S-Nitrosothiol-Based Rinse/Aerosol Solutions For Treatment/Prevention of Rhinosinusitis

 描述(申请人提供)：建议的研究目的是开发一种高效的鼻腔冲洗液，可以以一种全新的方式治疗慢性鼻窦炎(CRS)。CRS通常被忽视，因为它很少危及生命。根据1992年CDC生命和健康统计报告，CRS估计影响到惊人的13%的美国人口，每年的直接成本超过80亿美元，此外还导致7300万个有限的活动日。这种影响加上缺乏有效的治疗方法，创造了一个很好的机会来解决市场上一个主要的未得到满足的需求。许多CRS患者的窦腔内一氧化氮(NO)浓度降低。NO是一种强大的天然抗菌分子，健康的人在鼻窦中产生高水平的NO。Nota实验室有限责任公司已经确定了安全和自然发生的治疗剂，可以提高鼻窦呼吸道中的NO水平。NO已被证明可以促进粘液纤毛的清除，减少微生物生物膜的形成。迈耶霍夫博士在密歇根大学的实验室花了15年时间研究NO释放剂/材料的生物医学应用，并与几个外部机构合作，在医疗领域利用NO的治疗特性。Nota实验室的研究人员、化学家、肺病学家和耳鼻喉科医生团队相信这种创新疗法，并拥有进一步开发治疗/预防CRS的专业知识。利用这项来自美国国立卫生研究院科技研究中心的资金，该公司计划1)确定和优化含有S-亚硝基谷胱甘肽(GSNO)以及添加剂的典型盐水鼻窦冲洗液配方，并使用化学发光测量方法检测室温和37℃下的NO释放率；2)利用建立在黏液纤毛分化的原代鼻窦上皮细胞培养上清液上的生物膜，测试此类NO释放液在体外破坏细菌生物膜、杀灭生物膜细菌和增加纤毛跳动频率的能力。这些结果将推动第二阶段的研究，NOTA将在合适的动物模型上进行第一阶段的研究，作为与密歇根大学一个研究小组合作进行临床试验的前奏，从这一阶段第一阶段研究中获得最佳鼻液配方 医学院。

 DESCRIPTION (provided by applicant): The purpose of the research being proposed is to develop a highly effective nasal rinse that can treat chronic rhinosinusitis (CRS) in an entirely new way. Often CRS is overlooked because it is rarely life- threatening. CRS is estimated to affect an astounding 13% of the US population with direct costs exceeding $8 billion annually, and additionally causing 73 million limited activity days according to the 1992 CDC Vital and Health Statistics report. Coupling said impact with a lack of effective therapies creates a strong opportunity to address a major unmet need in the market. Many individuals suffering from CRS exhibit decrease nitric oxide (NO) concentrations in their sinus cavities. NO is a potent and natural antimicrobial molecule that healthy individuals produce at high levels in their sinuses. NOTA Laboratories, LLC, has identified safe and naturally occurring therapeutic agents that can enhance the levels of NO in the sinus airways. NO has been proven to stimulate mucociliary clearance and reduces microbial biofilm formation. Dr. Meyerhoff's laboratory at the University of Michigan has spent >15 years studying the biomedical applications of NO releasing agents/materials and has worked with several outside parties to harness the therapeutic properties of NO in the healthcare space. NOTA Laboratories' team of researchers, chemists, pulmonologists, and otolaryngologists believes in this innovative therapy, and has the expertise to further its development to treat/prevent CRS. Using funding from this NIH STTR, the company plans to 1) identify and optimize a formulation that incorporates S-nitrosoglutathione (GSNO) along with additives within typical saline sinus rinse solutions and examine the rates of NO release at room temperature and 37 oC using chemiluminescence measurements; and 2) test the ability of such NO-releasing solutions to disrupt bacterial biofilm, kill biofilm bacteriaand increase ciliary beat frequency in vitro using biofilms established on mucociliary- differentiated primary sinus epithelial cell cultures. The results will drive Phase II studies where NOTA will tes the optimal nasal rinse formulations derived from this Phase I study in suitable animal models as a prelude to clinical trials in collaboration with a research team at the University of Michigan Medical School.