大孔吸附树脂法分离纯化洛伐他汀Extraction and purification of lovastatin using macroporous adsorption resin
卜光明,康宁
BU Guang-ming1,KANG Ning2 (1.Zhejiang Ruibang Laboratories
摘要(Abstract):
目的用大孔吸附树脂法分离纯化洛伐他汀,提高洛伐他汀成品收率,适应工业化生产的需要。方法采用6种非极性树脂进行静态、动态筛选试验,确定分离纯化洛伐他汀的吸附剂,进一步优化分离纯化洛伐他汀的最佳条件。结果洛伐他汀从发酵液中溶出最佳pH为11;国产HZ-818作为分离纯化洛伐他汀的吸附剂;最佳树脂吸附流速为每min 1/40树脂床体积;解析采用含质量分数1%氢氧化钠的体积分数为75%的乙醇溶液,流速为每min 1/100树脂床体积。结论用上述方法纯化洛伐他汀成品收率质量分数可达70%以上,产品质量符合《美国药典》(27版)规定。
Objective To isolate and purify lovastatin from fermentation broth of Aspergillus terreus by macroporous adsorptive resins.Methods Six resins were screened for isolation and purification of lovastatin from the fermentation broth.Results The optimum pH value for releasing lovastatin from the fermentation broth was 11;HZ-818 was selected as the adsorbent for isolating lovastatin from the filtered fermentation broth.The optimum condition for the column chromatography were as follows:the flow rate for adsorption is 1/40 resin bed volume·min-1,and the colunm was eluted with 1% NaOH in 75% ethanol at a flow rate of 1/100 resin bed volume·min-1.Conclusions The yield of lovastatin can be increased to 70% under the optimal condition,and the quality of the final product meets that required in USP 27.
关键词(KeyWords):
洛伐他汀;大孔吸附树脂;吸附剂;分离;纯化
lovastatin;macroporous adsorptive resin;adsorbent;isolation;purification
基金项目(Foundation):
作者(Author):
卜光明,康宁
BU Guang-ming1,KANG Ning2 (1.Zhejiang Ruibang Laboratories
参考文献(References):
- [1]LAROSA J C,HE J,VUPPUTURI S,et al.Effect ofstatins on risk of coronary disease:A meta-analysis ofrandomized controlled trials[J].JAMA,1999,282:2340-2346.
- [2]ENDO A,MONACOLIN K.A new hypocholesterolemicagent produced by aMonascusspecies[J].J Antibiot,1979,32:852-854.
- [3]ALBERTS A W,CHEN J,KURON G,et al.Mevino-lin:A highly potent competitive inhibitor of hydrox-ymethylglutarylcoenzyme A reductase and a cholesterollowering agent[J].Proc Natl Acad Sci USA,1980,77:3957-3961.
- [4]HAJKO P.Process for the isolation of lovastatin:UnitedStates,5712130[P].1998-07-27.
- [5]KUMAR P.Process for the isolation of lovastatin:Unit-ed States,7052886[P].2006-05-30.
- [6]周鹃,印培民.用HP-20大孔吸附树脂提取Mevas-tatin的研究[J].江西科学,1999,17(2):117-119.
- [7]文镜,刘迪,金宗濂.洛伐他汀检测方法研究进展[J].北京联合大学学报,2003,17(3):71-74.
- [8]国家药典委员会.中华人民共和国药典:二部[M].北京:化学工业出版社,2005:附录ⅣA.