Nitric oxide gas (NO) is a small, naturally produced, hydrophobic, free-radical gas. NO plays a major role in innate immunity. It exhibits broad reactivity and rapid diffusive properties through biological entities. NO has been shown to directly inhibit the growth of bacteria and also functions as a killer molecule within activated immune cells. NO has also been demonstrated to maintain vasodilation.
A study funded by Enox demonstrated that NO can be impregnated into urinary catheters and then be released slowly over two weeks, preventing the formation of biofilm and the establishment of microorganisms on the surface of catheters . Other studies have demonstrated that NO kills many strains of bacteria in organisms as well as bacteria that commonly cause nosocomial pneumonia , .
Enox uses NO as an antimicrobial agent. Enox’s patented NO technologies can be utilized for a wide spectrum of medical devices for the prevention of hospital acquired infections (HAI) and protect people from a diverse array of life threatening, drug resistant infections.
Advantages of using gNO as antimicrobial agent:
• gNO is a naturally occurring substance in the body – leads to simpler regulatory requirements.
• gNO has a short half life – exhibits low cell toxicity. No traces are left in the body after its action.
• gNO antimicrobial activity has a broad scope – effective against wide range of infections.
• gNO is not an antibiotic or antiseptic compound – eliminates antimicrobial resistance issues.
The Company’s platform technology is to embed NO into existing medical devices that have previously been cleared for marketing (without NO) by regulatory agencies by CE marking (Conformité Européene) and/or the FDA. The product development focus is on devices such as urinary catheters, endotracheal tubes, central venous catheters, tympanostomy tubes and other tubes that are inserted on a temporary basis and while crucial for patients’ care, are often associated with high rates of infection. The Company has developed a proprietary method of impregnating polymer-based devices with NO that is released over extended periods of time at levels demonstrating anti-microbial activity.
The following photograph compares colonization of E. coli (a bacteria that is commonly found in the lower intestine of warm-blooded organisms) on control and gNO-impregnated catheters after immersion of the catheters for 24 hours in suspension comprising different concentrations of E. coli:
The Company envisions a product portfolio consisting of a number of NO releasing medical devices. The common characteristics of such devices include being:
• Made of polymer materials
• Inserted on a short-term basis or permanently implanted
• Associated with high rates of infection
• Have already been approved for medical use by appropriate regulatory agencies
Our technology platform allows us to expand our product line based on the market need for antimicrobial medical devices that can reduce infection rates associated with their use. For example, future products may include venous line access port that is externally located, yet represents a common entry point for bacteria causing bloodstream sepsis. The evaluation criteria will include such factors as the market need, market size, the regulatory path and manufacturing cost considerations. The Company anticipates that the manufacturing process of NO impregnated devices will be inexpensive and easily integrated into existing production lines.
1 Regev-Shoshani, G., Ko, M., Miller C. and Av-Gay, Y. 2010 "Slow Release of Nitric Oxide from Charged Catheters and Its Effect on Biofilm Formation by Escherichia coli". Antimicrobial Agents and Chemoterpy.
2 Änddard, E. 1994 "Nitric Oxide: Mediator, Murderer and Medicine". Lancet Journal; 343: 1199-206.
3 McMullin, B., Chittock, D., L Roscoe D., Garcha, H., Wang, L. and Miller, C. 2005 "The Antimicrobial Effect of Nitric Oxide on the Bacteria That Cause Nosocomial Pneumonia in Mechanically Ventilated Patients in the Intensive Care Unit". Respiratory Care Vol 50 No 11.