Formulation development and testing of a novel non-hormonal intravaginal ring to prevent pregnancy and sexually transmitted infections

用于预防怀孕和性传播感染的新型非激素阴道环的配方开发和测试

• 批准号: 10324916
• 负责人: BRUCE F VARIANO
• 金额: $ 87.19万
• 依托单位: POPULATION COUNCIL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10324916
• 关键词: Formulation; development; testing; novel; non

PROJECT I – ABSTRACT Despite extensive choice and increasing availability, current contraceptive options are not meeting the needs of many women, as is evident by high levels of typical-use failure, method non-use, switching, and discontinuation. Approximately half of all pregnancies (121 million) around the world are unintended and 218 million women have an unmet need for effective contraception. New technologies having attributes more closely aligned with users’ needs and expectations are urgently needed to fill this critical gap in sexual and reproductive healthcare. The overall goal of this P50 center is to bring together some of the leading research organizations in the world with unrivalled expertise and know-how around design, manufacture and testing of intravaginal ring (IVR) technology – including Population Council (PC), Queen's University Belfast (QUB), and Weill Cornell Medical College (WCMC) – in a concerted effort to develop a new, practical, easy-to-use, long-acting, multipurpose prevention technology (MPT) IVR offering both spermicidal activity and broad antibacterial/antiviral activity against various common sexually transmitted/vaginal infections, including chlamydia, gonorrhea, bacterial vaginosis (BV), and infection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV). Unlike other marketed and experimental contraceptive IVR products, we are committed here to the development of a non- hormonal contraceptive strategy, referred to as the CZL-IVR, in which copper ions or copper salts (C), zinc ions or zinc salts (Z), and lactide (L) are simultaneously administered to the vagina in a sustained/controlled manner over at least 30 days. The overarching goal of Project 2, which involves a strategic and highly integrated partnership between Queen's University Belfast (QUB) and Population Council (PC), is to provide formulation support for the P50 project. Specifically, this will involve all aspects of CZL-IVR product design, formulation, manufacture and in vitro testing, according to three key aims: In Aim 1, we will develop a CZL-IVR that releases copper, zinc and lactide for at least 30 days in quantities sufficient for clinical efficacy; in Aim 2, we will design, manufacture and characterize non-medicated IVRs and sensor- embedded IVRs for end-user testing; and in Aim 3, we will complete technology transfer between QUB and PC and GMP manufacture the IVRs for clinical evaluation for Project 3. Project 1 will be closely coordinated with Projects 2 and 3 to inform IVR loading and selection of the lead IVR. Our multidisciplinary collaborative team is uniquely qualified to advance the development of this novel MPT IVR. The CZL-IVR will address a critical gap in the non-hormonal contraceptive landscape, fill a niche that users want and deliver an important public health intervention.

项目I -摘要 尽管有广泛的选择和越来越多的可用性，目前的避孕选择不能满足需要， 许多妇女，这是明显的高水平的典型使用失败，方法不使用，转换，和中断。 全世界大约一半的怀孕（1.21亿）是意外怀孕，2.18亿妇女 有效避孕的需求未得到满足。新技术的属性与用户的需求更加一致 迫切需要满足各种需求和期望，以填补性保健和生殖保健方面的这一重大差距。的 这个P50中心的总体目标是汇集世界上一些领先的研究机构， 在阴道环（IVR）技术的设计、制造和测试方面拥有无与伦比的专业知识和技术诀窍 - 包括人口理事会（PC）、贝尔法斯特女王大学（QUB）和威尔康奈尔医学院 （世界养护监测中心）-共同努力开发一种新的、实用的、易于使用的、长效的多用途预防 技术（MPT）IVR提供杀精子活性和广泛的抗菌/抗病毒活性， 常见的性传播/阴道感染，包括衣原体、淋病、细菌性阴道病（BV）和 2型单纯疱疹病毒（HSV-2）和人类免疫缺陷病毒（HIV）感染。不像其他 市场和实验性的避孕IVR产品，我们在这里致力于开发一种非- 激素避孕策略，简称CZL-IVR，其中铜离子或铜盐（C）、锌离子 或锌盐（Z）和丙交酯（L）以持续/受控的方式同时施用至阴道 至少30天。项目2的总体目标涉及一个战略性和高度一体化的 女王大学贝尔法斯特（QUB）和人口理事会（PC）之间的伙伴关系，是提供 支持P50项目。具体来说，这将涉及CZL-IVR产品的各个方面 设计、配方、生产和体外测试，根据三个关键目标：在目标1中，我们将 开发一种CZL-IVR，释放铜、锌和丙交酯至少30天，数量足以 临床有效性;在目标2中，我们将设计、制造和表征非药物IVR和传感器， 在目标3中，我们将完成QUB与 PC和GMP生产用于项目3临床评价的IVR。项目1将密切 与项目2和3协调，以通知IVR加载和选择主导IVR。我们的多学科 协作团队是唯一有资格推动这种新型MPT IVR的发展。CZL-IVR将 解决非激素避孕领域的一个关键空白，填补用户想要的利基市场， 重要的公共卫生干预措施。