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Multifunctional targeted ultrasound contrast agent and preparation method thereof

An ultrasound contrast agent, a multi-functional technology, used in the fields of biotechnology and medicine to prevent tumor metastasis, enhance target-seeking ability, and improve accuracy

Active Publication Date: 2019-10-15
THE SECOND XIANGYA HOSPITAL OF CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the anti-human VEGFR-3 monoclonal antibody only has a targeting effect. How to combine the ultrasonography imaging and intraoperative indication functions to achieve labeling of tumors and tracking of lymphatic metastasis pathways is an urgent problem in this technical field.

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  • Multifunctional targeted ultrasound contrast agent and preparation method thereof
  • Multifunctional targeted ultrasound contrast agent and preparation method thereof
  • Multifunctional targeted ultrasound contrast agent and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] A multifunctional targeted ultrasound contrast agent of the present invention, the preparation method of the multifunctional targeted ultrasound contrast agent comprises the following steps:

[0050] (1) Dissolving the organic phase: first dissolve 0.5g of carboxyl-terminated polylactic acid (PLGA—COOH, the polymerization ratio of carboxyl and hydroxyl groups is 50:50) in 10mL of dichloromethane, then add 20mg of Sudan Black, and stir fully until Completely dissolved to obtain a mixed solution;

[0051] (2) Emulsification: Add 1 mL of ammonium carbonate solution with a mass concentration of 4% to the mixed solution obtained after the step (1), use a power of 110W to perform ultrasonic emulsification for 30 seconds to obtain the primary emulsion, add 50 mL of mass concentration The polyvinyl alcohol solution with a concentration of 4% is homogenized for 5 minutes with a homogenizer at a speed of 9000 rpm to obtain a double emulsion;

[0052] (3) Volatile organic phase: ...

Embodiment 2

[0071] A kind of multifunctional targeting ultrasound contrast agent of the present invention, its preparation steps are as follows:

[0072] (1) Dissolving the organic phase: first dissolve 0.5g of carboxyl-terminated polylactic acid (PLGA—COOH, the polymerization ratio of carboxyl and hydroxyl groups is 50:50) in 10mL of dichloromethane, then add 20mg of Sudan Black, and stir fully until Completely dissolved to obtain a mixed solution;

[0073] (2) Emulsification: Adding 1mL of mass concentration to the mixed solution obtained after the step (1) is 4% ammonium carbonate solution, and using a power of 110W to perform ultrasonic emulsification for 40s to obtain primary emulsion, add 50mL of mass concentration The polyvinyl alcohol solution with a concentration of 4% is homogenized for 5 minutes with a homogenizer at a speed of 9000 rpm to obtain a double emulsion;

[0074] (3) Volatile organic phase: adding 100 mL of mass concentration to the double emulsion obtained after th...

Embodiment 3

[0081] A kind of multifunctional targeting ultrasound contrast agent of the present invention, its preparation steps are as follows:

[0082] (1) Dissolving the organic phase: first dissolve 100 mg of carboxyl-terminated polylactic acid (PLGA—COOH, the polymerization ratio of carboxyl and hydroxyl groups is 50:50) in 2 mL of dichloromethane, then add 4 mg of Sudan Black, and stir until it is completely Dissolved to obtain a mixed solution;

[0083] (2) Emulsification: Add 200uL mass concentration to the mixed solution obtained after the step (1) and be 4% ammonium carbonate solution, use a power of 110W to perform ultrasonic emulsification for 30s to obtain the primary emulsion, add 10mL mass concentration The polyvinyl alcohol solution with a concentration of 4% is homogenized for 5 minutes with a homogenizer at a speed of 9000 rpm to obtain a double emulsion;

[0084] (3) Volatile organic phase: adding 20 mL of mass concentration to the double emulsion obtained after the st...

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Abstract

The invention discloses a multifunctional targeted ultrasound contrast agent. The contrast agent comprises carboxyl-terminated polylactic acid, wherein the carboxyl-terminated polylactic acid is filled with fluorocarbon gas to form carboxyl-terminated polylactic acid microspheres, the carboxyl-terminated polylactic acid loads Sudan black dye, and the carboxyl terminal of the carboxyl-terminated polylactic acid is coupled with an anti-human VEGFR-3 monoclonal antibody through a covalent bond. The contrast agent can more accurately and effectively perform positioning and be firmly combined on the surface of lymphatic endothelial cells, not only has strong target searching capability, but also has ultrasonic contrast imaging and intraoperative indication function, also has the function of preventing tumor metastasis, and is a multifunctional ultrasonic contrast agent with both blue staining trace effect and ultrasonic imaging effect and treatment. The invention also discloses a preparation method of the contrast agent, and the method utilizes a double emulsification method to prepare the ultrasonic contrast agent with the blue staining indication function, and uses EDC / NHS as a coupling activator, and covalently connects VEGFR-3 on the surface of the ultrasonic contrast agent. The method is simple and easy to operate, and is suitable for large-scale production.

Description

technical field [0001] The invention belongs to the technical fields of biotechnology and medicine, and in particular relates to a multifunctional targeted ultrasound contrast agent and a preparation method thereof. Background technique [0002] In clinical practice, two methods are usually used to find tumor sentinel lymph nodes: one method is radionuclide tracer method, such as dextran and plasma proteins labeled with radioactive isotope technetium 99m, which can be detected in the human body. Detected by radioactive detectors; another method is reactive blue dye tracing method, such as methylene blue, isosulfan blue, etc., which can stain lymph nodes blue, so that they can be found during surgery. Although these two methods are still used clinically, there are still many shortcomings, such as strong radiation, low spatial resolution of images detected by radioactive detectors, and inability to accurately locate surgical operations. Molecular substances, therefore inevita...

Claims

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Application Information

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IPC IPC(8): A61K49/22
CPCA61K49/221A61K49/225
Inventor 牛诚诚汪龙裴文婧
Owner THE SECOND XIANGYA HOSPITAL OF CENT SOUTH UNIV
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