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Preparation method of cholesterol oxidase modified hybrid metal organic framework tumor targeting nano preparation

A technology of metal-organic framework and cholesterol oxidase, which is applied in the field of medicine, can solve problems such as no public reports, and achieve the effect of enhancing anti-tumor effect, huge economic and social benefits, and low cost

Active Publication Date: 2021-01-29
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

So how to use the hydrogel formed by the cross-linking of endogenous molecular materials to wrap drug-loaded MOF, efficiently target tumor cells, and reverse the new preparation of tumor multidrug resistance has not been publicly reported so far.

Method used

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  • Preparation method of cholesterol oxidase modified hybrid metal organic framework tumor targeting nano preparation

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Embodiment 1

[0034] A method for preparing a cholesterol oxidase-modified hybrid metal-organic framework tumor-targeting nano-preparation comprises the following steps:

[0035] (1) Synthesis of hybrid metal-organic frameworks:

[0036] Take 16 mg of zirconium-based inorganic salt zirconium tetrachloride, add 10 mL of N,N-dimethylformamide, and sonicate for 10 minutes to obtain the first solution; then weigh 50 mg of organic ligand 2,2'-bipyridine-5, For 5'-dicarboxylic acid, add 5-25mL N,N-dimethylformamide, and sonicate for 10 minutes to obtain the second solution; mix the first solution and the second solution, then add 0.9mL acidic reagent acetic acid, and then sonicate React for 10 minutes, transfer the reaction mixture to a high-pressure reactor, and react at 120°C for 24 hours to obtain a solid product; the solid product is sequentially washed with N,N-dimethylformamide and absolute ethanol at 10000r / min for 4 Second, dry in a vacuum oven at 60°C for 24 hours to obtain a powdered z...

Embodiment 2

[0047] A method for preparing a cholesterol oxidase-modified hybrid metal-organic framework tumor-targeting nano-preparation comprises the following steps:

[0048] (1) Synthesis of hybrid metal-organic frameworks:

[0049] Take 20 mg of zirconium-based inorganic salt zirconium oxychloride octahydrate, add 8 mL of N,N-dimethylformamide, and sonicate for 10 minutes to obtain the first solution; then weigh 62 mg of organic ligand 2,2'-bipyridine- For 5,5'-dicarboxylic acid, add 12mL N,N-dimethylformamide, and sonicate for 10 minutes to obtain the second solution; mix the first solution and the second solution, then add 1.1mL acidic reagent acetic acid, and then sonicate After reacting for 10 minutes, the reaction mixture was transferred to a high-pressure reactor, and reacted at 120° C. for 20 hours to obtain a solid product; the solid product was sequentially washed with N,N-dimethylformamide and tetrahydrofuran at 10,000 r / min for 4 times, Dry in a vacuum oven at 55°C for 18 ...

Embodiment 3

[0060] A method for preparing a cholesterol oxidase-modified hybrid metal-organic framework tumor-targeting nano-preparation comprises the following steps:

[0061] (1) Synthesis of hybrid metal-organic frameworks:

[0062] Take 20mg of zirconium-based inorganic salt zirconium tetrachloride, add 9mL N,N-dimethylformamide, and sonicate for 10 minutes to obtain the first solution; then weigh 42mg of organic ligand trimesic acid, add 9mL N,N- - Dimethylformamide, sonicate for 10 minutes to obtain the second solution; mix the first solution and the second solution, then add 9 mL of formic acid, and then ultrasonically react for 10 minutes, transfer the reaction mixture to an autoclave, and heat at 140 ° C React at low temperature for 12 hours to obtain a solid product; the solid product was sequentially washed with N,N-dimethylformamide and absolute ethanol at 10,000 r / min for 4 times, and dried in a vacuum oven at 60°C for 24 hours to obtain powdered zirconium based metal organi...

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Abstract

The invention relates to a preparation method of a cholesterol oxidase modified hybrid metal organic framework tumor targeting nano preparation, which can effectively solve the problem that the treatment of tumor multidrug resistance is more accurate, safer and more efficient in targeting. The hybrid metal organic framework is a metal organic framework (MOF) with catalase-like activity, cholesterol oxidase is modified on the surface of the metal organic framework (MOF), an anti-tumor drug is physically loaded in the metal organic framework (MOF) to form nanoparticles, and finally, the nanoparticles are wrapped with a gel shell to obtain the pharmaceutical composition with the particle size of 250-300 nm. The preparation method is simple and convenient, the cost is low, and the prepared cholesterol oxidase modified hybrid metal organic framework gel shell pharmaceutical composition can enhance the anti-tumor effect, is an innovation in tumor treatment pharmaceutical preparations, and has huge economic and social benefits.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a method for preparing a tumor-targeted nano-preparation of a cholesterol oxidase-modified hybrid metal-organic framework, a small-molecule drug and a gel shell composition. Background technique [0002] Multi-drug resistance (MDR) is the main reason for tumor chemotherapy failure, recurrence and metastasis, and it is also a major problem in tumor treatment. Combination medication or P-glycoprotein (P-glycoprotein, P-gp) inhibitors, etc., "cure the symptoms" rather than "cure the root cause", the treatment mechanism is single, the side effects are large, and the curative effect is not good. Nanocarriers have the advantages of large drug loading capacity, easy functional modification, controlled release, targeting and low toxicity and side effects. Therefore, according to the pathological changes in drug-resistant cell membranes and cells, preparing a new nano-preparation that can break t...

Claims

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Application Information

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IPC IPC(8): A61K47/64A61K47/69A61K9/51A61K47/36A61K47/12A61K45/00A61P35/00B82Y5/00B82Y40/00
CPCA61K47/64A61K47/6929A61K45/00B82Y5/00B82Y40/00A61P35/00A61K9/5161A61K9/5123
Inventor 杜斌黄静姝郑梅王月华马惠珍白依梦焦晴晴赵蒙蒙庞梦雪于利利
Owner ZHENGZHOU UNIV
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