MICROBICIDES IN MODEL SYSTEMS

模型系统中的杀菌剂

• 批准号: 2672484
• 负责人: Mary K. Katherine Howett
• 金额: $ 86.87万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672484
• 关键词: antibacterial agents; antiviral agents; disease /disorder model; drug screening /evaluation; sexually transmitted diseases; vagina

The long-term objective of this Program Project is to develop a multiphased, preclinical laboratory system which can predict the effectiveness and safety of microbicides in clinical trials. A broad spectrum of sexually transmitted diseases (STDs) will be used including papillomavirus, HIV-1, HSV-2, T. pallidum, and Chlamydia. Microbicides will first be tested in vitro for mammalian cell toxicity and effectiveness against the STDs. However, the ultimate question is whether potential clinically useful microbicide can inhibit/destroy STD pathogens in the human vaginal environment with little or no toxicity to the vaginal wall. To this end, we have developed a unique model system in which xenografts of human vaginal tissue in immune deficient mice provide an environment similar to that which prevails in the human vagina. The microbicide which we shall initially evaluate include C31G, a surface active, two component agent. We shall evaluate structure/activity relationships, formulations, and delivery systems. Nonoxynol-9 will be included as a positive control. The laboratory systems which we shall refine in this project, should provide guidelines for the rapid, future development of more effective and safer microbicides.

该计划项目的长期目标是开发一个 多阶段临床前实验室系统，可以预测 临床试验中杀菌剂的有效性和安全性。广泛的 将使用一系列性传播疾病（STD），包括 乳头瘤病毒、HIV-1、HSV-2、梅毒螺旋体和衣原体。杀菌剂 首先将在体外测试哺乳动物细胞的毒性和有效性 对抗性病。然而，最终的问题是是否有潜力 临床上有用的杀菌剂可以抑制/消灭性病病原体 人类阴道环境，对阴道壁几乎没有或没有毒性。 为此，我们开发了一个独特的模型系统，其中异种移植物 免疫缺陷小鼠的人类阴道组织提供了环境 与人类阴道中普遍存在的情况相似。杀微生物剂其中 我们将首先评估包括 C31G，一种表面活性剂，两种成分 代理人。我们将评估结构/活性关系、配方、 和输送系统。 Nonoxynol-9 将作为阳性对照。 我们将在这个项目中完善的实验室系统应该 为未来快速发展更有效和更有效的技术提供指导 更安全的杀菌剂。