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Magnetic molecular targeted ultrasound contrast agent microsphere and preparation method thereof

An ultrasonic contrast agent and microsphere technology, applied in the direction of echo/ultrasonic imaging agent, can solve the problems of unsatisfactory and insufficient imaging effect, and achieve the effect of less equipment investment, simple operation, and easy process amplification

Inactive Publication Date: 2010-07-21
NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Parallel-plate flow chamber experiments show that by rapidly binding the ligand--P-SLe x Mediated by the mediation of this method, the targeting microvesicles carrying dual ligands can form a stable combination with parallel plates coated with ICAM-1 antigen of human endothelial cells under high-speed flow. Ultrasonic molecular imaging of lesions in middle arteries, the imaging effect is not ideal
In addition, theoretically speaking, the targeted ultrasonic microbubbles carrying the "double ligand" did not change the axial distribution trend of the ultrasonic microbubbles, and did not increase the chance of the targeted ultrasonic microbubbles contacting the target molecules on the vascular endothelium. Therefore, the There are also obvious deficiencies in technology

Method used

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  • Magnetic molecular targeted ultrasound contrast agent microsphere and preparation method thereof
  • Magnetic molecular targeted ultrasound contrast agent microsphere and preparation method thereof
  • Magnetic molecular targeted ultrasound contrast agent microsphere and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: Effect of Shear Rate on Microsphere Yield and Particle Size

[0044] Weigh phospholipids by 0.1% by weight, weigh polyethylene glycol (PEG) by 1% by weight, 0.01% by weight PEG polymerized phospholipids, 0.045% by weight biotinylated PEG polymerized phospholipids, and weigh 0.01% by weight phospholipid magnetic beads, Weigh the mixture of poloxamer at 0.03% by weight, add it to the water medium (distilled water) and mix it well under the condition of 50-80°C, inject perfluoropropane gas, and insert the dispersing cutter head of the high-speed liquid shearer into the liquid Next, the solution was subjected to high-speed shear dispersion at different rotational speeds, and the concentration and particle size data of the prepared microspheres are shown in Table 1.

[0045] Table 1 Effect of shear rate on microsphere concentration and particle size

[0046] Speed(r / min)

[0047] It can be seen from Table 1 that as the rotational speed of the dispersing...

Embodiment 2

[0048] Example 2: Effect of Adding Avidin and Biotinylated Monoclonal Antibody on Microsphere Size and Concentration

[0049] Weigh phospholipids by 0.1% by weight, weigh polyethylene glycol (PEG) by 1% by weight, 0.01% by weight PEG polymerized phospholipids, 0.045% by weight biotinylated PEG polymerized phospholipids, and weigh 0.01% by weight phospholipid magnetic beads, Weigh the mixture of poloxamer at 0.03% by weight, add it to the water medium (distilled water) and mix it well under the condition of 50-80°C, inject perfluoropropane gas, and insert the dispersing cutter head of the high-speed liquid shearer into the liquid Carry out high-speed shear dispersion (24000r / min) under the surface, make milky white contrast agent microsphere suspension liquid and pack in ampoule, observe under sampling microscope ( figure 1 A), use a Coulter counter to measure the concentration and particle size of the microspheres; after standing for 24 hours, discard the supernatant and add a...

Embodiment 3

[0053] Example 3: In vitro pressure resistance of ultrasound contrast agent microspheres of the present invention

[0054] Weigh phospholipids by 0.1% by weight, weigh polyethylene glycol (PEG) by 1% by weight, 0.01% by weight PEG polymerized phospholipids, 0.045% by weight biotinylated PEG polymerized phospholipids, and weigh 0.01% by weight phospholipid magnetic beads, Weigh the mixture of poloxamer at 0.03% by weight, add it to the water medium (distilled water) and mix it well under the condition of 50-80°C, inject perfluoropropane gas, and insert the dispersing cutter head of the high-speed liquid shearer into the liquid Perform high-speed shear dispersion (24000r / min) under the surface to prepare milky white contrast agent microsphere suspension and distribute it in ampoules; after standing for 24 hours, discard the supernatant and add an equal amount of distilled water to wash to remove unbound lipids 1. Purify 3 times to prepare biotin lipid microbubbles, add 0.005% by...

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Abstract

The invention relates to a novel magnetic molecular targeted ultrasound contrast agent, in particular to a gas-wrapped magnetic liposome microsphere suspension with the mean diameter of 1-4 micrometers and a preparation method thereof. The preparation method of the magnetic molecular targeted ultrasound contrast agent microsphere comprises a condition that a lipid layer of the microsphere and / or the surface of the lipid layer contains (or connects) magnetic response materials. A contrast agent microsphere wall material contains phospholipids, polyethylene glycol (PEG), PEG phospholipid polymers, biotinylated and / or polypeptide modificatory PEG phospholipid polymer, poloxamer, ligands (monoclonal antibodies or polypeptide, and the like) and the magnetic response materials and / or avidin bridging materials, wherein the ligand (monoclonal antibodies or polypeptide, and the like) has specific affinity to target molecules, the wrapped gas is a fluorine carbon gas, and a solvent is an aqueous medium (distilled water). The invention also provides the preparation method of the magnetic molecular targeted ultrasound contrast agent microsphere, which comprises a condition that the specific ligand is connected with the microsphere in a covalence and avidin bridging way. The novel magnetic molecular targeted ultrasound contrast agent has good targeted developing effect, can be used for evaluating the change of vessel endothelial molecules of an arterious and venous system of an organic tissue and has good application prospect in treatment.

Description

field of invention [0001] The present invention relates to a novel molecular targeting ultrasound contrast agent with magnetic properties, that is, liposome microspheres with magnetic properties encapsulating fluorocarbon insoluble gases, and the surface of the microspheres is equipped with ligands with specific affinity for target molecules. And relate to its composition and preparation method. The magnetically targeted ultrasound contrast agent includes: the case where a magnetic response material is attached to the lipid layer of the contrast agent microsphere and / or on the surface of the lipid layer of the contrast agent microsphere. Background of the invention [0002] Long before the obvious clinical manifestations of many important diseases, there are obvious pathophysiological changes at the cellular and molecular levels, and they run through the whole process of the disease. Therefore, evaluating the pathological imaging features of various diseased tissues and org...

Claims

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Application Information

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IPC IPC(8): A61K49/22
Inventor 宾建平吴爵非杨莉廖禹林刘伊丽侯连兵李贵平查道刚廖旺军高方王月刚蔡晶晶
Owner NANFANG HOSPITAL OF SOUTHERN MEDICAL UNIV
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