In vitro Microbiocidal Activity in Tears of N,N-dichloro-2,2-dimethyltaurine (NVC-422, AL-46383A), a Novel Topical Ophthalmic Agent

Abstract

 

Purpose:

 

To evaluate the microbicidal activity and chemical stabilityin synthetic tears of N,N-dichloro-2,2-dimethyltaurine (NVC-422),which is a synthetic analog of N-chlorotaurine (NCT). NCT isa relatively longer-lived endogenous antimicrobial componentproduced during oxidative burst by neutrophils and monocytes.

 

Methods:

 

Stability of NVC-422 in 10% synthetic tears containing lysozyme,IgG, albumin and other components was tested using HPLC withUV detection. Bacterial time kill kinetics was studied in 5mM acetate saline, pH 4 and in the presence of synthetic tears.Antiviral activity was determined by incubating viruses withserial dilutions of test compounds in 5 mM acetate saline, pH4 followed by cell infection. The titer of virus was calculatedbased on the number of wells that show cytopathic effect (CPE).The TCID₅₀ was determined from the dilution where 50% of thecultures were positive for CPE.

 

Results:

 

NVC-422 showed stability in 10% synthetic tears (97.5% remaining)after a 2 hr incubation. 0.3% NVC-422 in acetate saline pH 4in the presence of synthetic tears was bacteriocidal againstGram-positive and Gram-negative bacteria (Table1). Antiviralactivity of NVC-422 was retained in 10% synthetic tears. 0.1%NVC-422 reduced all viral titers to the limit of detection (Table2). See tables below.

 

Conclusions:

 

NVC-422 retains its chemical stability, virucidal and bactericidalactivity in presence of synthetic tears.  

 

 

Keywords: antiviral drugs • adenovirus • antibiotics/antifungals/antiparasitics