Outpatient treatment for portal hypertension

描述(申请人提供)：门脉高压(门静脉系统压力增加)是肝硬变的主要后果之一。尽管降低门静脉高压症可以防止发生危及生命的后果，包括食道静脉曲张出血和肝肾综合征(HRS)，但药物治疗的选择严重有限。合成肽药物特利加压素在过去的20年里一直作为最安全、最具成本效益和最经济的药物之一在欧洲使用，用于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，它的半衰期很短，需要每天静脉注射4-6倍，限制了它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，开发一种特利加压素的长效配方，该配方可以理想地通过SubQ注射进行管理，以便每天给药一次，以管理门脉高压。第一阶段项目的目的是证明用我们的专利纳米载体配制特利加压素可以延长半衰期，延长活性物质在体内的释放，延长体内的药理效应，与每天一次的剂量相容。特利加压素目前未在美国获得批准，设想的候选药物在门静脉高压症危及生命的急性护理环境中以及门静脉高压症预防性治疗的门诊环境中都将拥有巨大的市场机会。 与公共卫生相关：这种设想的候选药物有望成为第一种可用的药物，它将使肝硬变患者及其医生在门诊环境中降低门脉高压，从而避免对危及生命的静脉曲张破裂出血和肝肾综合征进行紧急治疗。

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.