Moisture curable materials for delivery of agents, methods, and medical devices

• US 20040228902A1
• Filed: 05/10/2004
• Published: 11/18/2004
• Est. Priority Date: 05/13/2003
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Benz, Michael E.
• Granted Patent: US 7,776,351 B2
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 2300/80 characterised by a special chemical form
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

The present invention provides curable materials, medical devices incorporating such materials, wherein the curable materials are capable of releasing hydrolyzable leaving agents upon hydrolysis that can form agents (e.g., pharmaceutically active agents), and methods of making and using such materials and devices.

Claims

1. An implantable medical device comprising a curable material comprising a prepolymer comprising at least one silicon atom and at least one hydrolyzable leaving group bonded to at least one silicon atom.

2. The device of claim 1 wherein the prepolymer comprises a monomer, an oligomer, a polymer, or mixtures thereof.

3. The device of claim 1 wherein the hydrolyzable leaving group forms a biocompatible compound upon hydrolysis of the prepolymer and release of the hydrolyzable leaving group.

4. The device of claim 1 wherein the hydrolyzable leaving group forms a pharmaceutically active agent upon hydrolysis of the prepolymer and release of the hydrolyzable leaving group.

5. The device of claim 4 wherein the pharmaceutically active agent includes one or more active hydrogen atoms.

6. The device of claim 5 wherein the pharmaceutically active agent comprises one or more hydroxyl groups, carboxylic acid groups, amine groups, amide groups, urea groups, carbamate groups, urethane groups, hemiketal groups, hemiacetal groups, or combinations thereof.

7. The device of claim 6 wherein the pharmaceutically active agent is selected from the group consisting of salicylic acid, fenbufen, cortisone, ibuprofen, diflunisal, sulindac, difluprednate, prednisone, medrysone, acematacin, indomethacin, meloxicam, camptothecin, benoxinate, benzocaine, procaine, ciprofloxacin, norfloxacin, clofoctol, and combinations thereof.

8. The device of claim 1 wherein a curable intermediate is formed upon hydrolysis of the prepolymer and release of the hydrolyzable leaving group.

9. The device of claim 8 wherein the curable intermediate forms a biocompatible polymer upon condensation in the body of a subject.

10. The device of claim 8 wherein the curable intermediate comprises at least two silanol groups.

11. The device of claim 1 wherein the prepolymer is a polymer and further comprises a poly(alkylene oxide) segment, a polysiloxane segment, a polyester segment, a poly(vinyl pyrrolidone) segment, a polyacrylate segment, a polymethacrylate segment, a polycarbonate segment, a hydrocarbon segment, a polycarbosilane segment, a fluoropolymeric segment, a polyoxazoline segment, or mixtures or copolymers thereof.

12. The device of claim 1 wherein the prepolymer comprises one or more silicon atoms per one hydrolyzable group.

13. The device of claim 12 wherein the hydrolyzable group is a terminal group bonded to the silicon atom.

14. The device of claim 1 wherein the prepolymer comprises one silicon atom per one or two hydrolyzable groups.

15. The device of claim 1 wherein the prepolymer comprises one silicon atom per one to three hydrolyzable groups.

16. The device of claim 1 wherein the prepolymer comprises two silicon atoms per one hydrolyzable group.

17. The device of claim 16 wherein the hydrolyzable group is bonded to the two silicon atoms to form a linear polymer.

18. The device of claim 16 wherein the hydrolyzable group is attached to the two silicon atoms to form a ring.

19. The device of claim 1 wherein the prepolymer comprises one or more silicon-bonded hydrolyzable leaving groups pendant from a polymeric chain.

20. The device of claim 1 wherein the curable material further comprises particulate material.

21. A curable material comprising a prepolymer comprising at least one silicon atom and at least one hydrolyzable leaving group bonded to at least one silicon atom, wherein the hydrolyzable leaving group forms a pharmaceutically active agent upon hydrolysis of the prepolymer and release of the hydrolyzable leaving group.

22. The material of claim 21 wherein the prepolymer comprises a monomer, an oligomer, a polymer, or mixtures thereof.

23. The material of claim 21 wherein the pharmaceutically active agent includes one or more active hydrogen atoms.

24. The material of claim 23 wherein the pharmaceutically active agent comprises one or more hydroxyl groups, carboxylic acid groups, amine groups, amide groups, urea groups, carbamate groups, urethane groups, hemiketal groups, hemiacetal groups, or combinations thereof.

25. The material of claim 24 wherein the pharmaceutically active agent is selected from the group consisting of salicylic acid, fenbufen, cortisone, ibuprofen, diflunisal, sulindac, difluprednate, prednisone, medrysone, acematacin, indomethacin, meloxicam, camptothecin, benoxinate, benzocaine, procaine, ciprofloxacin, norfloxacin, clofoctol, and combinations thereof.

26. The material of claim 21 wherein a curable intermediate is formed upon hydrolysis of the prepolymer and release of the hydrolyzable leaving group.

27. The material of claim 26 wherein the curable intermediate forms a biocompatible polymer upon condensation.

28. The material of claim 26 wherein the curable intermediate comprises at least two silanol groups.

29. The material of claim 21 wherein the prepolymer is a polymer and further comprises a poly(alkylene oxide) segment, a polysiloxane segment, a polyester segment, a poly(vinyl pyrrolidone) segment, a polyacrylate segment, a polymethacrylate segment, a polycarbonate segment, a hydrocarbon segment, a polycarbosilane segment, a fluoropolymeric segment, a polyoxazoline segment, or mixtures or copolymers thereof.

30. The material of claim 21 wherein the prepolymer comprises one or more silicon atoms per one hydrolyzable group.

31. The material of claim 30 wherein the hydrolyzable group is a terminal group bonded to the silicon atom.

32. The material of claim 21 wherein the prepolymer comprises one silicon atom per one or two hydrolyzable groups.

33. The material of claim 21 wherein the prepolymer comprises one silicon atom per one to three hydrolyzable groups.

34. The material of claim 21 wherein the prepolymer comprises two silicon atoms per one hydrolyzable group.

35. The material of claim 34 wherein the hydrolyzable group is bonded to the two silicon atoms to form a linear polymer.

36. The material of claim 34 wherein the hydrolyzable group is attached to the two silicon atoms to form a ring.

37. The material of claim 21 wherein the prepolymer comprises one or more silicon-bonded hydrolyzable leaving groups pendant from a polymeric chain.

38. The material of claim 21 further comprising particulate material.

39. The material of claim 21 wherein the prepolymer is formed by polymerizing a polymerizable monomer comprising at least one silicon atom and at least one hydrolyzable leaving group bonded to at least one silicon atom.

40. The material of claim 21 wherein the prepolymer is biocompatible.

41. The material of claim 39 wherein the polymerizable monomer is formed by reacting a pharmaceutically active agent and a silicon-containing starting material of the formula SiX_xR_y wherein:

each X is independently a halogen, pseudohalogen, alkoxy, or acetoxy;

each R is independently hydrogen or an organic group; and

x=0-4, y=0-4, and x+y=4.

42. The material of claim 39 wherein the polymerizing reaction is a hydrosilylation reaction.

43. The material of claim 39 wherein the polymerizing reaction is an alkene metathesis reaction.

44. The material of claim 39 wherein the prepolymer is formed by reacting a pharmaceutically active agent and a silicon-containing starting material of the formula X_x′

R_y′

Si—

R¹—

SiX_x′

R_y′

wherein;

each X is independently a halogen or pseudohalogen;

each R is independently hydrogen or an organic group; and

R¹ is an alkylene, a divalent siloxane, a divalent oligo- or poly-alkylene oxide, a divalent carbosilane; and

x′

=0-3, y′

=0-3, and x′

+y′

=3.

45. The material of claim 21 wherein the prepolymer is formed by reacting a pharmaceutically active agent and a silicon-containing polymer.