Construction Of Composite Cellulosic Imprinted Functional Material And Its Detoxification & Application In Ginkgolic Acids

Ginkgo biloba extract（GBE）is rich in flavonoids and ginkgo terpene lactones,which makes its preparation one of the most widely used natural drugs in the world to assist in the treatment of cardio-cerebrovascular diseases,but the untreated ginkgo biloba leaves contain a large amount of ginkgolic acids（GAs）.This 6-alkyl or 6-alkenyl derivatives of salicylic acid have serious side effects such as sensitization,induced gene mutation,nephrotoxicity,neurotoxicity,etc.However,some studies have also shown that GAs have significant anti-tumor,anti-inflammatory,antiviral and antibacterial effects.In the process of processing ginkgo biloba leaves,often regarded as waste,GAs are generally removed by solvent method or chromatography.However,these processes are expensive and time-consuming,which is not suitable for the actual processing of medicinal materials.In view of the complex pretreatment of ginkgo biloba leaves,the difficulty of detoxification of GAs,and the waste of a large number of resources,this study designed and synthesized two kinds of composite cellulosic imprinting materials（SCM-DMIP-GAs and MMCC-CD/CS-MIP）.Through molecular imprinting technology and chemical modification of cellulose materials with different degrees of polymerization,SCM-DMIP-GAs and MMCC-CD/CS-MIP have specific recognition function for GAs components.By exploring their best applicable conditions,specific adsorption process,performance of adsorption-desorption,fitting degree of theoretical models,and thermodynamic changes of adsorption process,the molecular recognition mechanisms in the adsorption process have been clarified,and the adsorption effect of SCM-DMIP-GAs and MMCC-CD/CS-MIP has been comprehensively evaluated.Finally,SCM-DMIP-GAs and MMCC-CD/CS-MIP were applied to the actual extract of ginkgo biloba leaves,and their effects on detoxification and slow release bacteriostat of ginkgo biloba acids were tested,respectively.The main research contents and results are as follows:Preparation,characterization and adsorption mechanism of GBE detoxification material（SCM-DMIP-GAs）.The absorbent cotton is dissolved by chemical derivatization method,while the cellulose matrix is obtained by mechanical stirring and reversed suspension method.After the substrate modified by silylation reagent,a cellulose-silylated matrix（SCM）that can be used for subsequent grafting of molecular imprinting layer has been prepared.SCM-DMIP-GAs,(Q_max=37.28 mg g^-1,IF=2.53)with the best adsorption and imprinting effect can be prepared under the conditions that the molar ratio of dummy template molecule to 4-VP is 1:3,the mass ratio of SCM/EGDMA/MA-POSS is 2:3:4,and the ratio of initiator is 5%.The porous structure of the material was verified by scanning electron microscopy（SEM）and nitrogen adsorption-desorption curve analysis（BET）.Fourier transform infrared spectroscopy（FT-IR）,energy dispersive X-ray spectroscopy（EDX）and X-ray diffraction（XRD）were used to prove the successful grafting of silane modification and imprinted layer.Simultaneous thermal analysis（TGA-DSC）and recycling experiments reveal the excellent stability and reproducibility of the material.The fitting results of adsorption models show that the adsorption behavior of SCM-DMIP-GAs meets the single-molecular layer adsorption（Langmuir model）,and the adsorption rate is mainly affected by chemical adsorption,which conforms to the pseudo-second-order kinetic model.Preparation,characterization and adsorption thermodynamics of GAs sustained-release material（MMCC-CD/CS-MIP）.The alkali-urea solution dissolves microcrystalline cellulose at low temperature,and nano-Fe₃O₄ was added to the transparent sol,assisted by mechanical stirring.The above Fe₃O₄-cellulose mixed solution was dropped into the suspension（chloroform:olive oil:glacial acetic acid=5:5:1）through a 32G microneedle by falling ball method,and the sol-gel turning was achieved by static curing to obtain a magnetic microcrystalline cellulose-gel core（MMCC）.Under the alkaline condition,when the mass ratio of MMCC/β-CD is 1:2,the mass ratio of MMCC/ECH is 1:7,and the concentration of chitosan sol is 20 mg m L^-1,the MMCC-CD/CS-MIP with the best adsorption performance can be prepared.Similarly,the morphology,structural composition and stability of MMCC-CD/CS-MIP were characterized.Through the vibration magnetometer（VSM）,it further proved that the material is easy to recycle.The experiments confirm that the best adsorption effect was obtained when the p H of the material is 7,the temperature is 25℃,and the adsorption time is 180 min.MMCC-CD/CS-MIP showed excellent desorption effect in methanol-HCl solution with p H≤3 for ultrasound-assisted treatment for 6 minutes.Thermodynamic research results areΔH°<0,ΔS°>0,ΔG°<0,which prove the thermodynamic feasibility and spontaneity of GAs adsorption.Application of two kinds of composite cellulosic imprinting materials to GBE.The prepared dry SCM-DMIP-GAs was loaded into a solid phase extraction（SPE）column.Loaded with GBE after activation and equilibrium,the SPE column was eluted with methanol-acetic acid solution,and the filtrate and eluate were analyzed by HPLC.The results showed that the detoxification rate of GAs in the extract of Ginkgo biloba leaves could reach 99.98%after once treatment,which indicated that SCM-DMIP-GAs had good detoxification effect.With Staphylococcus aureus,Escherichia coli,Bacillus subtilis and Candida albicans as the test strains,MMCC-CD/CS-MIP was adsorbed in the GBE,and then placed in the petri dish for culture.Compared with the GBE group,MMCC-CD/CS-MIP has a good slow-release antibacterial effect,which proves that the material can achieve targeted adsorption and slow-release reuse of GAs.To sum up,in this study,cellulose with different degrees of polymerization was used as the base material,and a composite cellulosic molecularly imprinted functional material capable of specifically adsorbing GAs was constructed by grafting molecularly imprinted layer after chemical modification.This kind of material has excellent selectivity,stability and recycling,which can realize detoxification of GBE and reuse of GAs.This study provides an economic,safe and fast solution for the detoxification of medicinal ingredients and furnishes a theoretical basis for the reuse of complex polysaccharide-based imprinted materials after targeted enrichment of target molecules.