Implant device having biocompatiable membrane coating

• US 5,840,083 A
• Filed: 11/15/1996
• Issued: 11/24/1998
• Est. Priority Date: 01/27/1989
• Status: Expired due to Term

• Current Assignee: Biosensor Enterprises, LLC
• Original Assignee: F.B. Rice & Co.
• Inventors: Braach-Maksvytis, Vijoleta Lucija Bronislava
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Swartz, Rodney P.
• Application Number:
  US08/749,670
• Time in Patent Office: 739 Days
• Field of Search: 623/8, 623/11, 623/16, 424/422, 424/423, 435/7.21
• US Class Current: 424/423
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61L 2300/256 Antibodies, e.g. immunoglobulins, vaccines
• CPC Class Codes: A61L 2300/438 Antigens
• CPC Class Codes: A61L 2300/442 Colorants, dyes
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 27/22 Polypeptides or derivatives thereof , e.g. degradation products
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 33/0082 by reacting with an organic compound other than heparin
• CPC Class Codes: B01D 2325/48 Antimicrobial properties
• CPC Class Codes: B01D 69/02 characterised by their properties
• CPC Class Codes: B01D 69/122 Separate manufacturing of ultra-thin membranes
• CPC Class Codes: B01D 69/141 Heterogeneous membranes, e.g. containing dispersed material; Mixed matrix membranes
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 33/5432 Liposomes or microcapsules
• CPC Class Codes: G01N 33/566 using specific carrier or receptor proteins as ligand binding reagents where possible specific carrier or receptor proteins are classified with their target compounds
• CPC Class Codes: Y10S 977/89 Deposition of materials, e.g. coating, cvd, or ald
• CPC Class Codes: Y10S 977/931 Medical device coating

Abstract

A device for implant having a biocompatible membrane coating. The membrane comprises a closely packed array of self-assembling amphiphilic molecules and two ionophore components. A receptor molecule reactive with the analyte is provided on one of the ionophore components. The binding of the analyte to the receptor molecule causes a change in the relationship between the ionophore components such that the flow of ion across the membrane is prevented or allowed. The ionophore components are preferably selected from the group consisting of amphotericin B, gramicidin A monomers and combinations thereof, with gramicidin A monomers being particularly preferred. The present invention also provides a membrane including receptors directed against the Fc region of antibodies. These receptors are preferably derived from polyclonal antibodies. These membranes provide a "generic" surface which will bind antibodies in a manner such that the antigen binding regions of the antibody are not hindered. The present invention further provides a device adapted for implantation in a mammalian body, the device being characterised in that it is coated with a membrane comprising a closely packed array of self-assembling amphiphilic molecules and receptor molecules, the receptor molecules being such that the attachment of specific cells to the membrane is enhanced or avoided. It is particularly preferred that the receptor molecules are directed against fibronectin, vitronectin, endothelial cells, or epithelial cells. It is further preferred that the membrane coating the device also includes a plurality of ion channels such as gramicidin.

Claims

1. A device or implantation in a mammalian body, the device being coated with a membrane comprising a closely packed array of self-assembling amphiphilic molecules in which at least a proportion of the self-assembling amphiphilic molecules comprise a receptor molecule conjugated with a supporting entity, the receptor molecule having a receptor site, the receptor molecule being selected from the group consisting of antibodies and antibody fragments Fab and F(ab'"'"')₂ ;

the supporting entity being selected from the group consisting of a lipid head group, a hydrocarbon chain(s), a cross-linkable molecule and a membrane protein;

the supporting entity being conjugated with the receptor molecule at an end remote from the receptor site and in a manner such that the receptor site is at or projects from the surface of the membrane remote from the device, the receptor molecule being such that the attachment of specific cells to the membrane is enhanced or avoided.

2. The device of claim 1 in which the membrane includes a plurality of ion channels.

3. A device as claimed in claim 2 in which the ion channels are gramicidin.

4. A device as claimed in claim 1 in which the receptor molecules are antibody fragments F(ab'"'"')₂ or Fab.

5. A device as claimed in claim 1 in which the receptor molecules bind fibronectin, vitronectin, endothelial cells, or epithelial cells.

6. A device as claimed in claim 5 in which the receptor molecules bind fibronectin.

7. A device as claimed in claim 1 in which the amphiphilic molecules are provided with cross-linkable moieties in a manner such that each cross-linkable moiety is cross-linked to a cross-linkable moiety on another molecule.

8. A device as claimed in claim 1 in which the amphiphilic molecules are non-cytotoxic amphiphilic molecules naturally occurring in the mammalian species into which the device is implanted, or derivatives of these amphiphiles, or synthetic amphiphiles, provided with thiol groups for attachment to metal surfaces selected from the group consisting of palladium, titanium, platinum, silver or gold.