柴胡药用成分的超临界CO_2萃取工艺及模型研究
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摘要
柴胡是我国的传统常用中药,其中柴胡挥发油和柴胡皂甙是柴胡的主要药用成分。柴胡挥发油具有解热、抗炎等功效,柴胡皂甙具有抗炎、保肝、降低胆固醇、免疫调节、抗癌等作用。利用传统的提取方法提取柴胡挥发油和柴胡皂甙常因提取时间长、提取温度高等导致有效成分热解,从而使药效降低。本文研究利用超临界CO2(SC-CO2)萃取这一新兴的高效洁净分离技术替代原有传统工艺的可行性,这一研究对提高现有制剂药效和促进中药产业的现代化和国际化,具有重要的意义。
本文首先利用小试超临界萃取设备研究了柴胡挥发油的SC-CO2萃取工艺。考察了原料粒径、CO2流速和用量、萃取温度、萃取压力对挥发油萃取率和吸光度的影响,实验结果表明,在萃取温度为50℃、压力为15～20MPa、CO2流速为1.5L/min和用量为39.28kg/kg原料条件下,萃取所得挥发油的吸光度为0.664～0.682,高于规定值0.625,而挥发油萃取率约是规定值的8～10倍(>0.28%)。5L中试放大实验萃取所得挥发油的吸光度比小试萃取所得挥发油的吸光度低6%,但仍高于规定值0.625,表明小试实验结果具有较好的工艺放大效果。与传统的水蒸汽蒸馏法提取相比,SC-CO2萃取挥发油萃取率约是水蒸汽蒸馏法提取所得挥发油萃取率的5倍,两种提取方法所得挥发油的化学成分有较大差异。利用GC-MS对挥发油成分进行了定性分析,从SC-CO2萃取的挥发油中鉴定出33种成分。本文还对三批不同来源的柴胡的提取物进行了比较,实验结果表明其含油量、萃取率和吸光度存在较大差异。
以萃取挥发油后的萃余物为原料,以乙醇-水溶液做共溶剂,对利用SC-CO2萃取柴胡皂甙进行了深入研究。分别采用三种不同方法加入共溶剂,即将共溶剂与原料混合后浸泡的静态加入方式;将共溶剂加入SC-CO2中的动态加入法以及同时采用动态和静态法加入共溶剂。重点考察了乙醇浓度、共溶剂用量、萃取温度、萃取压力等因素对浸膏收率、柴胡皂甙a和d的收率以及浸膏中柴胡皂甙a和d含量的影响。实验结果表明,采用动态法加入共溶剂,乙醇浓度为95%,用量为12mL/g萃余物,萃取温度为60℃,萃取压力为30MPa条件下,萃取所得浸膏收率、SSa和SSd收率分别为67.73%、156.87%和74.52%,浸膏中SSa和SSd含量分别为15.44mg/g浸膏和14.68mg/g浸膏。与柴胡皂甙现行水提醇沉工艺相比,SC-CO2+乙醇—水萃取工艺所用时间还不到水提醇沉工艺所用时间的一半,萃取所得浸膏中SSa含量约是现行工艺提取所得浸膏中SSa含量的3.2倍。表明本文采用的SC-CO2+乙醇—水萃取工艺具有萃取时间短、可以有效避免SSd的热解及浸膏中SSa含量高等优点。
本文还对SC-CO2萃取柴胡挥发油过程的模拟进行了研究。建立了萃取过程的集总热容法模型,并将模拟结果与经验模型和微分质量模型模拟结果进行了比较。此外,还计算了集总热容法模型中的传质系数。结果表明,两参数经验模型、微分质量模型(SMI和SMII)以及两参数集总热容法模型所得的计算值与实验值吻合很好,三种模型所得计算值和实验值的最大误差分别为1.67—9.90%、1.06—7.44%和1.98—7.89%。传质系数随萃取压力的升高而增大。
Radix Bupleuri is widely used in traditional Chinese medicine, in which volatile oils and saikosaponins(SS) are considered as two major bioactive components. Volatile oils are described as anti-inflammatory and anti-pyretic agent. SS especially saikosaponin-a (SSa) and saikosaponin-d (SSd) have the functions of anti-inflammation, liver-protecting, reducing plasma-cholesterol, immunoregulatory and anti-cancer. Traditional extraction methods of volatile oils and SS may result in thermal degradation of them because of long extraction time or high extraction temperature. With the modernization and internationalization of Traditional Chinese medicine has become a very hot topic in China, it is of great importance to investigate the feasibility of supercritical fluid extraction (SFE) of volatile oils and SS with CO2, which is considered as high effective and clean separation technology.
The process of extraction of volatile oils with SC-CO2 was firstly studied with lab-scale extraction apparatus. The absorbance and yield of the volatile oils were two main indexes for process control. The influences of particle size, flow rate and amount of CO2, extraction temperature and extraction pressure on the absorbance and yield were investigated. Experimental results show that under the conditions of extraction temperature of 50℃, extraction pressure ranging from 15-20MPa, CO2 flow rate of 1.5L/min with amount of 20L/g, the absorbance of volatile oils is 0.664-0.682, which is higher than the specified value of 0.625. The yield of valotile oils is 8 to 10 times of the specified value (>0.28%). The absorbance of valotile oils extracted with 5L extraction apparatus is 6% lower than that of the valotile oils extracted with lab-scale extraction apparatus, but still higher than the specified value, indicating that the experimental results can be successfully scaled up. Comparison between traditional steam distillation and SFE was made. The yield of valotile oils extracted with SC-CO2 is 5 times of that extracted with steam distillation. The chemical components of volatile oils obtained by these two methods also differed. Thirty-three components in the volatile oils were identified by GC–MS. The influences of different batch of herbs of radix bupleuri on the extraction yield, the absorbance and chemical components of the volatile oils were also compared and discussed.
Extraction of SS from the residues of extraction of volatile oils with SC-CO2 was further investigated, in which ethanol-water solution was used as co-solvent. Three kinds of methods for adding co-solvent were studied, which include adding the co-solvent to the residues in static mode, adding the co-solvent to SC-CO2 in flowing mode and combination of these two modes. The effect of ethanol concentration and amount of the co-solvent used, extraction temperature and extraction pressure on the recovery ratios of the total extractives, SSa and SSd as well as the contents of SSa and SSd in the extractives were investigated, and the optimum conditions were obtained. Experimental results show that when 95% of ethanol liquor solution was added in flowing mode to CO2 with amount of 12ml/g residues, and the extraction temperature was 60℃, extraction pressure was 30MPa, the recovery ratios of the total extractives, SSa and SSd are 67.73%, 156.87% and 74.5%, respectively. The contents of SSa snd SSd in the extractives are 15.44mg/g and 14.68mg/g, respectively. Compared with the current used production method of water extraction followed by ethanol precipitation(WEEP), The time extracted with SC-CO2 and ethanol-water solution is shorter than half of the time extracted with WEEP, but the yield of the extract obtained with SC-CO2 in the presence of co-solvent is 50% higher than that extracted with WEEP. The content of SSa in the extractive is 3.2 time of that extracted with WEEP. Moreover, the special advantage of SFE is that it can effectively avoid thermal-degradation of SSd compared with no SSd could be detected in the extractive with WEEP.
Lumped capacity method model (LCMM) was firstly found to simulate the process of extraction of volatile oils with SC-CO2 and the mass transfer coefficients were also calculated. The comparison between lumped capacity method model, empirical model (one and two parameters) and differential mass balance model(SM I and SM II) was also made. Simulating results show that empirical model with two parameters, differential mass balance model and LCMM with two parameters give satisfactory results. The average relative errors of empirical model with two parameters, differential mass balance model and lumped capacity method model are ranging from 1.67% to 9.90%, 1.06% to 7.44% and 1.98% to 7.89%, respectively. Mass transfer coefficients increase with the increasing pressure.
本文首先利用小试超临界萃取设备研究了柴胡挥发油的SC-CO2萃取工艺。考察了原料粒径、CO2流速和用量、萃取温度、萃取压力对挥发油萃取率和吸光度的影响,实验结果表明,在萃取温度为50℃、压力为15～20MPa、CO2流速为1.5L/min和用量为39.28kg/kg原料条件下,萃取所得挥发油的吸光度为0.664～0.682,高于规定值0.625,而挥发油萃取率约是规定值的8～10倍(>0.28%)。5L中试放大实验萃取所得挥发油的吸光度比小试萃取所得挥发油的吸光度低6%,但仍高于规定值0.625,表明小试实验结果具有较好的工艺放大效果。与传统的水蒸汽蒸馏法提取相比,SC-CO2萃取挥发油萃取率约是水蒸汽蒸馏法提取所得挥发油萃取率的5倍,两种提取方法所得挥发油的化学成分有较大差异。利用GC-MS对挥发油成分进行了定性分析,从SC-CO2萃取的挥发油中鉴定出33种成分。本文还对三批不同来源的柴胡的提取物进行了比较,实验结果表明其含油量、萃取率和吸光度存在较大差异。
以萃取挥发油后的萃余物为原料,以乙醇-水溶液做共溶剂,对利用SC-CO2萃取柴胡皂甙进行了深入研究。分别采用三种不同方法加入共溶剂,即将共溶剂与原料混合后浸泡的静态加入方式;将共溶剂加入SC-CO2中的动态加入法以及同时采用动态和静态法加入共溶剂。重点考察了乙醇浓度、共溶剂用量、萃取温度、萃取压力等因素对浸膏收率、柴胡皂甙a和d的收率以及浸膏中柴胡皂甙a和d含量的影响。实验结果表明,采用动态法加入共溶剂,乙醇浓度为95%,用量为12mL/g萃余物,萃取温度为60℃,萃取压力为30MPa条件下,萃取所得浸膏收率、SSa和SSd收率分别为67.73%、156.87%和74.52%,浸膏中SSa和SSd含量分别为15.44mg/g浸膏和14.68mg/g浸膏。与柴胡皂甙现行水提醇沉工艺相比,SC-CO2+乙醇—水萃取工艺所用时间还不到水提醇沉工艺所用时间的一半,萃取所得浸膏中SSa含量约是现行工艺提取所得浸膏中SSa含量的3.2倍。表明本文采用的SC-CO2+乙醇—水萃取工艺具有萃取时间短、可以有效避免SSd的热解及浸膏中SSa含量高等优点。
本文还对SC-CO2萃取柴胡挥发油过程的模拟进行了研究。建立了萃取过程的集总热容法模型,并将模拟结果与经验模型和微分质量模型模拟结果进行了比较。此外,还计算了集总热容法模型中的传质系数。结果表明,两参数经验模型、微分质量模型(SMI和SMII)以及两参数集总热容法模型所得的计算值与实验值吻合很好,三种模型所得计算值和实验值的最大误差分别为1.67—9.90%、1.06—7.44%和1.98—7.89%。传质系数随萃取压力的升高而增大。
Radix Bupleuri is widely used in traditional Chinese medicine, in which volatile oils and saikosaponins(SS) are considered as two major bioactive components. Volatile oils are described as anti-inflammatory and anti-pyretic agent. SS especially saikosaponin-a (SSa) and saikosaponin-d (SSd) have the functions of anti-inflammation, liver-protecting, reducing plasma-cholesterol, immunoregulatory and anti-cancer. Traditional extraction methods of volatile oils and SS may result in thermal degradation of them because of long extraction time or high extraction temperature. With the modernization and internationalization of Traditional Chinese medicine has become a very hot topic in China, it is of great importance to investigate the feasibility of supercritical fluid extraction (SFE) of volatile oils and SS with CO2, which is considered as high effective and clean separation technology.
The process of extraction of volatile oils with SC-CO2 was firstly studied with lab-scale extraction apparatus. The absorbance and yield of the volatile oils were two main indexes for process control. The influences of particle size, flow rate and amount of CO2, extraction temperature and extraction pressure on the absorbance and yield were investigated. Experimental results show that under the conditions of extraction temperature of 50℃, extraction pressure ranging from 15-20MPa, CO2 flow rate of 1.5L/min with amount of 20L/g, the absorbance of volatile oils is 0.664-0.682, which is higher than the specified value of 0.625. The yield of valotile oils is 8 to 10 times of the specified value (>0.28%). The absorbance of valotile oils extracted with 5L extraction apparatus is 6% lower than that of the valotile oils extracted with lab-scale extraction apparatus, but still higher than the specified value, indicating that the experimental results can be successfully scaled up. Comparison between traditional steam distillation and SFE was made. The yield of valotile oils extracted with SC-CO2 is 5 times of that extracted with steam distillation. The chemical components of volatile oils obtained by these two methods also differed. Thirty-three components in the volatile oils were identified by GC–MS. The influences of different batch of herbs of radix bupleuri on the extraction yield, the absorbance and chemical components of the volatile oils were also compared and discussed.
Extraction of SS from the residues of extraction of volatile oils with SC-CO2 was further investigated, in which ethanol-water solution was used as co-solvent. Three kinds of methods for adding co-solvent were studied, which include adding the co-solvent to the residues in static mode, adding the co-solvent to SC-CO2 in flowing mode and combination of these two modes. The effect of ethanol concentration and amount of the co-solvent used, extraction temperature and extraction pressure on the recovery ratios of the total extractives, SSa and SSd as well as the contents of SSa and SSd in the extractives were investigated, and the optimum conditions were obtained. Experimental results show that when 95% of ethanol liquor solution was added in flowing mode to CO2 with amount of 12ml/g residues, and the extraction temperature was 60℃, extraction pressure was 30MPa, the recovery ratios of the total extractives, SSa and SSd are 67.73%, 156.87% and 74.5%, respectively. The contents of SSa snd SSd in the extractives are 15.44mg/g and 14.68mg/g, respectively. Compared with the current used production method of water extraction followed by ethanol precipitation(WEEP), The time extracted with SC-CO2 and ethanol-water solution is shorter than half of the time extracted with WEEP, but the yield of the extract obtained with SC-CO2 in the presence of co-solvent is 50% higher than that extracted with WEEP. The content of SSa in the extractive is 3.2 time of that extracted with WEEP. Moreover, the special advantage of SFE is that it can effectively avoid thermal-degradation of SSd compared with no SSd could be detected in the extractive with WEEP.
Lumped capacity method model (LCMM) was firstly found to simulate the process of extraction of volatile oils with SC-CO2 and the mass transfer coefficients were also calculated. The comparison between lumped capacity method model, empirical model (one and two parameters) and differential mass balance model(SM I and SM II) was also made. Simulating results show that empirical model with two parameters, differential mass balance model and LCMM with two parameters give satisfactory results. The average relative errors of empirical model with two parameters, differential mass balance model and lumped capacity method model are ranging from 1.67% to 9.90%, 1.06% to 7.44% and 1.98% to 7.89%, respectively. Mass transfer coefficients increase with the increasing pressure.
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