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A kind of preparation method of ultrasound contrast agent

An ultrasound contrast agent and a technology for preparation steps, which are used in echo/ultrasound imaging agents, preparations for in vivo experiments, pharmaceutical formulations, etc., can solve problems such as failure to pass through the pulmonary circulation smoothly, the size of microbubbles is not uniform, and the residence time is short, etc. problem, to achieve the effect of long development time, moderate coating and long residence time

Inactive Publication Date: 2018-05-18
李彬
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The technical problem to be solved by the present invention: due to the thicker coating and poor elasticity of the current ultrasound contrast agent, and the wrapped air is easily soluble in water, etc., the residence time in the blood circulation is short, the size of the microbubbles is not uniform, and it is easy to rupture, causing it to fail to pass through the lung circulation smoothly, and effectively enhance the disadvantages of short developing time and poor imaging effect. It provides a chicken blood and fat as raw materials. After the chicken blood is repeatedly frozen and dissolved, it is mixed with saline and phosphate buffer The salt solution is mixed and centrifuged and purified to obtain chicken blood extract; then fat is selected and added to lipase enzymolysis, and centrifuged to obtain supernatant, which is concentrated and mixed with sodium nitrate to obtain glycerol, which is mixed with chicken blood extract, ammonium sulfate and The method of mixing phosphate buffered saline, then mixing with phosphate buffered saline, ultrasonically dispersing, and centrifuging to prepare an ultrasonic contrast agent

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

[0019] First collect fresh chicken blood and freeze it at -15°C for 2 hours. After the freezing is complete, put it at 25°C to thaw naturally. time, to obtain pretreated chicken blood; then according to the volume ratio of salt water and container 1:3, the mass fraction of 0.75% saline is loaded into the container, and the above pretreated chicken blood is added at the same time, and the addition amount is 1 to the mass ratio of saline : 2, let it stand for 1h, then place it in a refrigerated centrifuge, and centrifuge for 10min at a temperature of 3°C at a speed of 4000r / min to obtain a supernatant; :20, the concentration of 0.01mol / L phosphate buffered saline was added dropwise to the above-mentioned supernatant at a rate of 2 drops / s, stirred to make it fully mixed, left to stand at 3°C ​​for 1h, and then Centrifuge at a temperature of 3°C and a speed of 4000r / min for 15 minutes, collect the lower sediment, purify it by ion exchange chromatography, and obtain chicken blood ...

example 2

[0022]First collect fresh chicken blood, freeze at -18°C for 2.5 hours, after freezing, thaw naturally at 28°C, and freeze at -18°C for 2.5 hours after it is completely thawed. Circulate 4 times to get pretreated chicken blood; then put saline with a mass fraction of 0.83% into the container according to the volume ratio of saline to container 1:3, and add the above pretreated chicken blood at the same time, the ratio of the amount added to the mass of saline 1:2, let stand for 1.5h, then place it in a refrigerated centrifuge, centrifuge at a temperature of 6°C and a speed of 4000r / min for 13min to obtain a supernatant; then press phosphate buffered saline and supernatant The volume ratio is 1:20, and the phosphate buffered saline solution with a concentration of 0.01mol / L is added dropwise to the supernatant obtained above at a rate of 3 drops / s, stirred to make it fully mixed, and then allowed to stand at 4°C for 1.5 h, then centrifuge at a temperature of 6°C and a rotationa...

example 3

[0025] First collect fresh chicken blood and freeze it at -20°C for 3 hours. After the freezing is complete, put it at 32°C to thaw naturally. time, to obtain pretreated chicken blood; then according to the volume ratio of salt water and container 1:3, the mass fraction of 0.9% saline is packed into the container, and the above pretreated chicken blood is added at the same time, and the addition amount is 1 to the mass ratio of saline : 2, let it stand for 2h, then place it in a refrigerated centrifuge, and at a temperature of 9°C, the rotating speed is 4000r / min for centrifugal 15min to obtain the supernatant; :20, the concentration is 0.01mol / L the phosphate buffered saline solution is added dropwise in the supernatant liquid of above-mentioned gain with the speed of 3 drops / s, after stirring to make it fully mix, stand at 5 ℃ for 2h, then in Centrifuge at 9°C and rotate at 4000r / min for 25min, collect the lower sediment, purify it by ion exchange chromatography, and obtain ...

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PUM

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Abstract

The invention discloses a preparation method of an ultrasonic contrast agent, and belongs to the technical field of preparation of ultrasonic contrast agents. The preparation method adopting chicken blood and fat as raw materials comprises the following steps: repeatedly refrigerating and dissolving chicken blood, mixing the dissolved chicken blood with brine, carrying out standing centrifuge to obtain a supernatant, adding a phosphate buffered saline, mixing above materials, centrifuging the obtained mixture, collecting a lower layer precipitate, and purifying the collected precipitate to obtain a chicken blood extract product; selecting fat, adding lipase, carrying out enzymatic hydrolysis, centrifuging the obtained material to obtain a supernatant, mixing the supernatant, mixing the supernatant concentrate with sodium nitrate, distilling the obtained mixture, collecting the fraction glycerol, mixing glycerol with the chicken blood extract, ammonia sulfate and the phosphate buffered saline, centrifuging the obtained mixture to obtain a precipitate, washing the precipitate, mixing the washed precipitate with the phosphate buffered saline, carrying out ultrasonic dispersion treatment, and centrifuging the obtained solution to prepare the ultrasonic contrast agent. The above product has the advantages of moderate coating, good elasticity, long retention time in blood circulation, uniform dimension and difficult rupture of microbubbles, smooth passing of lung circulation in use, effective prolongation of the development time, and good imaging effect.

Description

technical field [0001] The invention relates to a method for preparing an ultrasonic contrast agent, belonging to the technical field of ultrasonic contrast agent preparation. Background technique [0002] Ultrasound contrast agent, referred to as UCA, is a class of chemical preparations that can significantly enhance the intensity of ultrasound backscattering. Its main component is microbubbles, generally 2-10um in diameter, which can pass through the pulmonary circulation. The earliest ultrasound contrast agents are microbubbles containing carbon dioxide, oxygen or air, which are mainly obtained by vibrating normal saline by hand and can only be used for imaging of the right heart system. It is a diagnostic reagent for improving medical ultrasound echo signals by improving the acoustic contrast between the target tissue and its surrounding tissue. Usually, the contrast agent is injected into the circulatory system of the body through the peripheral vein, and enters vario...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22
CPCA61K49/222
Inventor 李彬张士波刘继宽
Owner 李彬
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