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Novel preparation process for polyester hard-shell microbubble system with controllable particle size

A microbubble and system technology, applied in the direction of echo/ultrasonic imaging agents, etc., can solve the problems of complex preparation process, poor stability of soft-shell microbubbles, poor shell compressibility, etc., and achieve easy separation and purification, good biological Effects of compatibility and safety, good prospects for biomedical applications

Inactive Publication Date: 2014-10-22
刘哲
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The construction strategies of gas-carrying microbubbles reported in previous literature mostly use phospholipids, albumin, sugars, etc. Weak reflection ability and short imaging cycle (Feinstein SB, Cheirif J, Tencate FJ, et al. JAm Coll Cardiol 1990; 16: 316-24.)
There are not many reports on the use of polymers as microbubble shell materials (Yang F, Gu A, Chen Z, Gu N, Ji M Materials Letters 2008; 62:121-24.), but the preparation process is complicated and many Using toxic organic solvents as the reaction medium, the multi-step synthesis strategy of layer-by-layer construction makes the yield low, which is not suitable for the construction of multifunctional diagnostic and therapeutic integrated contrast agents such as imaging and drug loading.

Method used

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  • Novel preparation process for polyester hard-shell microbubble system with controllable particle size
  • Novel preparation process for polyester hard-shell microbubble system with controllable particle size
  • Novel preparation process for polyester hard-shell microbubble system with controllable particle size

Examples

Experimental program
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Effect test

Embodiment 1

[0028] Example 1: N-butyl acrylate, polyethylene glycol octylphenyl ether, and high-purity deionized water were fed into a 2-liter beaker at a ratio of 1:1:100, and the pH value of the reaction system was adjusted to weak acidity (about 2.5 ), stirred at a high speed (rpm=10000) at room temperature for 60 minutes, and after the reaction was terminated, the crude product was transferred to a separatory funnel and left to stand for 5 hours, the bottom layer residue was discarded, and the top layer of microbubbles were kept, and mixed with 0.02% polyethylene glycol Octylphenyl ether aqueous solution was washed three times. The obtained product was divided into centrifuge tubes, purified and centrifuged for 20 minutes, and the microbubble product layer on the top layer of the centrifuge tube was carefully collected, and the microbubble layer was combined after repeated centrifugation three times, and redispersed into 0.02% polyethylene glycol octylphenyl ether aqueous solution Sto...

Embodiment 2

[0029] Example 2: N-butyl acrylate, polyethylene glycol octylphenyl ether, and high-purity deionized water are fed into a 2-liter beaker at a ratio of 1:1:100, and the pH value of the reaction system is adjusted to weak acidity (about 2.5 ), stirred at a high speed (rpm=8000) at room temperature for 60 minutes, and after the reaction was terminated, the crude product was transferred to a separatory funnel and left to stand for 5 hours, the residue at the bottom was discarded, and the top layer of microbubbles was kept, and mixed with 0.02% polyethylene glycol Octylphenyl ether aqueous solution was washed three times. The obtained product was divided into centrifuge tubes, purified and centrifuged for 20 minutes, and the microbubble product layer on the top layer of the centrifuge tube was carefully collected, and the microbubble layer was combined after repeated centrifugation three times, and redispersed into 0.02% polyethylene glycol octylphenyl ether aqueous solution Stored...

Embodiment 3

[0030] Embodiment 3: N-butyl acrylate, polyethylene glycol octyl phenyl ether, and high-purity deionized water are fed into a 2-liter beaker at a ratio of 1:1:100, and the pH value of the reaction system is adjusted to weak acidity (about 2.5 ), stirred at a high speed (rpm=4000) at room temperature for 60 minutes, and after the reaction was terminated, the crude product was transferred to a separatory funnel and left to stand for 5 hours, the residue at the bottom was discarded, and the top layer of microbubbles was kept, and mixed with 0.02% polyethylene glycol Octylphenyl ether aqueous solution was washed three times. The obtained product was divided into centrifuge tubes, purified and centrifuged for 20 minutes, and the microbubble product layer on the top layer of the centrifuge tube was carefully collected, and the microbubble layer was combined after repeated centrifugation three times, and redispersed into 0.02% polyethylene glycol octylphenyl ether aqueous solution St...

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Abstract

The invention relates to a novel polyester hard-shell gas-carried microbubble system (shown in the figure), and a new preparation process for building the polyester hard-shell gas-carried microbubble system with controllable particle size. A gas core is air; a polyester shell material is poly(n-butyl acrylate); the microbubble diameter is controlled at different particle sizes of 3.03 microns, 2.43 microns and 341.4 nanometers. The preparation process comprises the steps: with a n-butyl acrylate monomer as a preparation starting material, carrying out room temperature high speed stirring for 60 minutes in a stabilizer (polyethylene glycol octylphenol ether) solution and a high-pure water reaction system, completing a reaction, then separating the liquid, standing, washing with the stabilizer solution to obtain a crude product, then carrying out low speed centrifugation and merging concentration, and redispersing into the stabilizer solution for preservation, and thus obtaining the pure polyester hard-shell gas-carried microbubble system with higher yield. The preparation process is green and mild, generates no noise, radiation and other pollutions, has simple and convenient separation and purification operations, and easily realizes industrialized production; and the microbubble system has controllable particle size, and has good biomedical application prospects.

Description

technical field [0001] The invention relates to a novel preparation process for constructing a polyester hard-shell gas-carrying microbubble system with controllable particle size. Background technique [0002] As early as 1968, gas-carrying microbubbles were known to be used as ultrasound contrast agents to improve the contrast and resolution of imaging. The difference in acoustic impedance between the gas contained in the gas-carrying microbubbles and the tissue in the body leads to the enhancement of the ultrasonic reflection ability of the gas-carrying microbubbles, and at the same time, the compressibility of the materials that make up the microbubble shell causes the nonlinear reflection of ultrasound. Based on this principle, ultrasonic As a medical contrast agent, microbubbles have become a common reagent in clinical diagnosis, which is used to improve the contrast effect of contrast and enhance the accuracy of diagnosis and treatment. Today, as people pay more and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/22C08F122/32
Inventor 刘哲
Owner 刘哲
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