苯扎氯铵溶液一次性用于感染腹腔冲洗的可行性研究

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (8): 885-890.

苯扎氯铵溶液一次性用于感染腹腔冲洗的可行性研究

刘小芳¹, 吴云明¹, 李建德², 左文子¹, 赵志鑫¹, 宋金方¹, 吴琏², 鲁茜¹, 杨海滨¹, 方翼³, 印晓星¹

¹徐州医学院药学院,徐州 221000,江苏;
²汕头保税区洛斯特制药有限公司,汕头 515000,广东;
³北京大学人民医院药剂科,北京 100044

收稿日期:2013-04-16 修回日期:2013-06-19 出版日期:2013-08-26 发布日期:2013-07-31
通讯作者: 方翼,男,博士,副教授,硕士生导师,主要研究方向:临床药理学。E-mail: Fygk7000@163.com; 印晓星,男,博士,教授,博士生导师,主要研究方向:肾脏药理学。E-mail: yinxx@xzmc.edu.cn
作者简介:刘小芳,女,在读硕士研究生,研究方向:临床药理学。Tel: 15162173617 E-mail: liuxiaofang1126@163.com

Benzalkonium chloride solution feasibility research on infected abdomen for disposable peritoneal irrigation

LIU Xiao-fang¹, WU Yun-ming¹, LI Jian-de², ZUO Wen-zi¹, ZHAO Zhi-xin¹, SONG Jin-fang¹, WU Lian², LU Qian¹, YANG Hai-bin¹, FANG Yi³, YIN Xiao-xing¹

¹School of Pharmacy, Xuzhou Medical College, Xuzhou 221000, Jiangsu, China;
²LUSTRE Pharmaceutical LAB.CO., LTD., Shantou F.T.Z., Shantou 515000, Guangdong,China;
³Pharmacy Department of Peking University People's Hospital, Bejing 100044,China

Received:2013-04-16 Revised:2013-06-19 Online:2013-08-26 Published:2013-07-31

摘要/Abstract

摘要： 目的: 苯扎氯铵溶液应用于腹腔感染的一次性冲洗,观察其抗菌作用和安全性。方法: 对铜绿假单胞菌、大肠埃希菌、金黄色葡萄球菌、枯草芽孢杆菌、白色念珠菌和黑曲霉菌的体外抑菌效果,以及SD大鼠和比格犬两种受试动物进行两个浓度苯扎氯铵溶液腹腔一次性冲洗后的安全性评价。体外抑菌试验采用二倍液体稀释法将 0.1%原液做15个稀释级,检测其对各菌种的最小抑菌浓度。安全性研究分为对照组,模型组以及 0.005%和 0.01%两个浓度的给药组;给药途径为一次性腹腔冲洗;大鼠给药体积为 180 mL/kg 体重;比格犬给药体积为 53.33 mL/kg 体重;给药后观察受试动物的一般行为表现;第8天检查腹腔内各器官的大体变化,并进行血常规检查以及取肝、脾、肠和腹膜等脏器标本做病理切片检查。结果: 苯扎氯铵溶液对铜绿假单胞菌、大肠埃希菌、金黄色葡萄球菌、枯草芽孢杆菌、白色念珠菌和黑曲霉菌的体外最小抑菌浓度分别为(6.25×10^-3)%、(3.12×10^-3)%、(9.76×10^-5)%、(9.76×10^-5)%、(3.91×10^-4)%和(6.25×10^-3)%;受试动物在手术后一周行为表现未见异常,腹腔各脏器没有明显肉眼可见毒性反应,血常规指标没有明显异常,肝、脾、肠和腹膜等脏器未见明显组织学变化。结论: 苯扎氯铵溶液对铜绿假单胞菌、大肠埃希菌、金黄色葡萄球菌、枯草芽孢杆菌、白色念珠菌和黑曲霉菌均有较强的体外抑菌效果;按SD大鼠 180 mL/kg 和比格犬 53.33 mL/kg 一次性给予 0.01%以下浓度(含 0.01%)的苯扎氯铵溶液腹腔冲洗是安全的。说明本溶液一次性用于感染腹腔冲洗具有可行性。

关键词: 苯扎氯铵溶液, 最小抑菌浓度, 腹腔冲洗, 安全性

Abstract: AIM: To observe the antibiosis effects and safety that Benzalkonium chloride (BAC) solution be used in infected abdomen for disposable irrigation.METHODS: To evaluate the antibiosis effects of BAC solution on Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans and Aspergillus niger in vitro and the safety for SD (Sprague Dawley) rats and beagle dogs after obtaining two concentrations of BAC solution by disposable peritoneal irrigation. The minimum inhibitory concentrations (MICs) of BAC solution on the cultures were observed by liquid double dilution method that 0.1% original solution was diluted into 15 levels in vitro antibiosis research.The animals were divided into control group, model group and two administration groups which concentrations were 0.005% and 0.01% in the safety research; the route of administration was disposable peritoneal irrigation; irrigating volume was 180 mL/kg body weight for rats and 53.33 mL/kg body weight for dogs; observe the animals' general behavior after the administration, on the eighth day, inspect the general changes of abdominal cavity and the organs in it, then draw blood to detect indexes of blood routine and the histopathology changes of liver, spleen, intestine and peritoneum.RESULTS: The MICs of BAC solution on Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans and Aspergillusniger were separately (6.25×10^-3)%、(3.12×10^-3)%、(9.76×10^-5)%、(9.76×10^-5)%、(3.91×10^-4)% and (6.25×10^-3)%. During a week after irrigation, there was no significant difference on general situation; the animals had no obvious visible abnormality in abdominal cavity organs; there was no significant influence on blood routine indexes,no significant histopathology changes on the liver, spleen, intestine and peritoneum in the animals.CONCLUSION: The antibiosis effects of BAC solution on Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans and Aspergillus niger in vitro are very good; and it is safe for SD rats and Beagle dogs with below 0.01% (including 0.01%) BAC solution for irrigation of peritoneal cavity only one time. It is feasible that BAC solution is used on infected abdomen for disposable peritoneal irrigation.

Key words: Benzalkonium chloride solution, MIC, Peritoneal irrigation, Safety

中图分类号:

R965.2

刘小芳, 吴云明, 李建德, 左文子, 赵志鑫, 宋金方, 吴琏, 鲁茜, 杨海滨, 方翼, 印晓星. 苯扎氯铵溶液一次性用于感染腹腔冲洗的可行性研究[J]. 中国临床药理学与治疗学, 2013, 18(8): 885-890.

LIU Xiao-fang, WU Yun-ming, LI Jian-de, ZUO Wen-zi, ZHAO Zhi-xin, SONG Jin-fang, WU Lian, LU Qian, YANG Hai-bin, FANG Yi, YIN Xiao-xing. Benzalkonium chloride solution feasibility research on infected abdomen for disposable peritoneal irrigation[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(8): 885-890.

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