Vaginal Ring for Preventing Bacterial Vaginosis

预防细菌性阴道病的阴道环

• 批准号: 8001552
• 负责人: Thomas Ray Moench
• 金额: $ 9.96万
• 依托单位: REPROTECT, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8001552
• 关键词: Antibiotics; Bacteria; Bacterial Vaginosis; Birth; Clindamycin; Coitus; Contraceptive methods; Culture Media; Diffuse; Dimensions; Dose; Epithelial; Epithelium; Gram' s stain; High Prevalence; High Risk Woman; Hormone replacement therapy; Hypoxia; In Vitro; Incubated; Isomerism; Lactic acid; Lactobacillus; Left; Liquid substance; Measurement; Measures; Menstrual cycle; Menstruation; Metabolism; Methods; Metronidazole; Organism; Outcome; Phase; Physiological; Pregnancy; Pregnancy Outcome; Premature Birth; Prevention; Protective Agents; Public Health; Relapse; Research; Risk; Sampling; Sexually Transmitted Diseases; Silicones; Small Business Technology Transfer Research; Smell Perception; Swab; Symptoms; Testing; Time; Universities; Vagina; Vaginal Gel; Vaginal Ring; Woman; base; design; falls; in vivo; prevent; prototype; public health relevance; routine Bacterial stain; vaginal lactobacilli; volunteer

DESCRIPTION (provided by applicant): Bacterial Vaginosis (BV) is an exceptionally common vaginal condition in which robust lactobacillus microflora in the vagina is replaced by a dense polymicrobial overgrowth. At any given time, about 1 in 3 women in the U.S. have BV; half are asymptomatic, and most women with symptomatic BV have only mild symptoms (increased discharge with a fishy smell). Despite these missing or mild symptoms, BV markedly increases risk of adverse birth outcomes (premature births and still births) and markedly increases risks of sexually transmitted infections (STIs). Thus BV poses a major and yet under-recognized public health problem. What causes the fluctuating instability of vaginal microflora between lactobacilli and BV is unknown. Episodes of BV can be treated transiently with antibiotics (metronidazole, clindamycin) but relapse occurs frequently. Women with BV typically have ~2 episodes per menstrual cycle. Given the markedly increased BV-associated risks, and the high prevalence of BV, there is a major unmet need for a vaginal product that will provide long-term prevention of BV especially during pregnancy and for women at high risk of STIs. Healthy vaginal lactobacilli continuously produce lactic acid at a rate that acidifies the vagina to pH~4. We recently discovered that lactic acid potently inactivates a broad range of BV-associated bacteria. The aim of this STTR application is to develop a vaginal ring that continuously releases lactic acid to prevent BV ("BVP-Ring"). The Ring will be designed to release lactic acid at a rate comparable to that produced by healthy lactobacilli and thus will not over-acidify the vagina. The Ring will provide a 'safe harbor' for lactobacilli whenever factors (e.g., menses, sexual intercourse) occur that might otherwise initiate an episode of BV. By supplying a naturally present protective agent the Ring will likely be safe and nontoxic, and there is a strong basis for expecting it to be effective: Lactic acid potently inactivates BV-associated bacteria in vitro, and vaginal gels with lactic acid, when applied frequently over many weeks, have been shown clinically to reduce BV relapse. Vaginal rings are highly user-acceptable for contraception and for hormone replacement therapy. Thus the BVP-Ring is likely to be user-acceptable, and much more acceptable than frequently applying a vaginal gel, or frequent doses of antibiotics. For STTR Phase I, Specific Aims at Johns Hopkins University are: (1) Determine the rate at which lactobacilli produce lactic acid in cervicovaginal fluid and (2) Determine the rate at which lactic acid applied to the vagina of women with BV leaves the vaginal lumen by diffusing through the vaginal epithelium. These measurements will be used to estimate the rate at which the vaginal ring should release lactic acid, The Specific Aim at ReProtect, Inc. is (3) Design a silicone BVP-Ring that releases lactic acid for 1 month at the rate determined in Aims 1 and 2, and produce prototype Rings ready to be tested in vivo in STTR Phase II. PUBLIC HEALTH RELEVANCE: Unfortunately, most women, most of the time, do not have robust vaginal lactobacilli that protect the vagina with lactic acid; at any given time about 1 in 3 women have bacterial vaginosis (BV), a condition that puts women at markedly increased risks of poor pregnancy outcomes and sexually transmitted infections. The aim of this STTR project is to develop a vaginal ring that releases lactic acid to prevent BV. The ring will likely be useful for women with frequent episodes of symptomatic BV, and especially useful for preventing BV during pregnancy. )

描述（由申请人提供）：细菌性阴道病（BV）是一种极其常见的阴道病症，其中阴道中强大的乳杆菌微生物群落被密集的多种微生物过度生长所取代。在任何特定时间，美国大约有三分之一的女性患有 BV；一半是无症状的，大多数有症状 BV 的女性只有轻微症状（分泌物增多，有鱼腥味）。尽管存在这些缺失或轻微的症状，细菌性阴道炎仍会显着增加不良分娩结局（早产和死产）的风险，并显着增加性传播感染 (STI) 的风险。因此，细菌性阴道病造成了一个重大但尚未得到充分认识的公共卫生问题。导致阴道菌群在乳酸杆菌和细菌性阴道病之间波动不稳定的原因尚不清楚。 BV发作可以用抗生素（甲硝唑、克林霉素）暂时治疗，但经常会复发。患有 BV 的女性通常每个月经周期会发作约 2 次。鉴于 BV 相关风险显着增加，且 BV 患病率较高，因此对能够长期预防 BV（尤其是怀孕期间和性传播感染高风险女性）的阴道产品的需求尚未得到满足。健康的阴道乳酸杆菌不断产生乳酸，其速度使阴道酸化至 pH~4。我们最近发现乳酸能有效灭活多种 BV 相关细菌。该 STTR 应用的目的是开发一种能够持续释放乳酸以预防 BV 的阴道环（“BVP-Ring”）。该环的设计释放乳酸的速度与健康乳酸杆菌产生的速度相当，因此不会过度酸化阴道。当发生可能引发 BV 发作的因素（例如月经、性交）时，该环将为乳酸菌提供一个“安全港”。通过提供天然存在的保护剂，环可能是安全无毒的，并且有充分的基础预期它是有效的：乳酸在体外有效地灭活 BV 相关细菌，并且临床证明，当经常使用数周时，含有乳酸的阴道凝胶可以减少 BV 复发。阴道环在避孕和激素替代治疗方面非常容易被用户接受。因此，BVP 环可能是用户可以接受的，并且比频繁使用阴道凝胶或频繁服用抗生素更容易接受。对于 STTR 第一阶段，约翰·霍普金斯大学的具体目标是：(1) 确定乳杆菌在宫颈阴道液中产生乳酸的速率，以及 (2) 确定应用于 BV 女性阴道的乳酸通过阴道上皮扩散而离开阴道腔的速率。这些测量结果将用于估计阴道环应释放乳酸的速率，ReProtect, Inc. 的具体目标是 (3) 设计一款硅胶 BVP 环，以目标 1 和 2 中确定的速率释放乳酸 1 个月，并生产原型环，准备在 STTR II 期体内进行测试。 公共卫生相关性：不幸的是，大多数女性在大多数时候都没有强大的阴道乳酸杆菌来用乳酸保护阴道；在任何特定时间，约有三分之一的女性患有细菌性阴道病 (BV)，这种疾病使女性妊娠结局不佳和性传播感染的风险显着增加。该 STTR 项目的目的是开发一种可释放乳酸以预防 BV 的阴道环。该环可能对经常出现症状性 BV 的女性有用，特别是在怀孕期间预防 BV 有用。 ）