权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Vaginal ring for sustained release of lactic acid to prevent bacterial vaginosis and associated health risks

用于持续释放乳酸以预防细菌性阴道病和相关健康风险的阴道环

基本信息

批准号：
10157763
负责人：
RICHARD CONE
金额：
$ 30.65万
依托单位：
MUCOMMUNE, LLC
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10157763
关键词：
Adherence Animal Model Animals Antibiotic Therapy Antibiotics Atopobium vaginae Bacteria Bacterial Vaginosis Blinded Buffers Chlamydia Clindamycin Clinical Data Development Ecosystem Effectiveness Elasticity Ensure Formulation Frequencies Gardnerella vaginalis Goals Gonorrhea HIV Health Human Human Papillomavirus Hydrophobicity Lactic acid Lactobacillus Lead Macaca Macaca nemestrina Measurement Measures Methods Metronidazole Microbe Organism Phase Physiological Placebos Polymers Population Predisposition Premature Birth Preparation Primates Probiotics Production Prophylactic treatment Public Health Recurrence Risk Role Safety Sampling Sexually Transmitted Diseases Small Business Innovation Research Grant Smell Perception Surface Swab Testing Time Toxicology Trichomonas Infections Vagina Vaginal Cream Vaginal Drug Administration Vaginal Gel Vaginal Ring Woman Work adverse birth outcomes adverse pregnancy outcome bacterial community base cost density design dysbiosis effective therapy experience in vivo low and middle-income countries mechanical properties microbicide microbiome novel pathogen prevent sexually active vaginal fluid vaginal microbiome vaginal microbiota

项目摘要

Project Summary Millions of women in the U.S. suffer from bacterial vaginosis (BV), a vaginal condition initiated by marked overgrowth of polymicrobial bacterial populations that can suppress protective lactobacilli. Healthy lactobacilli secrete lactic acid (LA) that acidifies the vagina and acts as a broad-spectrum microbicide that protects against many types of pathogens and also can suppress polymicrobial communities of BV species that produce little or no lactic acid. We do not know what initiates episodes of BV, but we do know that BV strongly increases risks of many sexually transmitted infections including HIV, and increases risks of premature births. At any given time, about 1/3 of sexually active women in the U.S. and world-wide have BV. Antibiotics can provide transient relief from the foul-smelling discharge caused by BV but they do not prevent BV from recurring (sometimes at a frequency up to twice a month). There is no product on the market that can provide sustained protection against BV. We and others have shown that LA can potently inactivate many types of BV- associated bacteria as well as many types of pathogens that cause sexually transmitted infections. Since LA is abundant in the healthy vaginas of women with protective lactobacilli, it has the potential to provide a safe nontoxic microbicide. We have recently determined the rate at which healthy lactobacilli continuously produce LA and hence for the first time know the rate at which lactic acid should be supplied to the vagina to treat and prevent BV. This has enabled us to develop an LA-releasing intravaginal ring (LA-IVR) that can provide sustained release of LA over 30 days at the rate needed to treat and prevent BV while not suppressing healthy lactobacilli. Through careful selection of polymers and formulation design, we have shown that we can tune the release rates of LA from various polymeric matrices, and achieve sustained release of LA. Building on our promising pilot work, we seek in Aim 1 to optimize our lead LA-IVR formulation, and perform various characterizations including LA release rates over time, hydrophobicity, and mechanical properties (elasticity, compressibility). We will then fabricate a macaque LA-IVR, and in Aim 2 test whether sustained release of LA by this IVR can suppress BV-like bacterial species in pigtail macaques. Successful demonstration of safety and efficacy in this highly relevant large animal model would support advancing Mucommune’s LA-IVR through IND-enabling activities. The simplicity of our LA-IVR design ensures both ease of production and likely very low manufacturing costs of the eventual product, which in turn should maximize potential public health impact and commercial viability of the product both in the U.S. and in low and middle income countries worldwide. (26 lines)

项目总结