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CN-121971649-A - Chitosan immobilized MOF808 particle and preparation method thereof

CN121971649ACN 121971649 ACN121971649 ACN 121971649ACN-121971649-A

Abstract

The invention discloses chitosan immobilized MOF-808 particles, and a preparation method and application thereof. The particles are subjected to in-situ self-assembly of trimesic acid and zirconium (IV) salt in a chitosan molecular chain under the conditions of room temperature and water phase to generate MOF-808 nanocrystalline, and then are subjected to reversed-phase microemulsion shearing-alkali induced phase separation for one-step molding. In the invention, MOF808 can realize effective self-assembly in acid solution, the product biocompatibility is high, zirconium ions and trimesic acid can form MOF808 in an acid chitosan sol system in a self-assembly mode, and the MOF808 is uniformly distributed, is different from the existing pure physical blending mode, does not have caking phenomenon, is immobilized in chitosan under the physical and chemical dual action, and has higher biocompatibility in the application process. The preparation process is simple and controllable, has good universality, is easy for industrial production, and has high practical value and popularization value in the technical field of functional materials.

Inventors

  • ZHU JIANJUN
  • ZHENG HE
  • ZHENG YONGCHAO
  • CUI YAN

Assignees

  • 中国人民解放军军事科学院防化研究院

Dates

Publication Date
20260505
Application Date
20260116

Claims (10)

  1. 1. The preparation method of the chitosan immobilized MOF808 particle is characterized by comprising the following steps of: S1 MOF808@CH sol system construction, namely dissolving water-soluble zirconium (IV) salt in an aqueous solvent of organic acid, adding chitosan for dissolution, adding trimesic acid, and fully reacting to obtain MOF-808@CH sol; the organic acid is one or more than two of formic acid, acetic acid, propionic acid and tartaric acid; S2, emulsifying, namely adding an oil phase containing an emulsifier into the S1 sol to form emulsion; the oil phase is cyclohexane One or more than two of chloroform mixture, liquid paraffin and soybean oil, wherein the emulsifier is one or more than two of span 80, span 60 and tween 20; S3, phase separation and solidification, namely adding an alkali solution into the mixed emulsion system to solidify sol particles; s4, washing and activating, namely washing sol particles by using an organic reagent, activating by using alcohol solution, and freeze-drying to obtain a final product; the organic reagent is one or more than two of ethyl acetate, ethanol, isopropanol and petroleum ether; the alcohol solution is one or more of methanol, ethanol, n-propanol, isopropanol, butanol and ethylene glycol.
  2. 2. The preparation method of the chitosan immobilized MOF808 particles according to claim 1, wherein in the step S1, the concentration of zirconium (IV) in a solution is 0.2-1 mol/L, the concentration of trimesic acid is 0.1-10 g/L, and the concentration of chitosan is 5-50 g/L; in the aqueous solution of the organic acid, the volume ratio of the organic acid to the water is 1:1-1:20.
  3. 3. The method of preparing chitosan immobilized MOF808 particles according to claim 2, wherein the zirconium (IV) salt comprises ZrOCl 2 ·8H 2 O、ZrCl 4 、Zr(NO 3 ) 4 、Zr(SO 4 ) 2 、Zr(CH 3 COO) 4 .
  4. 4. The method for preparing chitosan immobilized MOF808 particles according to claim 2, wherein the chitosan has a relative molecular mass of 5-50 ten thousand and a degree of deacetylation of 70-95%.
  5. 5. The method for preparing chitosan immobilized MOF808 particles according to claim 1, wherein in the step S2, the volume ratio of the oil phase containing the emulsifier to the sol is 3:1-1:1, and the treatment temperature is 30-80 ℃.
  6. 6. The method for preparing chitosan immobilized MOF808 particles according to claim 1, wherein the amount of the emulsifier added in the oil phase is 0.1% -7% of the volume of the oil phase.
  7. 7. The method for preparing chitosan immobilized MOF808 particles according to claim 1, wherein in the step S3, the concentration of OH - of the alkaline solution is 0.05-10M.
  8. 8. The method for preparing chitosan immobilized MOF808 particles according to claim 7, wherein the alkali solution is one or a mixture of more than two selected from KOH, liOH, ca (OH) 2 , ammonia, sodium carbonate, sodium bicarbonate, triethylamine, and ethanolamine.
  9. 9. A chitosan immobilized MOF808 microparticle obtained by the preparation method of any one of claims 1 to 8.
  10. 10. Use of chitosan immobilized MOF808 particles according to claim 9 for the preparation of antibacterial and hemostatic drugs.

Description

Chitosan immobilized MOF808 particle and preparation method thereof Technical Field The invention belongs to the field of medical materials, and particularly relates to chitosan immobilized MOF808 particles and a preparation method thereof. Background Metal Organic Frameworks (MOFs) have the characteristics of high porosity, high specific surface area, adjustable acidity/basicity, open metal sites, etc. The MOF808 has extremely high biocompatibility, the MOF-808 has a healing promotion effect on wounds, the MOF-808 removes pro-inflammatory mediators through a multi-scale adsorption mechanism (NO derivative is adsorbed in holes, cytokines are adsorbed on surfaces and ROS are removed through chemical reduction), the MOF-808 has the advantages of high efficiency in-vivo and in-vitro promotion of wound healing, NO toxicity, NO side effect and NO drug resistance, and provides a new scheme for skin problems related to the pro-inflammatory mediators. Meanwhile, according to the research surface, the Zr-MOF has a certain growth inhibition effect on staphylococcus aureus and escherichia coli, can depolarize bacterial cell membranes and inhibit bacterial protein synthesis due to the oxidizing property of the Zr-MOF, and simultaneously, the Zr 4+ can release and destroy the bacterial protein structure. Chitosan is a natural polysaccharide, obtained by deacetylation of chitin, and has natural procoagulant activity, good compatibility, antibacterial property and degradability, and is widely used in many fields such as medicine, food, chemical industry, cosmetics, metal extraction and recovery, water treatment and tissue engineering. Chitosan is a potentially suitable matrix for immobilizing MOFs. From the analysis of mechanism, the chitosan immobilized MOF808 has the theoretical basis that amino/hydroxyl functional groups in chitosan molecules are physically immobilized through hydrogen bond association with MOF808 metal nodes or ligands, and amino groups and carboxyl functional groups form amide bonds for chemical immobilization. However, how to realize the integration of high-loading-strong anchoring-controlled release of MOF-808 in chitosan matrix and to adapt to irregular bleeding channels of wound surface by taking the particle-level morphology (50-200 μm) into consideration is a technical problem to be solved in the art. Disclosure of Invention The invention aims to provide a preparation method and a product of chitosan immobilized MOF808 particles, aiming at the problems of weak interface combination between MOF-808 and chitosan, high burst release, wide particle size distribution, difficult synchronous amplification of hemostatic and bacteriostatic functions, agglomeration in a pure physical blending mode and the like in the prior art. The technical scheme adopted by the invention is as follows: in a first aspect, the invention provides a method for preparing chitosan immobilized MOF808 particles, comprising the steps of: S1 MOF808@CH sol system construction, namely dissolving water-soluble zirconium (IV) salt in an aqueous solvent of organic acid, adding chitosan for dissolution, adding trimesic acid, and fully reacting to obtain MOF-808@CH sol; the organic acid is one or more than two of formic acid, acetic acid, propionic acid and tartaric acid; S2, emulsifying, namely adding an oil phase containing an emulsifier into the S1 sol to form emulsion; the oil phase is cyclohexane One or more than two of chloroform mixture, liquid paraffin and soybean oil, wherein the emulsifier is one or more than two of span 80, span 60 and tween 20; S3, phase separation and solidification, namely adding an alkali solution into the mixed emulsion system to solidify sol particles; s4, washing and activating, namely washing sol particles by using an organic reagent, activating by using alcohol solution, and freeze-drying to obtain a final product; the organic reagent is one or more than two of ethyl acetate, ethanol, isopropanol and petroleum ether; the alcohol solution is one or more of methanol, ethanol, n-propanol, isopropanol, butanol and ethylene glycol. Preferably, in the step S1, the concentration of zirconium (IV) in the solution is 0.2-1 mol/L, the concentration of trimesic acid is 0.1-10 g/L, and the concentration of chitosan is 5-50 g/L; in the aqueous solution of the organic acid, the volume ratio of the organic acid to the water is 1:1-1:20. Further, the zirconium (IV) salt comprises ZrOCl2·8H2O、ZrCl4、Zr(NO3)4、Zr(SO4)2、Zr(CH3COO)4. Further, the relative molecular weight of the chitosan is 5-50 ten thousand, and the deacetylation degree is 70-95%. Further, in the step S2, the volume ratio of the oil phase containing the emulsifier to the sol is 3:1-1:1, and the treatment temperature is 30-80 ℃. Further, in the oil phase containing the emulsifier, the addition amount of the emulsifier is 0.1% -7% of the volume of the oil phase. Further, in the step S3, the concentration of OH - in the alkaline solution is 0.05-10M. Furth