Sterilization of heparinized Cuprophan hemodialysis membranes

Abstract

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.