Biocompatible metal surfaces

• US 5,356,433 A
• Filed: 11/03/1993
• Issued: 10/18/1994
• Est. Priority Date: 08/13/1991
• Status: Expired due to Term

• Current Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Original Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Inventors: Rowland, Stephen M., Stanley, Kimberly D.
• Primary Examiner(s): Green, Randall L.
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US08/147,017
• Time in Patent Office: 349 Days
• Field of Search: 424/422, 424/423, 427/2, 623/1, 623/11, 623/900, 623/901
• US Class Current: 424/422
• CPC Class Codes: A61F 2/88 the wire-like elements formed as helical or spiral coils forming a net-like or mesh-like structure A61F2/90
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0023 using a quaternized group or a protonated amine group of the substrate
• CPC Class Codes: C08L 83/04 Polysiloxanes
• CPC Class Codes: Y10S 623/90 Stent for heart valve
• CPC Class Codes: Y10S 623/901 Method of manufacturing prosthetic device

Abstract

Metallic surfaces of medical devices or components of medical devices are provided that have enhanced biocompatibility properties. The surfaces are prepared by a two-step procedure including covalently linking an organosilane having amine reactive sites with the surface of the metallic member, typically through a metal oxide thereof. Thereafter, a biologically active agent is covalently linked to the organosilane coating. The two-step process is particularly advantageous for preparing medical devices in the form of stents which need to be bent and flexed during implantation procedures.

Claims

1. A medical device having a biocompatible surface, the biocompatible surface having been made by a process comprising the steps of:

providing a metallic member having a tantalum oxide-containing surface thereof, said metallic member being flexible and being sized and shaped as a stent;

treating the tantalum oxide containing surface with an amino-terminated organosilane having amine reactive sites and covalently linking the organosilane with the flexible metallic member to effect a condensation reaction that covalently links the tantalum oxide and silicon moieties of the organosilane in order to form a flexible organosilane-coated tantalum stent;

applying a biologically active agent compostion to the organosilane-coated tantalum stent and forming a covalent linkage between the organosilane and the biologically active agent to provide a coated flexible tantalum stent; and

the coated flexible tantalum stent thus formed has a coating which withstands cracking upon flexure, and the tantalum stent thus formed is a biocompatible tantalum stent which, when implanted within a living body, prevents substantial thrombus from occurring on its surface while not significantly interfering with endothelialization of said surface.

2. The medical device in accordance with claim 1, wherein the covalent linkage of the applying and forming step is between the amine moiety of the amino-terminated organosilane and a carboxyl moiety of the biologically active agent.

3. The medical device in accordance with claim 1, wherein said step of treating and covalently linking includes dipping the metallic member into an organosilane of the formula NH₂ --R--Si--(OR'"'"')_n, wherein R is a short chain length aliphatic group, R'"'"' is selected from the group consisting of methyl and ethyl, and n is 3.

4. The medical device in accordance with claim 1, further including curing the organosilane-coated metallic member at an elevated temperature prior to said step of applying and forming.

5. The medical device in accordance with claim 1, wherein said flexible metallic member has a generally helical configuration.

6. The medical device in accordance with claim 1, wherein said flexible metallic member is a generally helically wound tantalum stent.

7. A medical device having a biocompatible anti-thrombogenic tantalum surface, comprising:

a metallic member for a medical device, the metallic member having a tantalum oxide surface and being flexible and being sized and shaped as a stent, the metallic member having a biologically active surface treatment covalently adhered to the tantalum oxide surface;

said biologically active surface treatment including an organosilane component having amine reactive sites, the organosilane component having silicon moieties covalently linked to tantalum oxide moieties of the metallic member, said biologically active surface treatment further including a biologically active agent covalently bound to the organosilane component to define a biocompatible tantalum stent; and

said biocompatible tantalum stent has a surface which substantially prevents thrombus formation thereonto while avoiding any significant interference of the development of endothelialization of the biocompatible tantalum stent, and said biocompatible tantalum stent has a coating which is flexible and which withstands cracking upon flexure.

8. The medical device in accordance with claim 7, wherein said flexible metallic member has a generally helical configuration.

9. The medical device in accordance with claim 7, wherein the metallic member is a generally helically wound tantalum stent.

10. The medical device in accordance with claim 9, wherein said organosilane component is of the formula NH₂ --R--Si(OR'"'"')₃, wherein R is a short chain length aliphatic group and R'"'"' is selected from the group consisting of methyl and ethyl, and said biologically active agent is selected from the group consisting of a mucopolysaccharide and a glucose amine.