NOTA Laboratories, Inc. — Department of Health and Human Services SBIR Phase I: NHLBI

Description

AbstractNitric oxideNOplays a critical role in a wide range of bodily functionsincluding vasodilationneurotransmissionwound healingsuppression of platelet activationand modulation of ciliary beat frequencyIn additionit is a potent and endogenous antimicrobial antiviral agent produced by macrophages and normally present at moderate levelsppmvwithin the upper airways sinuses of healthy individuals to help prevent chronic upper airway infectionsIt has been found that significant suppression of NO levels occurs in patients suffering from chronic rhinosinusitisCRSand difficult to treat lower respiratory infections associated with chronic obstructive pulmonary diseaseCOPDand cystic fibrosisCFConsequentlyit has been shown that patients with respiratory maladies benefit greatly from inhaled nitric oxideiNOtherapyIn additioniNO at higher levelsppmvis routinely used in the hospital setting to treat newborns with pulmonary hypertensionadults with acute respiratory distress syndromeARDSand patients with of other respiratory infections such as pneumonia and tuberculosisFurtherit has been demonstrated that iNO therapy improves reperfusion of brain tissue after a strokepromotes recovery in liver transplant patientsand prevents systemic inflammatory response syndromeSIRSwhen added to the oxygenator sweep gasin patients that undergo cardiopulmonary bypass surgeryCPBCurrentlythe high cost$per dayof iNO delivery systemswhich rely on low NO concentrations in metal gas cylindersrestricts the use of gas phase NO both within and outside of the hospital settingGiven the wide diversity of applications and the need to deliver NO in various health care settingsin patient out patient careand at a much lower costthere is a growing need for an inexpensiveportable and simple to use system to create gas phase NO on demandWorking in collaboration with researchers in the Department of Chemistry at the Univof MichiganNOTA Laboratories proposes to develop such an iNO delivery systemNOTA s proposed product will consist of a single use reel to reel cartridge containing a rollmof S nitrosothiolRSNOeither S nitroso N acetylpenicillamineSNAPor S nitroso glutathioneGSNOimmobilized onto a polymer carrierThe roll of RSNO film will be housed within a light resistant compartment and advanced through an illumination zone that is equipped with several light emitting diodesLEDsthat produce wavelengths at which NO can be efficiently photo released from the RSNO speciesnmThe advancement of the film through the translucent light compartment will be achieved using a motor driven pick up wheel that is controlled through a feedback loop employing a NO electrochemical gas phase sensor situated in line within the output air streamA stream of humidified air will be pumped through the NO generating chamberwith the LEDs intensity being adjusted via the feedback loop to release NO into the air stream to provide target concentrations of NOppmvThe NO released will then pass out of the LANOR system into the patient s nose via cannula nasal tubes or a nasal maskPhase I research will focus on the building a prototype device that can accommodate the reel toreel cartridge with an NOsuppression filter as well as developing the roll of film containing the immobilized RSNO speciesFinallya demonstration of the prototype device s ability to deliver pure NO at levels betweenandppmv for up toweek will be made through control of the film advancement and intensity of the illuminationLong term storage stability studies will demonstrate that the immobilized RSNO film is stable under ambient heat and humidity conditions when stored in an aluminum foil pouchIt is anticipated that the proposed LANOR system will be able to deliver a broad range of therapeutic iNO levels for at leastweekdepending upon the desired NO level and rate of air delivery NARRATIVE Neonate pulmonary hypertensionNPHand systemic inflammatory response syndromeSIRSassociated with cardiopulmonary bypassCPBsurgeryin the hospital setting can be treated with inhaled nitric oxideiNOtherapy or adding NO gas to the sweep gas of the oxygenatorrespectivelyChronic obstructive pulmonary diseaseCOPDand chronic rhinosinusitisCRStogether affect an estimatedof the US population and both diseases are associated with frequent respiratory tract infectionsCystic fibrosisCFaffects capatients in the U Sbut their risk for severe infection is greater because they have abnormally low levels of nitric oxideNOa potent endogenous antimicrobial antiviral agentwithin their airwaysThrough the research described in this applicationNOTA Laboratories will develop an inexpensive and simple gas phase NO generation system based on photolysis of immobilized S nitrosothiol species that can be used both in the hospital and at outpatient in home settings to treat these disorders by delivery of NO at levels betweenppmv for extended time periodsup tod of useat very low cost relative to using cylinders of NO gas