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

用于治疗/预防鼻窦炎的 S-亚硝基硫醇冲洗/气雾剂溶液

• 批准号: 8980847
• 负责人: Marc B. Hershenson
• 金额: $ 23.28万
• 依托单位: NOTA LABORATORIES, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2017-08-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8980847
• 关键词: Address; Adult; Aerosols; Affect; Amber; Animal Model; Antibiotics; Ascorbic Acid; Bacteria; Blood; Cell Culture Techniques; Centers for Disease Control and Prevention (U.S.); Chemicals; Chemiluminescence assay; Clinical Trials; Collaborations; Coupled; Coupling; Cysteine; Detection; Development; Devices; Direct Costs; Disease; Drug Formulations; Edetic Acid; Effectiveness; Epithelial Cells; Exhalation; Exhibits; Flushing; Frequencies; Funding; Gentian Violet; Glutathione; Health; Healthcare; Hour; Human; IL8 gene; Immune; Immunofluorescence Immunologic; In Vitro; Individual; Inflammatory Response; Innovative Therapy; Ions; Irrigation; Laboratories; Life; Marketing; Measures; Methods; Michigan; Microbial Biofilms; Microscope; Mucociliary Clearance; Mucous Membrane; Mucous body substance; Nasal cavity; Nitric Oxide; Nose; Organism; Otolaryngologist; Patients; Pharmaceutical Preparations; Phase; Population; Powder dose form; Prevention; Property; Pseudomonas aeruginosa; Reagent; Reporting; Research; Research Personnel; Risk; S-Nitrosoglutathione; S-Nitrosothiols; Saline; Selenocysteine; Sinus; Small Business Technology Transfer Research; Sodium Bicarbonate; Solutions; Specialist; Speed; Staining method; Stains; Staphylococcus aureus; Surface; Tablets; Technology; Temperature; Testing; Therapeutic; Therapeutic Agents; Time; Toxic effect; Trace metal; United States; United States National Institutes of Health; Universities; Vial device; Visit; Water; Work; antimicrobial; antimicrobial drug; base; chronic rhinosinusitis; cost; density; digital; economic impact; effective therapy; improved; killings; medical schools; microbial; microorganism; natural antimicrobial; phase 1 study; phase 2 study; prevent; productivity loss; public health relevance; reconstitution; rhinosinusitis; statistics

 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.

 描述（由申请人提供）：该研究的目的是开发一种高效的鼻腔冲洗剂，可以以全新的方式治疗慢性鼻窦炎（CRS）。CRS经常被忽视，因为它很少危及生命。据估计，CRS影响了令人震惊的13%的美国人口，每年的直接成本超过80亿美元，根据1992年CDC的生命和健康统计报告，还造成了7300万个有限的活动日。将上述影响与缺乏有效疗法相结合，为解决市场上未满足的主要需求创造了一个很好的机会。许多患有CRS的个体在他们的窦腔中表现出降低的一氧化氮（NO）浓度。NO是一种有效的天然抗菌分子，健康个体在鼻窦中产生高水平。NOTA实验室有限责任公司已经确定了安全和天然存在的治疗剂，可以提高窦气道中的NO水平。NO已被证明刺激粘膜纤毛清除并减少微生物生物膜形成。Meyerhoff博士在密歇根大学的实验室已经花了超过15年的时间研究NO释放剂/材料的生物医学应用，并与几个外部方合作，利用NO在医疗保健领域的治疗特性。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，并拥有专业知识，以进一步发展其治疗/预防CRS。利用NIH STTR的资金，该公司计划1）确定并优化一种配方，该配方将S-亚硝基谷胱甘肽（GSNO）沿着添加剂加入到典型的生理盐水鼻窦冲洗液中，并使用化学发光测量法检查室温和37 ℃下NO的释放速率;和2）测试这种NO释放溶液破坏细菌生物膜的能力，在体外使用在粘液纤毛分化原代窦上皮细胞培养物上建立的生物膜杀死生物膜细菌并增加纤毛搏动频率。这些结果将推动第二阶段研究，NOTA将在适当的动物模型中测试来自第一阶段研究的最佳鼻冲洗制剂，作为与密歇根大学研究小组合作进行临床试验的前奏。 医学院