation method thereof
  • Novel PLGA-PEG-PLGA multipolymer microbubble ultrasound contrast agent and preparation method thereof
  • Novel PLGA-PEG-PLGA multipolymer microbubble ultrasound contrast agent and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Embodiment 1: Synthesis and characterization of PLGA-PEG-PLGA copolymer

[0021] Put 15g (mass percentage 40%) polyethylene glycol with Mw of 1500 in the there-necked flask, stir for 3h under vacuum at 150°C, add 3.2g glycolide, 19.3g lactide (glycolide and lactide The molar ratio is 1:4) and 0.04 g of the catalyst stannous octoate, reacted for 8 hours under nitrogen protection to obtain the product. The product was dissolved in chloroform, purified by ethanol precipitation, and dried at room temperature to constant weight. The average molecular weight that adopts high-efficiency gel permeation chromatography analyzer to measure copolymer is 5880dal, Fourier transform infrared spectrum, 1 The H NMR spectrum shows a typical PLGA-PEG-PLGA structure.

Embodiment 2

[0022] Embodiment 2: Preparation of PLGA-PEG-PLGA microbubble

[0023] Microbubbles were prepared by water / oil / water double emulsion-solvent evaporation method. 1ml of PLGA-PEG-PLGA dichloromethane / ethyl acetate mixed solution with a concentration of 50mg / ml was added to 0.1ml of normal saline, stirred at a speed of 10,000 rpm for 1min to obtain primary emulsion, and poured into 4ml of 3% polyvinyl alcohol aqueous solution, Stir at 10,000 rpm for 1 min, then add 15ml of 3% polyvinyl alcohol aqueous solution, stir magnetically at 400 rpm for 3 h to completely evaporate the organic solvent, centrifuge, wash with distilled water, add antifreeze glycerin to the obtained microbubbles, and vacuum freeze-dry Then fill it with inert gas perfluoropropane and store it at low temperature.

Embodiment 3

[0024] Example 3: Characterization of PLGA-PEG-PLGA microbubbles

[0025] Disperse the microbubbles in normal saline, observe under the inverted microscope that the microbubbles are spherical, smooth in surface, well dispersed, non-adhesive, and relatively uniform in size (see figure 1 ). Take an appropriate amount of microbubble powder and disperse it in physiological saline, and the laser particle size analyzer measures the particle size of the microspheres to be 1.1-7.2 μm, with an average of 3.8 μm.

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Abstract

The invention discloses a novel PLGA-PEG-PLGA multipolymer microbubble ultrasound contrast agent and preparation method thereof. The microbubble ultrasound contrast agent is provided with an outer housing prepared from the polymer material PLGA-PEG-PLGA, the components of the inner core of gas include perfluoropropane, decafluorobutane or sulphur hexafluoride, and the like, and the molecular weight of the PLGA-PEG-PLGA multipolymer ranges from 2000 to 20000 dal. The preparation of the agent adopts the double emulsion method, and after being frozen and dried, gas molecules are led into microbubbles. The multipolymer microbubble contrast agent has favorable backscattering performance, shows the enhanced effect of ultrasonic contrast during in vivo and in vitro experiments, is safe and nontoxic, and meets the requirement of the ultrasound contrast agent.

Description

Technical field: [0001] The invention relates to a gas-containing microbubble ultrasonic contrast agent prepared from high molecular polymer materials, which belongs to the field of ultrasonic medical diagnosis and treatment. Background technique: [0002] Conventional ultrasound contrast agent is a micron-scale contrast agent, the average diameter of the microbubbles is about 2-4 μm, and it does not penetrate blood vessels. It is a blood pool imaging agent. Gas-containing microbubbles are used as ultrasound contrast agents, which use almost all of the microbubbles to reflect ultrasound energy, and produce a contrast imaging technology that is significantly different from the surrounding tissues after injection into the human body. Its clinical applications mainly include: after microbubbles are injected into blood vessels, they can effectively display small and low-speed blood flow signals; microbubbles can be used as tracers to provide information on tissue microcirculatio...

Claims

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Application Information

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IPC IPC(8): A61K49/22
Inventor 林礼务蔡敏娴陈志奎薛恩生
Owner FUJIAN MEDICAL UNIV UNION HOSPITAL
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