Yaso Therapeutics Inc, Scottsdale, AZ, USA.
College of Pharmacy, University of Illinois, Chicago, IL, USA.
Biol Reprod. 2020 Aug 4;103(2):299-309. doi: 10.1093/biolre/ioaa087.
Current modern contraceptives rely heavily on the use of hormones. These birth control drug products, including pills, patches, injections, and IUDS, have been extremely beneficial to millions of women and their families over the past 50 years. But a surprisingly high number of women abandon such modern methods, many because they cannot tolerate the side effects and others because they have medical issues for which hormonal methods are contraindicated. In addition, modern hormonal methods are simply not available to many women. The extent of this problem is steadily becoming more apparent. We present the case for developing simple nonhormonal vaginal products that women can use when needed, ideal products that are multipurpose and offer both contraception and sexually transmitted disease protection. Gel-based vaginal products are particularly well suited for this purpose. Gels are easy to use, highly acceptable to many women, and can be safely formulated to enhance natural vaginal defenses against infection. However, the development of a new chemical entity for this application faces significant technical and regulatory hurdles. These challenges and our solutions are described for polyphenylene carboxymethylene (PPCM), a novel topical drug in a vaginal gel nearing human clinical trials. We have advanced PPCM from benchtop to IND-enabling studies and provide a brief description of the complex development process. We also describe a simple lab assay which can be used as a biomarker for contraceptive activity to enable pharmacodynamic studies in vaginal contraceptive development, both preclinically and in early human clinical trials.
目前的现代避孕药具严重依赖激素的使用。这些避孕药物产品，包括药丸、贴片、注射剂和宫内节育器，在过去的 50 年里对数百万女性及其家庭极为有益。但令人惊讶的是，有相当多的女性放弃了这种现代方法，许多是因为无法忍受副作用，而其他则是因为存在激素方法禁忌的医疗问题。此外，许多女性根本无法获得现代激素方法。这个问题的严重程度正在稳步显现。我们提出了开发简单的非激素阴道产品的理由，这些产品是女性在需要时可以使用的理想产品，具有多功能性，可以提供避孕和性传播疾病保护。基于凝胶的阴道产品特别适合这种用途。凝胶易于使用，许多女性都能接受，并且可以安全地制成增强天然阴道对感染的防御能力。然而，为这种应用开发新的化学实体面临着重大的技术和监管障碍。我们为正在进行人体临床试验的新型阴道凝胶中的多酚亚甲基（PPCM）描述了这些挑战和我们的解决方案。我们已经将 PPCM 从实验室推进到 IND 预备研究，并提供了复杂开发过程的简要描述。我们还描述了一种简单的实验室检测方法，可用作避孕活性的生物标志物，以在阴道避孕药具开发的临床前和早期人体临床试验中进行药效学研究。
