Preparation and application of nanoparticles for thrombus-targeting and thermal-ablation

A nanoparticle, thermal ablation technology, applied in nanotechnology for materials and surface science, preparations for in vivo experiments, nanotechnology, etc., can solve combined circulatory dysfunction, systemic hemorrhage, and systemic hyperfibrinolysis and other problems to achieve the effect of overcoming continuous activation

Inactive Publication Date: 2016-04-06
南通市通州区人民医院
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, this type of drug has two major defects. The first is that this type of drug will cause continuous activation of plasminogen in the blood circulation, degrade blood coagulation factors, and lead to systemic hyperfibrinolysis. The common complication is systemic hemorrhage.
Another shortcoming is that due to the mechanism of old thrombus, it is difficult for such drugs to relieve deep old thrombus.
In addition, while thrombolytic therapy corrects hypotension and hypoxemia, the degraded thrombus fragments tend to block distal capillaries and form new thrombus, while medical treatment is usually ineffective for such secondary thrombus
Catheter interventional therapy, which is between medical drug thrombolysis, anticoagulant therapy and surgical treatment, can achieve relatively positive curative effect for patients with acute massive embolism and failure or contraindication of thrombolytic therapy, but there are also comorbid heart disease. Insufficiency, hypotension, combined cardiogenic shock, combined circulatory dysfunction and other sequelae

Method used

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  • Preparation and application of nanoparticles for thrombus-targeting and thermal-ablation
  • Preparation and application of nanoparticles for thrombus-targeting and thermal-ablation
  • Preparation and application of nanoparticles for thrombus-targeting and thermal-ablation

Examples

Experimental program
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Effect test

Embodiment 1

[0030] (1), weigh WCl 6 200 mg, dissolved in 50 mL of ethylene glycol under nitrogen protection, stirred and dissolved at room temperature to obtain a golden yellow solution, then added 300 mg of polyacrylic acid polymer with a molecular weight of 5KDa, stirred until completely dissolved, and then under nitrogen protection at 140°C Stir the reaction. After the system is heated, it is dark brown at first, then turns blue-green after 30 minutes, and finally turns dark blue after 1 hour, and remains unchanged. Continue heating for 1.5 hours, then cool down to 80 ° C, add 50 mL of deionized water, Continue to stir and react for 1 h, stop heating, centrifuge and purify the reacted solution, discard the supernatant, wash and disperse the product with deionized water, repeat this washing process three times, and finally obtain the purified product, which is dark blue W 18 o 49 granular powder ( figure 1 ), TEM shows that its average particle size is 4.9nm ( figure 2 ),

[0031] ...

Embodiment 2

[0035] (1), weigh WCl 6 200 mg, dissolved in 50 mL of ethylene glycol under nitrogen protection, stirred and dissolved at room temperature to obtain a golden yellow solution, then added 300 mg of polyacrylic acid polymer with a molecular weight of 5KDa, stirred until completely dissolved, and then under nitrogen protection at 140°C Stir the reaction. After the system is heated, it is dark brown at first, then turns blue-green after 30 minutes, and finally turns dark blue after 1 hour, and remains unchanged. Continue heating for 1.5 hours, then cool down to 80 ° C, add 50 mL of deionized water, Continue to stir and react for 1 h, stop heating, centrifuge and purify the reacted solution, discard the supernatant, wash and disperse the product with deionized water, repeat this washing process three times, and finally obtain the purified product, which is dark blue W 18 o 49 granular powder ( figure 1 ), TEM shows that its average particle size is 4.9nm ( figure 2 ),

[0036] ...

Embodiment 3

[0040] (1) 5ml, 0.2M cetyltrimethylammonium bromide (CTAB) was added to 5ml, 0.5mM HAuCl 4 After stirring and dissolving in the solution, add 0.6ml of 1.0mM sodium borohydride to react to obtain a blue solution.

[0041] (2) Take 0.912g CTAB and 0.08g sodium salicylate, dissolve them in 25ml of distilled water, after the dissolution is complete, add 0.5ml, 4mM silver nitrate, put it in a water bath at 30°C for about 15min, then add 25ml, 1mM HAuCl 4 and 0.2ml concentrated hydrochloric acid, stirred gently for 15min, then added 300 microliters of 0.1M ascorbic acid to obtain a colorless solution. Finally, 80 microliters of the blue solution obtained in step 1 was added, and after reacting for 12 to 24 hours, the reaction was terminated, centrifuged at 8500 rpm, and washed with distilled water three times. Gold nanorods were obtained with an aspect ratio of 4( image 3 ). Measure the ultraviolet absorption spectrum, and the obtained absorption peak has a small peak at ~523nm,...

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Abstract

Nanoparticles for thrombus-targeting and thermal-ablation are disclosed. According to the nanoparticles, the surface of nanoparticles with a photothermal conversion function is grafted with long-circulation hydrophilic functional group and thrombus-targeting functional group. The nanoparticles has a long-circulation effect in blood vessel and is targeted and enriched at the thrombus position. The nano-core of the nanoparticles has a photothermal conversion effect, the shell has long-circulation and thrombus-targeting functions, and particle size of the nanoparticles is 2-500 nm. The nanoparticles have a core-shell structure. The core is nanoparticles with the photothermal conversion function, and contains nonstoichiometric tungsten oxide nanoparticles or gold nanoparticles. The composite nanoparticles can circulate long in the blood vessel and are targeted and enriched at the thrombus position. By development under a CT technology, thrombus can be accurately positioned. Near infrared light with high skin permeability irradiates at the position of thrombus positioned by CT, and photothermal conversion is carried out. Then, local temperature of thrombus rises, and thermal-ablation of thrombus is carried out to achieve the thrombolysis effect.

Description

technical field [0001] The invention relates to the preparation of a thrombus-targeted nanoparticle, which can be used for CT imaging of the thrombus, and generates heat under the irradiation of visible-near-infrared light for ablation of the thrombus. Background of the invention [0002] Under the action of various pathological and physiological factors, the blood in the heart or blood vessels will change from a fluid state to a gel state, and this process is called thrombus formation. The formation of thrombus and the resulting complications, involving organs including the heart, brain, peripheral arteries and deep veins of the lower extremities, coronary heart disease, angina pectoris, acute myocardial infarction, thrombotic pulmonary embolism, ischemic stroke, lower extremity arteries Or deep vein thrombosis, as represented by various unfavorable factors such as hypertension, diabetes, obesity, etc., the morbidity, disability and death rate caused by thrombus are all inc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C01G41/02B22F9/24B82Y30/00A61B18/06A61K49/00A61K41/00
CPCC01G41/02A61B18/06A61K41/0052A61K49/00B22F9/24C01P2004/01C01P2004/04C01P2004/62C01P2004/64
Inventor 殷乐陈建霍达王纬经胡勇
Owner 南通市通州区人民医院
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