Implantable medical devices incorporating chemically conjugated polymers and oligomers of L-arginine

• US 7,056,523 B1
• Filed: 06/21/2002
• Issued: 06/06/2006
• Est. Priority Date: 06/21/2002
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Michal, Eugene T., Claude, Charles D.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US10/176,506
• Time in Patent Office: 1,446 Days
• Field of Search: 424/426
• US Class Current: 424/426
• CPC Class Codes: A61F 2/86 Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/114 Nitric oxide, i.e. NO
• CPC Class Codes: A61L 2300/25 Peptides having up to 20 amino acids in a defined sequence
• CPC Class Codes: A61L 31/047 Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• CPC Class Codes: A61L 31/084 Carbon; Graphite
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: B05D 1/62 Plasma-deposition of organic layers plasma deposition in general C23C14/00, C23C16/00
• CPC Class Codes: B05D 2350/60 Adding a layer before coating

Abstract

An implantable medical device, such as a stent, is disclosed comprising an amino acid or a polypeptide bonded to a plasma polymerized film layer formed on the device. A method of manufacturing the same is also disclosed.

Claims

1. An implantable medical device, comprising a plasma polymerized film layer and a polypeptide chemically bonded to the plasma polymerized film layer.

2. The device of claim 1, wherein the device comprises a stent.

3. The device of claim 1, wherein the plasma polymerized film layer comprises a component derived from an organic substance having carboxyl groups.

4. The device of claim 3, wherein the organic substance comprises a low molecular weight organic acid or a mixture of low molecular weight organic acids.

5. The device of claim 4, wherein the organic acid comprises a component selected from a group consisting of acrylic acid, propionic acid, butyric acid, valeric acid, and methacrylic acid.

6. The device of claim 1, wherein the polypeptide comprises poly(L-arginine), poly(D-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), or a mixture of poly(L-arginine) and poly(D-arginine).

7. The device of claim 1, wherein a surface of the device on which the plasma polymerized film layer is deposited includes a carbon deposit, wherein the plasma polymerized film layer is formed over and is bonded to the carbon deposit.

8. A method of forming a coating for an implantable medical device, comprising forming a plasma polymerized film layer on the device and bonding a polypeptide to the plasma polymerized film layer.

9. The method of claim 8, wherein the device comprises a stent.

10. The method of claim 8, wherein the polymerized film layer comprises a component derived from an organic substance having carboxyl groups.

11. The method of claim 10, wherein the organic substance comprises a low molecular weight organic acid or a mixture of low molecular weight organic acids.

12. The method of claim 11, wherein the organic acid comprises a component selected from a group consisting of acrylic acid, propionic acid, butyric acid, valeric acid, and methacrylic acid.

13. The method of claim 8, wherein the polypeptide includes poly(L-arginine), poly(D-arginine), poly(L-lysine), poly(D-lysine), poly(δ

-guanidino-α

-aminobutyric acid), or a mixture of poly(L-arginine) and poly(D-arginine).

14. The method of claim 8, additionally including implanting carbon deposits in the surface of the device prior to forming the plasma polymerized film layer, wherein the plasma polymerized film layer is formed on and is bonded to the carbon deposits.

15. The method of claim 8, wherein the bonding of the polypeptide to the plasma polymerized film layer comprises exposing the plasma polymerized film layer to a free base form of the polypeptide.

16. A method of treatment of a patient having a vascular occlusion, comprising implanting a stent at the site of the occlusion, the stent including a plasma polymerized film layer having a first charge and administering to the patient a polypeptide having an opposing second charge wherein some of the polypeptide circulating through the blood stream of the patient will couple to the plasma polymerized film layer.

17. The method of claim 16, wherein the polypeptide is administered orally, intravenously, or by a drug delivery catheter.