摘要
凡对细菌和其他微生物具有抑制和杀灭作用的物质统称为抗菌药,包括人工合成抗菌药(喹诺酮类等),和由微生物产生的、能杀灭或抑制其他病原微生物的次级代谢产物及其衍生物。对后者而言,参与次级代谢产物的生物合成酶的底物专一性差,导致在其发酵过程中会产生一系列结构类似的衍生物,不利于产物的分离纯化,但为抗菌药"共线联产"工艺创新创造了条件。在获得2019年国家科技进步二等奖的"依替米星和庆大霉素联产的绿色、高效关键技术创新及产业化"项目中,我们首先提出抗菌药"共线联产"的概念。抗菌药"共线联产"工艺创新,不是常规意义上的副产物回收,而是通过菌种选育和发酵调控技术平衡提高"被联产"产物的合成能力,以及根据目标产品的要求,通过分离纯化技术进行"主动调配"以实现经济效益和环境效益最大化。本文对抗菌药"共线联产"工艺创新的基本思路、条件,以及可"共线联产"工艺创新的抗菌药品种进行了分析和梳理。通过分析氨基糖苷类抗菌药"共线三联产"工艺创新的实践成果,为抗菌药工艺创新提供参考。
Antibacterial drugs,including synthetic antibacterial drugs(quinolones for example)and secondary metabolites and derivatives produced by microorganisms,are substances with inhibitory and killing effects on pathogenic bacteria and other microorganisms.Due to the poor substrate specificity of biosynthetic enzymes involved in secondary metabolites,a series of derivatives with similar structures will be produced during the fermentation of antibiotics,which is not conducive to the separation and purification of antibiotics,but it creates conditions for the technological innovation of"co-production"of antibiotics.In the project of"Green,High-efficiency Key Technology Innovation and Industrialization of Etimicin and Gentamicin Co-production",which won the second prize of the National Science and Technology Progress Award in 2019,we first proposed the concept of antibiotics"co-production".The technological innovation of antibiotics"co-production"is not a by-product recovery in the conventional sense.Indeed,it uses strain breeding and fermentation control technology to balance and improve the synthesis ability of the"co-produced"products.And according to the requirements of the target product,the separation and purification technology is used to carry out"active deployment"to realize the high-efficiency antibacterial preparation process that maximizes economic and environmental benefits.In this paper,the basic ideas and conditions of the process innovation of antibiotics"co-production"are analyzed,and some of the antibiotics that are suitable for"co-production"process are listed.Meanwhile,the practical results of the process innovation of aminoglycoside antibiotics"co-line triple production"are illustrated,which provides some references for the process innovation of antibiotics.
作者
李继安
林惠敏
陈代杰
LI Ji'an;LIN Huimin;CHEN Daijie(Shanghai Institute of Pharmaceutical Industry,China State Institute of Pharmaceutical Industry,Shanghai 201203;School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2020年第11期1347-1355,共9页
Chinese Journal of Pharmaceuticals
关键词
抗菌药
工艺创新
共线联产
平衡提高
主动分配
antibiotics
process innovation
co-line production
balancing improvement
active allocation
