头孢喹肟研究进展

摘要/Abstract

摘要： 头孢喹肟(cefquinome)是第4代头孢菌素类动物专用抗生素,是一种治疗动物严重感染的新药,具有独特的抗菌机制和良好的抗菌活性,其抗菌谱广、抗菌活性强,药动学优良,血药浓度达峰时间短、浓度高,无致癌性、致突变性、致畸性、无繁殖毒性。对其作用机理、理化性质、药理学性质及合成路线等方面进行综述,并分析头孢喹肟在合成中存在收率低、处理困难等问题,以便医药科技工作者全面了解,进而用以指导临床应用。

关键词: 头孢喹肟; 5,6,7,8-四氢喹啉; 药理学性质; 合成

Abstract: As the fourth generation of aminothiazolyl cephalosporin,cefquinome was developed especially for using in animals, and a new drug for animal severe infection, which had antibacterial mechanism and antibacterial activity. Cefquinome was known as broad antibacterial spectrum, strong antibacterial activity, superior pharmacokinetics, and no carcinogenicity, mutagenicity, teratogenicity, reproductive toxicity. The blood concentration of cefquinome reached its peak in short time, and had high concentration. The paper summarized the cefquinome’s antibacterial activity, physicochemical properties and pharmacological properties, synthetic routes, a number of problems in synthesizing cefquinome, such as low yield and post treatment difficult were also analyzed, to lead pharmaceutical scientific worker with thorough knowledge and guide clinical application.

Key words: cefquinome; 5,6,7,8-tetrahydroquinoline; pharmacological properties; synthesis

中图分类号:

S859.79⁺6

刘美端, 赵地顺, 刘宝树, 刘林英, 汪学良, 李俊盼, 葛京京. 头孢喹肟研究进展[J]. , 2013, 40(4): 216-221.

LIU Mei-duan, ZHAO Di-shun, LIU Bao-shu, LIU Lin-ying, WANG Xue-liang, LI Jun-pan, GE Jing-jing. Research Advance on Cefquinome[J]. , 2013, 40(4): 216-221.

参考文献

1 王玲,张振安,李树英,等. 硫酸头孢喹肟的合成方法: CN 102002058A.2011-04-06.
2 张许科,刘兴金,张永奎,等.一种制备硫酸头孢喹诺的方法:CN 101108858A.2008-01-23.
3 李长青,崔增学. 硫酸头孢喹肟的制备方法: CN 101307064A.2008-11-19.
4 李常青,闫祥华,薛俊娟,等. 硫酸头孢喹肟的合成[J].应用化工,2008,37(2):231~232.
5 杜向党,李新生,吴宇鹏,等.头孢喹诺的最新研究进展[J].中国畜牧兽医,2006,33(9):15~17.
6 杨美丽,郑国钧. 硫酸头孢喹诺的合成[J].化学试剂,2008,30(10):787~788.
7 辛海红,范中元. 头孢噻肟酸合成母液回收工艺的研究[J].黑龙江医药,2004,17(2):121~122.
8 邵意阳,屈一新,任慧. 硫酸头孢喹肟的合成[J].中国医药工业杂志,2007,38(6):405~406.
9 洪玲娟,郑叶敏,汤有坚,等. 头孢噻肟酸的环境友好合成工艺[J].浙江化工,2010,41(3):15~17.
10 荣俊,张军忍,余祖功,等. 国产硫酸头孢喹肟对小鼠的急性和蓄积毒性研究[J]. 动物医学进展,2008,29(2):48~51.
11 赵德明,竺三奇,费可方,等.头孢噻肟酸的合成研究[J]. 浙江工业大学学报,2010,38(1):7~10.
12 钟为慧,洪玲娟,汤有坚,等. 一种头孢噻肟酸的绿色合成方法: CN 101550149A. 2009-10-07.
13 谢英新,陈玉山,崔嵘,等.一种头孢噻肟的制备方法:CN 101613360A. 2009-08-07.
14 Aarestrup F M, Skov R L. Evaluation of ceftiofur and cefquinome for phenotypic detection of methicillin resistance in Staphylococcus aureus using disk diffusion testing and MIC-determinations. Veterinary Microbiology,2010,140(1~2):176~179.
15 Aurich C, Spergser J. Influence of bacteria and gentamicin on cooled-stored stallion spermatozoa. Theriogenology, 2007, 67(5):912~918.
16 Bottner A, Schmid P, Humke R. In vitro efficacy of cefquinome (INN) and other anti-infective drugs against bovine bacterial isolates from Belgium, France, Germany, the Netherlands, and the United Kingdom. Zentralbl Veterinarmed B,1995,42(6):377~386.
17 Bradley A J, Green M J. Factors affecting cure when treating bovine clinical mastitis with cephalosporin-based intramammary preparations. Journal of Dairy Science, 2009, 92(5):1941~1953.
18 Cerniglia C E, Kotarski S. Approaches in the safety evaluations of veterinary antimicrobial agents in food to determine the effects on the human intestinal microflora. Journal of Veterinary Pharmacology and Therapeutics,2005,28(1):3~20.
19 Chin N X, Gu J W, Fang W, et al. In vitro activity of cefquinome, a new cephalosporin, compared with other cephalosporin antibiotics.Diagn Microbiol Infect Dis,1992,15(4):331~337.
20 Deshpande P B, Deshpande P N, Srinivasan S, et al. Thioester derivatives of thiazolyl acetic acid and their use in the preparation of cephalosporin of cephalosporin compounds: US 6610845.2003-08-26.
21 Ehinger A M, Schmidt H, Kietzmann M. Tissue distribution of cefquinome after intramammary and "systemic" administration in the isolated perfused bovine udder. The Veterinary Journal, 2006,172(1):147~153.
22 Guerin-Faublee V, Carret G, Houffschmit P. In vitro activity of antimierobial 10 antimicrobial agents against bacteria isolated from cows with clincalmastitis. The Veterinary Record,2003,152(15):466~471.
23 Kang T W, Lee H W, Cha K H, et al. Diethyl chlorophosphate: An effective and convenient coupling reagent of cephalosporin derivatives. Synth Commun,1998,28:35~44.
24 Khanna J M, Handa V K, Dandala R, et al. Process for producing cephalosporin antibiotics: US 5869649.1999-02-09.
25 Knappstein K, Suhren G, Walte H G. Influence of milking frequency on withdrawal period after application of lactam antibiotic-based drugs. Analytica Chimica Acta,2003,483(1):241~249.
26 Lang I, Rose M, Thoms E. A field study of cefquinome for the treatment of pigs with respiratory disease. Revue de Medicine Veterinaire,2002,153(8~9):575~578.
27 Limbert M, Isert D, Klesel N, et al. Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin. Antimicrobial Agents and Chemotherapy,1991,35(1):14~19.
28 Macher. Production of cefotaxime and new sodium salts: WO 9620198.1996-07-04.
29 Melnikow E, Schoenfeld C, Spehr V, et al. A compendium of antibiotic-induced transcription profiles reveals broad regulation of Pasteurella multocida virulence genes. Veterinary Microbiology,2008,131(1~3):277~292.
30 Murphy S P, Erwin M E, Jones R N. Cefquinome (HR 111V). In vitro evaluation of a broad-spectrum cephalosporin indicated for infections in animals. Diagnostic Microbiology and Infectious Disease,1994,20(1):49~55.
31 Parlevliet J M, Lynn J W, Paccamonti D L. The use of cefquinome in equine semen extender. Journal of Equine Veterinary Science,2011,31(3):139~142.
32 Pejsak Z, Kolodziejezyk P. Incidence and drug sensitivity of bacterial isolated form diseased lungs in pigs. Medyeyna Weterynaryjna,2001,57:7480~7485.
33 Pengov A. Treament of clinical and subclinical mastitis cases with Gobactan. Veterinarske Novice(Slovenia), 2001, 27(4):145~148.
34 Rudolf L, Taunus K, Walter D, et al. Crystallized cephem-acid addition salts, and a pross for the preparation thereof: US 4845087.1989-07-04.
35 Shpigel N Y, Schmid P. Contribution to the treatment of acute bovine mastitis with cefquinome. Tierarztliche Praxis,1997a,25(3):200~206.
36 Shpigel N Y, Levin D, Winkler M,et al. Efficacy of cefquinome for treatment of cows with mastitis experimentally induced using Escherichia coli. Journal of Dairy Science,1997b,80(2):318~323.
37 Sørensen L K, Snor L K. Determination of cephalosporins in raw bovine milk by high-performance liquid chromatography. Journal of Chromatography A, 2000,882(1):145~151.
38 Suhren G, Knappstein K. Detection of cefquinome in milk by liquid chromatography and screening methods. Analytica Chimica Acta,2003,483(1): 363~372.
39 Sung K L, Soon K M, Gwan S L. Process for preparing cephem derivatives: EP 0175814. 1986-02-04.
40 Thomas E, Thomas V, Wilhelm C. Antibacterial activity of cefquinome against equine bacterial pathogens. Veterinary Microbiology,2006,115(1~3):140~147.
41 Uney K, Altan F, Elmas M. Development and validation of a high-performance liquid chromatography method for determination of cefquinome concentrations in sheep plasma and its application to pharmacokinetic studies. Antimicrobisal Agents And Chemotherapy, 2011, 55(2):854~859.
42 Wilfried S, Walter D, Reiner K, et al. Process for the preparation of cephem compounds: US 4667028.1987-05-19.

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