Multifunctional thrombo-resistant coating and methods of manufacture

• US 5,342,693 A
• Filed: 03/22/1993
• Issued: 08/30/1994
• Est. Priority Date: 06/08/1988
• Status: Expired due to Term

• Current Assignee: Biosurface Engineering Technologies, Inc. (Ferring Holding SA)
• Original Assignee: CardioPulmonics, Inc. (Johnson Controls International plc)
• Inventors: Mortensen, J. D., Winters, Suzanne, Berry, Gaylord, Solen, Kenneth A., Sanders, Clifton G.
• Primary Examiner(s): SZEKELY, PETER A
• Application Number:
  US08/035,426
• Time in Patent Office: 526 Days
• Field of Search: 523/112, 424/78.27, 530/812, 530/815, 530/816, 428/447, 428/451, 604/265, 604/266
• US Class Current: 428/447
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: A61L 33/0047 Enzymes, e.g. urokinase, streptokinase
• CPC Class Codes: A61M 1/1678 intracorporal peritoneal dialysis A61M1/28
• CPC Class Codes: A61M 1/1698 Blood oxygenators with or without heat-exchangers intracorporal A61M1/1678; manufacturing of membranes therefor B01D67/00; semi-permeable membranes for separation processes characterised by their properties B01D69/00; semi-permeable membranes characterised by their material B01D71/00
• CPC Class Codes: A61M 1/3673 Anticoagulant coating, e.g. Heparin coating
• CPC Class Codes: C08L 71/02 Polyalkylene oxides
• CPC Class Codes: Y10S 530/812 Peptides or proteins is immobilized on, or in, an organic carrier
• CPC Class Codes: Y10S 530/815 Carrier is a synthetic polymer
• CPC Class Codes: Y10S 530/816 Attached to the carrier via a bridging agent
• CPC Class Codes: Y10T 428/31663 As siloxane, silicone or silane
• CPC Class Codes: Y10T 428/31667 Next to addition polymer from unsaturated monomers, or aldehyde or ketone condensation product

Abstract

The present invention is directed to multifunctional thrombo-resistant coatings for use with biomedical devices and implants, such as a coating which includes a siloxane surface onto which a plurality of amine functional groups have been bonded. Covalently bonded to the amine functional groups are a plurality of poly(ethylene oxide) chains, such that a single poly(ethylene oxide) chain is bonded to a single amine functional group. A plurality of different bioactive molecules, designed to counteract specific blood-material incompatibility reactions, are covalently bonded to poly(ethylene oxide) chains, such that a single bioactive molecule is coupled to a single polyethylene oxide chain.

The methods of manufacturing the present invention include preparing a material having a siloxane surface onto which a plurality of amine functional groups have been bonded. This is achieved by plasma etching with ammonia gas or by plasma polymerization of a siloxane monomer in the presence of ammonia gas. The amine-containing siloxane surface is reacted with poly(ethylene oxide) chains terminated with functional groups capable of reacting with the amine groups on the siloxane surface. The material is then reacted with a plurality of different bioactive molecules which counteract the specific blood-material incompatibility reactions, such that a single bioactive molecule is coupled to a single poly(ethylene oxide) chain. The resulting siloxane surface contains a plurality of different bioactive molecules capable of reacting with blood components which come in proximity to the siloxane surface in order to resist blood-material incompatibility reactions.

Claims

1. A gas permeable membrane for effecting extrapulmonary blood gas exchange, the membrane comprising a gas permeable substrate which is coated with a polyfunctional thrombo-resistant composition comprising a siloxane surface which is permeable to a gas onto which a plurality of at least two different bioactive molecules are covalently bonded, the at least two different bioactive molecules being covalently bonded to the siloxane surface and away from the siloxane surface through a plurality of poly(ethylene oxide) chains without precluding the gas permeability of the substrate, said bioactive molecules being capable of counteracting specific blood-material incompatibility reactions.

2. A gas permeable membrane for effecting extrapulmonary blood gas exchange as defined in claim 1, wherein the poly(ethylene oxide) chains comprises poly(ethylene oxide) bis (glycidyl ether).

3. A gas permeable membrane for effecting extrapulmonary blood gas exchange as defined in claim 1, wherein the poly(ethylene oxide) chains comprises poly(ethylene oxide) bis(isocyanate).

4. A gas permeable membrane for effecting extrapulmonary blood gas exchange as defined in claim 1, wherein the plurality of at least two different bioactive molecules is selected from the group consisting of heparin, urokinase, plasmin, and ticiopidine.

5. A gas permeable membrane for effecting extrapulmonary blood gas exchange as defined in claim 1, wherein the plurality of at least two different bioactive molecules is selected from the group consisting of heparin, urokinase, TPA, and prostaglandin E_l.

6. A gas permeable membrane for effecting extrapulmonary blood gas exchange as defined in claim 1, wherein the plurality of at least two different bioactive molecules is selected form the group consisting of heparin, urokinase, TPA, plasmin, prostaglandin E₁, and ticiopidine.