Thermal treatment of an implantable medical device

• US 7,807,211 B2
• Filed: 05/27/2004
• Issued: 10/05/2010
• Est. Priority Date: 09/03/1999
• Status: Expired due to Fees

• Current Assignee: Advanced Cardiovascular Systems Incorporated
• Original Assignee: Advanced Cardiovascular Systems Incorporated
• Inventors: Tang, Yiwen, Gada, Manish, Hossainy, Syed F. A.
• Primary Examiner(s): Meeks; Timothy H
• Assistant Examiner(s): Sellman; Cachet I
• Application Number:
  US10/856,984
• Publication Number:
  US 20050233062A1
• Time in Patent Office: 2,322 Days
• Field of Search: 427/2.24, 427/2.25, 427/2.28, 427/2.1, 525/419, 623/1.1, 623/1.42, 623/1.44, 623/1.46
• US Class Current: 427/2.1
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• 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 2210/0004 bioabsorbable
• CPC Class Codes: A61F 2240/001 Designing or manufacturing processes
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• 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 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: B29C 71/02 Thermal after-treatment B29C71/0063 and B29C71/0072 take precedence
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

A method of manufacturing an implantable medical device, such as a drug eluting stent, is disclosed. The method includes subjecting an implantable medical device that includes a polymer to a thermal condition. The thermal condition can result in reduction of the rate of release of an active agent from the device subsequent to the implantation of the device and/or improve the mechanical properties of a polymeric coating on the device.

Claims

1. A method of manufacturing an implantable medical device, comprising:

applying a semicrystalline polymer to the implantable medical device; and

exposing the polymer to a temperature equal to the crystallization temperature of the polymer for a duration of time.

2. The method of claim 1, wherein the polymer comprises poly(lactic acid).

3. The method of claim 1, wherein the polymer comprises a block copolymer or a graft copolymer, and wherein a moiety of the block copolymer or the graft copolymer is poly(lactic acid).

4. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to or greater than the glass transition temperature of the polymer and less than the melting temperature of the polymer for a duration of time, wherein the temperature is

(a) equal to the glass transition temperature of the polymer plus the melting temperature of the polymer, divided by 2;

(b) equal to 0.9 times the melting temperature of the polymer, wherein the melting temperature of the polymer is expressed in Kelvin;

(c) equal to or greater than the crystallization temperature of the polymer;

or

(d) equal to the glass transition temperature of the polymer.

5. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to or greater than the glass transition temperature of the polymer and less than the melting temperature of the polymer for a duration of time, wherein the polymer comprises a block copolymer or a graft copolymer;

wherein a moiety of the block copolymer or the graft copolymer is poly(lactic acid);

and wherein the glass transition temperature is above room temperature.

6. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to the glass transition temperature of the polymer for a duration of time, wherein the device is a stent and wherein the act of exposing the device to the temperature is done concurrently with or subsequent to securing the stent onto a patient delivery device.

7. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to the glass transition temperature of the polymer for a duration of time, wherein the device is a stent and wherein the act of exposing the device to the temperature is done concurrently with crimping of the stent onto a catheter.

8. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to or greater than the glass transition temperature of the polymer and less than the melting temperature of the polymer for a duration of time, wherein during the act of exposing the device to the temperature, the temperature is changed to another temperature between the glass transition temperature and the melting temperature.

9. The method of claim 8, wherein the polymer is selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon caprolactone), random and block copolymers of α

-methylstyrene and vinyl acetate, random and block copolymers of α

-methylstyrene and vinyl chloride, random and block copolymers of α

-methylstyrene and styrene, random and block copolymers of styrene and butyl methacrylate, random and block copolymers of styrene and methyl methacrylate, random and block copolymers of styrene and ethylene oxide, random and block copolymers of styrene and isoprene, random and block copolymers of styrene and isobutylene, random and block copolymers of methyl methacrylate and ethyl acrylate, random and block copolymers of methyl methacrylate and vinyl acetate, random and block copolymers of methyl methacrylate and ethyl methacrylate, and any combination thereof.

10. The method of claim 9, wherein the polymer is selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon caprolactone), and any combination thereof.

11. The method of claim 8, wherein the polymer exhibits more than one glass transition temperature, and the exposure temperature is above the lowest of the glass transition temperatures.

12. The method of claim 8, wherein the polymer exhibits more than one glass transition temperature, and the exposure temperature is above the highest of the glass transition temperatures.

13. The method of claim 8, wherein the composition additionally comprises a second polymer such that the coating formed comprises a polymer blend, and the exposure temperature is above the lowest of the glass transition temperatures if the polymer blend exhibits more than one glass transition temperature.

14. The method of claim 13, wherein the exposure temperature is less than the lowest melting temperature if the polymer blend exhibits more than one melting temperature.

15. The method of claim 8, wherein the composition additionally comprises a second polymer such that the coating formed comprises a polymer blend, and the exposure temperature is above the highest of the glass transition temperatures if the polymer blend exhibits more than one glass transition temperature.

16. The method of claim 15, wherein the exposure temperature is less than the lowest melting temperature if the polymer blend exhibits more than one melting temperature.

17. The method of claim 8, wherein the duration of time is sufficient to improve the mechanical properties of the coating.

18. The method of claim 8, wherein the polymeric coating is free from any active agents and the polymeric coating comprises a primer layer.

19. The method of claim 18, wherein the implantable medical device is made of a metal, a metallic material, or a metal alloy.

20. The method of claim 19, wherein the duration of time is sufficient to improve the mechanical properties of the primer layer.

21. A method of coating an implantable medical device, comprising:

applying a first layer to the device comprising a first polymer having a first glass transition temperature;

applying a second layer over the first layer, the second layer comprising a second polymer having a second glass transition temperature; and

exposing the device to a temperature between the first glass transition temperature and the second glass transition temperature.

22. The method of claim 21, wherein the first glass transition temperature is higher than the second glass transition temperature.

23. The method of claim 21, wherein the first glass transition temperature is lower than the second glass transition temperature.

24. The method of claim 21, wherein at least one of the layers comprises a drug.

25. The method of claim 21, wherein the first and the second polymers are selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon caprolactone), random and block copolymers of α

-methylstyrene and vinyl acetate, random and block copolymers of α

-methylstyrene and vinyl chloride, random and block copolymers of α

-methylstyrene and styrene, random and block copolymers of styrene and butyl methacrylate, random and block copolymers of styrene and methyl methacrylate, random and block copolymers of styrene and ethylene oxide, random and block copolymers of styrene and isoprene, random and block copolymers of styrene and isobutylene, random and block copolymers of methyl methacrylate and thyl acetate, random and block copolymers of methyl methacrylate and vinyl acetate, random and block copolymers of methyl methacrylate and ethyl methacrylate, and any combination thereof.

26. The method of claim 24, wherein at least one of the first and the second polymers is selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon caprolactone), and any combination thereof.

27. The method of claim 21, wherein both the first and second glass transition temperatures are above room temperature.

28. A method of coating an implantable medical device, comprising:

applying a coating to the device, the coating comprising a polymer; and

exposing the coating to a temperature treatment so as to modify % crystallinity of the polymer such that the shallower regions of the coating will have a higher % of crystallinity than the deeper regions of the coating.

29. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to the glass transition temperature of the polymer for a duration of time;

wherein the glass transition temperature is not equal to room temperature.

30. The method of claim 29, wherein the polymer comprises a bioabsorbable polymer.

31. The method of claim 29, wherein the polymer comprises poly(lactic acid).

32. The method of claim 29, wherein the polymer comprises a block copolymer or a graft copolymer, and wherein a moiety of the block copolymer or the graft copolymer is poly(lactic acid).

33. The method of claim 29, wherein the device is a stent and wherein the act of exposing the device to the temperature is done concurrently with or subsequent to securing the stent onto a patient delivery device.

34. The method of claim 29, wherein the device is a stent and wherein the act of exposing the device to the temperature is done concurrently with crimping of the stent onto a catheter.

35. The method of claim 29, wherein the composition additionally comprises rapamycin, everolimus or functional analogs or structural derivatives thereof.

36. The method of claim 29, wherein the glass transition temperature is above room temperature.

37. The method of claim 29, wherein the composition additionally comprises a drug.

38. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to the glass transition temperature of the polymer for a duration of time;

wherein the polymeric coating is free from any active agents.

39. The method of claim 38, wherein the glass transition temperature is above room temperature.

40. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to the glass transition temperature of the polymer for a duration of time;

wherein the polymer comprises a crystalline component and an amorphous component such that the temperature is equal to the glass transition temperature of either of the components.

41. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to or greater than the glass transition temperature of the polymer and less than the melting temperature of the polymer for a duration of time, wherein the device is a stent and wherein the act of exposing the device to the temperature is done concurrently with or subsequent to securing the stent onto a patient delivery device; and

wherein the polymer is selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon caprolactone), random and block copolymers of α

-methylstyrene and vinyl acetate, random and block copolymers of α

-methylstyrene and vinyl chloride, random and block copolymers of α

-methylstyrene and styrene, random and block copolymers of styrene and butyl methacrylate, random and block copolymers of styrene and methyl methacrylate, random and block copolymers of styrene and ethylene oxide, random and block copolymers of styrene and isoprene, random and block copolymers of styrene and isobutylene, random and block copolymers of methyl methacrylate and ethyl acrylate, random and block copolymers of methyl methacrylate and vinyl acetate, random and block copolymers of methyl methacrylate and ethyl methacrylate, and any combination thereof.

42. The method of claim 41, wherein the polymer is selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon caprolactone), and any combination thereof.

43. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature equal to or greater than the glass transition temperature of the polymer and less than the melting temperature of the polymer for a duration of time, wherein the device is a stent and wherein the act of exposing the device to the temperature is done concurrently with crimping of the stent onto a catheter; and

wherein the polymer is selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon caprolactone), random and block copolymers of α

-methylstyrene and vinyl acetate, random and block copolymers of α

-methylstyrene and vinyl chloride, random and block copolymers of α

-methylstyrene and styrene, random and block copolymers of styrene and butyl methacrylate, random and block copolymers of styrene and methyl methacrylate, random and block copolymers of styrene and ethylene oxide, random and block copolymers of styrene and isoprene, random and block copolymers of styrene and isobutylene, random and block copolymers of methyl methacrylate and ethyl acrylate, random and block copolymers of methyl methacrylate and vinyl acetate, random and block copolymers of methyl methacrylate and ethyl methacrylate, and any combination thereof.

44. The method of claim 43, wherein the polymer is selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon caprolactone), and any combination thereof.

45. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature greater than the glass transition temperature of the polymer and less than the melting temperature of the polymer for a duration of time;

wherein the glass transition temperature is above room temperature; and

wherein the polymer is selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon caprolactone), random and block copolymers of α

-methylstyrene and vinyl acetate, random and block copolymers of α

-methylstyrene and vinyl chloride, random and block copolymers of α

-methylstyrene and styrene, random and block copolymers of styrene and butyl methacrylate, random and block copolymers of styrene and methyl methacrylate, random and block copolymers of styrene and ethylene oxide, random and block copolymers of styrene and isoprene, random and block copolymers of styrene and isobutylene, random and block copolymers of methyl methacrylate and ethyl acrylate, random and block copolymers of methyl methacrylate and vinyl acetate, random and block copolymers of methyl methacrylate and ethyl methacrylate, and any combination thereof.

46. The method of claim 45, wherein the polymer is selected from the group consisting of ethylene vinyl alcohol copolymer, poly(n-butyl methacrylate), poly(ethylene-co-vinyl acetate), poly(ethylene terephthalate), poly(vinylidene fluoride), poly(p-phenylene sulfide), poly(6-aminocaproic acid), poly(methyl methacrylate), poly(vinyl alcohol), poly(epsilon carpolactone), and any combination thereof.

47. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device, and

exposing the device to a temperature greater than the glass transition temperature of the polymer and less than the melting temperature of the polymer for a duration of time;

wherein the glass transition temperature is above room temperature; and

wherein the polymer exhibits more than one glass transition temperature, and the exposure temperature is above the highest of the glass transition temperatures.

48. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a first polymer, a second polymer, and a solvent to form the polymeric coating on the implantable medical device, the coating formed comprising a polymer blend; and

exposing the device to a temperature greater than the glass transition temperature of the polymer blend and less than the melting temperature of the polymer blend for a duration of time;

wherein the glass transition temperature is above room temperature; and

wherein the exposure temperature is above the lowest of the glass transition temperatures if the polymer blend exhibits more than one glass transition temperature.

49. The method of claim 48, wherein the exposure temperature is less than the lowest melting temperature if the polymer blend exhibits more than one melting temperature.

50. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a first polymer, a second polymer, and a solvent to form the polymeric coating on the implantable medical device, the coating formed comprising a polymer blend; and

exposing the device to a temperature greater than the glass transition temperature of the polymer blend and less than the melting temperature of the polymer blend for a duration of time;

wherein the glass transition temperature is above room temperature; and

wherein the exposure temperature is above the highest of the glass transition temperatures if the polymer blend exhibits more than one glass transition temperature.

51. The method of claim 50, wherein the exposure temperature is less than the lowest melting temperature if the polymer blend exhibits more than one melting temperature.

52. A method of applying a coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form a polymeric primer layer free from any active agents on the implantable medical device; and

exposing the device to a temperature greater than the glass transition temperature of the polymer and less than the melting temperature of the polymer for a duration of time;

wherein the glass transition temperature is above room temperature; and

wherein the duration of time is sufficient to improve the mechanical properties of the primer layer; and

after the exposure to the temperature, applying a second composition comprising a second polymer, which may be the same as or different from the polymer of the primer layer, and a solvent, which may be the same as or different from the solvent in the composition used to apply the primer layer, to form a second polymeric coating layer on the implantable medical device; and

wherein the exposure of the device to a temperature greater than the glass transition temperature of the polymer of the primer layer and less than the melting temperature of the polymer of the primer layer for a duration of time increase the effectiveness of the primer as an adhesive tie layer between the device and the second polymeric coating layer.

53. The method of claim 52 wherein the second composition further comprises a drug.

54. A method of applying a polymeric coating to an implantable medical device, comprising:

applying to the implantable medical device a composition comprising a polymer and a solvent to form the polymeric coating on the implantable medical device;

exposing the device to a temperature equal to or greater than the glass transition temperature of the polymer and less than the melting temperature of the polymer for a duration of time, wherein the polymer comprises a bioabsorbable polymer and wherein the glass transition temperature is above room temperature; and

wherein the bioabsorbable polymer is selected from the group consisting of poly(hydroxybutyrate) (PHB), poly(hydroxyvalerate) (PHV), poly(hydroxybutyrate-co-valerate), poly(caprolactone) (PCL), poly(lactide-co-glycolide) (PLGA), poly(glycerol-sebacate) (PGS), poly(ester amide), collagen, elastin, silk, AB and ABA block-copolymers of PEG with poly(butylene terephthalate) (PBT), poly(ethylene-glycol)-block-poly(butylene terephthalate) (PEG-PBT), poly(ethylene-glycol)-block-poly (butylene terephthalate)-block-poly(ethylene-glycol) (PEG-PBT-PEG), poly(butylene terephthalate)-block-poly(ethylene-glycol)-block poly(butylene terephthalate) (PBT-PEG-PBT), AB and ABA block-copolymers of PEG with PCL, poly(ethylene-glycol)-block-poly(caprolactone) (PEG-PCL), poly(ethylene-glycol)-block-poly(caprolactone)-block-poly(ethylene-glycol) (PEG-PCL-PEG), poly(caprolactone)-block-poly(ethylene-glycol)block-poly(caprolactone) (PCL-PEG-PCL), and any combination thereof.