Study On Extraction Technology And Preparation Of Sustained Release Pellets Of Flavonoids From Sophora Flavescens Seeds

As a traditional Chinese medicine,Sophora flavescens shows significant antibacterial activity,which can replace antibiotics in some degree used in bacterial infectious diseases due to its low side effects and non drug resistance.There are a lot of reseach reports about antibacterial action and its preparation.However,the output of Sophora flavescens root,a traditional medicinal part,can not meet clinical needs due to the severe destruction of traditional Chinese medicine resources in recent years.So,the antibacterial activity and preparation of other medicinal parts of Sophora flavescens would be inveistigeted.We had reported the flavonoids of the Sophora flavescens seeds shows good antibacterial activity in the previous study.In the present work,the process of extracting the flavonoids from Sophora flavescens seeds was optimized,the preparing conditions of sustained release preparation was studied according to the investigation of physicochemical properties of the extracts of flavonoids from Sophora flavescens seeds.The main research content and results are as follows:1.Optimization of extraction technology of flavonoids from Sophora flavescens seeds.The flaonovids from Sophora flavescens seeds was extracted by ultrasonic extraction and pressure extraction.In the ultrasonic extraction,the mainly factors(liquid-solid ratio,ultrasonic time and ultrasonic power)were investigated;in the pressure extraction,the mainly factors(extraction time,extraction temperature and extraction pressure)were investigated,and the extraction processes were optimized with the response surface method.The results showed that the optimal conditions for ultrasonic extraction were as follows: liquid-solid ratio 18 mg/L,ultrasonic time 105 min,ultrasonic frequency 70 W.Under this condition,the yield of flavonoids from Sophora flavescens seeds was 13.11 mg/g;the optimal extraction conditions for pressure extraction were extraction time 30 min,extraction temperature 104 °C,and extraction pressure 0.22 MPa.Under this condition,the optimal extraction amount of total flavonoids from Sophora flavescens seeds was 14.81 mg/g.2.Pre-prescription study on the formulation of flavonoids from Sophora flavescens seeds.Basic physical and chemical properties of flavonoid extracts of Sophora flavescens seeds were determined to provide the basis for selection of suitable preparations.The antibacterial properties of the flavonoids extracts of Sophora flavescens seeds were evaluated to provide the basis for determining the dosage.The method for the determination of the in vitro release rate of flavonoids from Sophora flavescens seeds were established to provide the basis for the quality control about formulation.The results showed that the flavonoid extracts of Sophora flavescens seeds had an equilibrium solubility of 1.791 mg/mL in 0.1 mol/L HCl solution and an apparent oil-water partition coefficient of-0.325< lgP<-0.003.Both physicochemical properties indicated that the flavonoids extracting from Sophora flavescens seeds are suitable for sustained-release preparations;the antibacterial properties of the extracts showed that the minimum inhibitory concentration of the extracts against Staphylococcus aureus was 0.144 mg/m L and of Escherichia coli was 0.216 mg/m L.Those results combined with the growth curve of the bacteria indicated the flavonoids of the Sophora flavescens seeds have good antibacterial effect.3.Preparation of sustained-release pellets of flavonoids from Sophora flavescens seeds.The pellets were prepared by the melt pelletization in a high-speed mixer.First,the starch blank pellets were prepared to determine the initial range of various prescriptions and process conditions.Then preparing process of the drug-containing pellets was determined according to the in vitro release properties of pellets.Finally,with the release rate as the main evaluation index,the roundness of pellet as the secondary evaluation index,the optimum formulation and process conditions for the preparation of flavonoid sustained-release pellets of Sophora flavescens seeds were determined by orthogonal test.The results showed lactose ratio 25%,glyceryl monostearate ratio 55%,charge amount 35 g,stirring speed 300 rpm.With this preparing condition,the prepared pellets complied with pharmacopoeia standards with good roundness,a uniform particle size,and favourable release level.4.Establishment of quality standard of sustained-release pellets of flavonoids from Sophora flavescens seeds.According to the relevant requirements for pills and granules in the 2015 edition of the Chinese Pharmacopoeia,the pellets were initially evaluated in terms of traits,identification,examination,and content determination.The stability of flavonoid sustained-release pellets was investigated with influencing factors experiments,accelerated experiments and long-term experiments.The results showed that the flavonoid sustained-release pellets meet the requirements of quality standards in all aspects.Stability experiments showed that the pellets are unstable under high temperature and high humidity conditions,and should be stored at normal temperature and dry conditions.In summary,the flavonoids of Sophora flavescens seeds have good antibacterial activity.The research and development of sustained-release pellets provided new prospects for the formulation study and clinical application of flavonoids from Sophora flavonoid seeds.It supplied evidence and guidance for traditional Chinese antibacterial medicine to replace or assist antibiotics to prevent bacterial infections.