Rational Development of Combination Microbicide Therapies

联合杀菌剂疗法的合理开发

基本信息

批准号：
7689759
负责人：
Robert Walter Buckheit
金额：
$ 43.54万
依托单位：
IMQUEST BIOSCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-30 至 2011-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The ability of a combination of antiviral agents to effectively prevent HIV transmission will be evaluated in newly developed and well established in vitro assays specifically designed to enhance the characterization and discovery of effective combination microbicide therapies. The novel assays that will be developed and utilized in this application will specifically address the ability of the combination therapeutic to inhibit cell-free and cell-to-cell virus transmission in a microbicide-appropriate environment. The therapeutic drug combination will be developed using new microbicide candidate molecules licensed by ImQuest Pharmaceuticals. These candidate microbicides target HIV replication at three steps of the replication cycle, including inhibition of virus entry to the target cells through two distinct mechanisms of action (attachment and pre-fusion), and act as a highly potent non-nucleoside reverse transcriptase inhibitor. Efficacious combinations identified in the in vitro analyses will be formulated for topical application using novel formulation techniques designed to place the agents at the correct place (intracellular, at the cell surface or within the gel as it mixes with the viral inoculum) at the time they are required for maximal inhibitory activity, yield the most effective combination therapy. Additionally, since the development of an appropriate pharmaceutical product for use as a microbicide requires a formulation for the active pharmaceutical ingredient (API) that will result in optimal efficacy while also including and emphasizing appropriate consideration for the social and behavioral concerns of acceptability and use of the formulated products, we propose to evaluate novel formulations to promote additional efficacy in the context of the social considerations of acceptability. Thus, this application will serve to develop an appropriately formulated and acceptable product with a highly defined biological profile including efficacy, toxicity, biopolymer properties and effectiveness as a biological barrier to HIV transmission. It is anticipated that the proposed research will yield significant advancements in microbicide biology and chemotherapy in several different areas, including the development of new and novel microbicide agents, the definition and validation of combination therapeutic strategies for microbicide use, the development of new in vitro tools for evaluating the clinical potential of microbicides, and the development of novel formulations designed to complement both the antiviral capacity of the combination therapy and the social issues of acceptability.

描述（由申请人提供）：将在新开发和良好建立的体外测定法中评估抗病毒剂有效预防HIV传播的能力，专门设计，以增强有效组合菌心治疗的表征和发现。在本应用中将开发和使用的新颖测定法将特别解决组合治疗方法在适合菌心剂的环境中抑制无细胞和细胞对细胞的病毒传播的能力。治疗性药物组合将使用由Imquest Pharmaceuticals许可的新的微生物候选分子开发。这些候选微生物在复制周期的三个步骤中靶向HIV复制，包括通过两种不同的作用机理（附着和融合前）抑制病毒进入靶细胞，并充当高度有效的非核苷逆转录酶抑制剂。在体外分析中确定的有效组合将使用新型配方技术制定用于局部应用，旨在将试剂放置在正确的位置（细胞内，在细胞表面或凝胶中与病毒接种物混合时）在最大抑制活性时所需的时间是最大有效的组合治疗所需的。此外，由于用于用作菌心用作的合适的药物产品需要为主动药物成分（API）制定配方，这将导致最佳功效，同时还包括并强调适当的考虑和行为关注，以对公式化产品的可接受性和使用，我们建议评估新的效率，以促进社交的效率。因此，该应用将用于开发具有高度定义的生物学特征的适当配方且可接受的产品，包括功效，毒性，生物聚合物特性和有效性，作为HIV传播的生物学障碍。预计拟议的研究将在几个不同领域的杀菌剂生物学和化学疗法方面取得重大进步，包括开发新的和新型的微生物剂，定义和验证菌心使用的结合治疗策略的定义和验证，用于开发新的体外工具，以评估新颖的杂交杂志和新颖的杂志临床范围，以及蚂蚁的临床范围，以及蚂蚁的临床成分量，蚂蚁的临床成分构成了蚂蚁的临床成分，构成了蚂蚁的临床成分。可接受性。