Intensification Of Extraction Process And Its Application In The Separation Of Triptolide From Tripterygium Wilfordii Hook F

Liquid-liquid extraction has the advantages of good selectivity, high separation efficiency, and easy to achieve continuous production as well as good flexibility. The extraction can be intensified by external forces (such as stirring, centrifugal force etc.) which can accelerate the mass transfer of the extraction process. During the extraction of active components from plants, it is of significant importance to develop a new process through the improvement of traditional separation process by means of extraction intensification. Some fundamental studies on the two kinds of intensified extraction devices, the pulsed packed extraction column and the high-speed counter-current chromatography (HSCCC), have been conducted in this dissertation. A new process for the separation and purification of triptolide from Tripterygium wilfordii Hook F (TWHF) leaves has been developed, and the pilot plant for this process has been designed.The main contents are as follows:1. The viscosities of liquid-liquid two-phase system have important effects on the hydraulic characteristic and mass transfer of extraction process. Though there are many methods to correlate the viscosities of liquid mixtures, the accuracies of these methods are not good for the aqueous solution which is of great nonideality. Thus, a shape factor has been introduced to the viscosity correlation for non-aqueous systems developed by our research group earlier, and a new viscosity equation for non-electrolyte aqueous solution has been proposed.54 binary aqueous non-electrolyte systems have been correlated using this new equation, and the binary parameters for the equation have been obtained. Using these parameters,7 ternary aqueous non-electrolyte solution systems have been predicted. The results show that this new equation is adequate for correlating the viscosities of binary aqueous non-electrolyte solutions and for predicting the viscosities of ternary aqueous non-electrolyte solutions.2. Pulsed packed extraction column is widespread used in the industry. A pulsed packed extraction column of rotary valve type developed by our laboratory has been improved to avoid the sticking of rotary valve and the stoppage of pulse tube. The hydraulic characteristic (flooding velocity) and mass transfer characteristics (height of a transfer unit and height equivalent to a theoretical plate) in this column at different pulsed speeds and different flow rates have been investigated using kerosene/benzoic acid/water extraction system. The results provide bases for the scaling up for the pulsed packed column of rotary valve type.3. HSCCC utilizes a special synchronous planet motion which produces a unique centrifugal force field, and the centrifugal force field can guarantee the retention of the stationary phase. Because of the complexity of the centrifugal force field acting on the two-phase solvent system in the tube, it is difficult to make out the effect of the centrifugal force on the mobile phase. The single-phase mode has been utilized to study the effect of centrifugal force field in this dissertation. At the single-phase mode, the effects of solvent velocity and rotary speed of centrifugal machine on axial diffusion coefficients in HSCCC have been studied with three solvents (ethyl acetate, ethanol and water). The results show that the single phase axial diffusion coefficient first increases and then decreases with the increase of rotary speed. The qualitative analysis of the results has been given.4. Triptolide is the main active component of TWHF and possesses anti-inflammatory, immunosuppressive, male anti-fertility and anticancer properties. Triptolide is used in Phase I clinical study for treatment of cancer, and has the prospect to be a new drug. It is of great value for the separation and purification of triptolide from the TWHF. In this dissertation, a new process for the separation and purification of triptolide from TWHF leaves has been developed, which includes 5 procedures:leaching using ethanol, extraction using ethyl acetate/water, extraction using n-hexane/methanol, silica gel column chromatography and HSCCC. Experiments have been conducted to optimize the liquid-solid ratio, temperature, time and leaching times in the leaching process; the phase ratio and extraction times in the extraction process using ethyl acetate/water; the phase ratio and extraction times in the extraction process using n-hexane/methanol; the system of eluent in the silica gel column chromatography; and the two-phase system for the purification of triptolide in the HSCCC. Finally, triptolide has been successfully separated from the TWHF leaves.5. Based on the process for the extraction and purification of triptolide from Tripterygium wilfordii Hook F leaves developed in this dissertation, a pilot plant has been designed for the preparation of triptolide with the scale of kilogram/year, and the pulsed extraction column is applied to the extraction processes using ethyl acetate/water and n-hexane/methanol.