Sterilization of heparinized Cuprophan hemodialysis membranes

The effects of sterilization of dry heparinized Cuprophan hemodialysis membranes by means of ethylene oxide (EtO) exposure, gamma irradiation, or steam on the anticoagulant activity and chemical characteristics of immobilized heparin and the permeability of the membrane were investigated. Sterilization did not result in a release of heparin or heparin fragments from heparinized Cuprophan. Sterilization of heparinized Cuprophan by means of EtO exposure and gamma irradiation induced a slight, insignificant decrease of the anticoagulant activity. In contrast, steam-sterilized heparinized Cuprophan showed a higher anticoagulant activity than unsterilized heparinized Cuprophan, which was most likely caused by cleavage of some of the covalent bonds between heparin and Cupropha. The effects of sterilization on the permeability of unmodified Cuprophan and heparinized Cuprophan were compared. The permeability of unmodified Cuprophan for vitamin B12 (Vit B12) and sulfobromophthalein (SBP) was reduced by 20–35% after EtO exposure and gamma irradiation and was reduced by 90–95% after steam sterilization. The water permeability of unmodified Cuprophan remained the same after EtO exposure and gamma irradiation but also dramatically reduced after steam sterilization. These reductions were ascribed to the collapse of pores of the membrane. The permeability of heparinized Cuprophan was not affected by EtO exposure and gamma irradiation but dramatically reduced after steam sterilization, although to a lesser extent than in the case of unmodified Cuprophan. Apparently, the presence of immobilized heparin (partially) prevented the collapse of pores during sterilization. Gamma irradiation was recommended as the preferred method of sterilization for heparinized Cuprophan.\u

Design of a new type of coating for the controlled release of heparin

Thrombus formation at the surface of blood contacting devices can be prevented by local release of heparin. Preferably, the release rate should be constant for prolonged periods of time. The minimum heparin release rate to achieve thromboresistance will be different for various applications and should therefore be adjustable. In this study a new type of heparin release system is presented which may be applied as a coating for blood contacting devices. The system is based on the covalent immobilization of heparin onto porous structures via hydrolysable bonds. This approach was evaluated by the immobilization of heparin onto a porous cellulosic substrate via ester bonds. Cuprophan was used as a model substrate and N,N¿-carbonyldiimidazole as a coupling agent. Heparinized Cuprophan incubated in phosphate buffered saline showed a release of heparin due to the hydrolysis of the ester bonds between heparin and Cuprophan. The release rate could be easily adjusted by varying the amount of coupling agent used during immobilization. Cuprophan with a rather stable heparin coating (release rate: 6.1 mU/cm2·h) and Cuprophan which shows a substantial release of heparin (release rate up to 23.0 mU/cm2·h) could be prepared. Except when the release was relatively high, release rates were constant for at least 1 week. Storage of the release system at ambient conditions up to 6 months or sterilization by means of steam, ethylene oxide exposure, or gamma irradiation did not affect the release properties. It was concluded that this concept for a heparin release system is highly promising to prepare thromboresistant surfaces for various blood contacting devices

Hydrophilic poly(ethylene oxide)-aramide segmented block copolymers

The present paper discusses block copolymers with segments of either poly(ethylene oxide), poly(propylene oxide), or mixtures of poly(ethylene oxide)/poly(propylene oxide) and monodisperse aramide segments. The length of the polyether segments as well as the concentration of polyethylene oxide was varied. The synthesized copolymers were analyzed by DSC, FTIR, AFM and DMTA. In addition, the hydrophilicity was studied. The crystallinity of the monodisperse aramide segments was found to be high and the crystals, dispersed in the polyether phase, displayed a nano-ribbon morphology. The PEO segments were able to crystallize and this crystalline phase reduced the low-temperature flexibility. The PEO crystallinity and melting temperature could be strongly reduced by copolymerization with PPO segments. By using mixtures of PEO and PPO segments, hydrophilic copolymers with decent low-temperature properties could be obtained

In vitro adsorption of oxalic acid and glyoxylic acid onto activated charcoal, resins and hydrous zirconium oxide

Patients suffering from primary hyperoxaluria show elevated plasma concentrations of oxalic acid and glyoxylic acid. The in vitro absorption of these compounds onto activated charcoal, a series of neutral and ion exchange resins and onto hydrous zirconium oxide has been investigated. Hydrous zirconium oxide was the most effective sorbent studied for the removal of both oxalic acid and glyoxylic acid. In batch experiments, the zirconium oxide was capable of binding 5.5 μ mol oxalic acid and 8 μ mol glyoxylic acid per gram sorbent using 0.5 gram sorbent and 50 ml of solutions with initial concentrations of 100 μ mol.L-1 and an ionic composition resembling that of plasma. Recirculation of 2 L of the same solutions through 12 gram of mixture of hydrous zirconium oxide and alumina for 6 hours at a flow rate of 12 ml.min-1, resulted in a final concentration of 70 μ mol.L-1 of oxalic acid and 50 μ mol.L-/ of glyoxylic acid