Low Molecular Weight Iron Chelate for Treatment of Anemia of Inflammation

低分子量铁螯合物治疗炎症性贫血

• 批准号: 8314514
• 负责人: DEANNA J. NELSON
• 金额: $ 9.49万
• 依托单位: BIOLINK LIFE SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8314514
• 关键词: Acute; Advanced Development; Adverse effects; Aftercare; Anemia; Anemia due to Chronic Disorder; Businesses; Carbohydrates; Cell membrane; Chronic; Chronic Disease; Clinical; Clinical Protocols; Complex; DNA Damage; Data; Deposition; Development; Devices; Dialysis patients; Dose; Drug Formulations; Elements; Erythrocytes; Erythropoiesis; Evaluation; Exhibits; FDA approved; Functional disorder; Generations; Growth; Hemoglobin; Hemoglobin concentration result; Hemorrhage; Hour; Hypoxia; Infection; Inflammation; Infusion procedures; Injection of therapeutic agent; Intensive Care; Intravenous; Intravenous infusion procedures; Iron; Iron Chelating Agents; Iron Overload; Iron deficiency anemia; Isotonic Exercise; Life; Lipid Peroxidation; Lipids; Liver; Marketing; Metabolic; Mission; Mitochondrial DNA; Molecular Weight; Necrosis; Oral; Oxidation-Reduction; Oxidative Stress; Pain; Patients; Phase; Physiological; Process; Production; Property; Proteins; Reactive Oxygen Species; Refractory; Regulation; Research; Research Support; Safety; Self Administration; Serum; Site; Small Business Innovation Research Grant; Sodium; Solutions; Time; Tissues; Toxic effect; Training; Transferrin; United States; apotransferrin; aqueous; biomaterial compatibility; cost; design; drug market; experience; extracellular; health care economics; hepcidin; intravenous administration; iron supplement; microcytic/hypochromic anemia; mitochondrial dysfunction; oxidation; patient safety; peptide hormone; response; saccharated ferric oxide; standard of care

DESCRIPTION (provided by applicant): Patients with chronic anemia (i.e., anemia of inflammation) frequently find that iron repletion cannot be achieved with oral iron fortificants. The current standard of care for these patients is infusion of intravenous (IV) iron-carbohydrate complexes. These complexes must be processed in the liver to render iron available for erythropoiesis. Therefore, after administration of an iron-carbohydrate complex, serum is temporarily iron-overloaded with catalytically active iron capable of initiating lipid peroxidation endothelial dysfunction, and added debilitating effects of oxidative stress. As a result, patients may experience serious side effects, both acutely and chronically. Preliminary studies of sodium ferricitropyrophosphate (FCP), a low molecular weight iron chelate, indicate that FCP, administered IV, may be useful to treat chronic anemia that is refractory to oral iron. The SBIR Phase I research proposed herein is designed to support the efficacy and safety of aqueous FCP solutions as a new IV iron treatment for this indication. The proposed studies will advance development of this potential product in two significant ways: " Specific Aim 1 (Safety): Determine whether FCP is stable in serum for 48 hours. Evaluation of the stability and redox activity of FCP in serum over a 48-hour period will show what potential FCP has to cause oxidative stress. "Specific Aim 2 (Safety): Formulate FCP to optimize biocompatibility for IV administration. In order to minimize side effects of administration, FCP should be formulated in aqueous solution, pH 7.4, isotonic with serum. If the resulting data demonstrate reduced potential for oxidative stress and enhancement of biocompatibility after IV administration, the data will lend credence to three expected benefits of FCP- containing IV products: (1) FCP solutions, administered using current clinical protocols, will exhibit enhanced efficacy and safety for the patient. (2) Rapid and complete apotransferrin saturation after infusion of FCP solutions may enable more efficient hemoglobin repletion using lower doses of iron. (3) Successful clinical implementation of FCP solutions may encourage development of self- administration devices, enabling daily infusion of very low doses of iron as FCP by the patient. Expected sweeping changes to the economics of health care are predicted to benefit companies which develop products having competitive advantages such as safety, convenience, and lower costs. If IV FCP therapy is successful, it could be a positive agent for change, one which enables small business growth and supports the mission of the Agency. Currently, the IV iron drug market is estimated at $560 million in the United States and $1 billion globally. PUBLIC HEALTH RELEVANCE: Patients with chronic anemia cannot use oral iron supplements to increase their hemoglobin levels and must undergo intravenous therapy with iron-carbohydrate complexes. Frequently they experience both acute and chronic side effects after treatment. The proposed research supports development of a new intravenous iron therapy which promises to provide effective hemoglobin repletion with enhanced efficacy and safety.

描述（由申请人提供）：患有慢性贫血（即炎症性贫血）的患者经常发现口服铁强化剂无法实现铁补充。目前这些患者的护理标准是静脉输注 (IV) 铁-碳水化合物复合物。这些复合物必须在肝脏中进行处理，以使铁可用于红细胞生成。因此，在施用铁-碳水化合物复合物后，血清中暂时铁超载，其中含有催化活性铁，能够引发脂质过氧化内皮功能障碍，并增加氧化应激的衰弱作用。因此，患者可能会经历严重的急性和慢性副作用。 对焦磷酸铁钠 (FCP)（一种低分子量铁螯合物）的初步研究表明，静脉注射 FCP 可能有助于治疗口服铁剂难治的慢性贫血。本文提出的 SBIR I 期研究旨在支持 FCP 水溶液作为该适应症的新 IV 铁剂治疗的有效性和安全性。拟议的研究将以两种重要方式推进这一潜在产品的开发：“具体目标 1（安全性）：确定 FCP 在血清中是否稳定 48 小时。评估 FCP 在血清中 48 小时内的稳定性和氧化还原活性期间将显示 FCP 可能导致氧化应激的情况“具体目标 2（安全性）：配制 FCP 以优化静脉注射的生物相容性。为了最大限度地减少给药副作用，FCP 应配制在 pH 7.4 的水溶液中，与血清等渗。 如果所得数据表明静脉注射后氧化应激的可能性降低且生物相容性增强，则该数据将证实含 FCP 的静脉注射产品的三个预期益处：(1) 使用当前临床方案施用的 FCP 溶液将表现出增强的功效和安全 为了病人。 (2)输注 FCP 溶液后快速、完全的脱铁转铁蛋白饱和可以使用较低剂量的铁更有效地补充血红蛋白。 (3) FCP 解决方案的成功临床实施可能会鼓励自我给药装置的开发，使患者能够每天输注极低剂量的铁作为 FCP。 预计医疗保健经济将发生彻底的变化，这将使开发具有安全、便利和低成本等竞争优势的产品的公司受益。如果 IV FCP 疗法成功，它可能成为变革的积极推动者，促进小企业增长并支持该机构的使命。目前，美国静脉铁剂药物市场估计为 5.6 亿美元，全球为 10 亿美元。 公共卫生相关性：慢性贫血患者不能使用口服铁补充剂来增加血红蛋白水平，必须接受铁-碳水化合物复合物的静脉治疗。他们经常在治疗后经历急性和慢性副作用。拟议的研究支持开发一种新的静脉铁剂疗法，该疗法有望提供有效的血红蛋白补充，并提高疗效和安全性。