Despite the use of antibiotics, antiseptics, and improved sterile techniques, infection remains one of the most frequent complications of wound healing. Infection must be avoided to permit proper wound healing. Systemic and topical antibiotics and antiseptics with broad antimicrobial spectra have been used. Antiseptics have not generally been reported to develop bacterial resistance like antibiotics. Several reports have suggested that antiseptics exhibit significant cytotoxicity toward wound bed cells and may interfere with the normal wound healing process. Thus, for chronic ulcers, the standard of care is debridment and moist dressing with saline. We will describe the properties of a new topical antimicrobial solution, NVC-101. These include its broad-spectrum antimicrobial activities against gram positive, gram negative bacteria, yeast and fungi pathogens, and its lower toxicity as compared to commonly used topical antiseptics. In addition, we will describe the safety profile of NVC-101 in the rabbit eye and guinea pig sensitization models, as well as 28-day application to full thickness wounds in rats and mini-pigs. Based on these findings, multicenter Phase II clinical trials on infected chronic ulcers are under way.

OBJECTIVE:Hypochlorous acid (HOCl), a major inorganic bactericidal compound of innate immunity, is effective against a broad range of microorganisms. Owing to its chemical nature, HOCl has never been used as a pharmaceutical drug for treating infection. In this article, we describe the chemical production, stabilization, and biological activity of a pharmaceutically useful formulation of HOCl.METHODS:Stabilized HOCl is in the form of a physiologically balanced solution in 0.9% saline at a pH range of 3.5 to 4.0. Chlorine species distribution in solution is a function of pH. In aqueous solution, HOCl is the predominant species at the pH range of 3 to 6. At pH values less than 3.5, the solution exists as a mixture of chlorine in aqueous phase, chlorine gas, trichloride (Cl(3) (-)), and HOCl. At pH greater than 5.5, sodium hypochlorite (NaOCl) starts to form and becomes the predominant species in the alkaline pH. To maintain HOCl solution in a stable form, maximize its antimicrobial activities, and minimize undesirable side products, the pH must be maintained at 3.5 to 5.RESULTS:Using this stabilized form of HOCl, the potent antimicrobial activities of HOCl are demonstrated against a wide range of microorganisms. The in vitro cytotoxicity profile in L929 cells and the in vivo safety profile of HOCl in various animal models are described.CONCLUSION:On the basis of the antimicrobial activity and the lack of animal toxicity, it is predicted that stabilized HOCl has potential pharmaceutical applications in the control of soft tissue infection.