Gottardi Waldemar, Arnitz Roland, Nagl Markus
Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Fritz-Pregl-Str. 3, A-6020 Innsbruck, Austria.
Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Fritz-Pregl-Str. 3, A-6020 Innsbruck, Austria.
Int J Pharm. 2007 Apr 20;335(1-2):32-40. doi: 10.1016/j.ijpharm.2006.11.003. Epub 2006 Nov 3.
The bactericidal activity of the endogenous antiseptic N-chlorotaurine (NCT) is significantly enhanced in the presence of ammonium chloride which induces the formation of monochloramine (NH(2)Cl) whose strong bactericidal activity is well known. In this study the properties of NCT plus ammonium chloride have been investigated. The reaction of active chlorine compounds like chloramine-T (N-chlorotoluene-sulfonamide sodium), chloroisocyanuric acid derivatives, hypochlorites (NaOCl, CaOCl(2)) with ammonium chloride did not stop at the stage of monochloramine, and the pungent smelling by-products di- and trichloramine, NHCl(2) and NCl(3), were also formed. This was not the case with NCT where only monochloramine was generated. The equilibrium constant of the reaction of NCT with ammonium was found to be [Formula: see text] , which allows to estimate the equilibrium concentration of monochloramine in aqueous solutions of NCT and ammonium chloride. At concentrations each ranging between 0.01% and 1.0% it comes to [NH(2)Cl]=3.5-254 ppm. As an unexpected result the monochloramine containing formulation turned out to be most stable in plain water without buffer additives. Quantitative killing assays revealed complete inactivation of 10(6) to 10(7)CFU/mL of seven bacterial strains by 0.1% NCT plus 0.1% ammonium chloride within 5 min, while with plain 0.1% NCT an incubation time of 2-4h was needed to achieve the same effect. The highly significant increase of bactericidal activity (200-300-fold) could be assigned to the presence of monochloramine which could be isolated by vacuum distillation. Aqueous solutions of NCT and ammonium chloride provide a highly effective and well tolerable antiseptic preparation appropriate to a treatment cycle of at least 1 month if stored in the refrigerator.
内源性防腐剂N-氯代牛磺酸（NCT）在氯化铵存在下杀菌活性显著增强，氯化铵可诱导生成一氯胺（NH₂Cl），其一强大的杀菌活性广为人知。本研究对NCT加氯化铵的性质进行了研究。氯胺-T（N-氯甲苯磺酰胺钠）、氯异氰尿酸衍生物、次氯酸盐（NaOCl、CaOCl₂）等活性氯化合物与氯化铵的反应并不止于一氯胺阶段，还会生成刺鼻气味的副产物二氯胺和三氯胺，即NHCl₂和NCl₃。而NCT的情况并非如此，其仅生成一氯胺。发现NCT与铵反应的平衡常数为[公式：见原文]，据此可估算NCT和氯化铵水溶液中一氯胺的平衡浓度。在浓度均介于0.01%至1.0%之间时，[NH₂Cl]为3.5 - 254 ppm。出乎意料的是，含一氯胺的制剂在无缓冲添加剂的纯水中最为稳定。定量杀菌试验表明，0.1% NCT加0.1%氯化铵可在5分钟内使7种细菌菌株的10⁶至10⁷CFU/mL完全失活，而单纯0.1% NCT则需要2 - 4小时的孵育时间才能达到相同效果。杀菌活性的显著提高（200 - 300倍）可归因于一氯胺的存在，一氯胺可通过减压蒸馏分离出来。如果储存在冰箱中，NCT和氯化铵的水溶液可提供一种高效且耐受性良好的防腐剂制剂，适用于至少1个月的治疗周期。
