中空纤维更新液膜用于青霉素G提取的工艺研究
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摘要
青霉素是一种重要的抗生素产品,我国的发酵生产能力已接近世界先进水平,但产物分离和纯化的“下游工程”尚难以跟上其发酵技术的发展步伐。目前,发酵液中青霉素提取方法主要是溶媒物理萃取法,但该提取方法存在操作条件苛刻、青霉素降解损失较大、回收率低、溶媒回收困难等问题,使得青霉素生产成本增高,经济效益下降。因此开发新型高效的提取工艺以提高收率、减少能耗、降低成本,是当前青霉素类抗生素药物工业生产中亟待解决的关键问题之一。
基于表面更新理论提出的中空纤维更新液膜(HFRLM)技术实现了反应萃取和反萃过程的耦合,具有非平衡传质的特点,传质效率高,溶剂用量少。
为了避免青霉素G在中空纤维更新液膜萃取/反萃过程中出现大量降解损失的问题,本文首先系统地考察了不同微量有机溶剂(萃取剂)及不同碱液环境(反萃剂)对于青霉素G稳定性的影响。结果表明,微量胺类萃取剂的存在对青霉素G稳定性的影响不大;碱液的pH值越高,青霉素G降解速度越快;青霉素G在低温、pH 6.0左右环境下较为稳定。由HFRLM循环实验研究表明青霉素G在HFRLM提取过程中降解较少,有较好的稳定性,为HFRLM工艺研究中获得理想的提取效果提供可能。
以串级操作为基础,进行了中空纤维更新液膜提取青霉素G的工艺研究,考察了料液相pH、料液相中缓冲液浓度、料液相青霉素G浓度、反萃剂种类、反萃相浓度、两相流速、载体浓度等对中空纤维更新液膜提取效果的影响。结果表明,在料液相pH5.0-7.0范围内,pH值对提取效果影响不大;提取过程的传质通量随着料液中青霉素G的初始浓度、液膜相中载体浓度、壳程流速等的增大而增大;0.2 mol·L~(-1)的磷酸二氢钾缓冲溶液以及0.5 mol·L~(-1)的碳酸钾溶液可以使青霉素G在操作时间内保持较好的稳定性,降解损失少,提取效果可达90%以上。
对发酵液中青霉素G的中空纤维更新液膜提取工艺进行了技术经济评价,并与溶媒萃取工艺进行了比较。结果表明,中空纤维更新液膜提取工艺的提取效率高、产量大、萃取剂消耗量较少、后续处理简单、能耗低。
Penicillin is a widely used antibiotic and also serves as an important raw material for semisynthetic penicillins. But its traditional recovery technologies have some disadvantages, such as low efficiency, high solvent consumption, loss of penicillin G, etc. It is necessary to develop a new technology to reduce production cost.
A new liquid membrane technique, named hollow fiber renewal liquid membrane (HFRLM), is proposed based on surface renewal theory, which also integrates the advantages of fiber membrane extraction process, liquid film permeation process and other liquid membrane systems.
Considering the sensitivity of penicillin G to the surroundings with slight amount of organic solvent (extractant) and alkaline solution (stripping agent), in this study, the effect of temperature, pH, organic solvents, stripping agents on the stability of penicillin G are investigated. It is proved that slight amount of amine extractant has no influence on the stability of penicillin G; in the alkaline solution with high concentration, penicillin G shows its instability; penicillin G is stable at low temperature and pH 6.0.
Based on the series operation, recovery technology of penicillin G by hollow fiber renewal liquid membrane is studied. The effects of pH, concentration of penicillin G and buffer solution in the feed phase, K_2CO_3 concentration in the stripping phase, carrier concentration in the organic phase, flow rates of two sides on the recovery results by HFRLM are considered. The results show that the mass transfer flux increases with increasing the concentration of penicillin G in the initial feed phase, carrier concentration in the liquid membrane and flow rate of shell side. 0.2 mol·L~(-1) KH_2PO_4 buffer solution in the feed phase and 0.5 mol·L~(-1) K_2CO_3 solution as stripping agent can keep the stability of penicillin G during the operation period.
After economic evaluation of hollow fiber renewal liquid membrane technique, HFRLM is proved to have the advantages of high efficiency, low solvent and energy consumption, etc. And compared with solvent extraction for the recovery of penicillin G, HFRLM is considered to have a greater economic benefit.
基于表面更新理论提出的中空纤维更新液膜(HFRLM)技术实现了反应萃取和反萃过程的耦合,具有非平衡传质的特点,传质效率高,溶剂用量少。
为了避免青霉素G在中空纤维更新液膜萃取/反萃过程中出现大量降解损失的问题,本文首先系统地考察了不同微量有机溶剂(萃取剂)及不同碱液环境(反萃剂)对于青霉素G稳定性的影响。结果表明,微量胺类萃取剂的存在对青霉素G稳定性的影响不大;碱液的pH值越高,青霉素G降解速度越快;青霉素G在低温、pH 6.0左右环境下较为稳定。由HFRLM循环实验研究表明青霉素G在HFRLM提取过程中降解较少,有较好的稳定性,为HFRLM工艺研究中获得理想的提取效果提供可能。
以串级操作为基础,进行了中空纤维更新液膜提取青霉素G的工艺研究,考察了料液相pH、料液相中缓冲液浓度、料液相青霉素G浓度、反萃剂种类、反萃相浓度、两相流速、载体浓度等对中空纤维更新液膜提取效果的影响。结果表明,在料液相pH5.0-7.0范围内,pH值对提取效果影响不大;提取过程的传质通量随着料液中青霉素G的初始浓度、液膜相中载体浓度、壳程流速等的增大而增大;0.2 mol·L~(-1)的磷酸二氢钾缓冲溶液以及0.5 mol·L~(-1)的碳酸钾溶液可以使青霉素G在操作时间内保持较好的稳定性,降解损失少,提取效果可达90%以上。
对发酵液中青霉素G的中空纤维更新液膜提取工艺进行了技术经济评价,并与溶媒萃取工艺进行了比较。结果表明,中空纤维更新液膜提取工艺的提取效率高、产量大、萃取剂消耗量较少、后续处理简单、能耗低。
Penicillin is a widely used antibiotic and also serves as an important raw material for semisynthetic penicillins. But its traditional recovery technologies have some disadvantages, such as low efficiency, high solvent consumption, loss of penicillin G, etc. It is necessary to develop a new technology to reduce production cost.
A new liquid membrane technique, named hollow fiber renewal liquid membrane (HFRLM), is proposed based on surface renewal theory, which also integrates the advantages of fiber membrane extraction process, liquid film permeation process and other liquid membrane systems.
Considering the sensitivity of penicillin G to the surroundings with slight amount of organic solvent (extractant) and alkaline solution (stripping agent), in this study, the effect of temperature, pH, organic solvents, stripping agents on the stability of penicillin G are investigated. It is proved that slight amount of amine extractant has no influence on the stability of penicillin G; in the alkaline solution with high concentration, penicillin G shows its instability; penicillin G is stable at low temperature and pH 6.0.
Based on the series operation, recovery technology of penicillin G by hollow fiber renewal liquid membrane is studied. The effects of pH, concentration of penicillin G and buffer solution in the feed phase, K_2CO_3 concentration in the stripping phase, carrier concentration in the organic phase, flow rates of two sides on the recovery results by HFRLM are considered. The results show that the mass transfer flux increases with increasing the concentration of penicillin G in the initial feed phase, carrier concentration in the liquid membrane and flow rate of shell side. 0.2 mol·L~(-1) KH_2PO_4 buffer solution in the feed phase and 0.5 mol·L~(-1) K_2CO_3 solution as stripping agent can keep the stability of penicillin G during the operation period.
After economic evaluation of hollow fiber renewal liquid membrane technique, HFRLM is proved to have the advantages of high efficiency, low solvent and energy consumption, etc. And compared with solvent extraction for the recovery of penicillin G, HFRLM is considered to have a greater economic benefit.
引文
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