桑根酮C、D的提取和精制
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摘要
本文系统地介绍了桑白皮的鉴别方法、药理作用、化学成分，并重点介绍了桑白皮中的活性物质桑根酮C、D的药理作用、物理化学性质、结构鉴定和分离分析方法。测定了桑白皮中桑根酮C、D的含量分别为2.955mg／g桑白皮、2.429mg／g桑白皮。然后对桑根酮C、D的分离精制工艺进行了深入、系统地研究，提出了分离和精制桑根酮C、D的新工艺，此工艺分为三个工序：溶剂浸取、溶剂萃取、柱层析。针对此工艺，重点考察了各工序的操作参数。
在浸取工序中，首先考察甲醇、乙醇、丙酮、乙醚、乙酸乙酯五种溶剂对桑根酮C、D提取率及产品纯度的影响，选取丙酮作为提取用溶剂。在此基础上，测定了所用桑白皮颗粒的粒径分布，丙酮浸取桑根酮C、D的浸取平衡常数、浸取动力学曲线，并通过传质模型拟合实验曲线得到丙酮浸取桑白皮时桑根酮C、D的内扩散系数。同时，根据所测定的浸取平衡常数，并应用传质平衡模型推导了搅拌釜分批式浸取操作方式下桑根酮C、D的提取率与溶剂用量、浸取次数之间的关系，根据此关系式得到搅拌釜分批式浸取操作方式下的最佳操作条件为：浸取溶剂用量4.0ml／g桑白皮，浸取次数2次，最佳的浸取时间为10～20min。考察了渗滤操作在不同操作条件下的溶剂消耗和生产能力，并与搅拌釜分批式操作进行了比较，结果认为渗滤操作优于搅拌釜分批式操作。在此基础上，用解吸理论建立了渗滤过程中的数学模型，本模型第一次综合考虑了渗滤过程中的内扩散、外扩散、非线性平衡等温线，并以表观空隙率反应了桑白皮固体颗粒对渗滤溶剂的吸收，通过此模型得到了高浓度时丙酮浸取桑根酮C、D的浸取平衡曲线及渗滤过程中的外扩散传质速度与流速的关系，这为渗滤过程的放大和工艺参数的选择提供了理论依据和指导。
在溶剂萃取工序中，重点考察了萃取溶剂的种类、用量、萃取次数对杂质去除率及桑根酮C、D损失率的影响，从而确定了溶剂萃取工序的最佳操作参数。
在柱层析工序中，重点考察了各种固定相(酸性氧化铝、硅胶、聚酰胺、凝胶、C18键合硅胶及苯基键合硅胶)对桑根酮C、D的分离性能的影响，并用硅胶、聚酰胺两种固定相时，对洗脱剂、洗脱方式、床层堆密度、上样量进行了深入研究，同时在理论的指导下，研究了硅胶柱层析的放大
一
问题。
考虑到通过溶剂浸取的方法从桑白皮中提取桑根酮C、D需耗费大量有
机溶剂，而桑根酮C、D具有酸性，可溶于碱性水溶液，在本文的最后，对
碱液法从桑白皮中提取桑根酮C、D的可能性进行了探讨，首先研究了桑根
酮C、D在不同种类、不同浓度的碱液中的稳定性，得到了桑根酮C、D在
碱液中的降解速度方程，然后考察了碱种类、浓度、用量、处理时间、提
取次数、提取温度，盐酸酸化的pH对碱液法提取桑根酮C、D的提取率的
影响。
The identification, pharmacology and chemical constitutes of SangBaiPi(root bark of morus), and the pharmacology, physical chemistry properties, chemical structure, analysis and separation method of Sanggenon C and D were reviewed. The content of Sanggenon C and D in SangBaiPi were determined as 2.429 and 2.955mg/g root bark respectively. The new separation process of Sanggenon C and D and the operation parameters was established.
The new process is composed of three parts: leaching, extraction and column chromatography.
In leaching operation, based on the investigation of the effect of solvent ( methanol, ethanol, acetone, ether and ethyl ester) on the yield and content of Sanggenon C and D of the extract, acetone was the best solvent selected. The particle size distribution of SangBaiPi powder, the equilibrium constants of Sanggenon C and D between acetone solution and root bark powder, leaching dynamic curves, and the internal diffusion coffecients of Sanggenon C and D were determined. At the while, the relationship between solvent to solid ratio, leaching stage numbers and yield of Sanggenon C and D by batch operation was achieved based on an equilibrium model. As a result, the optimal operation parameters were as follow: solvent to solid ratio was 4.0 mg/g root bark, leaching stage numbers was 2, leaching time was between 10 minutes and 20 minutes. Furthermore, percolation was studied as well. The results showed that percolation was better than leaching judging by solvent consumption and productivity. The percolation mo
del taking into account of internal diffusion, external diffusion and nonlinear equilibrium equation was established.
In extraction operation, the effect of solvent, solvent to solid ratio and extraction stadge numbers on loss of Sanggenon C and D and removal of impurity was studied. In column chromatography, the effect of different solid phases including active alumina, silica, polyamide, gel, ODS and phenyl silica on separation of Sanggenon C and D was researched, the results showed silica and polyamide were good solid phases for separation of Sanggenon C and D. Furthermore, the elution solvent, elution method, column density, sample capacity were studied in-depth. Sanggenon C and D could be extracted from root bark by using base because
Sanggenon C and D are acidic, but Sanggenon C and D can be degraded in strong base solution. In order to find out the feasibility of extration by base solution, the stability of Sanggenon C and D in 0.5%Na2CO3, 2.0%Na2CO3, 3.5%Na2CO3, 5.0%Na2CO3, 0.5%NaOH, 1.0%NaOH, 1.5%NaOH, 2.0%NaOH solution was investigated, and the degradation rate equations of Sanggenon C and D were as follow:
1) In NaOH solution
dC/dt = -1.308 × 1011exp(-77702.8/RT) CC1.401 for Sanggenon C,
dC/dt = -5.751 × l0111exp(-83037.4/RT)CC1.400 for Sanggenon D.
2) In Na2CO3 solution
dC/dt = -1.414 × 1015 exp(-102918.5/RT)CC0.2955 for Sanggenon C,
dC/dt = -6.163 × 1014 exp(-101951.3/RT)CC0.3081 for Sanggenon D.
The results showed that the lossity of Sanggenon C and D were below 5.0% in Na2CO3 solution concentration under 2.0% and NaOH solution concentration under 0.5% at room temperature if reaction time was shorter than 30 minutes. Furthermore, the effect of base, consumption, reaction time, extaction stadge numbers, pH on yield of Sanggenon C and D was researched.
在浸取工序中，首先考察甲醇、乙醇、丙酮、乙醚、乙酸乙酯五种溶剂对桑根酮C、D提取率及产品纯度的影响，选取丙酮作为提取用溶剂。在此基础上，测定了所用桑白皮颗粒的粒径分布，丙酮浸取桑根酮C、D的浸取平衡常数、浸取动力学曲线，并通过传质模型拟合实验曲线得到丙酮浸取桑白皮时桑根酮C、D的内扩散系数。同时，根据所测定的浸取平衡常数，并应用传质平衡模型推导了搅拌釜分批式浸取操作方式下桑根酮C、D的提取率与溶剂用量、浸取次数之间的关系，根据此关系式得到搅拌釜分批式浸取操作方式下的最佳操作条件为：浸取溶剂用量4.0ml／g桑白皮，浸取次数2次，最佳的浸取时间为10～20min。考察了渗滤操作在不同操作条件下的溶剂消耗和生产能力，并与搅拌釜分批式操作进行了比较，结果认为渗滤操作优于搅拌釜分批式操作。在此基础上，用解吸理论建立了渗滤过程中的数学模型，本模型第一次综合考虑了渗滤过程中的内扩散、外扩散、非线性平衡等温线，并以表观空隙率反应了桑白皮固体颗粒对渗滤溶剂的吸收，通过此模型得到了高浓度时丙酮浸取桑根酮C、D的浸取平衡曲线及渗滤过程中的外扩散传质速度与流速的关系，这为渗滤过程的放大和工艺参数的选择提供了理论依据和指导。
在溶剂萃取工序中，重点考察了萃取溶剂的种类、用量、萃取次数对杂质去除率及桑根酮C、D损失率的影响，从而确定了溶剂萃取工序的最佳操作参数。
在柱层析工序中，重点考察了各种固定相(酸性氧化铝、硅胶、聚酰胺、凝胶、C18键合硅胶及苯基键合硅胶)对桑根酮C、D的分离性能的影响，并用硅胶、聚酰胺两种固定相时，对洗脱剂、洗脱方式、床层堆密度、上样量进行了深入研究，同时在理论的指导下，研究了硅胶柱层析的放大
一
问题。
考虑到通过溶剂浸取的方法从桑白皮中提取桑根酮C、D需耗费大量有
机溶剂，而桑根酮C、D具有酸性，可溶于碱性水溶液，在本文的最后，对
碱液法从桑白皮中提取桑根酮C、D的可能性进行了探讨，首先研究了桑根
酮C、D在不同种类、不同浓度的碱液中的稳定性，得到了桑根酮C、D在
碱液中的降解速度方程，然后考察了碱种类、浓度、用量、处理时间、提
取次数、提取温度，盐酸酸化的pH对碱液法提取桑根酮C、D的提取率的
影响。
The identification, pharmacology and chemical constitutes of SangBaiPi(root bark of morus), and the pharmacology, physical chemistry properties, chemical structure, analysis and separation method of Sanggenon C and D were reviewed. The content of Sanggenon C and D in SangBaiPi were determined as 2.429 and 2.955mg/g root bark respectively. The new separation process of Sanggenon C and D and the operation parameters was established.
The new process is composed of three parts: leaching, extraction and column chromatography.
In leaching operation, based on the investigation of the effect of solvent ( methanol, ethanol, acetone, ether and ethyl ester) on the yield and content of Sanggenon C and D of the extract, acetone was the best solvent selected. The particle size distribution of SangBaiPi powder, the equilibrium constants of Sanggenon C and D between acetone solution and root bark powder, leaching dynamic curves, and the internal diffusion coffecients of Sanggenon C and D were determined. At the while, the relationship between solvent to solid ratio, leaching stage numbers and yield of Sanggenon C and D by batch operation was achieved based on an equilibrium model. As a result, the optimal operation parameters were as follow: solvent to solid ratio was 4.0 mg/g root bark, leaching stage numbers was 2, leaching time was between 10 minutes and 20 minutes. Furthermore, percolation was studied as well. The results showed that percolation was better than leaching judging by solvent consumption and productivity. The percolation mo
del taking into account of internal diffusion, external diffusion and nonlinear equilibrium equation was established.
In extraction operation, the effect of solvent, solvent to solid ratio and extraction stadge numbers on loss of Sanggenon C and D and removal of impurity was studied. In column chromatography, the effect of different solid phases including active alumina, silica, polyamide, gel, ODS and phenyl silica on separation of Sanggenon C and D was researched, the results showed silica and polyamide were good solid phases for separation of Sanggenon C and D. Furthermore, the elution solvent, elution method, column density, sample capacity were studied in-depth. Sanggenon C and D could be extracted from root bark by using base because
Sanggenon C and D are acidic, but Sanggenon C and D can be degraded in strong base solution. In order to find out the feasibility of extration by base solution, the stability of Sanggenon C and D in 0.5%Na2CO3, 2.0%Na2CO3, 3.5%Na2CO3, 5.0%Na2CO3, 0.5%NaOH, 1.0%NaOH, 1.5%NaOH, 2.0%NaOH solution was investigated, and the degradation rate equations of Sanggenon C and D were as follow:
1) In NaOH solution
dC/dt = -1.308 × 1011exp(-77702.8/RT) CC1.401 for Sanggenon C,
dC/dt = -5.751 × l0111exp(-83037.4/RT)CC1.400 for Sanggenon D.
2) In Na2CO3 solution
dC/dt = -1.414 × 1015 exp(-102918.5/RT)CC0.2955 for Sanggenon C,
dC/dt = -6.163 × 1014 exp(-101951.3/RT)CC0.3081 for Sanggenon D.
The results showed that the lossity of Sanggenon C and D were below 5.0% in Na2CO3 solution concentration under 2.0% and NaOH solution concentration under 0.5% at room temperature if reaction time was shorter than 30 minutes. Furthermore, the effect of base, consumption, reaction time, extaction stadge numbers, pH on yield of Sanggenon C and D was researched.
引文
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[2] 李振国，贾敏如，川、黔产桑白皮的品种调查，中药材，1991，14(8)：23
[3] 隋长惠，许春泉，白石明，桑白皮混淆品—构棘根皮的生药学鉴定，沈阳药科大学学报，1997，14(1)：36
[4] 王冬宫，我省桑白皮及其伪品鉴别，福建中医药，1996，27(6)：37
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