Described herein are compositions for use in medicine as anti-ischemic organ storage and perfusion solutions.

Methods for making hemoglobin based blood substitute preparations and hemoglobin based blood substitute preparations. The methods involve preparing a low purity erythrocyte protein fraction comprising hemoglobin protein and endogenous non-hemoglobin protein complement, and chemically modifying the proteins in the protein fraction to form a cross-linked hemoglobin containing blood substitute preparation. The low purity erythrocyte protein preparation can contain from at least about 0.2% (mole/mole) up to about 20% (mole/mole) endogenous non-hemoglobin protein complement. At least about 90% (mole/mole) of the hemoglobin proteins can be cross-linked, so that the average molecular mass of cross-linked proteins comprising hemoglobin protein molecules in the preparation is at least about 300 kDa. The preparations can be used to prepare finished blood substitute formulations for in-vivo and ex-vivo use.

Methods for making hemoglobin based blood substitute preparations and hemoglobin based blood substitute preparations. The methods involve preparing a low purity erythrocyte protein fraction comprising hemoglobin protein and endogenous non-hemoglobin protein complement, and chemically modifying the proteins in the protein fraction to form a cross-linked hemoglobin containing blood substitute preparation. The low purity erythrocyte protein preparation can contain from at least about 0.2% (mole/mole) up to about 20% (mole/mole) endogenous non-hemoglobin protein complement. At least about 90% (mole/mole) of the hemoglobin proteins can be cross-linked, so that the average molecular mass of cross-linked proteins comprising hemoglobin protein molecules in the preparation is at least about 300 kDa. The preparations can be used to prepare finished blood substitute formulations for in-vivo and ex-vivo use.

The present invention relates to the use of a molecule selected from an Annelid globin, an Annelid globin protomer, and an Annelid extracellular haemoglobin, to treat acute respiratory distress syndrome.

Disclosed herein are oxygen transporting formulations, in particular those composed of hemoglobin-based nanoparticles, and their use and process of manufacture. These formulations are more uniform and monodisperse than prior hemoglobin-based oxygen carriers, such as polymeric hemoglobin. In addition, these formulations provide higher hemoglobin encapsulation efficiencies and higher hemoglobin content that hemoglobin-containing vesicles.

Disclosed herein are oxygen transporting formulations, in particular those composed of hemoglobin-based nanoparticles, and their use and process of manufacture. These formulations are more uniform and monodisperse than prior hemoglobin-based oxygen carriers, such as polymeric hemoglobin. In addition, these formulations provide higher hemoglobin encapsulation efficiencies and higher hemoglobin content that hemoglobin-containing vesicles.

Nanoparticle mediated microvascular embolization (NME) of tumor tissue may occur after systemic administration of PEM, leading to widespread shutdown of vascular flow, hemorrhage, and necrosis. PEM constructs are developed that incorporate large amounts of iron-containing protein, possess high oxygen affinities, and demonstrate delayed nitric oxide binding. Such properties induce selective NME of tumors after extravasation, and will likely enhance the effect of VEGFR TKIs and/or mTOR inhibitors.

Nanoparticle mediated microvascular embolization (NME) of tumor tissue may occur after systemic administration of PEM, leading to widespread shutdown of vascular flow, hemorrhage, and necrosis. PEM constructs are developed that incorporate large amounts of iron-containing protein, possess high oxygen affinities, and demonstrate delayed nitric oxide binding. Such properties induce selective NME of tumors after extravasation, and will likely enhance the effect of VEGFR TKIs and/or mTOR inhibitors.

Nanoparticle mediated microvascular embolization (NME) of tumor tissue may occur after systemic administration of PEM, leading to widespread shutdown of vascular flow, hemorrhage, and necrosis. PEM constructs are developed that incorporate large amounts of iron-containing protein, possess high oxygen affinities, and demonstrate delayed nitric oxide binding. Such properties induce selective NME of tumors after extravasation, and will likely enhance the effect of VEGFR TKIs and/or mTOR inhibitors.

Nanoparticle mediated microvascular embolization (NME) of tumor tissue may occur after systemic administration of PEM as a result of the nitric oxide sequestration by PEM. Nitric oxide sequestration may cause a reduction in available extracellular nitric oxide in the tumor endothelium, which may prompt a widespread shutdown of vascular flow, hemorrhage, and necrosis. In particular, shutdown of vascular flow may trigger changes in nitric oxide production as well as trigger an acute inflammatory response, which may create reactive nitrogen species that are particularly destructive to the microvasculature. PEM constructs are developed that incorporate large amounts of iron-containing protein, possess high oxygen affinities, and demonstrate delayed nitric oxide binding. Such properties induce selective NME of tumors after extravasation, and will likely enhance the effect of VEGFR TKIs and/or mTOR inhibitors.