Study On Release Of Berberine Hydrochloride And Catalysis By Porous Polymer And Its Derivatives

The low solubility of insoluble drugs greatly limits its clinical application.Therefore,improving the solubility of drugs to improve bioavailability of insoluble drugs is an effective measure to solve their limited clinical use.With the rapid development of drug carrier systems,it has been found that loading insoluble drugs into porous organic polymers（POP）can effectively improve the solubility of drugs.However,developing a drug carrier system with suitable pore size and good biocompatibility remains a challenge.In recent years,POP,as a class of versatile functional materials,can not only play a role as a drug carrier,but also play an important role in the field of catalysis.In this study,we tried to optimize the synthesis of POP materials to give them different application properties through different modification methods.First,a simple and controllable method was used to prepare a POP material with suitable pore size to support the insoluble drug berberine hydrochloride in one-pot to improve its solubility.In addition,based on the easily functionalized scaffold of POP,we further synthesized a drug carrier system with higher biosafety and a bifunctional synergistic catalytic system through high-temperature carbonization and post-synthesis modification strategies for application in drug carrier and CO₂cycloaddition catalyzed reaction,respectively.The main research contents are as follows:（1）A series of porous polymer materials with different specific surface areas and different pore sizes were synthesized by a simple Friedel-Crafts alkylation reaction:Porous bromomethylbenzene polymer（X:Y）（X:Y is the molar ratio of 4,4′-（bromomethyl）biphenyl and 1,3,5-tris（bromomethyl）benzene）（PBTP（X:Y））,and screened PBTP（4:1）with suitable pore size as the best carrier material.After loading berberine hydrochloride（BBH）with PBTP（4:1）,the drug was successfully transformed from crystalline state to amorphous state,which made the drug carrier complex（PBTP（4:1）/BBH）in the drug in vitro dissolution test.The extent of drug release and solubility were significantly increased.In addition,PBTP（4:1）/BBH has good stability in stability experiments and good biocompatibility in cytotoxicity experiments.（2）Porous bromomethyl carbide（PBTC）with less biotoxicity was successfully prepared by high-temperature carbonization of porous polymer PBTP（1:4）,and the pore size of the porous carbon material was regulated by controlling the carbonization temperature of the polymer precursor.The berberine hydrochloride was transformed from a crystalline state to an amorphous state after the carrier material PBTC-1000 was used to load the berberine hydrochloride.In the drug release experiment in vitro,the loaded drug carrier complex（PBTC-1000/BBH）greatly improved the drug release rate and release degree.Drug stability experiments show that the drug carrier complex has good stability.The cytotoxicity experiment showed that the carrier material PBTC-1000 was very weak in cytotoxicity and had better biocompatibility than PBTP（4:1）.（3）The metal halide bifunctional catalyst（PBTP（1:4）-Me6Tren（Ni））was obtained by two-step continuous post-synthesis modification of the synthesized porous polymer PBTP.The catalyst PBTP（1:4）-Me6Tren（Ni）was able to catalyze the CO₂ and epichlorohydrin to the corresponding cyclic carbonates in 97.5%yield under mild conditions（80 mg catalyst,0.5 m L DMF,CO balloon,80°C,24 h）.Besides,the bifunctional catalyst PBTP（1:4）-Me6Tren（Ni）has abundant substrate applicability and good recycling performance.In terms of catalytic mechanism,the active sites of Ni and Br in the catalyst can synergize with the used alkaline solvent DMF to catalyze the conversion of CO₂ efficiently.