CRL-1072 FOR TREATMENT OF MYCOBACTERIUM

I期研究表明CRL 1072对急性白血病有效 禽分枝杆菌(MAI)感染合并 克拉霉素、利福平和克林霉素。第二阶段的目标是 推荐特定剂型的特定药物组合 将有效治疗耐药生物，减少出现 耐药生物，并最大限度地减少与多种 MAI感染的药物治疗。第一个目标是优化 CRL 1072与克拉霉素、利福布汀联合应用方案 和克林霉素在清除、复发方面的完全性 感染和抗药性的出现。一个标准化的米色小鼠模型 是为解决这些问题而开发的。下一个目标是使用 这些方法考察了CRL 1072与几种 克拉霉素耐药临床分离株的抗生素耐药研究 使用U937巨噬细胞模型，随后在米色小鼠中进行研究。一秒钟 共聚物CRL 1605已被证明通过不同的机制作用于 CRL 1072，并与其产生协同效应。它将在一个 努力进一步降低药物治疗的剂量和毒性。下一首, 将进行实验以制定口服给药的方案 使用来自父母研究的最有效的组合的药物。 最后，我们将研究CRL 1072对已知限制的影响 一线和二线抗分枝杆菌药物的毒性。 建议的商业应用：治疗MAI感染的新药物 由于耐药性和药物问题，需要对艾滋病毒患者进行治疗 毒性。新药增效剂S的研制 活性和降低毒性将填补一个重要的需求，因此 商业应用。

Studies in Phase I demonstrated that CRL 1072 is effective against acute infection with Mycobacterium Avium (MAI) in combination with clarithromycin, rifabutin and clindamycin. The goal of Phase II is to recommend a specific combination of drugs in specific dosage forms that will effectively treat drug resistant organisms, reduce the emergence of drug resistant organisms, and minimize toxicity associated with multiple drug therapy of infections with MAI. The first aim is to optimize protocols for using CRL 1072 in combination with clarithromycin, rifabutin and clindamycin in terms of completeness of clearance, recrudescence of infection and emergence of resistance. A standardized beige mouse model has been developed to address these questions. The next aim is to use these methods to investigate the effects of CRL 1072 with several antibiotics on a series of clarithromycin resistant clinical isolates using a U937 macrophage model followed by studies in beige mice. A second copolymer, CRL 1605, has been shown to act via different mechanisms from CRL 1072 and to produce synergy with it. It will be evaluated in an effort to further reduce the dose and toxicity of drug therapy. Next, experiments will be done o develop protocols for oral administration of drugs using the most effective combinations from parental studies. Finally, we will investigate effects of CRL 1072 on the known limiting toxicities of first and second line antimycobacterial drugs. PROPOSED COMMERCIAL APPLICATION: Novel agents for treating MAI infections in HIV patients are needed because of problems in drug resistance and drug toxicity. The development of CRL-1072 s a novel agent to increase drug activity and reduce toxicity will fill in an important need and thus have commercial applications.