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3

项与 1608557 Ontario, Inc. 相关的药物

HML-110

靶点

Hemoglobins

作用机制

血红蛋白调节剂

在研机构-

原研机构

1608557 Ontario, Inc.

在研适应症-

非在研适应症

再灌注损伤

最高研发阶段终止

首次获批国家/地区-

首次获批日期-

HRC-201

靶点

Hemoglobins

作用机制

血红蛋白调节剂

在研机构-

原研机构

1608557 Ontario, Inc.

在研适应症-

非在研适应症

肝癌

最高研发阶段终止

首次获批国家/地区-

首次获批日期-

HML-109

靶点

Hemoglobins

作用机制

血红蛋白调节剂

在研机构-

原研机构

1608557 Ontario, Inc.

在研适应症-

非在研适应症

输血反应

最高研发阶段终止

首次获批国家/地区-

首次获批日期-

1

项与 1608557 Ontario, Inc. 相关的临床试验

NCT00038454 / Suspended临床2/3期

A Phase II, Randomized, Single-Blind, Controlled Clinical Trial to Evaluate the Efficacy and Safety of Hemolink[Tm] (o-Raffinose Cross-Linked Human Hemoglobin) in Subjects Undergoing Primary Coronary Artery Bypass Grafting Surgery

To evaluate the efficacy of Hemolink™ in combination with Intraoperative Autologous Donation (IAD) versus control (IAD alone) in facilitating avoidance of allogeneic RBC transfusion during and following primary CABG surgery

开始日期-

申办/合作机构

1608557 Ontario, Inc.

100 项与 1608557 Ontario, Inc. 相关的临床结果

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0 项与 1608557 Ontario, Inc. 相关的专利（医药）

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2

项与 1608557 Ontario, Inc. 相关的文献（医药）

2006-03-01·Bioconjugate Chemistry2区 · 化学

Synthesis and Characterization of a Hemoglobin−Ribavirin Conjugate for Targeted Drug Delivery

2区 · 化学

Article

作者: Ng, Nancy F. L. ; Bell, David N. ; Brookes, Steve ; Adamson, Gord ; Biessels, Pieter ; Woods, Caroline

A novel conjugate of human hemoglobin (Hb) and the nucleoside analogue ribavirin (RBV) was synthesized to demonstrate the utility of Hb as a biocompatible drug carrier for improved drug delivery in the treatment of liver disease. RBV is used in combination with interferon for the treatment of hepatitis C, but its side effects can result in dose limitation or discontinuation of treatment. Targeted delivery of RBV may help to prevent or minimize its toxicity. The hemoglobin-ribavirin conjugate (Hb-RBV) was designed to release bioactive drug upon endocytosis by cells and tissues involved in extracellular Hb catabolism and clearance. Ribavirin-5'-monophosphate (RBV-P) was prepared from RBV and activated as the 5'-monophosphorimidazolide (RBV-P-Im) for reaction with carbonmonoxyhemoglobin to yield Hb-RBV consisting of multiple RBV drugs covalently attached as physiologically labile phosphoramidates via their 5'-hydroxyl groups. A molar drug ratio of six to eight RBV molecules per Hb tetramer was obtained with near complete haptoglobin (Hp) binding of the drug modified Hb maintained. The conjugate complex (Hp-Hb-RBV) was selectively taken up in vitro by cells that express the hemoglobin-haptoglobin receptor, CD163. Recovered ribavirin enzymatically cleaved from Hb-RBV showed equipotent antiproliferative activity compared to control unconjugated RBV against human HepG2 and mouse AML12 liver cell lines. Based upon the reported high level of Hb uptake in the liver, Hb-RBV may be useful in the treatment of certain liver diseases, as well as inflammatory disorders associated with CD163-positive macrophages.

Hemoglobin-drug conjugates for targeted delivery of nucleoside drugs

作者: Adamson, Gord ; Bell, David N.

Hb-drug conjugates (HDCs) may improve the safety and efficacy of the attached drugs for treatment of liver viral infection and cancer.HDCs target drugs to liver cells through the endogenous pathway for Hb catabolism through the liver.Several nucleoside drugs including ribavirin (an essential co-therapy for hepatitis C virus infection with significant dose-limiting toxicity) were conjugated to Hb as 5′-monophosphoramidates, allowing for intracellular drug release.HDCs with molar drug ratios up to 15 retained the ability to bind haptoglobin (the natural ligand for acellular Hb) and to be taken up by cells expressing the Hb-haptoglobin receptor, CD163.In a viral hepatitis mouse model, ribavirin-HDC prolonged survival, improved behavior, and reduced histol. signs of disease.Viral replication and inflammatory cytokine production were inhibited in vitro.HDCs of the anti-cancer nucleoside floxuridine showed increased cytotoxicity against lymphoma cells expressing CD163.Further investigation of HDCs for targeted therapy of hepatic diseases is warranted.

100 项与 1608557 Ontario, Inc. 相关的药物交易

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100 项与 1608557 Ontario, Inc. 相关的转化医学

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