Development of Dendrimer and Combination Microbicides

树枝状聚合物和组合杀菌剂的开发

• 批准号: 7490395
• 负责人: Jeremy Paull
• 金额: $ 62万
• 依托单位: STARPHARMA, LTD
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490395
• 关键词: Development; Dendrimer; Combination; Microbicides

DESCRIPTION (provided by applicant): The human immunodeficiency virus (HIV) pandemic continues to ravage the world with substantial loss of life and reduced quality of life. Approximately 42 million people are infected with HIV worldwide. Currently, approximately 50% of HIV infections are in women and there is a desperate need to develop microbicides to prevent HIV infection. Topical microbicides are vaginally and rectally applied biomedical products with or without contraceptive activity that safely prevent infection of HIV and sexually transmitted infections (STI). This Program will endeavor to produce combination microbicides generated by combining the technology of Starpharma dendrimers and ReProtect's BufferGel TM. The combination of these two active agents with different mechanisms of action will potentially improve efficacy and duration of protection, and broaden the protective spectrum against HIV and other STI pathogens when compared to either parent microbicide while maintaining an adequate safety profile. A multidisciplinary team has been assembled to participate in 3 Projects, 3 Scientific Cores and an Administrative Core. Preclinical developments of combination formulations are planned and will result in pilot Phase 1 clinical evaluation. In addition, this Program will evaluate novel technology for the evaluation of microbicides, optical coherence tomography (OCT). OCT is an imaging technique that detects morphological changes to the cervix and vagina. This non-invasive technique provides results similar to those observed histologically using light microscopy of biopsy specimens. Previously the assessment of the effects of microbicides on the integrity of the cervicovaginal epithelium has relied on colposcopic examination and biopsy. Unfortunately colposcopy is relatively insensitive and biopsies are invasive. The integrated approach in this Program will rapidly advance the field of microbicides by developing combination microbicides and by introducing novel, non-invasive analysis for the evaluation of microbicide safety.

描述（由申请人提供）：人类免疫缺陷病毒（HIV）大流行继续以大幅丧失生命和生活质量降低而破坏世界。全世界大约有4200万人感染了艾滋病毒。目前，大约50％的艾滋病毒感染是女性的，并且迫切需要开发杀菌剂以防止艾滋病毒感染。局部微生物是阴道和直肠施用的生物医学产品，具有或没有避孕活性，可以安全防止感染HIV和性传播感染（STI）。该程序将努力通过结合Starpharma树枝状聚合物的技术和Repotect的Fashertect TM来产生产生的杀菌剂。这两种活性药物与不同的作用机制的组合将有可能提高功效和保护持续时间，并在保持适当的安全性的同时，扩大了针对HIV和其他STI病原体的保护谱。一支多学科团队已经组装，参加了3个项目，3个科学核心和一个行政核心。计划组合制剂的临床前发展，并将导致1阶段临床评估。此外，该程序将评估新技术，以评估微生物，光学相干断层扫描（OCT）。 OCT是一种检测子宫颈和阴道的形态变化的成像技术。这种非侵入性技术提供了与使用活检标本的光学显微镜在组织学上观察到的结果相似的结果。以前，评估微生物对子宫颈上皮完整性的影响依赖于阴道镜检查和活检。不幸的是，阴道镜检查相对不敏感，活检是侵入性的。该程序中的综合方法将通过开发组合杀菌剂和引入新颖的非侵入性分析来评估杀crickicide安全性，从而迅速推进生液剂领域。