Extraction And Micronization Of Ginkgo Flavonoids From Ginkgo Biloba Leaves Using Supercritical Carbon Dioxide

Ginkgo biloba is attracting much attention due to its ability of protecting angiocarpy, and many researchers are involved in the study on the active ingredients and their functions in Ginkgo biloba in recent years. In this thesis, Ginkgo flavonoids were extracted and micronized from Ginkgo biloba leaves using supercritical carbon dioxide, and the supercritical solution impregnation of Ginkgo flavonoids to PLA microparticles was further explored.Firstly, Ginkgo flavonoids were extracted from Ginkgo biloba leaves using supercritical carbon dioxide extraction with ethanol as the entrainer. Some key factors including extraction pressure, extraction temperature, the flow rate of ethanol, the flow rate of CO2. which determined the extraction efficiency were investigated. The optimal experimental conditions were operating at 20 MPa of extraction pressure. 40℃of extraction temperature.6 ml/min flux of ethano1.10 g/min flux of CO2 in 90 min extraction time, and the extraction yield was 0.36% under optimized conditions. After purification, the purity of the crude extracts was increased from 2.1% to 19.3 %.Then, supercritical fluid assisted atomization introduced by a hydrodynamic cavitation mixer (SAA-HCM) was used to obtain microparticles of Ginkgo flavonoids. The temperature and pressure in the mixer was optimized and the influences of the solute concentration(Csol) as well as the mass flow ratio of the CO2/liquid solution(R) on particle size (PS) and particle size distribution (PSD) were investigated. When the R value increased from 1.5 to 2.3, the mode (the most frequent particle size) decreased from 0.58 to 0.45μm, and an contraction of the distributions was observed; when the Csol increased from 5 mg/ml to 40 mg/ml, the mode increased from 0.45 to 0.75 (μm, and an enlargement of the distributions was also observed. Well-defined, spherical, and separated particles with a controlled particle size ranging between 0.2 and 3.0μm were successfully obtained in this work.Monodisperse poly(lactic-co-glycolic acid)/poly(lactic acid) (PLGA/PLA) microparticles were prepared by a device with a T-shaped microchannel junction. The effects of some important parameters such as the amount of emulsifier used in the continuous phase, the concentration of the disperse phase, the disperse phase flow rate, and the continuous phase flow rate on the average diameter of the droplets/microparticles and the coefficient of variation were examined in detail. The experimental results indicated that a decrease of the disperse phase flow rate, an increase of the continuous phase flow rate and the amount of emulsifier used in the continuous phase led to the decrease of the average diameter of microparticles. The fine particles were successfully obtained with variation coefficient of microparticles below 13.0% and the average diameters of particles range from 30μm to 200μm at different operating conditions.Finally, Ginkgo flavonoids were loaded into the prepared PLA microparticles using supercritical solution impregnation (SSI), with ethanol as the assisted liquid. Cholesterol were also loaded into the prepared PLA microparticles using SSI, without any assisted liquid. The drug loading of Ginkgo flavonoids to PLA microparticles in SSI process was compared with that of cholesterol, and the parameters that influenced the drug loading were preliminary discussed.