Cervical Cancer Prevention Prebiotic Device

预防宫颈癌益生元装置

• 批准号: 10252708
• 负责人: Joanna Elizabeth Ellington
• 金额: $ 40万
• 依托单位: GLYCIOME, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-17 至 2023-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10252708
• 关键词: Acidity; Advanced Development; American; Bacteria; Biology; Biometry; Buffers; Businesses; Cancer Patient; Caring; Cell Proliferation; Cells; Cervicitis; Cessation of life; Clinical Trials; Data; Devices; Diagnosis; Direct Costs; Disease; Dose; Ecology; Enrollment; Epithelial; Ethnic Origin; Evaluation; Event; Excipients; Gel; Genitourinary system; Growth; Guidelines; HPV-High Risk; Health; Healthcare; High Prevalence; High-Risk Cancer; Hospitals; Human; Human Papillomavirus; Human papilloma virus infection; Incidence; Inflammation; Insurance; Lactobacillus; Legal patent; Link; Lubricants; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Manufacturer Name; Marketing; Measures; Medicaid; Medical Device; Mucous Membrane; Oncogenic; Osmolalities; Pathway interactions; Perception; Phase; Physiological; Poverty; Prevention; Process; Property; Public Health; Publishing; Puerto Rican; Puerto Rico; Race; Records; Reporting; Resistance; Resources; Risk Factors; Rural; Safety; Sales; Self-Direction; Shipping; Small Business Technology Transfer Research; Time; Tissue Model; Underserved Population; Vagina; Vaginal Douching; Water; Woman; base; biomaterial compatibility; black women; cancer care; cancer cell; cancer prevention; cancer risk; cell injury; cervical cancer prevention; cervicovaginal; commercialization; cost; cytokine; design; dysbiosis; efficacy trial; flexibility; health care availability; immunotoxicity; improved functioning; in vitro Model; innovation; manufacturing scale-up; medical schools; microbial; microbiota; mortality; mortality risk; multidisciplinary; novel; pathobiont; pathogen; pre-clinical; prebiotics; preclinical safety; prevent; product development; prototype; reproductive tract; tumorigenesis; vaginal microbiome; vaginal microbiota; vaginal mucosa; wasting

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.

通过优化，提出了一种新型的，经生元的遗前固醇（“生物学prebiogyn”），以预防宫颈癌 阴道健康和阴道营养不良的治疗（病原体和病原体过度生长 ），与高风险有关 人乳头瘤病毒（HRHPV）持久性和肿瘤发生。 prebiogyn是 OTC用户指导，第2类 医疗设备，在低资源环境（LRS）中为妇女提供独特的创新，最大的死亡风险 宫颈癌。 HRHPV持久性和宫颈癌的率提高直接与间接相关 阴道营养不良，由于阴道pH水平的升高，有益的阴道菌群的耗竭（例如， 乳酸乳杆菌）和粘膜屏障的破坏。宫颈炎和阴道降低处于领先地位 宫颈癌形成和进展的危险因素。非常需要负担得起的易于 使用优化阴道pH的阴道产品 微生物群和粘膜功能，以预防宫颈癌 。 现有的阴道pH“纠正”缓冲凝胶较低，但会伤害乳酸杆菌 和粘膜细胞和/或不 符合谁阴道安全指南。这是至关重要的公共卫生意义 考虑到约90％ 妇女报告在过去的90天内使用至少一种阴道产品，使用此类产品增加 泌尿生殖事件（例如阴道失调）3倍。实际上，高妇女之间发生了重大重叠 阴道产品使用，HRHPV持续性和宫颈癌事件部分归因于产品相关的阴道 微生物组和粘膜损伤。初步数据表明，Bibiogyn申请专利的凝胶，带有新颖的凝胶 益生元成分的组合，支持crispatus乳杆菌，同时抑制颈癌连接的Bivia生长 并且在粘膜安全性方面是无与伦比的。 Glyciome和学术合作伙伴（Brigham＆妇女医院和大学 Puerto Rico医学院）提案第1阶段研究，以建立临床前安全，效率和 益生元凝胶和新颖涂抹器的可行性（低垃圾和运输成本，增强的用户份额和 舒适）。成功完成第1阶段将证明以下内容。 1）凝胶的阴道生物相容性 在与物理相关的人类内部模型与领先的缓冲凝胶中，基于：no的定量措施 宫颈阴道细胞损伤，感染和/或免疫毒性；乳酸杆菌的选择性上皮定植； 并且没有增强病原体或宫颈癌细胞的增殖。 2）用户感知和凝胶的可接受性 和涂抹器与引导凝胶的量化剂量的量化里程碑。 3）物理化学和功能 凝胶的特性随着时间的流逝和VS引导凝胶以证明稳定性，优势功能和 符合建议的准则。 4）综合制造原型的最终设计 与拟议的制造商协调。成功完成项目将导致STTR阶段2 制造规模扩大，优化阴道健康和预防宫颈癌的临床试验，以及 提交FDA设备清除，并提出从头阴道健康声明。 Glyciome已组建了一个专家团队： 产品开发；制造/销售；生物统计学；生殖道生物学；和全球宫颈癌护理。