Teuchner Barbara, Schmid Eduard, Ulmer Hanno, Gottardi Waldemar, Nagl Markus
Department of Ophthalmology, Innsbruck Medical University, Innsbruck, Austria.
Graefes Arch Clin Exp Ophthalmol. 2008 Dec;246(12):1723-30. doi: 10.1007/s00417-008-0900-x. Epub 2008 Aug 12.
N-chlorotaurine (NCT), an endogenous mild antiseptic, is well-tolerated by application to the human conjunctiva and has been shown to offer beneficial effects in infectious conjunctivitis. Animal tests revealed improved efficacy of a combination of NCT with ammonium chloride in adenoviral conjunctivitis. The aim of this study was to evaluate the tolerability of NCT plus ammonium chloride in the healthy rabbit and human eye.
First, a tolerability study was performed in rabbits. In a blinded and randomized fashion, one eye was treated with the test medication, the other one with 0.9% saline. Twenty-one animals (three per concentration) were treated with one drop every 2 hours for 6 days. Second, in two volunteers one drop of a defined concentration was applied to one eye every 15 min for 1 hour, saline to the control eye. Four different concentrations were tested on different days. Third, a double-blind, randomized phase 1 study in 13 healthy volunteers was performed. One drop of 0.1% NCT plus 0.1% NH(4)Cl versus saline was applied every 15 min within the first hour, followed by four drops every 2 hours. This regimen was done daily for 5 days.
In rabbits, no side effects were seen with 0.1% NCT plus 0.1% NH(4)Cl, while higher concentrations sometimes caused short-time and minimal conjunctival injection and secretion after dosing. By 1% NCT plus 1% NH(4)Cl, these effects were moderate, but disappeared again without any detectable residues. In the pilot study with two volunteers, treatment with 0.5% NCT plus 0.1% NH(4)Cl caused medium-scale eye burning for 30 seconds, while 0.1% NCT plus 0.1% NH(4)Cl was very well-tolerated, with no or minimal burning for a few seconds. In the subsequent phase 1 study, 0.1% NCT plus 0.1% NH(4)Cl was well-tolerated by all subjects except for minimal eye burning for a few seconds after dropping. No objective signs of eye changes could be detected in the human beings.
The results of this study clearly demonstrate the good tolerability of a promising NCT formulation with improved activity.
N-氯代牛磺酸（NCT）是一种内源性温和防腐剂，应用于人体结膜时耐受性良好，且已证实在感染性结膜炎中具有有益作用。动物试验显示，NCT与氯化铵联合使用对腺病毒性结膜炎具有更高疗效。本研究旨在评估NCT加氯化铵在健康兔眼和人眼中的耐受性。
首先，在兔身上进行耐受性研究。采用双盲随机方式，一只眼用受试药物治疗，另一只眼用0.9%生理盐水治疗。21只动物（每种浓度3只）每2小时滴一滴，共治疗6天。其次，在两名志愿者中，每15分钟向一只眼滴一滴特定浓度的药物，共滴1小时，对照眼滴生理盐水。在不同日期测试四种不同浓度。第三，对13名健康志愿者进行双盲随机1期研究。在第1小时内每15分钟向一只眼滴一滴0.1%NCT加0.1%NH₄Cl，对照滴生理盐水，随后每2小时滴4滴。该方案每天进行，共5天。
在兔中，0.1%NCT加0.1%NH₄Cl未观察到副作用，而较高浓度有时在给药后会引起短暂且轻微的结膜充血和分泌物增多。在1%NCT加1%NH₄Cl时，这些效应较为中度，但再次消失且无任何可检测到的残留。在两名志愿者的初步研究中，0.5%NCT加0.1%NH₄Cl治疗引起中等程度的眼部灼痛30秒，而0.1%NCT加0.1%NH₄Cl耐受性良好，仅有几秒的轻微灼痛或无灼痛。在随后进行的1期研究中，除滴药后有几秒轻微眼部灼痛外，所有受试者对0.1%NCT加0.1%NH₄Cl耐受性良好。在人体中未检测到眼部变化的客观体征。
本研究结果清楚地证明了一种有前景的、活性增强的NCT制剂具有良好的耐受性。
