Enteric Elimination and Degradation of Oxalic Acid

草酸的肠消除和降解

• 批准号: 6337796
• 负责人: Marguerite Hatch
• 金额: $ 24.98万
• 依托单位: IXION BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-15 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6337796
• 关键词: bacteria characteristic; bacterial proteins; biological products; biotherapeutic agent; dietary calcium; gastrointestinal absorption /transport; gram negative bacteria; infection; laboratory rat; membrane channels; microorganism mass culture; microorganism metabolism; nephrocalcinosis; oxalates; primary hyperoxalurias

Approximately one million cases of stone disease are diagnosed in the United States every year and hyperoxaluria is considered to be a major risk factor. Our goal is to reduce the burden of oxalate excretion by the kidneys before the onset of renal failure caused by the oxalate-induced insults of hyperoxaluria, oxalate crystal deposition in tissue, and the formation of calcium oxalate stones. The studies proposed here represent a continuation of investigations that were initiated to specifically develop an oral supplementation therapy, using the substrate-specific, gut bacteria Oxalobacter or its products, for the control of hyperoxaluric conditions. Thus far, our studies have revealed the important physiological role of intestinal secretory/excretory pathways in shifting the balance of oxalate excretion between the renal and enteric routes of elimination. We have shown that a cell lysate preparation from Oxalobacter stimulated the active transport systems involved in colonic oxalate excretion in addition to enzymically degrading oxalate in solution. Subsequently, we showed an impressive reduction in urinary oxalate excretion in vivo, in rats with oxalate- induced renal failure by administering encapsulated Oxalobacter lysate compared to placebo. The present objective is to produce a therapeutic supplement which will maximally exploit the combination of these two actions in order to control hyperoxaluric conditions. PROPOSED COMMERCIAL APPLICATIONS: The development of an effective supplementation therapy for the control of hyperoxaluric conditions is timely. Currently, there are 1 million patients with kidney stone disease and there are patients with other oxalate-associated diseases, including primary hyperoxaluria which invariably results in death at an early age due to oxalate-induced kidney failure. The potential for the clinical application of a novel treatment strategy to reduce urinary oxalate excretion is broad-based and highly significant.

在美国，大约有一百万例结石病被诊断出来。 美国每年和高尿酸被认为是一个主要的 风险因素我们的目标是减少草酸排泄的负担， 肾功能衰竭的病因有哪些？ 高尿酸血症、组织中草酸盐结晶沉积以及 草酸钙结石的形成。这里提出的研究 这是调查的继续， 专门开发口服补充疗法，使用 基质特异性，肠道细菌Oxalcadine或其产品，用于 控制高尿酸状况。到目前为止，我们的研究表明 肠道分泌/排泄的重要生理作用 肾脏和肾脏之间草酸排泄平衡的转移途径 和肠道消除途径。我们已经证明细胞裂解物 草酸钙制剂刺激主动转运系统 参与结肠草酸排泄，除了酶 在溶液中降解草酸盐。随后，我们展示了令人印象深刻的 在体内，草酸盐大鼠的尿草酸盐排泄减少， 通过给予包封的草酸钙裂解物诱导肾衰竭 与安慰剂相比。本发明的目的是生产一种治疗性的药物， 补充将最大限度地利用这两个组合 采取行动，以控制高尿酸状况。 拟议的商业应用： 开发一种有效的补充疗法， 及时控制高尿酸情况。目前，有1 肾结石患者有哪些？ 其他尿酸盐相关疾病，包括原发性高尿酸血症 这总是导致死亡，在早期的年龄， 肾衰竭一种新的临床应用的潜力 减少尿草酸排泄的治疗策略是广泛的 而且意义重大