BIOCATALYTIC AND BIOMIMETIC GENERATION OF NITRIC OXIDE IN SITU AT SUBSTRATE/BLOOD INTERFACES

摘要

Biocompatible materials that have the ability to release nitric oxide (NO) in situ at the surface-blood interface when in contact with blood. The materials which may be polymers (e.g., polyurethane, poly(vinyl chloride), silicone rubbers), metals, such as stainless steel, carbon, and the like are provided with biocatalysts or biomimetic catalysts on their surface that have nitrite, nitrate and/or nitrosothiol-reducing capability that. Illustratively, the catalysts are adsorbed or immobilized at the surface of the material. The catalysts can act on endogenous nitrite/nitrate or nitrosothiols within the blood creating a local increase in the NO levels at the surface of the material. An illustrative enzymatic biocatalyst is mammalian xanthine oxidase. In another illustrative embodiment, a biomimetic catalyst is a copper (Cu(II)-ligands complex, e.g., dibenzo[e,k]-2,3,8,9-tetraphenyl-1,4,7,10-tetraaza-cyclododeca-1,3,7,9 -tetraene. In some cases, lipophilic salts of nitrite/nitrate (e.g., tridodecylmethylammonium nitrite (TDMA<+>NO2<->/NO3<->)) or certain salts of nitrosothiols can be doped within a polymer material, or an underlying polymeric film, to create a reservoir of nitrite or nitrosothiol that continuously leaks into the immobilized catalytic layer. Adequate levels of endogenous reducing equivalents are present within blood to provide catalytically-generated surface levels of NO that are above the threshold reportedly required to prevent platelet adhesion or activation.