A kind of ultrasonic contrast agent for HIFU and its preparation method and application

A technology of ultrasound contrast agent and diluent, which is applied in echo/ultrasound imaging agents, medical preparations containing active ingredients, and pharmaceutical formulas, etc. It can solve the problems of weakened echoes and the inability to accurately and real-time display the overall damage area, etc. Achieve enhanced cavitation effect, good imaging effect, and enhanced treatment effect

Active Publication Date: 2018-10-30
广州康臣药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] From the above, it can be seen that most of the currently developed ultrasound contrast agents belong to the category of HIFU synergists. Although these contrast agents can enhance the thermal effect and cavitation effect of focused ultrasound in HIFU treatment, the microbubbles will still dissolve gradually after a certain period of time. Blasting, the echo in this area will gradually weaken until it disappears. Due to the cavitation phenomenon, the bright spot on the B-ultrasound image cannot always exist stably. Although it can be used to monitor the focal spot area instantaneously, it cannot be displayed accurately and in real time. overall damage area

Method used

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  • A kind of ultrasonic contrast agent for HIFU and its preparation method and application
  • A kind of ultrasonic contrast agent for HIFU and its preparation method and application
  • A kind of ultrasonic contrast agent for HIFU and its preparation method and application

Examples

Experimental program
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Effect test

Embodiment 1

[0048] This embodiment provides an ultrasound contrast agent and its preparation method

[0049] (1) Ultrasonic dispersion method prepares liposome

[0050] a. Dissolved phospholipids: Weigh 2.08mg of DPPC, 0.5mg of DSPE-PEG2000 and 0.43mg of DSPG (the molar ratio of DPPC, DSPE-PEG2000 and DSPG is 80:5:15) into the test tube, and add 1mL of chloroform dissolve;

[0051] b. Removal of hydrophobic solvent: in N 2 Under the action of air flow, place the test tube on a vortex instrument to promote the evaporation of chloroform and form a film of phospholipid; vacuumize, place the test tube formed into a film in a flat-bottomed flask, connect a vacuum pump, and evacuate for about 3 to 5 hours;

[0052] c. Hydration: Add 1 mL of PBS solution into the test tube after vacuuming to hydrate the film.

[0053] d. Sonic vibration: heat the ultrasonic water bath to above 65°C, place the hydrated test tube in hot water and vibrate until the liquid is clear, and obtain a PBS solution cont...

Embodiment 2

[0063] In vitro verification of the effect of HIFU contrast agent for sealing microbubbles and real-time imaging

[0064] Put the HIFU ultrasound contrast agent prepared in Example 1 into the EP tube, seal the opening of the EP tube with a parafilm, and heat the EP tube in a water bath with a water temperature higher than 65°C for 10 minutes, which is higher than that of perfluorinated The boiling point of hexane is 59°C. Immediately use a diagnostic ultrasound probe to scan the imaging effect in the EP tube. The resulting image is as follows: Figure 2A As shown in the figure, it can be seen from the figure that the HIFU contrast agent of Example 1 responds with temperature, releases a large number of bubbles, greatly enhances the cavitation effect of focused ultrasound, and has a high echo signal; after cooling for 10 minutes, use a diagnostic ultrasound probe Scanning the imaging effect in the EP tube, the resulting image is as follows Figure 2B As shown, it can be seen f...

Embodiment 3

[0067] Example 3 Real-time imaging of HIFU contrast agent and enhancement of HIFU ablation performance in solid tissues or animals

[0068] Use tumor grafts or degassed animal livers, inject HIFU contrast agent locally, and turn on HIFU irradiation to compare the imaging effects of the simple HIFU group and the HIFU combined with contrast agent group, as well as the differences in treatment outcomes. Animal models such as mice with tumors can also be used, after tail vein injection or intratumoral injection of HIFU contrast agent, HIFU is turned on at the right time to irradiate the tumor, and the imaging effects and treatment results of the simple HIFU group and the HIFU combined with contrast agent group can be compared difference.

[0069] Experimental results show that the ultrasonic contrast agent of the present invention has real-time imaging and enhanced HIFU ablation performance in solid tissues or animals.

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Abstract

The invention provides an ultrasonic contrast agent applicable to HIFU (high intensity focused ultrasound) as well as a preparation method and application of the ultrasonic contrast agent. The ultrasonic contrast agent consists of 30-70 parts of a solution containing fluorocarbon drops by volume, 40-70 parts of egg white by volume and 10-40 parts of a thinner by volume, wherein the fluorocarbon drop consists of lipidosome and liquid fluorocarbon covered in the lipidosome. With the existence of the egg white, the ultrasonic contrast agent disclosed by the invention can coagulate at transient high temperature so as to take an effect of sealing bubbles, therefore a stable echo enhancing signal is generated in a focused target area to accurately monitor tissue injury region range in the focused area in real time; in addition, by virtue of the fluorocarbon drops, the ultrasonic contrast agent can release a great amount of bubbles in response to controllable local temperature so as to greatly enhancing a cavitation effect of focused ultrasound; and moreover, on the basis of the property of the egg white which coagulates at high temperature, the composition disclosed by the invention can also block blood vessels, so as to achieve effects such as inhibiting the reoccurrence of tumors.

Description

technical field [0001] The present invention relates to a contrast agent, in particular to an ultrasonic contrast agent for HIFU and its preparation method and application. Background technique [0002] Ultrasound imaging technology has the advantages of non-invasive, non-radiation, cheap, dynamic and real-time, diverse diagnostic parameters and flexible engineering. It has been widely used in the field of clinical medicine and has become an effective means of medical examination and imaging diagnosis of diseases. Compared with other medical imaging techniques such as CT and MRI, ordinary ultrasound images have higher noise, poorer resolution, and lower contrast. Therefore, a class of reagents that can significantly enhance medical ultrasound detection signals—ultrasound contrast agents—is introduced. Traditional ultrasound contrast agents are generally gas-encapsulated microbubbles with a diameter of 1-10 μm, which are injected into the blood. Because the acoustic impedance...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22A61K41/00A61P35/00
Inventor 肖杨严飞郑海荣张雪邓志婷唐家伟牛丽丽
Owner 广州康臣药业有限公司
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