固体药用硬片的微生物污染状况分析
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摘要
目的:通过对158批聚氯乙烯固体药用硬片的微生物限度检查及其污染菌株的鉴定与分析,探讨国内固体药用硬片的微生物污染现状,为制定其微生物限度检查项和限值提供参考。方法:按照《国家药包材标准》,分别采用《中华人民共和国药典》2010年版二部和《中华人民共和国药典》2015年版四部的微生物限度检查方法对聚氯乙烯固体药用硬片进行细菌数、霉菌和酵母菌数、需氧菌总数、霉菌和酵母菌总数的测定以及大肠埃希菌的检查,并利用全自动微生物鉴定系统对样品中检出的污染菌株进行鉴定。结果:《中华人民共和国药典》2015年版四部的微生物限度检查方法对于聚氯乙烯固体药用硬片中污染微生物的检出率明显高于《中华人民共和国药典》2010年版二部,样品中检出的污染菌株中既有革兰氏阳性芽孢菌,也有革兰氏阴性菌。结论:固体药用硬片的生产和储运流程中存在微生物污染的风险,应建立关键环节的微生物污染物监控和追溯调查体系,并建议进一步完善其微生物限度检查标准和方法。
Objective:To investigate the microbial contamination in China and provide a reference for the microbial limit standard by microorgaMnismh oiddesntification and the microbial limit test of 158 batches of PVC sheet for solid pharmaceutical packaging. et:According to National Drug Packaging Standard and the microbial limit test adopted in Chinese Pharmacopoeia(2010 &2015 edition),the species and amounts of the total number of aerobe microbial,the total yeasts and molds,the number of bacteria,fungi and yeast strains and the E.coli,and the pollution strains were identified by the automatic bacteria identification test system,respectively. Results:The detection rate of microbial contamination by the method adopted in Chinese Pharmacopoeia(2015 edition)was significantly higher than the results by the method in Chinese Pharmacopoeia(2010 edition),and the identification result showed both gram-positive spore bacteria and gram-negative bacteria in the samples. Conclusion:Bacterium identification and microbial limit test results indicate that the production and storage of PVC sheet for solid pharmaceutical packaging have a high risk of microbial contamination. So microbial monitoring and retrospective investigation system in the key link should be established,and standards and methods of microbial limit test should be further improved.
Objective:To investigate the microbial contamination in China and provide a reference for the microbial limit standard by microorgaMnismh oiddesntification and the microbial limit test of 158 batches of PVC sheet for solid pharmaceutical packaging. et:According to National Drug Packaging Standard and the microbial limit test adopted in Chinese Pharmacopoeia(2010 &2015 edition),the species and amounts of the total number of aerobe microbial,the total yeasts and molds,the number of bacteria,fungi and yeast strains and the E.coli,and the pollution strains were identified by the automatic bacteria identification test system,respectively. Results:The detection rate of microbial contamination by the method adopted in Chinese Pharmacopoeia(2015 edition)was significantly higher than the results by the method in Chinese Pharmacopoeia(2010 edition),and the identification result showed both gram-positive spore bacteria and gram-negative bacteria in the samples. Conclusion:Bacterium identification and microbial limit test results indicate that the production and storage of PVC sheet for solid pharmaceutical packaging have a high risk of microbial contamination. So microbial monitoring and retrospective investigation system in the key link should be established,and standards and methods of microbial limit test should be further improved.
引文
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[2]李宝林.关于直接接触药品的包装材料和容器标准化管理的探讨和改进[J].中国药品标准,2012,13(2):129LI BL.Suggestions on administration of standardization for drug immediate packaging materials and containers[J].Drug Stand China,2012,13(2):129
[3]国家药包材标准[S].2015:188National Drug Packaging Standard[S].2015:188
[4]中华人民共和国药典2010年版.二部[S].2010:附录107Ch P 2010.VolⅡ[S].2010:Appendix 107
[5]中华人民共和国药典2015年版.四部[S].2015:通则1105Ch P 2015.VolⅣ[S].2015:Appendix 1105
[6]关维,陈仪本.枯草杆菌耐药转运蛋白Bmr及其基因Bmr的表达调控研究进展[J].微生物学通报,2012,39(2):246GUAN W,CHEN YB.Advances in multidrug resistance transporter Bmr of Bacillus subtilis and transcriptional regulation mechanism of its gene Bmr[J].Microb Chin J,2012,39(2):246
[7]蓝晓红,周永刚.临床药师在创伤术后枯草芽孢杆菌感染中的药学监护[J].抗感染药学,2013,10(1):68LAN XH,ZHOU YG.Clinical pharmacists in the trauma of pharmaceutical guardianship of postoperative infection of Bacillus subtilis[J].Anti Infect Pharm J,2013,10(1):68
[8]李国红,张克勤,沈月毛.枯草芽孢杆菌对50种中药的发酵及抗菌活性检测[J].中药材,2006,29(2):154LI GH,ZHANG KQ,SHEN YM.The fermentation of 50 kinds of TCMs by Bacillus subtilis and the a ssay of antibacterial activities of fermented products[J].Chin Med Mater J,2006,29(2):154
[9]房海,陈翠珍,张晓君.肠杆菌科病原细菌[M].北京:中国农业科技出版社,2011:89FANG H,CHEN CZ,ZHANG XJ.Pathogenic Bacteria of Enterobacteriaceae[M].Beijing:China Agricultural Science Press,2011:89
[10]时布卿.赣榆县人民医院条件致病菌发布及其耐药情况分析[J].医学动物防制,2011,27(11):1048SHI BQ.Pathogens release Ganyuxian people’s hospital and its drug resistance analysis[J].Med Post Control,2011,27(11):1048
[11]方四倍.希瓦菌血流感染2例实验诊断和临床分析[J].淮海医药,2013,31(2):139FANG SB.Shiva bacterial blood infection,2 cases of laboratory diagnosis and clinical analysis[J].Huaihai Med,2013,31(2):139
[12]梅玲.条件致病菌所致腹泻的病原学分析[J].临床医学,2004,24(10):49MEI L.Condition the etiology of diarrhea caused by pathogenic bacteria[J].Clin Med,2004,24(10):49
[13]贾红岩,崔婧,王轶.金黄色葡萄球菌感染的发布特征及耐药性分析[J].中华医院感染学杂志,2013,23(1):190JIA HY,CUI J,WANG Y.Distribution of Staphylococcus aureus infections and analysis of drug resistance[J].Chin J Nosocomiol,2013,23(1):190
[14]李颜颜,史峰,李烨.细菌类脂A结构与功能研究进展[J].微生物学报,2008,48(6):845LI YY,SHI F,LI Y.Structure and function of lipopolyaccharide lipid A in bacteria-A review[J].Acta Microbiol Sin,2008,48(6):845
[15]王小元,宋鸿军.细菌内毒素的生物合成途径及分子结构多样性[J].食品与生物技术学报,2013,32(10):1009WANG XY,SONG HJ.Biosynthesis pathway and structure variability of bacterial endotoxin[J].J Food Sci Biotechnol,2013,32(10):1009
[16]许文艳.医药塑料包装材料[M].北京:中国医药科技出版社,2003:68XU WY.Pharmaceutical Plastic Packaging Materials[M].Beijing:China Medical Science Press,2003:68
[17]鲁军,欧阳素英.塑料滴眼瓶微生物限度检查方法探讨[J].怀化学院学报,2007,26(2):11LU J,OUYANG SY.Study for microbial limit inspection method of eye drug plastic tube[J].Huaihua Univ J,2007,26(2):11
[18]刘倩,张媛,高华.对现行《国家药品包装容器(材料)方法标准》中生物安全相关标准的几点修改建议[J].药物分析杂志,2012,32(10):1889LIU Q,ZHANG Y,GAO H.Biosafety suggestions in current national drug packaging containers(material)standard[J].China J Pharm Anal,2012,32(10):1889
[19]JP16[S].2011:120
[20]EP 7.0[S].2010:5798
[21]USP 36-NF 31[S].2012:2023
[22]由亚宁,陈雪芹,周志云,2005年版《中国药典》和《欧洲药典》菌落计数培养基比较[J].中国药事,2010,24(6):587YOU YN,CHEN XQ,ZHOU ZY.Compare the colony counting method between the 2005 version Chinese Pharmacopeia and EP[J].Chin Pharm Aff,2010,24(6):587
[23]王似锦,刘文杰,牛振东.参苓白术丸微生物学质量分析与评价)[J].药物分析杂志,2013,33(4):673WANG SJ,LIU WJ,NIU ZD.Microbiological quality analysis and evaluation of Shenling Baizhu pills[J].Chin Pharm Anal,2013,33(4):673
[24]郭健.安徽省药包材监督抽验情况分析[J].中国药事,2008,22(12):1072GUO J.Analysis on surveillance of drugs packing material and containers in Anhui Province[J].Chin Pharm Aff,2008,22(12):1072
[25]高用华,张军.药包材企业构建质量管理体系的研究[J].中国药事,2012,26(7):659GAO YH,ZHANG J.Quality management system building for pharmaceutical packaging material enterprises[J].Chin Pharm Aff,2012,26(7):659
[26]冯殊良.高分子材料在药包材中的应用研究[J].当代化工研究,2016,8:134FENG SL.Research on the application of high polymer material in pharmaceutical packaging materials[J].Chem Intermed,2016,8:134