Development of Non-Narcotic Intravenous Analgesics

描述（由申请方提供）：静脉给药在临床上通常比口服给药更理想，特别是对于因疾病或状况（例如，无意识、麻醉）而难以口服药物的患者。IV给药还产生更快的治疗起效，并允许更准确的剂量给药和滴定。尽管IV给药可以避免与药物吸收相关的变量，但IV药物必须具有良好的水溶性，以避免与血液凝固和栓塞形成相关的问题。因此，新药候选物的溶解度特性对其治疗（和商业）成功的机会具有显著影响。我们一直在探索一系列新的和专有的对乙酰氨基酚类似物，显示良好的口服疗效，但没有肝毒性作用。在第一阶段项目中，我们将制备这些化合物的水溶性类似物，并确定进一步开发这些目标候选化合物作为IV镇痛药的可行性。这项技术将满足我们的目标之一，定义为临床上可用作术后疼痛和其他类型疼痛的IV治疗的药物，包括可能肝功能受损的患者（例如，老年人、癌症患者和酒精性肝损伤或肝炎患者）。

DESCRIPTION (provided by applicant): Intravenous drug administration is often clinically desired over oral administration, particularly for patients who have difficulty taking an oral drug due to their disease or condition (eg, unconsciousness, anesthetized). IV administration also produces a faster therapeutic onset and permits more accurate dose administration and titration. Although variables related to drug absorption are circumvented by IV administration, IV drugs must have good water solubility to avoid issues related to blood clotting and formation of embolisms. Therefore, the solubility characteristics of new drug candidates have a significant effect on their chance for therapeutic (and commercial) success. We have been exploring a series of new and proprietary analogs of acetaminophen that show good oral efficacy but are devoid of hepatotoxic effects. Under this Phase I project we will prepare water-soluble analogs of these compounds, and determine the feasibility for further development of each of these target-candidate compounds as IV analgesics. This technology will fulfill one of our target profiles, defined as a drug that is clinically useful as an IV treatment for postoperative pain and other types of pain, including patients that may have compromised liver function (eg. elderly, cancer patients, and patients with alcoholic liver injury or hepatitis).