Acido hipocloroso

Hypochlorous Acid as a Potential Wound Care Agent
Part I. Stabilized Hypochlorous Acid: A Component of the Inorganic Armamentarium of Innate Immunity
Wang L, PhD, a Bassiri M, PhD, a Najafi R, PhD, a Najafi K, MD, b Yang J, BS, a Khosrovi B, PhD, a Hwong W, BS, a Barati E, BS, a Belisle B, PhD, a Celeri C, MS a , and Robson MC, MD c
a

NovaBay Pharmaceuticals, Inc, Emeryville, CA; b EyeInstitute San Rafael, CA; and c Institute for Tissue Regeneration, Repair and Rehabilitation, Bay Pines, FL. Correspondence: mcrobson@earthlink.net Published April 11, 2007

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 drugfor 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 predominantspecies 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− ), and HOCl. At pH greater than 5.5, sodium hypochlorite (NaOCl) starts to form 3 and becomes the predominant species in the alkaline pH. To maintain HOCl solution in a stable form, maximize its antimicrobial activities, and minimizeundesirable 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 ofanimal toxicity, it is predicted that stabilized HOCl has potential pharmaceutical applications in the control of soft tissue infection.

A remarkable feature of the immune system is its ability to launch an effective response against invading pathogens by deploying a group of highly reactive chemicals, including oxidized halogens, oxidizing radicals, and singlet oxygen.1,2 As depicted in Figure1, the precursor of these reactive oxygen species (ROS) is the oxygen radical (O2 ), which is generated by specialized immune cells—neutrophils, eosinophils, mononuclear phagocytes, and B lymphocytes.1−9 Production of ROS in these cells is
This work was fully supported by NovaBay Pharmaceuticals, Inc, Emeryville, CA.

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VOLUME 6

Figure 1. A schematicrepresentation of hypochlorous acid (HOCl) production during the oxidative burst process. During this process, cells utilize O2 and convert it to hydrogen peroxide (H2 O2 ) using a mitochondrial-membrane–bound enzyme NADPHase. Then, myeloperoxidase catalyzes the reaction between H2 O2 and Cl− to generate HOCl. As deregulations take place, the lumen of the phagasome progressively becomes more acidicand leaves the bacterium within a vacuole (phagolysosome) containing MPOse and H2 O2 in a medium containing 0.1 M Cl− at estimated pH 4 to 6. During this process, conditions are optimal for MPOse-catalyzed generation of HOCl as depicted in this figure. On the basis of these principles, we set out to establish the conditions of generating the stable form of HOCl (NVC-101).

accompanied by asignificant rise in oxygen consumption, a series of events collectively referred to as the oxidative burst. The primary enzyme responsible for ROS production is a mitochondrial-membrane–bound enzyme known as respiratory burst NADPH oxidase.1 Patients with chronic granulomatous disease have oxidase defective genes, which makes them susceptible to repeated infection.10,11 During a respiratory burst,...