Cervical Cancer Prevention Prebiotic Device

通过优化，提出了一种用于预防宫颈癌的新型阴道内益生菌凝胶(PreBioGyn)。 阴道健康和治疗阴道生物失调(病原体和病原体过度生长) )，与高风险相关 人乳头瘤病毒(HrHPV)持续感染与肿瘤发生PreBioGyn是 OTC用户指导，2类 医疗设备，为低资源设置(LRS)中的女性提供独特的创新，具有最大的死亡风险 宫颈癌。HrHPV持久率增加和宫颈癌直接或间接相关 由于阴道pH值升高、有益的阴道微生物区系枯竭(例如： 皱纹乳杆菌)，以及粘膜屏障的破坏。宫颈炎症和阴道酸度降低是主要原因。 宫颈癌形成和发展的危险因素。非常需要一种负担得起的、易于使用的 使用能优化阴道酸碱度的阴道产品， 微生物区系和粘膜功能，预防宫颈癌 。 现有的阴道pH值“修正”缓冲液--凝胶降低了pH值，但对乳杆菌有害 和粘膜细胞和/或不 符合世卫组织关于阴道安全的指南。这对公共卫生具有重大意义。 鉴于~90%的 女性报告说，在过去的90天里，至少使用了一种阴道产品，这类产品的使用量也在增加 泌尿生殖系统事件(如阴道生物失调)3倍。事实上，在患有高血压病的女性之间存在显著的重叠 阴道产品的使用，hrHPV的持续存在和宫颈癌的发病率，部分原因是与产品相关的阴道 微生物群和粘膜损伤。初步数据显示，正在申请专利的PreBioGyn凝胶，具有一种新颖的 益生菌成分组合，支持卷曲葡萄球菌，同时抑制与宫颈癌相关的P.bivia生长 而且在粘膜安全性方面是无与伦比的。Glyciome和学术合作伙伴(布里格姆妇女医院和大学 波多黎各医学院)提出了第一阶段STTR研究，以建立临床前的安全性、有效性和 益生菌凝胶和新型涂敷器的可行性(低废物和运输成本、增强的用户便利性和 舒适度)。第1阶段的成功完成将展示以下内容。1)凝胶的阴道生物相容性 在生理相关的人体体外模型与领先的缓冲胶之间，基于以下定量测量：NO 宫颈阴道细胞损伤、炎症和/或免疫毒性；乳杆菌选择性上皮定植； 也没有促进病原体或宫颈癌细胞的增殖。2)Gel的用户感知和可接受性 在可量化的接受里程碑中，涂抹者与领先凝胶的对比。3)物理化学和功能性 凝胶的性能随时间的变化以及与领先凝胶的对比，以展示稳定性和卓越的功能性 符合建议的指南。4)集成制造原型的最终设计 与建议的制造商进行协调。该项目的成功完成将导致STTR第二阶段 扩大生产规模，优化阴道健康和预防宫颈癌的临床试验，以及 申请FDA的设备许可和从头开始的阴道健康声明。Glyciome在以下方面组建了一个专家团队： 产品开发；制造/销售；生物统计；生殖道生物学；以及全球宫颈癌护理。

A novel, intravaginal prebiotic-gel (“PreBioGyn”) is proposed for cervical cancer prevention, through optimization of vaginal health and treatment of vaginal dysbiosis (pathogen and pathobiont overgrowth ), related to high-risk human papillomavirus (hrHPV) persistence and oncogenesis. PreBioGyn is an OTC user-directed, Class 2 medical device, uniquely innovative for women in Low Resource Settings (LRS), at greatest risk of death from cervical cancer. Increased rates of hrHPV persistence and cervical cancer are directly and indirectly linked to vaginal dysbiosis, due to elevations in vaginal pH levels, depletion of beneficial vaginal microbiota (e.g. Lactobacillus crispatus), and disruption of the mucosal barrier. Cervicitis and reduced vaginal acidity are leading risk factors for cervical cancer formation and progression. There is a significant need for an affordable, easy-to use vaginal product that optimizes vaginal pH, microbiota and mucosal function, to prevent cervical cancer . Existing vaginal pH “correcting” buffer-gels lower pH, but harm Lactobacillus and mucosal cells and/or don’t conform to WHO guidelines for vaginal safety. This is of critical public health significance given that ~90% of women report use of at least one vaginal product in any past 90 days, with use of such products increasing urogenital events (e.g. vaginal dysbiosis) 3-fold. In fact, a significant overlap occurs between women with high vaginal product use, hrHPV persistence and cervical cancer incidence, due, in part, to product-related vaginal microbiome and mucosa damage. Preliminary data show that the PreBioGyn patent-pending gel, with a novel prebiotic ingredient combination, supports L. crispatus while suppressing cervical cancer-linked P. bivia growth and is unparalleled in mucosal safety. Glyciome and academic partners (Brigham &Women’s Hospital and Univ of Puerto Rico School of Medicine) propose Phase 1 STTR studies to establish preclinical safety, efficacy and feasibility of the prebiotic gel and novel applicator (low-waste and shipping cost, enhanced user-ease and comfort). Successful completion of Phase 1 will demonstrate the following. 1) Vaginal biocompatibility of the gel in a physiologically relevant human in-vitro model vs leading buffer-gels, based on quantitative measures of: no cervicovaginal cell damage, inflammation and/or immunotoxicity; selective epithelial colonization by Lactobacilli; and no enhanced proliferation of pathobionts or cervical cancer cells. 2) User perception and acceptability of gel and applicator vs leading gels in quantifiable milestones of acceptance. 3) Physicochemical and functional properties of the gel over time and vs leading gels to demonstrate stability, and superior functionality and conformance with recommended guidelines. 4) Final design of an Integrated Manufacturing Prototype for coordination with the proposed manufacturer. Successful completion of the project will lead to STTR Phase 2 manufacturing scale up, clinical trials for optimization of vaginal health and prevention of cervical cancer, and filing for FDA device clearance with de novo vaginal health claims. Glyciome has assembled an expert team in: product development; manufacturing/sales; biostatistics; genital tract biology; and global cervical cancer care.