DEVELOPMENT OF GD DTPA BISGLUCOSAMIDE FOR MRI CONTRAST

磁共振成像(MRI)是一种安全而强大的诊断工具 适用于多种临床情况。物美价廉 磁性药物将在健康方面发挥越来越重要的作用 使用核磁共振进行护理管理。Gd DTPA双葡萄糖胺(Gd DTPA Iga) 作为一种毒性极低的核磁共振造影剂前景看好 提高了肝脏、肾脏和高剂量成像的通用性。的目标是 这笔SBIR资助金将用于： (1)优化我们在第一阶段开发的实验室合成方法 大规模的工业生产。 (2)经济地规模化生产Gd DTPA Biga。 (3)参观和审核选定的代工工厂。 (4)配制并无菌灌装Gd DTPA Biga，用量为0.5摩尔 在第一阶段开发的配方数据 (5)建立和验证IND所需的程序和协议 呈件。 (六)进行急性毒性、亚慢性毒性、致突变性、 药代动力学和生物分布研究被认为是必要的 IND在第一阶段的应用 (7)参观和审核选定的合同毒理学设施。 (8)对Gd DTPA的体内解离进行了详细的研究 大鼠的BIGA与FDA批准的其他造影剂的关系。 (9)参观和选择FDA第一阶段和第二阶段临床研究的地点。 (10)与FDA一起审查IND要求，并提交IND。 建议的商业应用：磁共振造影剂，具有 全球销售额超过10亿美元/年，构成了重要的 辅助核磁共振扫描。目前销售了四个代理商，这些代理商分发 进入细胞外液间隙，占所有MRI对比度的95%(+) 申请。每一家都由一家外国公司所有。其中三个是FDA批准的和 在这个国家可以买到。UnivisionTM，DTPA双葡糖胺 Magic Research，Inc.正在开发的化合物显示出良好的前景 比市场上已有的产品更具优势。

Magnetic resonance imaging (MRI) is a safe and powerful diagnostic tool for a wide range of clinical conditions. Inexpensive and efficient magnetopharmaceuticals will play an increasingly important role in health care management with MRI. Gadolinium DTPA Bisglucosamide (Gd DTPA BIGA) has great promise as an MRI contrast agent with very low toxicity and improved versatility for liver, renal, and high dose imaging. The goal of this SBIR grant is to: (1) Optimize our lab synthetic methodologies developed in Phase I for large scale industrial production. (2) Economically produce Gd DTPA BIGA in large scale. (3) Visit and audit selected contract manufacturing facility. (4) Formulate and sterile fill Gd DTPA BIGA at 0.5 Molar using formulation data developed in Phase I. (5) Establish and validate required procedures and protocols for IND submission. (6) Conduct acute toxicity, sub-chronic toxicity, mutagenicity, pharmacokinetics and biodistribution studies identified as necessary for IND application in Phase I. (7) Visit and audit selected contract toxicology facility. (8) Carry out a detailed investigation of in vivo de-chelation of Gd DTPA BIGA in rats in relation to other FDA-approved contrast agents. (9) Visit and select sites for Phase I and Phase II FDA clinical studies. (10) Review IND requirements with the FDA, and submit an IND. PROPOSED COMMERCIAL APPLICATION: Magnetic resonance contrast media, with worldwide sales exceeding $1 billion/year, constitutes an important adjuvant to MRI scanning. Currently four agents are sold which distribute into the extracellular fluid space and comprise 95(+)% of all MRI contrast applications. Each is owned by a foreign firm. Three are FDA-approved and available in this country. UnivisionTM, the Gadolinium DTPA Bisglucosamide compound being developed by Magnetic Research, Inc., shows promising advantages over those already on the market.