Implantable or insertable medical devices containing silicone copolymer for controlled delivery of therapeutic agent

• US 20050027283A1
• Filed: 07/31/2003
• Published: 02/03/2005
• Est. Priority Date: 07/31/2003
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Inventors: Schwarz, Marlene C., Richard, Robert E., Strickler, Frederick H.
• Granted Patent: US 8,870,814 B2
• Time in Patent Office: Days
• US Class Current: 604/890.100
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• 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: C08L 83/04 Polysiloxanes

Abstract

Implantable or insertable medical devices are described. The medical devices comprise (a) a therapeutic agent and (b) a polymeric release region, which controls the release of the therapeutic agent upon administration to a patient. The polymeric release region further comprises a silicone copolymer that contains a plurality of siloxane units and a plurality of non-siloxane units. Also described are methods for administering a therapeutic agent to a patient using the above implantable or insertable medical devices as well as methods of making the above devices.

Claims

1. An implantable or insertable medical device comprising (a) a therapeutic agent and (b) a polymeric release region that controls the release of said therapeutic agent upon administration to a patient, said polymeric release region comprising a silicone copolymer comprising a plurality of siloxane units and a plurality of non-siloxane units.

2. The implantable or insertable medical device of claim 1, wherein said polymeric release region is a carrier region that comprises said therapeutic agent.

3. The implantable or insertable medical device of claim 1, wherein said polymeric release region is a barrier region disposed over a therapeutic-agent-containing region that comprises said therapeutic agent.

4. The implantable or insertable medical device of claim 1, wherein said polymeric release region is in the form of a coating layer that covers all or a part of said medical device.

5. The implantable or insertable medical device of claim 1, wherein said implantable or insertable medical device is selected from a catheter, a guide wire, a balloon, a filter, a stent, a stent graft, a vascular graft, a vascular patch and a shunt.

6. The implantable or insertable medical device of claim 1, wherein said implantable or insertable medical device is adapted for implantation or insertion into the coronary vasculature, peripheral vascular system, esophagus, trachea, colon, biliary tract, urinary tract, prostate or brain.

7. The implantable or insertable medical device of claim 1, wherein said therapeutic agent is selected from one or more of the group consisting of anti-thrombotic agents, anti-proliferative agents, anti-inflammatory agents, anti-migratory agents, agents affecting extracellular matrix production and organization, antineoplastic agents, anti-mitotic agents, anesthetic agents, anti-coagulants, vascular cell growth promoters, vascular cell growth inhibitors, cholesterol-lowering agents, vasodilating agents, and agents that interfere with endogenous vasoactive mechanisms.

8. The implantable or insertable medical device of claim 1, wherein said silicone copolymer has an elogation at break of at least 25% at ambient temperature.

9. The implantable or insertable medical device of claim 1, wherein said non-siloxane units are elevated T_g non-siloxane units corresponding to monomers selected from vinyl monomers, aromatic monomers, methacrylic monomers, acrylic monomers and alkene monomers.

10. The implantable or insertable medical device of claim 1, wherein said copolymer is a block copolymer comprising (a) a block of said siloxane units and (b) a block of elevated T_g non-siloxane units.

11. The implantable or insertable medical device of claim 10, wherein said block of said elevated T_g non-siloxane units is selected from poly(vinyl monomer) blocks, poly(aromatic monomer) blocks, poly(methacrylic monomer) blocks, poly(acrylic monomer) blocks and poly(alkene monomer) blocks.

12. The implantable or insertable medical device of claim 10, wherein said block of said elevated T_g non-siloxane units is selected from substituted and unsubstituted polystyrene blocks.

13. The implantable or insertable medical device of claim 10, wherein said block of said elevated T_g non-siloxane units is selected from substituted and unsubstituted poly(alkyl methacrylate) blocks.

14. The implantable or insertable medical device of claim 10, wherein said block of said elevated T_g non-siloxane units is selected from poly(styrene) blocks, poly(methyl methacrylate) blocks, poly(ethyl methacrylate) blocks, poly(isopropyl methacrylate) blocks, poly(isobutyl methacrylate) blocks, poly(t-butyl methacrylate) blocks and poly(cyclohexyl methacrylate) blocks.

15. The implantable or insertable medical device of claim 10, wherein said block copolymer comprises (a) a first glass transition temperature that is greater than ambient temperature and (b) a second glass transition temperature that is less than ambient temperature.

16. The implantable or insertable medical device of claim 15, wherein said first glass transition temperature that is greater than 75°

C. and said second glass transition temperature that is less than 0°

C.

17. The implantable or insertable medical device of claim 1, wherein said non-siloxane units are low T_g non-siloxane units corresponding to monomers selected from acrylic monomers, methacrylic monomers, vinyl ether monomers, cyclic ether monomers, ester monomers, unsaturated hydrocarbon monomers, and halogenated unsaturated hydrocarbon monomers.

18. The implantable or insertable medical device of claim 1, wherein said polymeric release region further comprises a supplemental polymer.

19. The implantable or insertable medical device of claim 10, wherein said block copolymer comprises at least two different types of said elevated T_g non-siloxane units.

20. The implantable or insertable medical device of claim 1, wherein said medical device is sterilized using a quantity of radiation effective to kill pathogens.

21. The implantable or insertable medical device of claim 1, wherein said silicone copolymer comprises first and second glass transition temperatures, and wherein said first glass transition temperature is below ambient temperature and wherein said second glass transition temperature is above ambient temperature.

22. The implantable or insertable medical device of claim 10, wherein said block of said siloxane units corresponds to a rubbery phase within said release region at ambient temperatures, and wherein said block of said elevated T_g non-siloxane units corresponds to a hard phase within said release layer at ambient temperatures.

23. The implantable or insertable medical device of claim 10, wherein said block copolymer is selected from a diblock copolymer, a triblock copolymer and a graft copolymer.

24. A method of forming the implantable or insertable medical device of claim 1, comprising:

(a) providing a solution comprising (i) a solvent system and (ii) said silicone copolymer; and

(b) forming said release region from said solution by removing said solvent system from said solution.

25. The method of claim 24, wherein said solution further comprises a therapeutic agent in dissolved or dispersed form.

26. The method of claim 24, wherein said solution is applied over a therapeutic-agent-containing region that comprises said therapeutic agent.

27. The method of claim 24, wherein said release region is formed by a technique comprising a spraying process.