Outpatient treatment for portal hypertension

门静脉高压症的门诊治疗

• 批准号: 7801161
• 负责人: Elijah M. Bolotin
• 金额: $ 22.34万
• 依托单位: PHARMAIN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-03-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7801161
• 关键词: Acute; Address; Adrenergic beta-Antagonists; Adverse event; Alcoholism; American; Animal Model; Area Under Curve; Binding; Blood Pressure; Blood flow; Caring; Cirrhosis; Cleaved cell; Clinical; Collaborations; Complex; Development; Dissociation; Dose; Drug Delivery Systems; Drug Formulations; Emergency Situation; Emergency treatment; Employee; Endopeptidases; Equilibrium; Esophageal Varix; Europe; Evaluation; Fright; Funding; General Hospitals; Goals; Half-Life; Hemorrhage; Hepatic; Hepatitis B; Hepatorenal Syndrome; Human; In Vitro; Injection of therapeutic agent; Intravenous Bolus; Investigational Drugs; Licensing; Life; Liver Cirrhosis; Liver diseases; Lysine; Marketing; Massachusetts; Metal Binding Site; Metals; Monitor; Mus; Nanotechnology; New Agents; New Drug Approvals; Operative Surgical Procedures; Orphan; Outpatients; Patients; Peptide Hydrolases; Peptides; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Physicians; Portal Hypertension; Portal Pressure; Portal Venous System; Portal vein structure; Preparation; Prodrugs; Prophylactic treatment; Proteins; Rattus; Rupture; Safety; Serum; Small Business Innovation Research Grant; Steatohepatitis; Survival Rate; Therapeutic; Toxic effect; United States Food and Drug Administration; Varicosity; Vascular resistance; Vasopressins; analog; commercialization; comparative efficacy; copolymer; cost; drug candidate; hemodynamics; improved; in vivo; mortality; nanocarrier; new technology; pressure; prevent; public health relevance; response; success; synthetic peptide; vasoactive agent

DESCRIPTION (provided by applicant): Portal hypertension (increased pressure in the portal venous system) is one of the main consequences of cirrhosis. Although the reduction of portal hypertension is well documented to prevent the development of life-threatening consequences, including bleeding esophageal varices and hepatorenal syndrome (HRS), pharmacological treatment options are severely limited. The synthetic peptide drug terlipressin has been used in Europe for the past twenty years as one of the safest, most cost-effective and economical drugs to reduce portal hypertension and treat bleeding varices and hepatorenal syndrome. However, its short half life necessitates its administration by IV 4-6x daily, limiting its application to the acute care setting. Our long term goal, in collaboration with our commercialization partner LAT-Pharma LLC, is to develop a long-acting formulation of terlipressin that can be ideally administered by sub-Q injection allowing for once daily administration for the management of portal-hypertension. The aims of the Phase I project are directed toward demonstrating that formulation of terlipressin with our proprietary nanocarrier affords an increase in half-life and a sustained release of the active agent with a prolonged pharmacological effect in vivo compatible with once-daily dosing. Terlipressin is currently not approved in the US and the envisioned drug candidate would have a significant market opportunity both in the acute care setting for life-threatening consequences of portal hypertension, and in the outpatient setting for the prophylactic treatment of portal hypertension. PUBLIC HEALTH RELEVANCE: The envisioned drug candidate is expected to be the first agent available that will allow cirrhotic patients and their physicians reduce portal hypertension in the outpatient setting, thereby avoiding emergency treatment of life-threatening bleeding variceal ruptures and Hepatorenal syndrome.

描述（由申请人提供）：门静脉高压（门静脉系统压力升高）是肝硬化的主要后果之一。虽然门静脉高压的降低被充分证明可以防止危及生命的后果的发展，包括出血性食管静脉曲张和肝肾综合征（HRS），但药物治疗选择非常有限。合成肽类药物特利加压素在过去的二十年里一直在欧洲使用，作为最安全，最具成本效益和经济的药物之一，以降低门静脉高压症和治疗出血静脉曲张和肝肾综合征。然而，其短半衰期需要每天IV 4- 6次给药，限制了其在急性护理环境中的应用。我们的长期目标是与我们的商业化合作伙伴LAT-Pharma LLC合作，开发一种长效特利加压素制剂，该制剂可以理想地通过sub-Q注射给药，允许每天给药一次，用于门脉高压的管理。I期项目的目的是证明特利加压素与我们专有的纳米载体的制剂提供了半衰期的增加和活性剂的持续释放，具有与每日一次给药相容的体内延长的药理学作用。特利加压素目前尚未在美国获得批准，预期的候选药物将在门静脉高压危及生命后果的急性护理环境和门静脉高压预防性治疗的门诊环境中具有重要的市场机会。 公共卫生相关性：预期的候选药物有望成为第一个可用的药物，将允许门静脉高压症患者及其医生在门诊环境中降低门静脉高压症，从而避免危及生命的静脉曲张破裂出血和肝肾综合征的紧急治疗。