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Antitumor photodynamic-sensitivity-enhanced-treatment photosensitizer/enzyme combined delivery system and preparation method therefor

A photodynamic and delivery system technology, applied in photodynamic therapy, biochemical equipment and methods, anti-tumor drugs, etc., can solve the problem of poor targeting, difficult to improve photosensitizer stability, nano-targeted delivery, difficult to achieve enzyme/ Issues such as targeted co-delivery of photosensitizers

Active Publication Date: 2021-06-08
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the relevant research on anti-tumor nano-delivery systems for photodynamic therapy mainly focuses on modifying the structure of photosensitizers, increasing the drug loading of photosensitizers, and using organic or inorganic materials to catalyze hydrogen peroxide. It is difficult to solve the oxygen dependence of photosensitizers, Poor targeting and poor biocompatibility
In addition, there is a patent to modify catalase on liposomes by co-incubation, which lacks the protection of catalase and has low encapsulation efficiency, making it difficult to achieve targeted co-delivery of enzyme / photosensitizer
There are also patents that use polymers to encapsulate catalase, but the photosensitizer is exposed on the surface of nanoparticles, which makes it difficult to improve the stability of the photosensitizer and achieve nano-targeted delivery

Method used

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  • Antitumor photodynamic-sensitivity-enhanced-treatment photosensitizer/enzyme combined delivery system and preparation method therefor
  • Antitumor photodynamic-sensitivity-enhanced-treatment photosensitizer/enzyme combined delivery system and preparation method therefor
  • Antitumor photodynamic-sensitivity-enhanced-treatment photosensitizer/enzyme combined delivery system and preparation method therefor

Examples

Experimental program
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Effect test

Embodiment 1

[0052] Synthesis of boric acid-epoxy polymers

[0053] According to the molar ratio of diethylaminoethyl methacrylate to 4-bromomethylphenylboronic acid 1:0.5, a small amount of potassium iodide was added, dissolved in 6 mL N,N dimethylformamide, and reacted in the dark for 24 h. Under the condition of nitrogen protection, the prepared monomer, glycidyl methacrylate and N,N-methylenebisacrylamide were dissolved in 4 mL of N,N dimethyl formaldehyde according to the molar ratio of 1:1:0.5 amides. According to the molar ratio of boric acid-acrylic acid compound to the initiator azobisisobutyronitrile of 1:0.5, after vigorous reaction at 65°C for 12 h, the boric acid-epoxy polymer was obtained by extraction and purification with n-hexane, and rotary evaporation.

Embodiment 2

[0055] Synthesis of boric acid-epoxy polymers

[0056] According to the molar ratio of N-vinylpyrrolidone and 4-bromomethylphenylboronic acid 1:1, add a small amount of potassium iodide, dissolve in 6 mL N,N dimethylformamide, and react in the dark for 24 h. Under nitrogen protection, the prepared compound, glycidyl methacrylate and N,N-methylenebisacrylamide were dissolved in 4 mL N,N dimethylformamide at a molar ratio of 1:1:0.5 middle. According to the molar ratio of boric acid-acrylic acid compound and initiator azobisisobutyronitrile 1:0.5, after a vigorous reaction at 65°C for 12 h, the boric acid-epoxy polymer was obtained by extraction and purification with n-hexane, and rotary evaporation.

Embodiment 3

[0058] Synthesis of boric acid-epoxy polymers

[0059] According to the molar ratio of diethylaminoethyl methacrylate to 4-bromomethylphenylboronic acid of 1:2, add a small amount of potassium iodide, dissolve in 6 mL N,N dimethylformamide, and react in the dark for 24 h. Under the condition of nitrogen protection, the prepared compound, glycidyl acrylate and N,N-methylenebisacrylamide were dissolved in 4 mL N,N dimethylformamide according to the molar ratio of 1:1:0.5 . According to the molar ratio of boric acid-acrylic acid compound and initiator azobisisobutyronitrile 1:0.5, after a vigorous reaction at 65°C for 12 h, the boric acid-epoxy polymer was obtained by extraction and purification with n-hexane, and rotary evaporation.

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Abstract

The invention discloses an antitumor photodynamic-sensitivity-enhanced-treatment photosensitizer / enzyme combined delivery system and a preparation method therefor and belongs to the field of pharmaceutical preparations. The combined delivery system comprises photosensitizer-loaded polymeric nanoparticles and enzyme nanocapsules, wherein the polymeric nanoparticles and enzyme nanocapsules are connected through chemical bonds to form a nano composite, and the surface of the nano composite is further modified with targeting biological macromolecules. According to the combined delivery system disclosed by the invention, efficient enriching of identical-target-region co-delivery tumor regions of a photosensitizer and an enzyme can be achieved; and through flexibly adjusting an assembling ratio between the polymeric nanoparticles and the nanocapsules, the oxygen yield and oxygen utilization ratio of a focus region are increased, a hypoxic microenvironment of tumor tissue is effectively improved, the photodynamic treatment effect is enhanced, and the combined delivery system can be applied to application of preparations in tumor diagnosis or treatment drugs.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a nano drug combination delivery system and a preparation method thereof, in particular to a photosensitizer / enzyme combination delivery system and a preparation method for anti-tumor photodynamic sensitization therapy. Background technique [0002] For the treatment of tumors, the main methods are surgical resection, chemotherapy and radiation therapy. In recent years, with the rapid development of nanometer and radiation technology, phototherapy has become a modern non-invasive new radiation therapy method. Photodynamic therapy (PDT) can be divided into type I PDT and type II PDT, among which type II PDT is the main research direction, and its mechanism of action is that photosensitizers stimulate oxygen in tumor cells to become singlet oxygen, which can Nucleic acids, proteins and biofilms in cells with oxidative stress disrupt the normal metabolism of tumor cells and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K9/51A61K47/32A61P35/00A61K38/44
CPCA61K41/0057A61K41/0071A61K38/44A61K9/5138C12Y111/01006A61P35/00A61K2300/00
Inventor 丁杨周建平孙晨凯程皓张华清
Owner CHINA PHARM UNIV
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