Study On Particle Growth Characteristics And Settling Model For Alcohol Precipitation Process Of Several Traditional Chinese Medicine

Alcohol precipitation is the most widely used technology in the production of TCM to achieve initial purification and separation of a crude extract. Unfortunately, most of the reported researches about alcohol precipitation of TCM mainly paid attention to parameters optimization and content analysis in the precipitation stage, while few researches focused on particle growth characteristics, morphology and settling model. Danshen (Salvia Miltiorrhiza Bunge) and Chishao (Radix Paeoniae Rubra) and other extracts were used to systematical study the particle growth characteristics, morphology and settling model of the alcohol precipitation process. The contents and results of the dissertation were described as follows:1. The focused beam reflectance measurement (FBRM) and particle video microscope (PVM) technologies were introduced to study the particle growth and agglomeration processes during alcohol precipitation process of Danshen extract. The results showed that both initial extract density and initial alcohol concentration have significant effects on the particle growth and agglomeration. The variation of particle counts during the alcohol precipitation process of Danshen extract showed a significant bimodal distribution at initial alcohol concentration of95%. The particle growth process can be divided into five stages according to the variation of particle counts: induction, growth, agglomeration, breakage and relative stable stage. As the initial extract density and initial alcohol concentration increase, the induction time reduces, while the average and maximum particle growth rates increase. The particle counts increases gradually and finally reaches to almost a flat distribution at the initial alcohol concentration lower than90%. The result indicates different particle precipitation kinetics under different conditions. It can be inferred from the particle PVM images that there are some correlations between active component loss and particle morphology. Higher agglomeration leads to more droplets and greater active components loss. The results of zeta potential show that increase charge on the particles in agree with the increase ratio of polysaccharide/protein in the solid phase, indicating that electrostatic attraction is not the main reason for particle agglomeration during the alcohol precipitation process of Danshen. The mechanism of agglomeration is probably related to the particle morphology and the binding forces between particles. Further research is needed to gain a better understanding of the mechanism of agglomeration.2. FBRM combined with PVM were applied for studying the variation of particle number, CLD and micron morphology characteristics in the alcohol precipitation process of Danshen (Salvia Miltiorrhiza Bunge), Qinghao (Artemisiae Annua), Yimucao (Leonurus japonicus), Jinyinhua (Flos Lonicerae), Zhiqiao (Fructus Aurantii). The distribution of total protein and polysaccharide in the solid and liquid phase during the alcohol precipitation process was also investigated. The results showed that the particle growth behavior is different for different extracts. The kinetics of particle counts and growth rate are also different for different alcohol precipitation processes. During the alcohol precipitation process of Danshen extract, the chord counts and growth rate of particles are found to be a quadratic parabola function of polysaccharide concentration in the liquid phase. The kinetics of chord counts and growth rates for Qinghao, Yimucao and Jinyinhua are very similar, which shows a negative and positive linear function of polysaccharide concentration in the precipitate phase, respectively. The kinetics of chord counts and growth rates for Zhiqiao are linear functions of polysaccharide/protein in the liquid phase. The validation results of the kinetics of particle counts and growth rate for the alcohol precipitation process of Danshen extract show that the developed models performance good prediction and have potential applications.3. The second alcohol precipitation mixture of Danshen was used to investigate the effects of alcohol precipitation parameters on the settling process of mixture. The settling results indicated that the settling process of second alcohol precipitation mixture of Danshen can be divided into zone settling and compression settling, which is similar to the settling process of activated sludge. Based on the Vesilind function, a modified zone settling velocity model of second alcohol precipitation mixture of Danshen was developed and the expression is:Vzs=8.75×10-35e195.4p. The effects of alcohol precipitation mixture density on zone settling were investigated. The results showed that the zone settling velocity increases as the increasing of mixture density. The zone settling velocity increased from0.262to3.23cm·min-1as the mixture density increased from0.916to0.934g·mL-1, increased by as much as1130%. Meanwhile, a model describing the interface height was developed and the model parameters prediction formulas were provided. A velocity function for the compression settling was deduced from the model and a method for determining the critical time when the zone settling stage ends was established. Finally, a segmented model for describing the complete settling process was developed. The interface height equations for zone settling and compression settling stages are respectively given in the following:The method was applied to predict the interface height during the complete settling process of second alcohol precipitation mixture, the results showed that the settling processes could be simulated well.4. In order to study the settling characteristics for different alcohol precipitation process of TCM. The first and second alcohol precipitation of Chishao (Radix Paeoniae Rubra) extract were used to investigate the effects of alcohol concentration of mixture, the extract density, the initial alcohol concentration, the ratio of height to diameter (H/D) and the settling temperature on the settling process. The results showed that three factors, including mixture alcohol concentration, initial extract density and initial alcohol concentration, have significant influence on the settling process. The settling velocity increases as mixture alcohol concentration increases. Meanwhile, the Precipitate settling volume ratio (PSV) decreases, indicating settling performance improvements. Smallest precipitate volume and greatest settling velocity were obtained at initial extract density of1.140g-mL"1and initial alcohol concentration of95%, respectively. The results also showed that the higher the mixture alcohol concentration, the smaller the precipitate settling volume for same settling mixture volume. This will reduce the process load of precipitate and help to improve the efficiency of the solid-liquid separation. Therefore, settling performance of the alcohol precipitation mixture of TCM can be taken as an evaluation index in the optimization and industrial scale-up research. Under the condition of required retention rate of the active components, parameters which obtain better settling performance will accelerate the particle settling velocity and reduce the settling time, as well as the process load of precipitate.Furthermore, a model describing the compression settling process of first and second alcohol precipitation processes of Chishao was developed based on batch tests. The equation is:Vs=(93.52-0.946PSV0.5h) x [1-(0.00153+0.008IP ?)×x]4.65The model was validated by experiments and the results showed that the compression settling processes could be simulated well by the developed model. In addition, the model shows good prediction for the production scale alcohol precipitation sample and potential industrial application.