Duet cervical barrier device for maximizing protective efficacy of microbicides

Duet 宫颈屏障装置可最大限度地提高杀菌剂的保护效果

• 批准号: 7933370
• 负责人: RICHARD CONE
• 金额: $ 21.62万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7933370
• 关键词: AIDS prevention; AIDS/HIV problem; Acetic Acids; Acidity; Acids; Animal Model; Area; Authorization documentation; BufferGel; Buffers; Cells; Cervical; Cervix Uteri; Chlamydia; Clinical Trials; Contraceptive methods; Couples; Development; Devices; Drug Formulations; Feedback; Funding; Gel; Goals; Gonorrhea; HIV; Human; In Vitro; Infection; Lactic acid; Lactobacillus; Life; Measures; Membrane; Methods; Microbe; Modeling; Mus; Oryctolagus cuniculus; Phase; Physiological; Placebos; Predisposition; Pregnancy; Procedures; ReProtect' s BufferGel; Resources; Respiratory Diaphragm; Safety; Simplexvirus; Site; Speed; Surface; Testing; Toxic effect; Toxicity Tests; Trichomonas; Trichomonas Infections; United States National Institutes of Health; Vagina; Woman; base; biomaterial compatibility; clinical efficacy; cost; cytokine; design; efficacy trial; irritation; microbicide; mouse model; pathogen; pre-clinical; prevent; protective efficacy; prototype; sperm cell; stability testing; vaginal transmission

DESCRIPTION (provided by applicant): The "Duet" is a cervical barrier device that, unlike a diaphragm, delivers gel on both its upper and lower surfaces to protect the vagina as well as the cervix. This application proposes 3 related projects: 1) "BufferGel-Duet", a single-use product for protection against STIs, HIV/AIDS, BV, and pregnancy. (a) Complete development of manufacturing steps to produce Duet for clinical efficacy trials. (b) Complete development of packaging, stability, and shelf-life testing of BufferGel-Duet. (c) Seek FDA permission via ReProtect's BufferGel IND to pursue clinical trials of BufferGel-Duet for preventing STIs (chlamydia, gonorrhea, trichomoniasis, and HIV), BV, and for contraception. 2) Reusable Duet, a low-cost, and maximally protective barrier device for use in low resource areas. Submit IDE to FDA for Duet as an OTC cervical barrier device for use with microbicides. 3) Membrane permeant acids: Determine whether lactic and acetic acid can safely increase microbicide efficacy. Lactobacilli acidify the vagina to pH~4 by secreting lactic and acetic acids. At this pH these acids can rapidly inactivate pathogens by permeating cell and bacterial membranes, but these permeant acids can also be toxic to mucosal surfaces. We hypothesize that adding lactic and acetic acids at physiological concentrations to microbicides formulated at pH~4 will speed acid-inactivation of pathogens without causing significant toxicity. To test this hypothesis: (a) Measure in vitro the speed at which lactic acid and acetic acid at vaginal pH (~4) inactivate sexually transmitted pathogens, BV-associated microbes, and sperm, (b) Add physiological concentrations of these acids to BufferGel (which uses an impermeant buffering gel to reinforce vaginal acidity) and measure the extent to which they increase its protective efficacy in animal models for herpes, chlamydia, and trichomonas. (c) Test whether adding these acids to BufferGel increases vaginal toxicity, or susceptibility to herpes or chlamydia, by using sensitive tests in mouse and rabbit models. RELEVANCE: The aim is to maximize protective efficacy of microbicides that women can use for protection against STIs and HIV. The products will also prevent pregnancy and help prevent BV. BufferGel is now in clinical trials for contraception (used with a diaphragm) and HIV prevention (used alone). "Duet" covers the cervix for maximum protection of this susceptible site for infections, and delivers microbicide gel to protect both the cervix and vagina. The reusable Duet will be low in cost and useful for low-resource areas.

描述(申请人提供)：“Duet”是一种宫颈屏障装置，与隔膜不同，它在上下表面都提供凝胶，以保护阴道和宫颈。本申请提出了3个相关项目： 1)“BufferGel-Duet”，一款一次性使用的产品，用于防止性传播感染、艾滋病毒/艾滋病、BV和怀孕。(A)完成生产用于临床疗效试验的DUET的制造步骤。(B)完成BufferGel-Duet的包装、稳定性和保质期测试。(C)通过ReProtect的BufferGel Ind寻求FDA的许可，以进行BufferGel-Duet用于预防性传播感染(衣原体、淋病、滴虫病和艾滋病毒)、BV和避孕的临床试验。 2)可重复使用的Duet，这是一种低成本、最大限度保护屏障的装置，适用于低资源地区。向FDA提交IDE作为非处方药宫颈屏障装置的Duet，与杀菌剂一起使用。 3)膜透析酸：确定乳酸和醋酸是否能安全地提高杀菌剂的杀菌效果。乳杆菌通过分泌乳酸和醋酸将阴道酸化到pH~4。在这种pH值下，这些酸可以通过渗透细胞和细菌膜来迅速灭活病原体，但这些特指的酸也可能对粘膜表面产生毒性。我们推测，在pH~4配制的杀菌剂中加入生理浓度的乳酸和醋酸，可以加速病原菌的酸灭活，而不会造成明显的毒性。为了验证这一假设：(A)在体外测量乳酸和醋酸在阴道pH值(~4)下灭活性传播病原体、BV相关微生物和精子的速度，(B)将这些酸的生理浓度添加到BufferGel(它使用一种无意义的缓冲凝胶来增强阴道酸度)，并测量它们在动物模型中增加对疱疹、衣原体和滴虫的保护效果的程度。(C)通过在小鼠和兔模型上进行敏感性试验，测试在BufferGel中添加这些酸是否会增加阴道毒性或对疱疹或衣原体的易感性。 相关性：目的是最大限度地提高妇女可用于防止性传播感染和艾滋病毒的杀微生物剂的保护效力。这些产品还将防止怀孕，并有助于预防BV。BufferGel目前正在进行避孕(与避孕膜一起使用)和艾滋病毒预防(单独使用)的临床试验。Duet覆盖在宫颈上，最大限度地保护这一易受感染的部位，并提供杀菌剂凝胶来保护宫颈和阴道。可重复使用的二重奏将成本低，对低资源地区有用。

项目成果

The microstructure and bulk rheology of human cervicovaginal mucus are remarkably resistant to changes in pH.

• DOI: 10.1021/bm401356q
• 发表时间: 2013-12-09
• 期刊: BIOMACROMOLECULES
• 影响因子: 6.2
• 作者: Wang, Ying-Ying;Lai, Samuel K.;Ensign, Laura M.;Zhong, Weixi;Cone, Richard;Hanes, Justin
• 通讯作者: Hanes, Justin