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）：拟议研究的目的是开发一种高效的鼻冲洗剂，以全新的方式治疗慢性鼻窦炎（CRS），因为它很少危及生命。根据 1992 年 CDC 生命和健康统计报告，估计会影响 13% 的美国人口，每年直接损失超过 80 亿美元，此外还造成 7300 万天的活动受限。 Coupling 表示，缺乏有效疗法的影响为解决市场上未满足的主要需求创造了一个强有力的机会，许多患有 CRS 的人表现出鼻窦腔内一氧化氮 (NO) 浓度的降低，NO 是一种有效的天然抗菌分子。健康个体的鼻窦中产生高水平的 NO，NOTA Laboratories, LLC 已发现安全且天然存在的治疗剂，可以提高鼻窦气道中的 NO 水平，并已被证明可以刺激粘膜纤毛清除和清除。减少微生物生物膜的形成 密歇根大学 Meyerhoff 博士的实验室花费了超过 15 年的时间研究 NO 释放剂/材料的生物医学应用，并与多个外部机构合作，在医疗保健领域利用 NO 的治疗特性。由研究人员、化学家、肺科医生和耳鼻喉科医生组成的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，该公司计划利用 NIH STTR 的资金。 1) 确定并优化一种配方，该配方可使用化学发光测量来检查 S-亚硝基谷胱甘肽 (GSNO) 以及典型的鼻窦冲洗盐水中的添加剂以及室温和 37 oC 下的 NO 释放速率；2) 测试此类 NO 的能力； -使用在粘液纤毛分化的原代窦上皮细胞培养物上建立的生物膜，释放溶液来破坏细菌生物膜、杀死生物膜细菌并增加体外纤毛跳动频率。结果将推动 II 期研究，NOTA 将在合适的动物模型中测试从 I 期研究得出的最佳鼻冲洗配方，作为与密歇根大学研究团队合作进行临床试验的前奏 医学院。