Lipid targeted ultrasound contrast agent and preparation method thereof

A contrast agent and targeting technology, applied in the direction of echo/ultrasound imaging agent, etc., can solve the problems of poor stability of targeted ultrasound contrast agents, the influence of changes in the physical properties of the solution, and limited selection of multifunctional reagents, etc., to achieve the target The effect of high probe binding rate, less preparation raw materials and suitable size

Active Publication Date: 2010-02-03
王维 +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The disadvantage is that the prepared targeted ultrasound contrast agent is not stable and is easily affected by changes in the physical properties of the solution. Some studies have shown that the targeting

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1: The influence of the power and time of probe ultrasound on the preparation of microbubbles:

[0037] Fully suspend 40mg DSPC, 4mgDPPA, 5mg poloxamer in 5ml double distilled water at 40-50℃ to make suspension A; then dissolve 5mg FITC-KGDS-Palm (palmitic acid with fluorescent peptide) Dissolve completely in 200 μl of absolute ethanol at 40°C to make Solution B; Suspension A is sonicated in a probe ultrasonic instrument (work for 3 seconds, pause for 3 seconds, power 30%, 3 minutes), ultrasonic The number of times is once or twice, and the solution B is added dropwise during the ultrasonic process, and the clarity of the obtained solution is observed. The results are shown in the table below.

[0038]

[0039] The clarity of solution C directly affects the concentration and particle size of the prepared microbubbles. The clearer the solution, the higher the degree of molecular dispersion of the lipid components in the solution, the more uniform the part...

Embodiment 2

[0041] Fully suspend 40mg DSPC, 4mgDPPA, 5mg poloxamer in 5ml double distilled water at 40-50°C to make suspension A; then dissolve 8mg FITC-KGDS-Palm in 250μl absolute ethanol, at 60°C Dissolve completely under the condition, make solution B; Suspension A carries out sonication in probe sonicator (work 3 seconds, pause 3 seconds, power 30%, 3 minutes), ultrasonic frequency is once or twice, in ultrasonic process Solution B was added dropwise to the solution, and the obtained solution was observed to be clear.

[0042] The probe polypeptide is KGDS or RGDS, designed and synthesized by 9-fluorenylmethoxycarbonyl (fluorenylmethoxycarbony, Fmoc) solid-phase synthesis method, directly linked to the peptide ligand palmitic acid, purified by high performance liquid chromatography, with a purity > 95%, and identified by mass spectrometry The molecular structure is correct, and the binding ratio of the probe polypeptide to palmitic acid is 1mol:1mol. The probe polypeptide synthesis a...

Embodiment 3

[0043] Embodiment 3: the impact of high shear rate on microbubble yield and particle size:

[0044] Add 5 mg of PEG-4000 into the clear liquid C prepared in Examples 1 and 2, and dissolve completely; pass through perfluoropropane gas to fully saturate the clear liquid C, and at the same time, process the solution C at different shear rates and different shear times, The prepared microbubble suspension particle size and concentration are as follows:

[0045]

[0046] The palmitic acid content of the binding polypeptide in Example 1 is 0.1% by weight of the contrast agent, the content of synthetic phospholipids is 0.9% by weight of the contrast agent, the content of PEG-4000 is 0.1% by weight of the contrast agent, and the content of poloxamer is 0.1% by weight of the contrast agent. 0.1% by weight.

[0047] The palmitic acid content of the binding polypeptide in Example 2 is 0.16% by weight of the contrast agent, the content of synthetic phospholipids is 0.9% by weight of t...

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Abstract

The invention relates to a lipid targeted ultrasound contrast agent and a preparation method thereof. The preparation method of the contrast agent comprises the following steps: adding synthetic phospholipids and poloxamer to deionized double distilled water and uniformly mixing the mixed liquid to prepare a mixed suspension A; adding palmitic acid which combines probe polypeptide to absolute alcohol which is an organic solvent to dissolve the palmitic acid so as to prepare a solution B; ultrasonically treating the mixed suspension A, meanwhile, dropping the solution B into the mixed suspension A, and uniformly mixing the mixed suspension A and the solution B to obtain a settled solution C; adding PEG-4000 to the settled solution C to dissolve the PEG-4000; introducing perfluoropropane gasinto the settled solution C, and at the same time of sufficient saturation, applying high-speed mechanical shearing equipment to process the settled solution C to form a microvesicle mixed suspensionwith an average grain diameter of 1-4 micrometers. Prepared ultrasound microvesicles have proper size, uniform and stable grain diameter distribution, proper concentration and high targeted probe binding rate; and reagent materials used for connecting ligands except preparation raw materials of the contrast agent do not need to be added. The invention has simple preparation method, small interference to the characteristics of the microvesicles and is beneficial to purify the targeted contrast agent.

Description

technical field [0001] The invention relates to a targeted ultrasound contrast agent using synthetic phospholipids, palmitic acid with probes and the like as membrane materials and a preparation method thereof. Background technique [0002] As the third revolution in the development of ultrasonic medicine, contrast-enhanced ultrasonography is widely and profoundly affecting the application and development of ultrasonic medicine, and has played a revolutionary role in the diagnosis of space-occupying lesions. The use of ultrasound contrast agents greatly increases the diagnostic confidence of doctors and improves the level of clinical ultrasound diagnosis. Play an important role in improving the accuracy of patient diagnosis. Ultrasound contrast agent is a kind of micro-bubbles in the blood pool, the particle size is slightly smaller than that of red blood cells, about 10um, and the gas is wrapped in it. Using the strong reflection mechanism of gas to ultrasound, it can obse...

Claims

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Application Information

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IPC IPC(8): A61K49/22
Inventor 王维高峰丁燕飞盛小茜罗卓琼
Owner 王维
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