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Ultrasonic contrast agent loaded with therapeutic drug and preparation method thereof

A technology of ultrasound contrast agents and therapeutic drugs, which is applied in echo/ultrasound imaging agents, drug combinations, and pharmaceutical formulations, etc. It can solve problems such as side effects of ultrasound therapy, large ultrasound doses, and hemolysis in the heart chamber, and reduce side effects on the human body. Ensure safe use and avoid side effects

Active Publication Date: 2018-01-19
河北艾圣科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

With the gradual and in-depth research on therapeutic microbubble ultrasound contrast agents, it is found that the wall thickness of multi-layer phospholipids or single-layer long-chain phospholipids leads to excessive ultrasound dose required for ultrasonic cavitation, and cells and tissues are damaged by transient cavitation. The risk of biological damage is high. High-intensity pressure waves can cause cell damage, rupture, and DNA fragmentation, as well as blood hemolysis, tissue damage, and bleeding. It has been reported that the combination of microbubble contrast agents and ultrasound Sometimes it can cause intracardiac hemolysis, bring serious side effects to ultrasound therapy, and limit the development of ultrasound therapy technology

Method used

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  • Ultrasonic contrast agent loaded with therapeutic drug and preparation method thereof
  • Ultrasonic contrast agent loaded with therapeutic drug and preparation method thereof
  • Ultrasonic contrast agent loaded with therapeutic drug and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] This embodiment relates to a group of ultrasound contrast agents loaded with therapeutic drugs, and the raw material components of the contrast agents are shown in the following table:

[0042]

[0043]

[0044]

[0045] The raw material components in the above table are prepared according to the following steps:

[0046] a. Preparation of targeted polymerized phospholipids: four-arm or multi-arm-N-hydroxysuccinimide succinate-based polyethylene glycol, and polypeptide, dipalmitoylphosphatidylethanolamine, or four-arm or multi-arm Arm-N-hydroxysuccinimide succinate-based polyethylene glycol, polypeptide, distearoyl phosphatidylethanolamine, physically mixed evenly, using disodium bicarbonate and sodium dihydrogen carbonate to adjust the mixed solution to The alkaline condition of pH 8.0~10.0 makes the electrophilic group-NHS of PEG derivatives, and the nucleophilic group-NH 2 , to carry out covalent binding to obtain polymerized phospholipids containing ligand...

Embodiment 2

[0056] This example relates to the influence of factors such as the selection of film-forming phospholipid raw materials and contrast agent preparation conditions on the performance of the ultrasound contrast agent of the present invention.

Embodiment 21

[0058] This embodiment involves the influence of film-forming phospholipid raw materials on the ultrasonic cavitation frequency performance of the obtained ultrasonic contrast agent. Different film-forming phospholipid raw materials are used, and other raw materials and preparation conditions are the same for comparison. The results are shown in the following table:

[0059]

[0060] It can be seen from the results in the above table that the film-forming phospholipid selected in the present invention can significantly reduce the ultrasonic cavitation frequency of the ultrasonic contrast agent, which is beneficial to the safety of use.

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Abstract

The invention discloses an ultrasonic contrast agent loaded with a therapeutic drug and a preparation method thereof. The ultrasonic contrast agent contains the following raw material components: membrane formation phospholipid formed by compounding of phospholipid with carbon chain number of 20-22 and phospholipid with carbon chain number of 16-18, four-arm or multi-arm N-hydroxy succinimide succinate-base polyethylene glycol, polypeptide, double-arm or multi-arm carboxyl-N-hydroxy succinimide succinate-base polyethylene glycol, dipalmitoyl phosphoethanolamine or 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine, a stabilizing agent, drugs and fluorine-containing inert gas. According to the ultrasonic contrast agent, the side effect of the cavitation effect to a human body is reduced,and the use safety is guaranteed; the personalized drug loading capacity, the multifunctional targeted drug delivery, and the slow release effect of targeted part drugs can be realized; the ultrasoniccontrast agent also has the advantages of use comfort, safety, good microvesicle dispersion, denseness, and good radiography and treatment effect. The ultrasonic contrast agent is used for carrying out targeted radiography, drug treatment and cavitation treatment on solid tumors and breaks through the bottle neck problem of tumor treatment.

Description

technical field [0001] The invention relates to the technical field of ultrasound contrast agents, in particular to an ultrasound contrast agent loaded with therapeutic drugs and a preparation method of the ultrasound contrast agent. Background technique [0002] Ultrasound contrast agent, referred to as UCA, is a kind of chemical preparation that can significantly enhance the intensity of ultrasonic backscattering. Improve the ability of ultrasound to distinguish the shape and type of lesions, enhance the sensitivity and specificity of ultrasound diagnosis, and enable ultrasound diagnosis technology to obtain extensive research and clinical applications in tissue perfusion of various organs, inflammation detection and tumor detection. In recent years, the application of ultrasound contrast agents in the field of ultrasound therapy has become a research hotspot. [0003] Microbubbles in tissues and body fluids under ultrasonic irradiation will undergo cavitation effect. Th...

Claims

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Application Information

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IPC IPC(8): A61K49/22A61K47/60A61K47/64A61K31/704A61K31/4745A61K33/24A61K31/555A61P35/00
Inventor 袁哲史静宏陶秀梅尚丽霞冷鸿飞徐小雨刘培岩
Owner 河北艾圣科技有限公司