Core--Formulation Science

核心--配方科学

• 批准号: 6809167
• 负责人: Russell J Mumper
• 金额: $ 18.47万
• 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: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6809167
• 关键词: HIV infections; acid base balance; antiAIDS agent; antiinfective agents; biomedical facility; buffers; chemical synthesis; chemoprevention; combination chemotherapy; cooperative study; disease /disorder prevention /control; drug design /synthesis /production; gel; human immunodeficiency virus; nanomedicine; polymers; sexually transmitted diseases; spermicide; topical drug application; vagina

The overall goal of this program is to combine ReProtect's BufferGel technology with Starpharma's dendrimer technology in order to develop combination topical microbicide candidates with a dual mode of action against the sexually transmission of HIV. Subproject 0001 will seek to combine Starpharma's established microbicide candidate SPL7013 with ReProtect's BufferGel technology. Subproject 0002 will seek to combine ReProtect's BufferGel technology with a second generation dendrimer based microbicide microbicide with enhanced efficacy relative to SPL7013. Subproject 0003 will assess the safety of the combination microbicide candidates developed in Subprojects 0001 and 0002 in pilot Phase I clinical trials and develop optical coherence tomography as a new cervicovaginal imaging technique in microbicide clinical research. This Core will contribute to each of these projects and the overall goal of the program through the development of prototype formulations of SPL7013 and BufferGel (Subproject 0001) and second generation dendrimer based microbicide candidates and BufferGel (Subproject 0002). Selected protoptypes arising from both Subprojects 0001 and 0002 will be maunfactured to support preliminary aminal safety and efficacy studies. Final prototypes will be maunfactured to support macaque and GLP pre-clinical studies. Clinical trial material will also be maunfactured to supply the clinical trial site (Subproject 0003). As a result this Core has four Specific Aims: Specific Aim 1 (Year 1 and 2): Develop optimal formulations based on a combination of BufferGel and SPL7013, and to formulate second generation dendrimers as they are identified. Specific Aim 2 (Years 1-4): Provide well-characterized vaginal gel formulations to support animal efficacy and toxicity studies in the Program Project Grant. Specific Aim 3 (Year 1 and 3): Complete scale-up of final gel prototypes and GMP manufacturing at the CPST to support preclinical GLP Safety/Toxicity Studies. Specific Aim 4 (Year 2 and 4): Complete GMP Manufacturing and Formal ICH Stability Studies at the CPST to support human clinical trials.

该项目的总体目标是将 ReProtect 的 BufferGel 技术与 Starpharma 的 dendrimer 技术相结合，开发具有双重作用模式的组合外用杀菌剂候选物，以对抗 HIV 的性传播。子项目 0001 将寻求将 Starpharma 成熟的候选杀菌剂 SPL7013 与 ReProtect 的 BufferGel 技术相结合。子项目 0002 将寻求将 ReProtect 的 BufferGel 技术与第二代基于树枝状聚合物的杀微生物剂相结合，该杀微生物剂的功效相对于 SPL7013 有所增强。子项目0003将在试点I期临床试验中评估子项目0001和0002中开发的组合杀菌剂候选物的安全性，并开发光学相干断层扫描作为杀菌剂临床研究中的一种新的宫颈阴道成像技术。该核心将通过开发 SPL7013 和 BufferGel（子项目 0001）的原型配方以及基于第二代树枝状大分子的候选杀菌剂和 BufferGel（子项目 0002），为每个项目和该计划的总体目标做出贡献。将制造子项目 0001 和 0002 中选定的原型，以支持初步的动物安全性和功效研究。最终原型将用于支持猕猴和 GLP 临床前研究。还将生产临床试验材料供应临床试验场地（子项目0003）。因此，该核心有四个具体目标： 具体目标 1（第 1 年和第 2 年）：基于 BufferGel 和 SPL7013 的组合开发最佳配方，并在确定第二代树枝状聚合物时配制它们。具体目标 2（1-4 年）：提供特性良好的阴道凝胶配方，以支持计划项目拨款中的动物功效和毒性研究。 具体目标 3（第 1 年和第 3 年）：在 CPST 完成最终凝胶原型和 GMP 生产的扩大规模，以支持临床前 GLP 安全性/毒性研究。具体目标 4（第 2 年和第 4 年）：在 CPST 完成 GMP 生产和正式 ICH 稳定性研究，以支持人体临床试验。