Study On Thermosensitive Madecassoside Liposomes And Quality Evaluation And Processing Of Polygoni Multiflori Radix

Due to the high fluidity,traditional MA liposomes can not ahere to skin,resulting in drug loss,which limits the application of sustainable topical drug delivery.PECE is a biodegradable,thermosensitive material with low toxicity,and its gel-sol can limit the fluidity of liposomes.Due to diverse processing norm,the quality of Polygoni Multiflori Radix(PMR)is not consistent.Besides,the quality of PMR is the one of the main causes that PMR induces liver injury.Therefore,it’s nessessary to control the quality of PMR.On the other hand,the components of PMR are complex,and the material basis and mechanism of its hepatotoxicity are still not clear.Molecular simulation could be applied to discovering hepatotoxical components from PMR,which providing the theoretical datum for toxicology of PMR.This thesis is mainly as follows:1.Thermosensitive hydrogel PECE(PEG-PCL-PEG)was used to modify madecassoside liposomes to obatain PECE@MA liposomes.The results showed that PECE@MA liposomes were spherical with uniformed size distribution and exhibited high gel-sol phase transition temperature(>37 ℃).Molecular simulation results suggested that MA had interaction with two phospholipid molecules.2.The quality of different batches of PMR was estimated via TLC,water content,ash content and ethanol extract content and HPLC.The results demonstrated that some of the bathches were not in conformity with Chinese Pharmacopeia with the respect to water,ehtnaol extract and index components content.In addition,the quality of each batch of PMR has great difference.3.NIR was used to evaluate the quality of PMR.The NIR results MSC+first derivative spectral processing method was applied to the NIR models of THSG and free anthraquinone,while SNV was applied to the NIR model of water conten.Due to the inadequency of samples,the prediction accuracy needs to be improved.4.Compared different processing technique,high pressure steaming was the best processing technique.The results demonstrated that high pressure steaming was conducive to the dissolution of free anthraquinone and polysaccharide,and the less destructive to THSG and the steaming time should be 4～5h.5.Molecualr simulation was used to predict the toxical compounds from PMR.The molecular docking results showed that 3-O-galloyl-(-)-catechin,3-O-galloyl-(-)-epicatechin,3-O-galloyl-procyanidin B2 exhibited potential hepatotoxicity.Besides,these compounds all had hydrogen binding with residue Arg105,suggesting strong bingding with protein CYP3A4.Molecular dynamics simulation results demonstrated that THSG had a strong inhibitory effect on protein CYP1A2,followed by emodin then emodin-8-O-β-D-glucopyranoside or physcion.