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Metal-organic framework-superoxide dismutase assembly, preparation method and application thereof in preparation of drugs for treating Parkinson

A metal-organic framework and superoxide technology, which can be used in drug combinations, medical preparations without active ingredients, and medical preparations containing active ingredients, etc. Poor stability and other problems, to achieve the effect of small effect on enzyme activity, protection stability, and mild synthesis conditions

Inactive Publication Date: 2019-06-04
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although SOD has the above-mentioned important functions, there are still many bottlenecks in its in vivo treatment: poor stability, poor gastrointestinal absorption capacity, poor active transmembrane ability, etc.

Method used

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  • Metal-organic framework-superoxide dismutase assembly, preparation method and application thereof in preparation of drugs for treating Parkinson
  • Metal-organic framework-superoxide dismutase assembly, preparation method and application thereof in preparation of drugs for treating Parkinson
  • Metal-organic framework-superoxide dismutase assembly, preparation method and application thereof in preparation of drugs for treating Parkinson

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Add 2 mL of dimethylimidazole aqueous solution (160 mM) into 2 mL of zinc acetate aqueous solution (40 mM) dissolved with 1 mg of SOD, and the solution temperature is 25°C. The molar ratio of dimethylimidazole to SOD is 1:8000. Then 200 μL of methanol was added to initiate the reaction, and the reaction was carried out at 25° C. for 32 h. The system was centrifuged at 8000rpm / min for 5min, and the precipitate was collected. The precipitate was washed 3 times with distilled water, and freeze-dried to obtain the final product, SOD@ZIF-8, with a mass of 10mg.

[0025] from figure 1 The scanning electron microscope of the synthesized product found that the SOD@ZIF-8 synthesized by the above method was approximately diamond-shaped nano-scale particles with a regular shape and a particle size between 200 and 400 nm.

Embodiment 2

[0027]Add 4 mL of dimethylimidazole aqueous solution (160 mM) into 4 mL of zinc acetate aqueous solution (40 mM) dissolved with 2 mg of SOD, and the solution temperature is 25°C. The molar ratio of dimethylimidazole to SOD is 1:8000. Then, 400 μL of methanol was added to initiate the reaction, and the reaction was carried out at 25° C. for 32 h. The system was centrifuged at 8000rpm / min for 5min, and the precipitate was collected. The precipitate was washed 3 times with distilled water, and freeze-dried to obtain the final product, SOD@ZIF-8, with a mass of 20mg.

[0028] from figure 2 The scanning electron microscope of the synthesized product found that, using the above method, the SOD@ZIF-8 synthesized after increasing the input amount of reactants in equal proportions was approximately rhomboid nano-scale particles with regular shape and a particle size between 200 and 400 nm. In terms of particle size and morphology, it is consistent with SOD@ZIF-8 synthesized by the m...

Embodiment 3

[0030] After fully drying the SOD@ZIF-8, ZIF-8 and free SOD synthesized in Example 1 at 100°C, infrared spectroscopic analysis was performed.

[0031] Such as image 3 As shown, there is a 1460-1560cm -1 and 1640-1700cm -1 The characteristic absorption of the amide I and II bands at the position is the characteristic vibration of the loaded SOD enzyme, while the above-mentioned characteristic vibration does not exist in the infrared spectrum of ZIF-8, which proves that the SOD enzyme was successfully immobilized into ZIF-8.

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Abstract

The invention provides a metal-organic framework-superoxide dismutase assembly, a preparation method and an application thereof in preparation of drugs for treating Parkinson, and belongs to the technical field of biology. The framework makes use of biomimetic mineralization assembly strategy to immobilize SOD enzyme molecules into a metal-organic framework ZIF-8, coordination bonds are formed between SOD amino and zinc ions of ZIF-8, so that metal organic framework-SOD enzyme assembly (SOD@ZIF-8) are constructed based on enzymes. The temperature stability of SOD enzyme molecules and pH tolerance are improved through the frame work, by treating the SOD@ZIF-8 assembly as a therapeutic drug, at the cellular level, active oxygen produced by stimulation of MPP+ can be removed effectively, so as to relieve apoptosis caused by active oxygen; at the animal level, after intravenous chemotherapy by the assembly, the barrier in sports ability of Parkinson model mouse constructed by MPTP can be relieved, the expression level of tyrosine hydroxylase in substantia nigra is improved, the therapeutic effect is good.

Description

technical field [0001] The invention belongs to the field of biotechnology, and specifically relates to a metal-organic framework-superoxide dismutase (SOD) assembly constructed on the basis of bionic mineralization technology, a preparation method and its application in the preparation of drugs for treating Parkinson's. Background technique [0002] Parkinson's is a neurodegenerative disease that has attracted much attention in recent years. Its pathology is the degeneration of dopaminergic neurons in the substantia nigra region of the brain, which further leads to motor dysfunction. Clinically, it is manifested as resting tremor, bradykinesia and muscle rigidity . The weight of the brain only accounts for about 2% of the body weight, but it consumes about 20% of the metabolic oxygen. Due to the insufficient production of reduced glutathione by neuronal cells, the ability of the brain to remove metabolically generated reactive oxygen species is limited. Thus, neurons are ...

Claims

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Application Information

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IPC IPC(8): A61K38/44A61K47/22A61P25/16
Inventor 李全顺李青柏韶伟邵新欣刘勇
Owner JILIN UNIV
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