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:
- 金额:$ 30.65万
- 依托单位:
- 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:
- 关键词:AdherenceAnimal ModelAnimalsAntibioticsAtopobium vaginaeBacteriaBacterial VaginosisBlindedBuffersCellsChlamydiaClindamycinCombined Modality TherapyDataDevelopmentDoseEnsureEnvironmentEpidemicFemaleFormulationFoundationsFreeze DryingFrequenciesGardnerella vaginalisGelatinGlycogenGoalsGonorrheaGrowthHIVHuman PapillomavirusLactic acidLactobacillusLeadMacacaMacaca nemestrinaMarketingMeasurementMethodsMetronidazoleMicrobeMucous body substanceOdorsOrganismPhasePhysiologicalPlacebosPopulationPowder dose formPredispositionPremature BirthPrimatesProbioticsProductionPublic HealthRecurrenceReproducibilityResistanceRiskSafetySamplingSexually Transmitted DiseasesSmall Business Innovation Research GrantSmell PerceptionSwabTestingTimeToxic effectToxicologyTrichomonas InfectionsVaginaVaginal CreamVaginal GelVaginal RingWomanWorkadverse birth outcomesadverse pregnancy outcomebacterial communitybacterial resistancecapsulecervicovaginalcombinatorialcostdensitydesigndysbiosiseffective therapyexperiencein vivolow and middle-income countriesmanufacturemanufacturing costmicrobicidemicrobiomemicrobiome compositionmicrobiotanovelpathogenpreventsexually activevaginal microbiomevaginal 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
项目成果
期刊论文数量(0)
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Keiichiro Kushiro其他文献
Keiichiro Kushiro的其他文献
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{{ truncateString('Keiichiro Kushiro', 18)}}的其他基金
Fast dissolving antibody tablets for preventing vaginal HSV transmission
用于预防 HSV 阴道传播的快速溶解抗体片
- 批准号:
10547476 - 财政年份:2022
- 资助金额:
$ 30.65万 - 项目类别:
User-based identification of preferred design features for MM008, a non-hormonal contraceptive vaginal ring
基于用户的非激素避孕阴道环 MM008 的首选设计特征识别
- 批准号:
10459077 - 财政年份:2022
- 资助金额:
$ 30.65万 - 项目类别:
Development of a qualified pharmacokinetic bioassay to support preclinical and clinical studies of MM-008, a non-hormonal contraceptive antibody
开发合格的药代动力学生物测定法以支持非激素避孕抗体 MM-008 的临床前和临床研究
- 批准号:
10459074 - 财政年份:2022
- 资助金额:
$ 30.65万 - 项目类别:
Capsule-intravaginal ring for sustained release of antibodies for non-hormonal contraception and vaginal protection against HIV
胶囊阴道环,用于持续释放抗体,用于非激素避孕和阴道艾滋病毒保护
- 批准号:
9799170 - 财政年份:2021
- 资助金额:
$ 30.65万 - 项目类别:
Capsule-intravaginal ring for sustained release of antibodies for non-hormonal contraception and vaginal protection against HIV
胶囊阴道环,用于持续释放抗体,用于非激素避孕和阴道艾滋病毒保护
- 批准号:
10381449 - 财政年份:2021
- 资助金额:
$ 30.65万 - 项目类别:
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