| Dihydromyricetin(DMY),also known as Ampelopsis,is a dihydroflavonol compound and mainly distributed in the stems and leaves of the vines in the middle and southern regions of China.It has obvious phlegm,anti-inflammation,cough reduction,lipid-lowering,hepatoprotective liver protection,mild ethanol poisoning,and anti-tumor effects.However,the poor stability,poor absorption,and low bioavailability of dihydromyricetin limit the development and clinical application of related preparations.PEG-modified long-circulating liposomes increase the flexibility and surface steric hindrance of the liposomal membrane due to the presence of polar long-chain PEGs,effectively protecting the lipid bilayer structure and avoiding phagocytosis and destruction by RES.Increases circulation time of the drug in the blood.In this study,PEG-modified long-circulating liposomes were selected as delivery vehicles,and thin-film ultrasound was used as the preparation method.We hope to provide theoretical support for the study of its formulation.This paper is divided into the following four chapters:The first chapter is divided into two parts:The first part reviews the research progress of liposomes,including the preparation technology of liposomes,the influencing factors of stability,pharmacokinetics characteristics,and the application research progress;The research progress of dihydromyricetin has been reviewed,including its physicochemical properties,preparation research status,and so on.In the second chapter,a HPLC method was established for the determination of dihydromyricetin content in vitro.The results showed that the method was accurate and efficient.Then,we have prepared dihydromyricetin-loaded liposomes using thin-film ultrasound.The formulation of dihydromyricetin liposomes was optimized using the single factor experiment and the orthogonal experiment design with the encapsulation ratio as the evaluation index.The optimal prescription was 75:20:5 for soybean phospholipid-cholesterol-mPEG2000-DSPE,and 1:12 for DMY-lipid(wt/wt)with the ultrasonic time of 20 min and loading temperature of 60? in pH 5.0 PBS buffer.Under the optimized conditions,DMY liposomes was sphere with mean particle size of 117.9 nm and mean zeta potential of-2.6 mV,the encapsulation efficiency and drug-loading content was 54.7%and 4.3%,respectively.the results of particle size distribution and transmission electron microscopy(sem)observed particle morphology results remain consistent.The results of in vitro drug release showed that the release rate of dihydromyricetin liposomes was slower than that of free ones in pH 1.2 and pH 6.8 release media,and all had the highest degree of fit in the first-order kinetic model.It was shown that the prepared liposomes can slowly released dihydromyricetin.The third chapter studies the preliminary stability of dihydromyricetin and lipsome.According to the requirements of the 2015 edition of the Chinese Pharmacopoeia,the appearance traits,content,and oxidation index were selected as the investigation items.Influencing factors and accelerated experiments of dihydromyricetin liposomes were performed.And the selected appearance traits,content and impurity content were investigated for the influencing factors and accelerated experiments of dihydromyricetin.The effects of temperature,light,and high humidity on dihydromyricetin and its liposomes were investigated.The results showed that temperature,light,and high humidity all have effects on dihydromyricetin and its liposomes.Encapsulation of dihydromyricetin in liposomes can improve its stability,and liposomes should be protected from light and stored in a cool dry place.In the fourth chapter,a method was established to determine and verification the content of dihydromyricetin in rat plasma by UPLC-MS/MS method,the results showed that the method is accurately,reliable,and good stability.At the dose of 100 mg/kg,SD rats were orally given the same amount of dihydromyricetin suspension and dihydromyricetin long-circulating liposomes to investigate its pharmacokinetic properties in rats.The results showed that after oral administration of dihydromyricetin and its liposome preparations,the MRT0?? and ti/2z of dihydromyricetin liposomes in rats were 2.2 and 2.7 times that of free dihydromyricetin.There was a significant difference,indicating that the elimination of dihydromyricetin in liposome preparations in rats slowed down,prolonged the residence time,and had the characteristics of sustained release in vivo;AUC0?? was 1.8 times that of free dihydromyricetin.There are significant differences,indicating that dihydromyricetin liposomes can significantly prolong the circulation time of drugs in vivo,and significantly increase the bioavailability of dihydromyricetin in vivo. |
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