NOVEL TREATMENT OF IRRITABLE BOWEL SYNDROME

拟议研究的长期目标将导致 能有效治疗某些疾病的临床有用组合物 患有肠易激综合征(IBS)的个人。该方法 包括使用大肠注射解痉剂 前药方法。前药从上半部吸收不良 胃肠道对结肠中的水解物很敏感。 这项拟议的研究有两个具体目标。第一个是 薄荷脑胶囊的药代动力学考察 薄荷脑或其葡萄糖醛酸苷灌胃后 前药；局部盲肠和结肠给药的主要指标将是 药物释放指数(DDI)。DDI和其他几个 药代动力学参数将通过稳态给药确定 药物或前药。第二个具体目标将涉及研究 通过测量整个肠道的变化来评价前药的疗效 用木炭试验餐测量大鼠的转运(胃排空 和小肠运输)和运输一类珠来评估 结肠运输。这项工作的成功结果将有助于 患有IBS症状的个人。 建议的商业应用：假设15%的成年人口 美国人患有肠易激综合征(3000万人)，其中14%到50%寻求 医疗援助(420万至1500万)和建议的治疗方案 到5%(每20个人中就有一个)，将有一个患者群体 每年21万到75万。假设每年治疗200天 而每天2美元的AHP，每年的收入将从84美元到300美元不等。

The long-term objectives of the proposed research will lead to a clinically useful composition capable of effectively treating certain individuals suffering from irritable bowel syndrome (IBS). The approach involves delivery of a spasmolytic agent to the large intestine using the prodrug approach. The prodrug is poorly absorbed from the upper gastrointestinal tract yet is susceptible to hydrolysis in the colon. There are two specific aims for the proposed research. The first is to examine the pharmacokinetics of delivery of the carminative menthol following intragastric administration of menthol or its glucuronide prodrug; the primary indicator of local cecal and colonic delivery will be the Drug Delivery Index (DDI). The DDI, along with several other pharmacokinetic parameters will be determined by steady-state dosing of the drug or prodrug. The second specific aim will involve studying the efficacy of the prodrug by measuring alterations in overall intestinal transit as measured with a charcoal test meal in the rat (gastric emptying and small intestinal transit) and transit of a class bead to assess colonic transit. The successful outcome of this work will help those individuals suffering from symptoms of IBS. PROPOSED COMMERCIAL APPLICATION: Assuming 15% of the adult population in the U.S. suffer from IBS (30 million) and out of these 14 to 50% seek medical help (4.2 to 15 million) and the proposed treatment is prescribed to 5% (1 in 20) of these individuals, there will be a patient population of 210,000 to 750,000 annually. Assuming 200 days per year of treatment and a daily AHP of 2$, revenues would range from $84 to $300 annually.