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

Highly Acidifying Intravaginal Rings with Lactobacillus Probiotics to Treat Bacterial Vaginosis

含乳酸菌益生菌的高度酸化阴道环可治疗细菌性阴道病

基本信息

批准号：
10699458
负责人：
Keiichiro Kushiro
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：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10699458
关键词：
Adherence Animal Model Animals Antibiotics Atopobium vaginae Bacteria Bacterial Vaginosis Blinded Buffers Cells Chlamydia Clindamycin Combined Modality Therapy Data Development Dose Ensure Environment Epidemic Female Formulation Foundations Freeze Drying Frequencies Gardnerella vaginalis Gelatin Glycogen Goals Gonorrhea Growth HIV Human Papillomavirus Lactic acid Lactobacillus Lead Macaca Macaca nemestrina Marketing Measurement Methods Metronidazole Microbe Mucous body substance Odors Organism Phase Physiological Placebos Population Powder dose form Predisposition Premature Birth Primates Probiotics Production Public Health Recurrence Reproducibility Resistance Risk Safety Sampling Sexually Transmitted Diseases Small Business Innovation Research Grant Smell Perception Swab Testing Time Toxic effect Toxicology Trichomonas Infections Vagina Vaginal Cream Vaginal Gel Vaginal Ring Woman Work adverse birth outcomes adverse pregnancy outcome bacterial community bacterial resistance capsule cervicovaginal combinatorial cost density design dysbiosis effective therapy experience in vivo low and middle-income countries manufacture manufacturing cost microbicide microbiome microbiome composition microbiota novel pathogen prevent sexually active vaginal microbiome vaginal microbiota

项目摘要

Abstract 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 (LB), in particular lactobacillus crispatus, 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 LB, particularly in women with Lactobacillus crispatus (L.c), it has the potential to serve as a safe, non-antibiotics 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 in turn guided our development of 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 LB. We have further synthesized macaque-sized LA-IVR that, when inserted into the macaque vagina, could lower the vaginal pH substantially without causing any toxicity. Building on our promising work, we seek to combine this LA-IVR with a L.c probiotics in the form of capsules containing lyophilized L.c powder, in order to achieve a synergistic alteration to the vaginal environment to best promote the re-establishment of a L.c-dominated microflora. In Aim 1, we plan to identify a lead strain of L.c based on growth rates as well as acidification rates and extent, then formulate them into lyophilized powders and load into capsules. In Aim 2, we will fabricate the macaque-sized LA-IVRs, and test whether combinatorial treatment of sustained LA release by this IVR with the L.c probiotics capsules can suppress BV-like bacterial species in pigtail macaques. Successful demonstration of safety and efficacy in this highly relevant large animal model would support the design requirements of an optimal LB-LA-IVR that Mucommune can advance through IND-enabling activities. The simplicity of our LA-IVR and L.c loaded capsule designs 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.

摘要