Gas permeable thrombo-resistant coatings and methods of manufacture

A method for producing a thrombo-resistant coating for use on gas permeable surfaces which contact blood, the method comprising the steps of:

• (a) obtaining a gas permeable material having a siloxane surface;
• (b) introducing ammonia gas within a plasma chamber capable of performing plasma etching;
• (c) exposing the ammonia gas to a radio frequency of sufficient power to create a plasma;
• (d) exposing the siloxane surface to the ammonia plasma for sufficient time to introduce amine functional groups onto the siloxane surface, thereby resulting in a product having a plurality of amine functional groups bonded onto the siloxane surface;
• (e) reacting the product of step (d) with a solution having a plurality of poly(ethylene oxide) spacer chains, having the following general formula
• R.sub.1 --(CH.sub.2 CH.sub.2 O).sub.n --R.sub.2
• wherein R.sub.1 and R.sub.2 are suitable functional groups capable of reacting with the amine functional groups on the siloxane surface;
• and
• (f) reacting the product of step (e) with a solution of at least one bioactive molecule capable of counteracting specific blood-material incompatibility reactions such that a single bioactive molecule is correspondingly coupled to a single poly(ethylene oxide) spacer chain, thereby resulting in a siloxane surface to which are attached, by a poly(ethylene oxide) chain, a plurality of the at least one bioactive molecules which react with blood components which come in proximity to the surface of the material in order to resist at least one blood-material incompatibility reaction.

A thrombo-resistant composition for use on gas permeable surfaces which contact blood, the composition being made by a process comprising the steps of:

• (a) obtaining a gas permeable material having a siloxane surface onto which a plurality of amine functional groups have been bonded;
• (b) reacting the amine functional groups on the siloxane surface with poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine functional groups on the siloxane surface such that a single poly(ethylene oxide) chain is bonded to a corresponding single amine functional group;
• and
• (c) reacting the product of step (b) with heparin such that a single heparin molecule is covalently bonded to a single poly(ethylene oxide) chain, thereby resulting in a siloxane surface to which are attached, by a poly(ethylene oxide) chain, a plurality of heparin molecules capable of reacting with blood components which come in proximity to the siloxane surface of the material in order to resist at least one blood-material incompatibility reactions.

A thrombo-resistant composition comprising a plurality of compounds having the formula

• X--NH--R.sub.1 ----(CH.sub.2 CH.sub.2 O).sub.n ----R.sub.2 --Y
• wherein X is a siloxane surface;
• and wherein R.sub.1 are R.sub.2 are the residue resulting from a reaction between a poly(ethylene oxide) terminal group capable of reacting with an amine and capable of reacting with a bioactive molecule, respectively;
• and wherein Y is a bioactive molecule capable of counteracting a specific blood material incompatibility reaction.

An apparatus for effecting extrapulmonary blood gas exchange comprising:

• a plurality of gas permeable tubes, each tube having a proximal end and a distal end, said gas permeable tubes being coated with a thrombo-resistant composition comprising a plurality of compounds having the formula
• X--NH--R.sub.1 ----(CH.sub.2 CH.sub.2 O).sub.n ----R.sub.2 --Y
• wherein X is a siloxane surface on a gas permeable tube;
• and wherein R.sub.1 are R.sub.2 are the residue resulting from a reaction between a poly(ethylene oxide) terminal group capable of reacting with an amine and capable of reacting with a bioactive molecule, respectively;
• and wherein Y is a bioactive molecule capable of counteracting at least one blood-material incompatibility reaction;
• a dual lumen coaxial tube comprising an inner lumen and an outer lumen, said inner lumen extending between the proximal and distal ends of the gas permeable tubes and said outer lumen terminating adjacent to the proximal ends of the gas permeable tubes and the inner lumen terminating adjacent to the distal ends of the gas permeable tubes, such that the gas permeable tubes are in gaseous communication with both the inner lumen and the outer lumen;
• means for introducing oxygen from the inner lumen into the distal ends of the gas permeable tubes whereby blood in contact with the gas permeable tubes receives oxygen from the gas permeable tubes and releases carbon dioxide gas to the gas permeable tubes;
• and
• means for collecting carbon dioxide at the proximal ends of the gas permeable tubes and introducing said carbon dioxide into the outer lumen for removal therethrough.