'Duet' cervical barrier device for maximizing protectiv*

“Duet”宫颈屏障装置可最大限度地提供保护*

• 批准号: 7072294
• 负责人: RICHARD CONE
• 金额: $ 55.19万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7072294
• 关键词: acetates; acid base balance; antiinfective agents; biomaterial development /preparation; clinical research; communicable disease control; cooperative study; human subject; laboratory mouse; lactates; nondrug contraceptive; sexually transmitted diseases; vagina

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（由申请人提供）：“Duet”是一种宫颈屏障装置，与隔膜不同，它在其上下表面上输送凝胶，以保护阴道和宫颈。本申请提出3个相关项目： 1)“BufferGel-Duet”，一种预防性传播感染、艾滋病毒/艾滋病、BV和怀孕的一次性产品。(a)完成生产步骤的开发，以生产Duet用于临床疗效试验。(b)完成BufferGel-Duet包装、稳定性和有效期试验的开发。(c)通过ReProtect的BufferGel IND寻求FDA的许可，以进行BufferGel-Duet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，一种低成本，最大限度地保护屏障设备，用于低资源地区。向FDA提交Duet作为OTC宫颈屏障器械与杀微生物剂联合使用的IDE。 3)膜渗透酸：确定乳酸和乙酸是否可以安全地增加杀微生物剂的效力。乳酸杆菌通过分泌乳酸和乙酸使阴道酸化至pH~4。在此pH下，这些酸可通过渗透细胞和细菌膜而快速杀灭病原体，但这些渗透酸也可对粘膜表面有毒。我们假设，在pH~4的杀菌剂中加入生理浓度的乳酸和乙酸，将加速病原体的酸灭活，而不会引起明显的毒性。为了检验这一假设：（a）在体外测量乳酸和乙酸在阴道pH（~4）下杀灭性传播病原体、BV相关微生物和精子的速度。（B）将生理浓度的这些酸加入到BufferGel（其使用不渗透的缓冲凝胶来增强阴道酸度）中，并测量它们在疱疹、衣原体和滴虫的动物模型中增加其保护功效的程度。(c)通过在小鼠和家兔模型中进行敏感性试验，测试在BufferGel中加入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杀微生物剂的保护效力，使妇女能够使用这些杀微生物剂来预防性传播感染和艾滋病毒。这些产品还可以预防怀孕，并有助于预防BV。BufferGel目前正在进行避孕（与隔膜一起使用）和艾滋病毒预防（单独使用）的临床试验。“Duet”覆盖宫颈，最大限度地保护这个易受感染的部位，并提供杀微生物剂凝胶，以保护宫颈和阴道。可重复使用的Duet成本低，对低资源地区有用。