Screening of complex fucoidans from four brown algae species as procoagulant agents.

Fucoidans are complex sulfated polysaccharides extracted from brown algae. Depending on the concentration, they have been shown to stimulate and inhibit blood coagulation in vitro. Promotion of coagulation is mediated by blocking tissue factor pathway inhibitor (TFPI).

Surface modification of diaspirin cross-linked hemoglobin (DCLHb) with chondroitin-4-sulfate derivatives. Part 1.

Synthetic methodology was developed for the preparation of chondrotin-4-sulfate reagents that could be specifically attached to the surface of diaspirin cross-linked hemoglobin (DCLHb), a chemically stabilized human hemoglobin. The surface-modified hemoglobin solutions had a significantly higher colloidal osmotic pressures (COP) than DCLHb. The P(50) of the modified DCLHb was dependent upon the reactive end group of the chondrotin-4-sulfate reagents that was used for the protein modification.

Evaluation and validation of virus removal by ultrafiltration during the production of diaspirin crosslinked haemoglobin (DCLHb).

Virus retention during ultrafiltration through A/G Technology filter cartridges was investigated to characterize the removal process and validate the degree of virus titre reduction during the filtration of red blood cell haemolysates performed as part of the production of diaspirin crosslinked haemoglobin (DCLHb). When viruses were suspended in phosphate buffered saline solution, retention was greater with larger sized viruses and smaller filter pore size. Virus titre was maintained at starting levels in the filter retentate circuit during the course of filtration, suggesting that the virus removal mechanism is predominantly size exclusion.

Polymerization of diaspirin cross-linked hemoglobin (DCLHb) with water-soluble, nonimmunogenic polyamide cross-linking agents.

Diaspirin cross-linked hemoglobin (DCLHb), a human hemoglobin that is intramolecularly cross-linked between the alpha chains (lysine 99(alpha)(1)-lysine 99(alpha)(2)), was polymerized with a number of water-soluble, nonimmunogenic polyamide cross-linking agents. The degree of polymerization and the oxygen-carrying capacity depended upon the polyamide reagent, the starting concentration of DCLHb, the molar ratio of the polyamide reagent to DCLHb used, the reaction pH, and whether oxy- or deoxy-DCLHb was used in the polymerization reaction.

Validation of the heat treatment step used in the production of diaspirin crosslinked hemoglobin (DCLHb) for viral inactivation--effect of crosslinking.

Two experiments were performed to assess viral inactivation during the crosslinking and heat treatment steps of the DCLHb manufacturing process. Stroma free hemoglobin (SFHb) collected from a large scale manufacturing lot was tested in a 1:680 scaled down system in which the key parameters used in the manufacturing process were replicated. In the first study Porcine Parvovirus (PPV), a non-enveloped virus, was used to assess inactivation, while in the second study Bovine Viral Diarrhea Virus (BVDV), an enveloped virus, was utilized.