MICROBICIDES IN MODEL SYSTEMS

模型系统中的杀菌剂

• 批准号: 6373469
• 负责人: Mary K. Katherine Howett
• 金额: $ 97.56万
• 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 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373469
• 关键词: antibacterial agents; antiviral agents; disease /disorder model; drug screening /evaluation; microorganism disease chemotherapy; sexually transmitted diseases

The research described in this competing renewal focuses on three main areas of our current research: a.) Continued development and characterization of model in vitro and in vivo systems, including human xenografts, as targets for STDs including herpes simplex virus type 2 (HS-2), human papillomaviruses (HPVs), Chlamydia trachomatis and human immunodeficiency virus (HIV). b.) Expansion of studies with formulated C31G preparations to optimize delivery and microbicidal activity, including pharmacodynamics of the delivered product. c.) Establishment of formulated alkyl sulfates as topical microbicides that can be applied to the vagina and provide protection from HPVs in addition to the other agents. Formulations that include N-9 or C31G in combination with alkyl sulfates will also be evaluated. The application will have four main projects including: The first Project will focus on the xenograft model and the demonstration of the efficacy of the alkyl sulfate compounds. Cellular and enzymatic profiles of the xenografts will be compiled. The second Project will focus on continued studies with C31G, alone and ir combination with alkyl sulfate microbicides. The pharmacodynamics in humans and in vitro models will be studied. The third Project will focus on the three selected viral STDs. Natural history of these infections in the vaginal xenograft model will be carried out as well as intervention studies with selected microbicides. Other model virus systems (for example, the rabbit oral papillomavirus) will also be used as surrogate systems. The four Project will focus on C. trachomatis infection and identification of effective microbicidal interventions as well as the consequences thereof for intracellular chlamydiae in already infected natural infections of C. trachomatis in a porcine model will be established and microbicides tested in this system.

本次竞争性更新中描述的研究重点关注我们当前研究的三个主要领域：a.) 体外和体内系统模型（包括人类异种移植物）的持续开发和表征，作为包括单纯疱疹病毒 2 型（HS- 2）、人乳头瘤病毒（HPV）、沙眼衣原体和人类免疫缺陷病毒（HIV）。 b.) 扩大配制 C31G 制剂的研究，以优化递送和杀菌活性，包括递送产品的药效学。 c.) 建立了作为局部杀微生物剂的烷基硫酸盐配方，除了其他药剂外，还可以应用于阴道并提供针对 HPV 的保护。还将评估包含 N-9 或 C31G 与烷基硫酸盐组合的配方。该申请将有四个主要项目，包括：第一个项目将重点关注异种移植模型和烷基硫酸盐化合物功效的演示。将编译异种移植物的细胞和酶谱。第二个项目将重点关注 C31G 单独使用以及与烷基硫酸盐杀菌剂组合的持续研究。将研究人体和体外模型的药效学。第三个项目将重点关注三种选定的病毒性 STD。将在阴道异种移植模型中进行这些感染的自然史以及使用选定的杀菌剂的干预研究。其他模型病毒系统（例如兔口腔乳头瘤病毒）也将用作替代系统。这四个项目将重点关注沙眼衣原体感染，确定有效的杀菌干预措施，以及对已感染沙眼衣原体的猪模型中细胞内衣原体的影响，并在该系统中测试杀菌剂。