N,N-DICHLORO-2, 2-DIMETHYLTAURINE, N-MONOCHLORO-2, 2-DIMETHYLTAURINE, AND N-CHLOROTAURINE ARE SAFE AND EFFECTIVE BACTERICIDAL AGENTS IN CORNEAL MODELS.
Background: N-chlorotaurine, NVC-422 (N,N-dichloro-dimethyltaurine) and NVC-612 (N-monochloro-dimethyltaurine) are potent anti-infective agents useful for the treatment of conjunctivitis and keratitis. The aim of this study is to show that these compounds are safe in an EpiOcular model and effective in corneas infected ex vivo with P. aeruginosa and S. aureus. Methods: Corneal disks were punched with a Trepan from Tyrolean farm pigs and scarified to produce artificial erosions. Disks were incubated with bacteria and subsequently washed with saline. The different test compounds were applied to the corneas in phosphate buffer at pH 7.1. Disks were homogenized followed by quantitative bacterial cultures or subjected to histological preparation. Ocular irritancy was tested using the EpiOcular™ tissue system (MatTek Corporation). Results: In histological sections, bacteria attached to the surface and accumulations of bacteria in the upper third of the stroma could be seen. All test compounds 1% (55 mM) NCT, 1.35% (55 mM) NVC-422, 1.15% (55 mM) NVC-612, 0.2% (11 mM) NCT + 0.2% (37mM) NH2Cl, or 0.1%(5.5 mM) NCT+ 0.1% (18.5 nM)) NH2Cl reduced the bacterial counts by approximately 5 log 10 after 60 min (P. aeruginosa) and 120 min (S. aureus) incubation. Significant cidal activity occurred after only 5 min incubation and increased over time. While surface bacteria were killed by using 70% ethanol for 0.5 min giving a 0.5-1 log 10 kill, additional treatment with the test compounds resulted in kill to the limit of detection suggesting that the test compounds killed tissue resident bacteria. Using an EpiOcular™ tissue model developed for in vitro irritancy testing, we further show that NCT, NVC-422 and NVC-612 have no or very low irritancy potential to corneal tissue in this study. Conclusions: The results demonstrate that NCT, NVC-422 and NVC-612 have the ability to kill P. aeruginosa and S. aureus, are non-irritating in cornea, and are potential therapeutic agents for the treatment of conjunctivitis and keratitis
Bactericidal agents, EpiOcular OCL-200, Neat protocol, Ocular irritation
N,N-dichloro-2, 2-dimethyltaurine, N-chlorotaurine, N-monochloro-2, 2-dimethyltaurine
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