Local delivery of rapamycin for treatment of proliferative sequelae associated with PTCA procedures,Including delivery using a modified stent

• US 20050085902A1
• Filed: 09/28/2004
• Published: 04/21/2005
• Est. Priority Date: 04/18/1997
• Status: Active Grant

• Current Assignee: Cardinal Health Switzerland 515 GmbH (Cardinal Health, Inc.)
• Original Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Inventors: Rakos, Ronald, Llanos, Gerard H., King, Kristen, Wright, Carol
• Granted Patent: US 7,223,286 B2
• Time in Patent Office: Days
• US Class Current: 623/1.460
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2002/91541 Adjacent bands are arranged out of phase
• CPC Class Codes: A61F 2002/91558 connected peak to peak
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• 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 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

Methods of preparing intravascular stents with a polymeric coating containing macrocyclic lactone (such as rapamycin or its analogs), stents and stent graphs with such coatings, and methods of treating a coronary artery with such devices. The macrocyclic lactone-based polymeric coating facilitates the performance of such devices in inhibiting restenosis.

Claims

1-3. -3. (canceled)

4. A method of treating a coronary artery, comprising:

locating a stent having a coating containing macrocylic lactone in the coronary artery, said coating formed from a polymer mixed carrier containing the macrocyclic lactone, and said coating applied to said stent; and

expanding said stent in the coronary artery such that said coating is in contact with the coronary artery.

5. A method of treating a coronary artery, comprising:

locating a stent having a coating containing macrocyclic lactone in the coronary artery, wherein said macrocyclic lactone is contained in the coating at a weight percentage of 0.0001% to 30%; and

expanding said stent in the coronary artery such that said coating is in contact with the coronary artery.

6. A method of treating a coronary artery, comprising:

locating a stent having a coating containing macrocyclic lactone in the coronary artery, said coating formed from a polymer mixed carrier containing the macrocyclic lactone, and said coating applied to said stent; and

expanding said stent in the coronary artery such that said coating is in contact with the coronary artery, wherein,

said stent comprises a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts with a channel formed in at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said strut, said channel containing a reservoir of said macrocyclic lactone coating applied therein.

7. A method of treating a coronary artery, comprising:

locating a stent graft having a coating containing rapamycin or its analogs in the coronary artery, said coating formed from a polymer mixed carrier containing the rapamycin or its analogs, and said coating applied to said stent graft; and

expanding said stent graft in the coronary artery such that said coating is in contact with the coronary artery at one or more locations.

8. A method of treating a coronary artery, comprising:

locating a stent graft having a coating containing rapamycin or its analogs in the coronary artery, wherein said rapamycin or said analogs are contained in the coating at a weight percentage of 0.0001% to 30%; and

expanding said stent graft in the coronary artery such that said coating is in contact with the coronary artery at one or more locations.

9. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft;

wherein the polymer is biocompatible and degradable; and

wherein the polymer is chosen from;

lactone-based polyesters, lactone-based copolyesters;

polyanhydrides;

polyaminoacids;

polysaccharides;

polyphosphazenes;

poly(ether-ester) copolymers, and blends of such polymers.

10. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft; and

wherein the polymer is chosen from;

lactone-based polyesters, lactone-based copolyesters;

polyanhydrides;

polyaminoacids;

polysaccharides;

polyphosphazenes;

poly(ether-ester) copolymers, and blends of such polymers.

11. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft;

wherein the polymer is nonabsorbable; and

wherein the polymer is chosen from;

polydimethylsiolxane;

poly(ethylene)vinylacetate;

poly(hydroxy)ethylmethylmethacrylate, polyvinyl pyrrolidone;

polytetrafluoroethylene; and

cellulose esters.

12. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft; and

wherein the polymer is chosen from;

polydimethylsiolxane;

poly(ethylene)vinylacetate;

poly(hydroxy)ethylmethylmethacrylate, polyvinyl pyrrolidone;

polytetrafluoroethylene; and

cellulose esters.

13. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft; and

further comprising;

a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts, said applied to said strut, and a channel formed in at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said strut, said channel containing a reservoir of said rapamycin coating applied therein.

14. A stent graft having a coating containing macrocyclic lactone, wherein said macrocyclic lactone is contained in the coating at a weight percentage of 0.0001% to 30%, wherein the coating is a polymer.

15. A stent graft containing a polymer and macrocyclic lactone wherein said macrocyclic lactone is contained in a therapeutically beneficial amount to combat restenosis.

16. A method for preparing a stent, comprising:

preparing a solution containing a polymer and macrocyclic lactone, wherein said macrocyclic lactone is in a concentration range of 0.001 weight % to 30 weight % in said solution; and

applying said solution to a surface of said stent; and

allowing said solution to leave a film with entrapped macrocyclic lactone as a coating on the stent.

17. A method for preparing a stent graft, comprising:

preparing a solution containing a polymer and macrocyclic lactone, wherein said macrocyclic lactone is in a concentration range of 0.001 weight % to 30 weight % in said solution; and

applying said solution to a surface of said stent graft; and

allowing said solution to leave a film with entrapped macrocyclic lactone as a coating on the stent graft.

18. A method for preparing a stent, comprising:

preparing a solution of macrocyclic lactone in an organic solvent, said macrocyclic lactone constituting 0.001 weight % to saturated in said solution; and

applying said solution to a surface of said stent, said stent having micropores or channels; and

allowing said solution to permeate into said pores.

19. A method for preparing a stent, comprising:

modifying a macrocyclic lactone to contain a hydrolytically or enzymatically labile covalent bond;

chemically preparing a surface of the stent to permit covalent bonding of the modified macrocyclic lactone to the surface; and

attaching the modified macrocyclic lactone to the surface of the stent via covalent bonding.

20. The stent prepared according to the method of claim 19.

21. A stent having a coating containing a macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone, and said coating applied to said stent.

22. The stent of claim 21, wherein the stent is dip-coated.

23. The stent of claim 21, wherein the stent is sprayed with said coating.

24. A stent having a coating containing a macrocyclic lactone, wherein said macrocyclic lactone is contained in the coating at a weight percentage of 0.0001% to 30%.

25. The stent of claim 24, wherein a polymer is mixed to the macrocyclic lactone.

26. The stent of claim 24, wherein a polymer is bound to the macrocyclic lactone.

27. The stent of claim 24, wherein the macrocyclic lactone is entrapped on the surface of the stent by a polymer.

28. A stent having a coating containing a macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone, and said coating applied to said stent, wherein the polymer is biocompatible and degradable, and wherein the polymer is chosen from:

lactone-based polyesters, lactone-based copolyesters;

polyanhydrides;

polyaminoacids;

polysaccharides;

polyphosphazenes;

poly(ether-ester) copolymers, and blends of such polymers.

29. A stent having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone or its analogs and said coating applied to said stent, and wherein the polymer is chosen from:

lactone-based polyesters, lactone-based copolyesters;

polyanhydrides;

polyaminoacids;

polysaccharides;

polyphosphazenes;

poly(ether-ester) copolymers, and blends of such polymers.

30. A stent having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone, and said coating applied to said stent, wherein the polymer is nonabsorbable, and wherein the polymer is chosen from:

polydimethylsiolxane;

poly(ethylene)vinylacetate;

poly(hydroxy)ethylmethylmethacrylate, polyvinyl pyrrolidone;

polytetrafluoroethylene; and

cellulose esters.

31. A stent having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone, and said coating applied to said stent, and wherein the polymer is chosen from:

polydimethylsiolxane;

poly(ethylene)vinylacetate;

poly(hydroxy)ethylmethylmethacrylate, polyvinyl pyrrolidone;

polytetrafluoroethylene; and

cellulose esters.

32. A stent having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic and said coating applied to said stent, and further comprising:

a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts, said applied to said strut, and a channel formed in at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said strut, said channel containing a reservoir of said macrocyclic lactone coating applied therein.

33. A stent having a coating containing macrocyclic, wherein said macrocyclic lactone are contained in the coating at a weight percentage of 0.0001% to 30%, wherein the coating is a polymer.

34. The stent of claim 33, wherein said polymer is mixed to the macrocyclic lactone.

35. The stent of claim 33, wherein said polymer is bound to the macrocyclic lactone.

36. The stent of claim 33, wherein the macrocyclic lactone is entrapped on the surface of the stent by said polymer.

37. A stent containing a polymer and macrocyclic lactone wherein said macrocyclic lactone are contained in a therapeutically beneficial amount to combat restenosis.

38. The stent of claim 37, wherein said polymer is mixed to the macrocyclic lactone.

39. The stent of claim 37, wherein said polymer is bound to the macrocyclic lactone.

40. The stent of claim 37, wherein the macrocyclic lactone is entrapped on the surface of the stent by said polymer.

41. A stent having a coating containing macrocyclic lactone, wherein said macrocyclic lactone is contained in the coating at a weight percentage of 0.0001% to 30%, said stent further comprising a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts, said coating applied to at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said at least one strut, said channel containing a reservoir of said macrocyclic lactone contained coating applied therein.

42. A stent having a coating containing macrocyclic lactone, wherein said macrocyclic lactone is contained in the coating at a weight percentage of 0.0001% to 30%, wherein the coating is a polymer, said stent further comprising a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts, said coating applied to at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said at least one strut, said channel containing a reservoir of said macrocyclic lactone contained coating applied therein.

43. A stent containing a polymer and macrocyclic lactone wherein said macrocyclic lactone is contained in a therapeutically beneficial amount to combat restonosis, said stent further comprising a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts, said coating applied to at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said at least one strut, said channel containing a reservoir of said macrocyclic lactone contained coating applied therein.

44. A stent having a coating containing macrocyclic lactone, wherein said macrocyclic lactone is contained in the coating at a weight percentage of 0.00001% to 30%, said stent further comprising a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts, said coating applied to said struts.

45. A stent having a coating containing macrocyclic lactone, wherein said macrocyclic lactone is contained in the coating at a weight percentage of 0.00001% to 30%, wherein the coating is a polymer, said stent further comprising a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts, said coating applied to said struts.

46. A stent containing a polymer and macrocyclic lactone wherein said macrocyclic lactone is contained in a therapeutically beneficial amount to combat restenosis, said stent further comprising a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts, said coating applied to said struts.

47. A stent comprising:

a generally thin walled cylinder, said cylinder containing a plurality of struts, said struts having a generally uniform thickness; and

a channel formed in at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said strut, said channel containing a therapeutic agent applied therein and wherein the therapeutic agent is macrocyclic lactone.

48. The stent of claim 47, wherein said channel is rectangular in shape.

49. The stent of claim 48, wherein said channel is laser cut into said strut.

50. A stent comprising:

a generally thin walled cylinder, said cylinder containing a plurality of struts, said struts expandable dependent on the amount of force applied to said strut, and said struts having a generally uniform thickness; and

a channel formed in at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said strut, said channel containing a therapeutic agent applied therein; and

wherein said therapeutic agent is macrocylic lactone.

51. A stent comprising a generally thin walled cylinder, said cylinder containing a plurality of struts, said struts expandable dependent on the amount of force applied to said strut, and said struts having a generally uniform thickness;

and a channel formed in at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said strut, said channel containing a therapeutic agent applied therein; and

wherein said channel has a generally rectangular perimeter; and

wherein said therapeutic agent is macrocylic lactone coated to said channel.

52. A stent comprising a generally thin walled structure containing a plurality of struts, the struts expandable to assume the shape of a lumen into which the stent is emplaced, said struts having a thickness, and a channel formed in at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said strut, said channel containing a therapeutic agent applied therein and wherein the therapeutic agent is macrocyclic lactone.

53. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft.

54. A stent graft having a coating containing macrocyclic lactone, wherein said macrocyclic lactone are contained in the coating at a weight percentage of 0.0001% to 30%.

55. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft;

wherein the polymer is biocompatible and degradable; and

wherein the polymer is chosen from;

lactone-based polyesters, lactone-based copolyesters;

polyanhydrides;

polyaminoacids;

polysaccharides;

polyphosphazenes;

poly(ether-ester) copolymers, and blends of such polymers.

56. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft; and

wherein the polymer is chosen from;

lactone-based polyesters, lactone-based copolyesters;

polyanhydrides;

polyaminoacids;

polysaccharides;

polyphosphazenes;

poly(ether-ester) copolymers, and blends of such polymers.

57. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft;

wherein the polymer is nonabsorbable; and

wherein the polymer is chosen from;

polydimethylsiolxane;

poly(ethylene)vinylacetate;

poly(hydroxy)ethylmethylmethacrylate, polyvinyl pyrrolidone;

polytetrafluoroethylene; and

cellulose esters.

58. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft; and

wherein the polymer is chosen from;

polydimethylsiolxane;

poly(ethylene)vinylacetate;

poly(hydroxy)ethylmethylmethacrylate, polyvinyl pyrrolidone;

polytetrafluoroethylene; and

cellulose esters.

59. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft; and

further comprising;

a generally thin walled cylinder, said cylinder containing a plurality of generally solid struts, said applied to said strut, and a channel formed in at least one of said struts, said channel having a closed perimeter on all sides and an open top, and said channel smaller in all dimensions than said strut, said channel containing a reservoir of said rapamycin coating applied therein.

60. A stent graft having a coating containing macrocyclic lactone, wherein said macrocyclic lactone is contained in the coating at a weight percentage of 0.0001% to 30%, wherein the coating is a polymer.

61. A stent graft containing a polymer and macrocyclic lactone wherein said macrocyclic lactone is contained in a therapeutically beneficial amount to combat restenosis.

62. A stent graft having a coating containing macrocyclic lactone, said coating formed from a polymer mixed carrier containing the macrocyclic lactone;

and said coating applied to said stent graft.

63. A stent graft having a coating containing macrocyclic lactone, wherein said macrocyclic lactone is contained in the coating at a weight percentage of 0.0001% to 30%.