PS/CHX
Kane Biotech has developed a broad-spectrum anti-infective composition PS/CHX comprising two FDA-approved compounds protamine sulfate (PS) and chlorhexidine (CHX) (U.S. Patent Publication No.20070003538 A1 and PCT International Publication No. WO/2007003028 A1). Protamine sulfate and chlorhexidine are combined because the former facilitates the transport of antimicrobial compounds to the cytoplasm (Antohi and Popescu, 1979) and the latter is a broadspectrum antimicrobial agent that has been demonstrated to successfully prevent clinical infections associated with catheters (Maki et al., 1997).
Protamine sulfate alters the permeability of microbial cell membrane and the dilation of ion channels, which facilitate the transport of antimicrobial compounds to the cytoplasm. In addition, antimicrobial activity of PS is presumably due to electrostatic attraction between the positively charged molecule and the negatively charged cell envelop, and appropriate concentrations cause growth inhibition or cell death because of leakage of K+, ATP and intracellular enzymes (Johansen, et al., 1997). Furthermore, PS has been reported to prevent Staphylococcus sp. adhesion to stainless steel (Matsumura, et al., 2007). Presumably, PS impairs bacterial biofilms by binding to polysaccharides and disrupting the microbes' hydrophilic surface coat (Teichman, et al., 1994).
Chlorhexidine is a membrane-active agent, causing protoplast and spheroplast lysis. At a higher concentration, it causes precipitation of proteins and nucleic acids (McDonnell and Russell, 1999). When PS is used in combination with CHX, it facilitates the transport of CHX to cytoplasm and thus reduces the effective concentration of CHX (Darouiche, et al. 2008). Protamine sulfate has been shown to enhance both in vitro and in vivo antimicrobial as well as antibiofilm activities of antibiotics and non-antibiotic compounds (Burton, et al., 2006; Hansen, et al., 2001; Richards, et al., 1990; Soboh, et al., 1995; Teichman, et al., 1994; Yakandawala, et al., 2007; U.S. Patent No. 7,144,992; U.S. Patent No. 7,314,857; Canadian Patent No. 2452032).
Kane Biotech Inc. has entered into a global commercial license agreement with Harland Medical, Inc. which provides Harland with world-wide rights to Kane's PS/CHX antimicrobial technology for use in coatings for urinary, venous access and veterinary catheters.
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