Medical device polymer

• US 5,569,463 A
• Filed: 06/07/1995
• Issued: 10/29/1996
• Est. Priority Date: 05/17/1990
• Status: Expired due to Term

• Current Assignee: Harbor Medical Devices Incorporated
• Original Assignee: Harbor Medical Devices Incorporated
• Inventors: Raleigh, Carol L., Helmus, Michael N., Tolkoff, M. Joshua
• Primary Examiner(s): AZPURU, CARLOS A
• Application Number:
  US08/479,513
• Time in Patent Office: 510 Days
• Field of Search: 424/426, 424/423, 424/424, 424/425, 424/450, 427/2.12, 514/772.2, 514/822, 523/112, 523/113, 604/53, 604/266, 623/12
• US Class Current: 424/426
• CPC Class Codes: A61L 2300/22 Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/608 having two or more layers
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/0047 Enzymes, e.g. urokinase, streptokinase
• CPC Class Codes: A61L 33/007 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61M 5/14276 specially adapted for implantation

Abstract

A medical device and a method for its manufacture. The function of the medical device requires exposure of the device to the tissue of a patient. The device has a tissue-exposed portion constructed to release an agent that inhibits adverse reaction to the presence of the device defined by a polymeric surface-layer overlying in a supported manner a polymer defining a reservoir. The reservoir incorporates the agent in a manner that permits substantially free outward release of the agent from the reservoir and the overlying layer defines metering outward passages constructed to control the outward migration of the agent to enable prolonged release of the agent from the surface of the medical device to prevent the adverse reaction due to the presence of the device.

Claims

1. A method for forming a medical device the function of which requires exposure to the tissue of a patient, comprising:

forming an internal polymer layer defining a reservoir for a therapeutic agent selected from the group consisting of antithrombogenic agents, antiplatelet agents, prostaglandins, thrombolytic drugs, antiproliferative drugs, antirejection drugs, antimicrobial drugs, growth factors, and anticalcifying agents, that inhibits adverse reaction to the presence of the device, the internal polymer layer comprising a polymer selected from the group consisting of polyurethanes and its copolymers, silicone and its copolymers, ethylene vinylacetate, thermoplastic elastomers, polyvinylchloride, polyolefins, cellulosics, polyamides, polytetrafluoroethylenes, polyesters, polycarbonates, polysulfones, acrylics, and acrylonitrile butadiene styrene copolymers, and,

forming a tissue-exposed overlying outer polymer metering layer supported by said internal polymer layer, said outer polymer metering layer having a stable, uniform, predetermined thickness covering the underlying reservoir so that no portion of the reservoir is directly exposed to body fluids, and incorporating a distribution of an elutable component which, upon exposure to body fluids, elutes from said outer polymer metering layer to form a predetermined porous network capable of exposing said therapeutic agent in said reservoir in said internal polymer layer to said body fluid, said elutable component being selected from the group consisting of polyethylene oxide, polyethylene glycol, polyethylene oxide/polypropylene oxide copolymers, polyhydroxyethylmethacrylate, polyvinylpyrollidone, polyacrylamide and its copolymers, liposomes, albumin, dextran, proteins, peptides, polysaccharides, polylactides, polygalactides, polyanhydrides, polyorthoesters and their copolymers, and soluble cellulosics,

wherein said reservoir defined by said internal polymer layer incorporates said therapeutic agent in a manner that permits substantially free outward release of said agent from said reservoir into said porous network of said outer polymer metering layer as said elutable component elates from said polymer metering layer,

said predetermined thickness of said outer polymer layer and the concentration and particle size of said elutable component are selected to enable said outer polymer metering layer to meter the rate of outward migration of the therapeutic agent from the reservoir through the outer polymer metering layer, and

said outer polymer metering layer and said internal polymer layer, in combination, enable prolonged controlled release, at said predetermined dosage level, from said exposed surface of said medical device to the tissue of said patient to inhibit adverse reaction of the patient to the prolonged presence of the body of said medical device in said patient.

2. The method of claim 1 wherein said forming said reservoir portion further comprises:

forming a mixture including a reservoir polymer and said elutable component,

forming said reservoir from said mixture;

forming a mixture including a surface-layer polymer and said agent; and

forming said surface layer by applying said surface-layer mixture to said reservoir.

3. The method of claim 2 wherein said forming said reservoir mixture further comprises:

mixing said reservoir polymer and said elutable component in a solvent;

and said forming said reservoir further comprises

evaporating said solvent to form said reservoir.

4. The method of claim 3 wherein said mixing further comprises:

suspending a particulate elutable component in said solvent.

5. The method of claim 3 wherein said mixing further comprises:

forming a colloidal suspension in said solvent.

6. The method of claim 5 further comprises:

selecting said elutable component from the group consisting of polyethylene oxide, polyethylene glycol, polyethylene oxide/polypropylene oxide copolymers, polyhydroxyethyl methacrylate, polyvinylpyrollidone, polyacrylamide and copolymers thereof cellulosics and liposomes.

7. The method of any one of claims 4 or 5 further comprising:

selecting the size and concentration of said elutable component to produce a continuous network in said polymer.

8. The method of claim 2 or 3 wherein forming said surface layer mixture further comprises:

mixing said reservoir polymer and said agent in a solvent; and

forming said surface layer further comprises,

evaporating said solvent to form said reservoir.

9. The method of claim 8 further comprising:

selecting the size and concentration of said agent to produce a continuous network in said polymer.

10. The method of claim 1 further comprising:

applying said tissue-exposed portion as a coating to the surface of a medical device substrate.

11. The method of claim 10 further comprising:

forming said tissue exposed portion at least as flexible as said substrate.

12. The method of claim 10 further comprising:

applying said coating by successively passing portions of said device, without substantial deformation, through said mixtures so that said successive portions are exposed to said mixtures for substantially the same time.

13. The method of claim 1 wherein said forming said polymeric reservoir and surface layer comprises forming by thermal extrusion.