Method of making a drug eluting stent

• US 5,599,352 A
• Filed: 09/15/1994
• Issued: 02/04/1997
• Est. Priority Date: 03/19/1992
• Status: Expired due to Term

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Schwartz, Robert S., Tuch, Ronald J., Dinh, Thomas Q.
• Primary Examiner(s): BRITTINGHAM, DEBRA
• Application Number:
  US08/306,785
• Time in Patent Office: 873 Days
• Field of Search: 623/1, 623/11, 623/12, 600/36, 606/191-200, 606/151-158, 604/8, 604/104
• US Class Current: 128/898
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• 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 2300/606 Coatings
• CPC Class Codes: A61L 2420/08 Coatings comprising two or more layers
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/046 Fibrin; Fibrinogen
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/128 containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: B05C 3/20 for applying liquid or other fluent material only at particular parts of the work B05C3/02 takes precedence
• CPC Class Codes: C08L 89/00 Compositions of proteins; Compositions of derivatives thereof foodstuff preparations A23J3/00
• CPC Class Codes: Y10S 623/921 Blood vessel

Abstract

An intraluminal stent comprising fibrin and an elutable drug is capable of providing a treatment of restenosis.

Claims

1. A method for making a drug eluting intravascular stent comprising the steps of:

(a) providing a generally cylindrical stent body;

(b) applying to the stent body a first layer which is a solid composite of polymer and therapeutic substance; and

(c) applying as a second layer a layer of fibrin over the composite.

2. The method of claim 1 wherein the first layer is applied by the steps of:

(a) applying to the stent body a solution which includes a solvent, a polymer dissolved in the solvent and a therapeutic substance dispersed in the solvent; and

(b) evaporating the solvent to form a composite of polymer and therapeutic substance.

3. A method according to claim 2 wherein the solution is applied by spraying.

4. A method according to claim 2 wherein the solution is applied in a plurality of application and drying steps.

5. A method according to claim 2 wherein the ratio of therapeutic substance to dissolved polymer in the solution is varied in some of the plurality of application steps.

6. A method according to claim 2 wherein the polymer is a bioabsorbable polymer.

7. A method according to claim 6 wherein the polymer is selected from the group consisting of poly(L-lactic acid), poly(lactide-co-glycolide) and poly(hydroxybutyrate-co-valerate).

8. A method according to claim 2 wherein the polymer is a biostable polymer.

9. A method according to claim 8 wherein the polymer is selected from the group consisting of silicones, polyurethanes, polyesters, vinyl homopolymers and copolymers, acrylate homopolymers and copolymers, polyethers and cellulosics.

10. The method of claim 1 wherein the first layer is applied by the steps of:

(a) applying to the stent body a solution which includes fibrinogen;

(b) applying thrombin to the fibrinogen on the stent body to effect polymerization of the fibrinogen; and

(c) applying a therapeutic substance to the fibrinogen as the fibrinogen is polymerizing.

11. The method of claim 1 wherein the first layer is applied by the steps of:

(a) applying to the stent body a solution which includes fibrinogen and a dispersed therapeutic substance; and

(b) applying thrombin to the fibrinogen on the stent body to effect polymerization of the fibrinogen.

12. A method according to claim 1 wherein the therapeutic substance is selected from the group consisting of glucocorticoids, heparin, hirudin, tocopherol, angiopeptin, aspirin, ACE inhibitors, growth factors, oligonucleotides, antiplatelet agents, anticoagulant agents, antimitotic agents, antioxidants, antimetabolite agents, and anti-inflammatory agents.

13. A method according to claim 1 wherein the fibrin is applied by molding a polymerization mixture of fibrinogen and thrombin onto the composite.