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）是一种异常常见的阴道疾病，在该疾病中，在该阴道中，稳健的乳酸杆菌菌群被阴道中的坚固乳杆菌被致密的多肌醇过度生长所取代。在任何给定时间，美国大约有3分之一的妇女有BV；一半是无症状的，大多数有症状BV的妇女只有轻度的症状（由于气味而增加出院）。尽管存在这些缺失或轻度的症状，但BV显着增加了出生不良后果的风险（早产和仍然出生），并显着增加了性传播感染的风险（STIS）。因此，BV构成了一个重大却被低估的公共卫生问题。导致乳酸和BV之间阴道菌群不稳定的不稳定性尚不清楚。 BV的发作可以用抗生素（甲硝唑，克林霉素）瞬时治疗，但经常发生复发。 BV的女性通常每个月经周期有〜2个发作。鉴于BV相关的风险显着增加，并且BV的高龄率很高，因此对阴道产物的主要未满足需要，可以长期预防BV，尤其是在怀孕期间和具有性传播感染风险高的妇女。健康的阴道乳酸杆菌不断产生乳酸，使阴道酸化至pH 〜4。我们最近发现，乳酸会有效地失活了广泛的BV相关细菌。该STTR应用的目的是开发一个阴道环，该阴道环连续释放乳酸以防止BV（“ BVP环”）。该环将设计为以与健康乳酸杆菌产生的速率相当的速率释放乳酸，因此不会过度染色。每当发生因素（例如月经，性交）时，该戒指将为乳杆菌提供“安全港”，否则可能会发起BV的发作。通过提供自然存在的保护剂，该环可能是安全的和无毒的，并且有很强的基础可以使其有效：乳酸在体外有效地使BV相关的细菌在体外与乳酸相关的细菌，而乳酸的阴道凝胶经常在临床上经常施用，以减少BV Relapse。阴道环可用于避孕和激素替代疗法的用户高度可接受。因此，BVP环可能是可以接受的，并且比经常使用阴道凝胶或频繁剂量的抗生素更容易接受。对于I阶段I期，针对John Hopkins大学的特定目的是：（1）确定乳酸杆菌在宫颈阴道流体中产生乳酸的速率，（2）（2）确定乳酸在BV妇女的阴道上施用乳酸的速率，使BV的阴道散布在阴道中，通过通过阴道上皮散射阴道。这些测量值将用于估计阴道环应释放乳酸的速率，乳酸的特定目的是（3）设计一种有机硅BVP环，该硅酸BVP环在目标1和2中确定的速率释放1个月，并在STTR阶段II II II in Vivo中测试。 公共卫生相关性：不幸的是，大多数情况下，大多数女性都没有使用乳酸保护阴道的强大阴道乳酸杆菌。在任何给定时间，大约有3个女性患有细菌性阴道病（BV），这种情况使妇女的妊娠结局不良和性传播感染的风险显着增加。该STTR项目的目的是开发一个阴道环，该阴道释放乳酸以防止BV。该环可能对经常发作的BV发作，对于预防怀孕期间的BV特别有用。 ）