Development of a new treatment of urinary stone disease

开发尿路结石新疗法

• 批准号: 6485376
• 负责人: PAUL A VOZIYAN
• 金额: $ 10万
• 依托单位: BIOSTRATUM, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-04 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6485376
• 关键词: atomic absorption spectrometry; biosynthesis; drug design /synthesis /production; drug screening /evaluation; fluorescence spectrometry; high performance liquid chromatography; laboratory rat; oxalates; primary hyperoxalurias; urinary calculi; urinary tract disorder chemotherapy; urinary tract pharmacology; vitamin B6

DESCRIPTION (provided by applicant): Development of a new method for prophylaxis and treatment of urinary stone disease is proposed. Since a majority of urinary stones are made of calcium oxalate, the level of urinary oxalate is one of the major risk factors of stone formation. Unfortunately, there is no effective pharmacological treatment of stone disease that targets urinary oxalate concentration. Our method is based on chemical trapping of carbonyl precursors of oxalate biosynthesis and, thus, decreasing urinary oxalate concentration. In the preliminary experiments we have effectively trapped oxalate precursors glycolaldehyde and glyoxylate in vitro, and have reduced urinary oxalate excretion in normal animals (rats). In the current Phase I application we propose to check whether our treatment will result in trapping of oxalate precursors and reduction of urinary oxalate levels in the rat model of hyperoxaluna. If these Phase I experiments demonstrate the feasibility of the proposed approach, in Phase Il we will conduct human studies and optimize our method for patient treatment. Proposed Commercial Applications: Given the frequency of urinary stone disease and high rates of recurrent stone formation, there is a significant market potential for the proposed pharmacological treatment.

描述（由申请人提供）：开发一种新方法 提出了预防和尿石病的治疗。自从 大多数尿结石是用草酸钙制成的，尿液水平 草酸盐是石材形成的主要危险因素之一。很遗憾， 没有针对石材疾病的有效的药理学治疗 草酸盐浓度。我们的方法是基于化学诱捕的 草酸盐生物合成的羰基前体，从而减少尿 草酸盐浓度。在初步实验中，我们有效 在体外捕获的草酸盐前体甘油醛和甘酰胺，并具有 正常动物（大鼠）中草酸盐排泄减少。在电流中 我们建议检查我们的治疗是否会导致 草酸盐前体的捕获和尿中草酸盐水平的降低 Hyperoxaluna的大鼠模型。如果这些阶段I实验证明了 拟议方法的可行性，在IL期，我们将进行人类研究 并优化我们的患者治疗方法。 拟议的商业应用： 鉴于尿结石疾病的频率和较高的复发石材形成率，拟议的药理治疗具有巨大的市场潜力。