Subcutaneous Drug Development for Portal Hypertension Ascites
门静脉高压腹水的皮下药物开发
基本信息
- 批准号:10469005
- 负责人:
- 金额:$ 98.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-09-22 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAlcoholismAmericanAnimalsAscitesBindingBloodBolus InfusionCessation of lifeChronicCirrhosisClinical TrialsConfidential InformationCreation of peritoneovascular shuntDataDiureticsDoseEquilibriumEuropeExcipientsFluid overloadFormulationFunctional disorderFundingFurosemideGreater sac of peritoneumHalf-LifeHealth Care CostsHemorrhageHepatic EncephalopathyHepatorenal SyndromeHospital CostsHumanInfusion proceduresInjectionsIntravenousIntravenous BolusLeadLiquid substanceLiver CirrhosisLiver diseasesLysineMedicalModelingModificationNecrosisNo-Observed-Adverse-Effect LevelOperative Surgical ProceduresOrphan DrugsOutpatientsParacentesisPatientsPeritoneal FluidPharmaceutical PreparationsPharmacologyPhasePortal HypertensionPortal vein structurePractice GuidelinesPrevalenceProceduresProdrugsQuality of lifeRattusRecommendationRefractorySafetySecureSmall Business Innovation Research GrantSodium ChlorideSodium-Restricted DietSpironolactoneSurvival RateTestingTherapeuticTherapeutic IndexTimeTissuesToxic effectTransjugular intrahepatic portosystemic shunt procedureTransplant RecipientsUrineVaricosityVasopressinsViral hepatitisacute careanalytical methodbasecost effectivedietary restrictiondrug developmenteffective therapyefficacy testinghemodynamicsinfection risklead candidateliquid formulationliver transplantationmeetingsmethod developmentmortalitynonalcoholic steatohepatitispharmacokinetics and pharmacodynamicsphase 1 studypreferencepressurereceptorside effectsubcutaneoussuccess
项目摘要
ABSTRACT: The prevalence of all types of ascites, irrespective of the cause, is 41.7 in 100,000 with
80% of these due to cirrhosis. Ascites is treated with a salt restricted diet and pharmacologic therapy using
diuretics. However, in 5% to 10% of patients with ascites becomes refractory to medical therapy. Half of
patients who develop refractory ascites due to advanced liver cirrhosis will die within a year without a liver
transplant and therefore expedited referral for liver transplantation is recommended. Temporary treatment
while waiting includes large volume paracentesis, transjugular intrahepatic portasystemic shunt (TIPS), and
peritoneovenous shunt surgical procedures. Complications from these procedures that can further increase
mortality include paracentesis-induced circulatory dysfunction (PICD) and chronic hepatic encephalopathy
from TIPS. Pharmacological therapies that can stop the progression or extend survival and act as a
therapeutic bridge to liver transplantation are thus desperately needed. Terlipressin, tri-glycyl [8-lys]
vasopressin, is an inactive pro-drug of Lysine-vasopressin (LVP) that releases active LVP slowly to
minimize LVP spike that can cause ischemic side effect. LVP reduces portal vein pressure, restores
hemodynamic balance, and is an effective treatment for portal hypertension ascites. Because of slow LVP
release, terlipressin is well tolerated and has a far better safety profile than human native vasopressin ([8-
Arg] vasopressin). Intravenous terlipressin has been available in Europe for the past twenty years and it is
one of the most cost-effective and economical drugs for treating bleeding varices and hepatorenal
syndrome (HRS) with improvement in survival rates that is well documented. Despite its good safety
profile, the use of terlipressin is currently limited to the acute care setting because the short half-life (26
min) that necessitates administration by IV bolus injection every 4-6h. We developed a new terlipressin
derivative (dTer) that has much slower LVP release and found to be effective rat model of cirrhosis induced
portal hypertension ascites when administered subcutaneously as once-daily bolus. This product can have
a significant market opportunity in the U.S. especially in an outpatient setting (which will reduce overall
health care cost by eliminating cost of hospitalization) for the treatment of refractory ascites from cirrhosis-
induced portal hypertension ascites. This product (dTer) provides sustained release of active LVP and
demonstrated a substantially longer blood presence with lower LVP Cmax (eliminating ischemic side effect)
than terlipressin. This proposal is intended to collect IND enabling data package for submission to the FDA
to begin clinical trial. We already secured an orphan drug status for the use of dTer in patient with cirrhosis
induced ascites.
PharmaIN Corp. Confidential Information
摘要:所有类型腹水的患病率,不论病因,为41.7 / 100000
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Gerardo M. Castillo其他文献
Compositions de supports a noyau hydrophobe pour l'administration d'agents therapeutiques, et procedes de preparation et d'utilisation
支持治疗剂施用、制备和利用过程的疏水性组合物
- DOI:
- 发表时间:
2006 - 期刊:
- 影响因子:0
- 作者:
Gerardo M. Castillo;Elijah M. Bolotin - 通讯作者:
Elijah M. Bolotin
Erratum to: Protected Graft Copolymer Excipient Leads to a Higher Acute Maximum Tolerated Dose and Extends Residence Time of Vasoactive Intestinal Peptide Significantly Better than Sterically Stabilized Micelles
- DOI:
10.1007/s11095-013-1061-0 - 发表时间:
2013-05-09 - 期刊:
- 影响因子:4.300
- 作者:
Sandra Reichstetter;Gerardo M. Castillo;Israel Rubinstein;Akiko Nishimoto-Ashfield;ManShun Lai;Cynthia C. Jones;Aryamitra Banerjee;Alex Lyubimov;Duane C. Bloedow;Alexei Bogdanov;Elijah M. Bolotin - 通讯作者:
Elijah M. Bolotin
Gerardo M. Castillo的其他文献
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{{ truncateString('Gerardo M. Castillo', 18)}}的其他基金
CMC of Peptide Formulation for the Treatment of ARDS
用于治疗 ARDS 的肽制剂的 CMC
- 批准号:
10839580 - 财政年份:2022
- 资助金额:
$ 98.23万 - 项目类别:
CMC of Peptide Formulation for the Treatment of ARDS
用于治疗 ARDS 的肽制剂的 CMC
- 批准号:
10379771 - 财政年份:2022
- 资助金额:
$ 98.23万 - 项目类别:
Subcutaneous Drug Development for Portal Hypertension Ascites
门静脉高压腹水的皮下药物开发
- 批准号:
10320316 - 财政年份:2014
- 资助金额:
$ 98.23万 - 项目类别:
Subcutaneous Drug Development for Portal Hypertension Ascites
门静脉高压腹水的皮下注射药物开发
- 批准号:
8930140 - 财政年份:2014
- 资助金额:
$ 98.23万 - 项目类别:
Subcutaneous Drug Development for Portal Hypertension Ascites
门静脉高压腹水的皮下注射药物开发
- 批准号:
8776220 - 财政年份:2014
- 资助金额:
$ 98.23万 - 项目类别:
Nanocarrier-formulated NF-kB inhibitors for Inflammatory diseases
纳米载体配制的用于炎症疾病的 NF-kB 抑制剂
- 批准号:
8300786 - 财政年份:2011
- 资助金额:
$ 98.23万 - 项目类别:
Nanocarrier-formulated NF-kB inhibitors for Inflammatory diseases
纳米载体配制的用于炎症疾病的 NF-kB 抑制剂
- 批准号:
8196005 - 财政年份:2011
- 资助金额:
$ 98.23万 - 项目类别:
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