A preparation method of lymphatic targeting ultrasound contrast agent

A technology of ultrasound contrast agent and lymphatic targeting, applied in the direction of echo/ultrasound imaging agent, etc., can solve the problems of weak combination, small dosage, long residence time, etc., to improve diagnostic accuracy and efficiency, technical preparation method Simple, biocompatible results

Active Publication Date: 2017-10-27
SHANGHAI NAT ENG RES CENT FORNANOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the resolution and clarity of ultrasound diagnosis itself is low, and gas has a great influence on ultrasound, so the role of targeted contrast-enhanced ultrasound in disease diagnosis is getting more and more attention
Targeted ultrasound contrast agents can be combined with specific ligands in the body, and can be targeted and accumulated on specific target tissue cells through blood circulation, so that target tissues can be specifically marked and enhanced in ultrasound images. Ideal targeted ultrasound contrast agents Need to meet the following requirements (Lanza G M, Wickline S A. Targeted ultrasonic contrast agents formolecular imaging and therapy[J]. Progress in cardiovascular diseases, 2001,44(1): 13-31.): 450-700nm in diameter, able to flow through Target area; long circulation half-life, and long residence time in the target area; can selectively and sensitively bind to the surface antigenic determinant of the area of ​​interest; the contrast agent should be firmly bound to the target site and the contrast agent should be bound to the target site The agent should remain stable during the ultrasound examination; the dosage should be small, preferably in milligrams or less; the toxicity is small; it has the potential to carry therapeutic drugs or genes It is prepared by combining with the surface of microbubbles. The specific methods include electrostatic adsorption and covalent binding. The electrostatic adsorption method uses the chemical and charge characteristics of the contrast agent shell itself to adsorb antibodies or ligands on the surface of microbubble contrast agents, The combination is not firm and reliable. The ideal way should be to link specific antibodies or ligands on the surface of microbubble contrast agents by covalent binding.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] a. Add 20 parts by mass of surfactant to 10 parts of alkaline solution, stir at 30°C for 5 minutes, after the surfactant is completely dissolved, add 100 parts of silicon source into the solution, continue After stirring at 30°C for 5 minutes, a sol mixture was formed, then stirred at 30°C for 6 hours, washed with alcohol and deionized water at 5000 rpm, and then dried in an oven at 60°C for 20 hours to obtain a powder product;

[0030] b. After firing the powder obtained in the above a at 500° C. for 4 hours, a powdered nanoporous material from which the surfactant has been removed is obtained;

[0031] c. Disperse 50 parts by mass of nanoparticles obtained in b above in 500 parts of organic solvent, add 10 parts of silane coupling agent, stir at 30°C for 6 hours, wash with ethanol three times and use Washed twice with deionized water, and centrifuged at 6000 rpm, then dried in an oven at 60°C for 20 hours to obtain a powder product;

[0032] d. Disperse 100 parts by...

Embodiment 2

[0035] a. Add 25 parts by mass of surfactant to 15 parts of alkaline solution and stir at 30°C for 8 minutes. After the surfactant is completely dissolved, add 150 parts of silicon source into the solution and continue After stirring at 30°C for 10 minutes, a sol mixture was formed, then stirred at 40°C for 7 hours, washed with alcohol and deionized water at 6500 rpm, and then dried in an oven at 65°C for 24 hours to obtain a powder product;

[0036] b. After the powder obtained in above a is roasted at 550° C. for 6 hours, a powdered nanoporous material from which the surfactant has been removed is obtained;

[0037] c. Disperse 60 parts by mass of nanoparticles obtained in b above in 700 parts of organic solvent, add 20 parts of silane coupling agent, stir at 30°C for 7 hours, wash with ethanol three times and use Washed twice with deionized water, and centrifuged at 6500 rpm, then dried in an oven at 75°C for 25 hours to obtain a powder product;

[0038] d. Disperse 100 p...

Embodiment 3

[0041] a. Add 25 parts by mass of surfactant to 20 parts of alkaline solution, stir at 40°C for 10 minutes, after the surfactant is completely dissolved, add 200 parts of silicon source to the solution, continue After stirring at 40°C for 15 minutes, a sol mixture was formed, then stirred at 40°C for 6 hours, washed with alcohol and deionized water at 6000 rpm, and then dried in an oven at 80°C for 20 hours to obtain a powder product;

[0042] b. After the powder obtained in above a is roasted at 550° C. for 6 hours, a powdered nanoporous material from which the surfactant has been removed is obtained;

[0043] c. Disperse 100 parts by mass of nanoparticles obtained in b above in 500 parts of organic solvent, add 20 parts of silane coupling agent, stir at 30°C for 6 hours, wash with ethanol three times and use Washed twice with deionized water, and centrifuged at 6000 rpm, then dried in an oven at 70°C for 30 hours to obtain a powder product;

[0044] d. Disperse 100 parts b...

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PUM

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Abstract

The invention discloses a preparation method of a lymphatic-targeted ultrasound contrast agent. The surfactant is added to an alkaline solution, stirred, and after being completely dissolved, a silicon source is added to the above solution, and the stirring is continued, and then a sol mixture is formed. After stirring, washing, centrifuging, and drying, the powdery product is obtained; after the product is calcined at a high temperature, the powdery nanoporous material that removes the surfactant is obtained; the powdery porous material is dispersed in an organic solvent, and a silane coupling agent is added. After stirring, wash with ethanol and water, and centrifugally dry to obtain a powder product; disperse the powder in deionized water, add a crosslinking agent and sodium hyaluronate, stir, wash with water, and centrifugally dry to obtain nanoparticles; Disperse the particles in deionized water, add fluorocarbon compound dropwise, stir, wash and dry with ion water, and obtain the lymphatic-targeted ultrasound contrast agent. The invention can realize the integration of lymphatic targeting function and contrast-enhanced ultrasound.

Description

technical field [0001] The invention relates to the field of preparation of nanomaterials, in particular to a preparation method of a lymphatic targeting ultrasound contrast agent. Background technique [0002] Modern medical imaging has gradually developed from traditional anatomical structure imaging to the era of functional imaging and molecular imaging. Traditional molecular imaging techniques include MRI SPECT / PET optical imaging and ultrasonic molecular imaging. Combine ultrasound contrast agents with specific ligands in vivo, and observe the imaging of target tissues at the tissue cell and subcellular levels, so as to reflect the molecular changes of diseased tissues in vivo (Lanza G M, Wickline SA. Targeted ultrasound contrast agents for molecular imaging and therapy [J]. Progress in cardiovascular diseases, 2001, 44(1): 13-31). With the development of medical engineering and computer technology, medical imaging provides medical images of various modalities for clin...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22
Inventor 何丹农朱君刘恬姚燕杰周涓
Owner SHANGHAI NAT ENG RES CENT FORNANOTECH
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