NOTA Laboratories, Inc. — Department of Health and Human Services SBIR Phase I: 400

Description

ABSTRACT Nitric oxideNOplays a critical role in a wide range of bodily functionsincluding vasodilationneurotransmissionwound healingsuppression of platelet activationand modulation of ciliary beat frequencyFurtherinhaled gas phase NO is now routinely used to treat neonatal pulmonary hypertensionIn infectionNO released by neutrophils and macrophages functions as a potent antimicrobial antiviral agentand low nM concentrations of NO efficiently disperse biofilm formed by a variety of bacterial strainsRecent clinical trials have demonstrated its benefit in treating a variety of airway infectionsIn contrasttraditional antibiotics exhibit reduced efficacy against established bacteria coloniesi ebiofilmsand when used within a catheter lock solution they do not mitigate other catheter dysfunction problemsincluding thrombotic complications related to platelet activation along the outer surface of the catheterThusthe combined antimicrobial and antithrombotic properties of NO make it an ideal candidate to prevent catheter related blood stream infectionsCRBSIand thrombotic complications for end stage renal diseaseESRDpatients with tunneled dialysis cathetersTDCsRecentlyit has been shown that stabilized forms of NOS nitrosothiolsRSNOsare a convenient way to deliver therapeutic levels of NO for some of these medical applicationsNOTA Laboratories now proposes to use RSNO chemistry to develop two related disposable insert device variants for use with TDCs that are capable of releasing significant NO fluxes fordaysOne device variant would be a catheter insert cap that bathes the extracorporeal portionabove the pinch clampthe hub areaof a TDCto deliver bactericidal levels of NO in the catheter region most prone to bacterial intrusionThe second product variant would be a longer insert that would extend to the distal tip and release NO through the entire length of the TDCThese devices would consist of an appropriate narrow diameter polymeric tube packed with the RSNO in a hydratable matrixAfter each dialysis session the lumens of the TDC will be filled with saline lock solution and the devices will be inserted into both lumens where they will spontaneously generate NO until the next dialysis sessiontypicallydaysIf the TDC is composed of a NO permeable materialfibrin sheath formation on the outer surface of the TDC should also be suppressedPhase I research will focus on three aimsidentifying the optimal RSNO chemistry and tubing to make the deviceevaluating the NO release of the inserts within dual lumen medical grade TDC tubinganddemonstrating the antimicrobial activity of optimized disinfection inserts on the inner and outer surfaces of TDC catheter tubing NARRATIVE End Stage Renal Disease DialysisESRDi ekidney failureis a significant health problem in the United States and is commonly treated with hemodialysisHDeither by use of a surgically constructed shuntor by use of a tunneled dialysis central venous catheterTDCHoweverwidely used TDCs are associated with decreased patient survival due to multiple complications including central venous stenosisas well as high rates of infection and thrombosisrequiring an average ofhospitalizations per patient yearwithbeing infection relatedNOTA Laboratories now plans to develop a new product line of disinfection devices that consist of a tube packed with a dry reagent formulation containing a S nitrosothiolRSNOalong with appropriate additivesthat when inserted into the lumens of TDCswith lock solution withinis activated to release nitric oxideNOa potent bactericidal and anti thrombotic agentfor up todaysNOa gasdisperses throughout the catheter lumenspreventing bacterial colonization inside the catheter and furthermore permeates the walls of the catheternot possible with antibioticsto serve as a localized antimicrobial and anti thromboticanti platelet activationagent on the outer surfaces of the TDC