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Phase-change multi-modal nano contrast agent for targeted therapy of vulnerable plaques

A nano-contrast agent and vulnerable plaque technology, applied in the field of medicine and diagnosis, can solve the problems of limited drug loading, drug inactivation, and poor thrombolytic effect

Pending Publication Date: 2021-04-16
THE SECOND AFFILIATED HOSPITAL OF CHONGQING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Solve the problem of poor thrombolytic effect caused by drug-loaded nanoparticles in the prior art due to limited drug load or drug inactivation
However, the inventors found that if the treatment conditions and mechanism of the phase-change thrombolytic nanoparticle thrombolysis are used for plaque treatment, it is easy to cause plaque rupture, cause vascular embolism, and aggravate the progression of the disease.

Method used

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  • Phase-change multi-modal nano contrast agent for targeted therapy of vulnerable plaques
  • Phase-change multi-modal nano contrast agent for targeted therapy of vulnerable plaques
  • Phase-change multi-modal nano contrast agent for targeted therapy of vulnerable plaques

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057]Example 1 Preparation of Ultrasonic Phase Variable Duquel Tubs

[0058]Add 50mg PLGA-PEG-PLGA to 2 ml of dichloromethane, add 100 μl of Fe3O4The solution (concentration is 25 mg / ml, the particle size is 10 nm) until completely dissolved. Then, 200 μL of PFH was added as an inner water phase, using an ultrasonic oscillator (VCY-500, Yysonics Co., Ltd.) with 130W power emulsified for 3 minutes, poured into the outer water phase, the external water phase 3 ml 4% PVA solution and 3 ml 2% CS solution (CS is dissolved in a 3% acetic acid solution), and acoustic emulsification for 5 minutes, a brown solution was formed, and a 2% (volume concentration) isopropyl alcohol solution was added, and stirred continuously 3 hours, until the surface of Fe-PFH-P / CS non-targeted nanoparticles and the organic solvent was completely volatilized. Under the ice rocking bar, DS (10 mg) was added to Fe-PFH-P / CS dispersion, and Fe-PFH-P / CS-DS targeted nanoparticles was prepared by electrostatic ab...

Embodiment 2

[0063]Example 2 In vitro experiment

[0064]Nanoparticle ultrasound imaging:

[0065]Fe-P / CS-DS and Fe-PFH-P / CS-DS nanoparticles (5 mg / ml) were placed in a gel mold and used LiFu Instruments (Hafu Medical Technology Co., Ltd., Chongqing, China) at 2.5W. / cm2Separation of acoustic power is continuously irradiated for 20 minutes. Type B and contrast enhanced ultrasound (CEUS) images at different points in time (0, 2, 5, 10, and 20 minutes), and obtain nanoparticles ultrasound imaging,Figure 5 . The average sound intensity of the ultrasound image is calculated using a sound strength quantitative analysis software (the ultrasound imaging research institute, Chongqing Medical University, Chongqing) to obtain a quantitative quantitative map of nanoparticles.Figure 6 The region of interest (ROI) is 100 pixels. At the same time, the related optical microscope images (Leica DMI1, Leica Co., Ltd., TD, Heidelberg, Germany) were collected at 0, 2, 5, 10, and 20 minutes, and the nanoparticles w...

Embodiment 3

[0080]Example 3 Animal Experiment

[0081]Plaque model establishment and targeting assessment:

[0082]Establish APOE - / - mice aortic flavue model by high fat feeding. In order to verify the targeting effect of Fe-PFH-P / CS-DS nanoparticles in the exile plaque, normal C57 mice were selected as a control group, and APOE - / - model mice were used as an experimental group. Non-targeted nanoparticles (Fe-PFH-P / Cs) and Targeted nanoparticles (Fe-PFH-P / CS-DS) C57 mouse aorta and APOE - / - mouse aorta 4 hours, the iron-containing nanoparticles in Macrophages were locked with Pusher blue. Immunofluorescence staining detects macrophages. SeeFigure 21 .Figure 21 A shows a large number of Fe-PFH-P / CS-DS-containing FE-PFH-P / CS-DS-containing nanoparticles, while the remaining control group is not seen in the comparative blue dyeing nanoparticles. ;Figure 21 B Displays co-positioning of Fe-PFH-P (DII) / CS-DS nanoparticles (red fluorescence) and macrophages (green fluorescence). Red fluore...

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Abstract

The invention discloses a phase-change multi-modal nano contrast agent for targeted therapy of vulnerable plaques. The contrast agent comprises a shell membrane and a core wrapped by the shell membrane, the shell membrane is PLGA-PEG-PLGA, the core is PFH and Fe3O4, the shell membrane is connected with CS (chitosan), and the CS is connected with DS (dextran sulfate). The multi-modal nano contrast agent has a remarkable targeted therapy effect on vulnerable plaques.

Description

Technical field[0001]The invention belongs to the field of medicine and diagnosis, and more particularly to a phase change type targeted treatment of the proliferative polymorphism nano-containing agent.Background technique[0002]Cardiovascular disease is the main cause of death globally, most of the cardiovascular events (such as stroke and myocardial infarction) are caused by high-risk immersed atherosclerotic plaques. The clinical treatment of current atherosclerotic plaques mainly includes changing lifestyle, lowering cholesterol, blood pressure monitoring, antithrombotic drugs and surgical surgery, there is no specific treatment for high-risk impaired plaques, nor available The clinical method can evaluate the vulnerability of the plaque, and a specific treatment of eliminate plaques prior to the occurrence of cardiovascular events.[0003]Macrophages are closely related to plaque inflammation, compared to stable plaques, the number of lipid macrophages containing lipid macrophage...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/00A61K49/12
Inventor 周君侯静馨郭大静徐杰
Owner THE SECOND AFFILIATED HOSPITAL OF CHONGQING MEDICAL UNIV
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