Drug delivery coating for use with a stent

• US 8,263,102 B2
• Filed: 09/28/2005
• Issued: 09/11/2012
• Est. Priority Date: 09/28/2004
• Status: Active Grant

• Current Assignee: Atrium Medical Corporation (Getinge AB)
• Original Assignee: Atrium Medical Corporation (Getinge AB)
• Inventors: Labrecque, Roger, Moodie, Geoffrey, Ferraro, Joseph, Rogers, Lisa, Martakos, Paul, Karwoski, Theodore, Herweck, Steve A.
• Primary Examiner(s): Long, Scott
• Assistant Examiner(s): BECKHARDT, LYNDSEY MARIE
• Application Number:
  US11/236,908
• Publication Number:
  US 20060067974A1
• Time in Patent Office: 2,540 Days
• Field of Search: None
• US Class Current: 424/423
• 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 2/86 Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• CPC Class Codes: A61L 2300/22 Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
• 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 2300/428 Vitamins, e.g. tocopherol, riboflavin
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/802 Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 31/08 Materials for coatings
• 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: A61M 25/0009 Making of catheters or other medical or surgical tubes
• CPC Class Codes: A61M 25/0045 multi-layered, e.g. coated coating materials A61L29/08
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

A coated medical device an a method of providing a coating on an implantable medical device result in a medical device having a bio-absorbable coating. The coating includes a bio-absorbable carrier component. In addition to the bio-absorbable carrier component, a therapeutic agent component can also be provided. The coated medical device is implantable in a patient to effect controlled delivery of the coating, including the therapeutic agent, to the patient.

Claims

1. A coated medical device, comprising:

a coating having cross-linked bio-absorbable carrier component, the bio-absorbable carrier component being at least partially formed of cellular uptake inhibitor and cellular uptake enhancer;

wherein the cellular uptake enhancer comprises one or more fatty acids selected from the group consisting of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA);

wherein the coating is cured using at least one of heat and ultraviolet light and further includes a therapeutic agent;

wherein the bioabsorbable carrier component comprises two or more of the fatty acids cross-linked into a substantially random configuration by ester bonds; and

controlled delivery of the therapeutic agent to the patient.

2. The device of claim 1, wherein the cellular uptake inhibitor comprises alpha-tocopherol.

3. The device of claim 1, wherein the cellular uptake enhancer further comprises myristic acid.

4. The device of claim 1, wherein the bio-absorbable carrier component comprises at least one component selected from a group of components comprised of a naturally occurring oil, and an oil composition.

5. The device of claim 1, wherein the bio-absorbable carrier component further comprises a fish oil.

6. The device of claim 1, wherein the bio-absorbable carrier component is modified from its naturally occurring state to a state of increased viscosity in the form of a cross-linked gel.

7. The device of claim 6, wherein the modification of the bio-absorbable carrier component from its naturally occurring state to the state of increased viscosity occurs prior to formation of the coating on the device.

8. The device of claim 1, wherein the bio-absorbable carrier component contains omega-3 fatty acids.

9. The device of claim 1, wherein the therapeutic agent component comprises an agent selected from the group consisting of antioxidants, anti-inflammatory agents, anti-coagulant agents, drugs to alter lipid metabolism, anti-proliferatives, anti-neoplastics, anti-fibrotics, immunosuppressive, tissue growth stimulants, functional protein/factor delivery agents, anti-infective agents, imaging agents, anesthetic agents, chemotherapeutic agents, tissue absorption enhancers, anti-adhesion agents, germicides, antiseptics, proteoglycans, GAG'"'"'s, gene delivery (polynucleotides), analgesics, prodrugs, and polysaccharides (heparin).

10. The device of claim 1, wherein the therapeutic agent component comprises an agent selected from the group consisting of cerivastatin, cilostazol, fluvastatin, lovastatin, paclitaxel, pravastatin, rapamycin, and simvastatin.

11. The device of claim 1, wherein the coating is bio-absorbable.

12. The device of claim 1, wherein the coating inhibits restenosis.

13. The device of claim 1, wherein the coating is prepared by mixing the fatty acids and a solvent.

14. The device of claim 13, wherein the solvent comprises N-Methyl-2-Pyrrolidone (NMP).

15. The device of claim 1, wherein the coating further comprises a compatibilizer and preservative.

16. The device of claim 1, wherein the medical device comprises a stent.

17. The device of claim 16, wherein the stent is formed of a substance selected from the group consisting of stainless steel, Nitinol alloy, nickel alloy, titanium alloy, cobalt-chromium alloy, ceramics, metals, plastics, and polymers.

18. The device of claim 1, wherein the bio-absorbable carrier component is hardened.

19. The device of claim 1, wherein the bio-absorbable carrier component is hardened by mixing the bio-absorbable carrier component with linseed oil.

20. The device of claim 1, further comprising a pre-treatment provided between the medical device and the coating comprising the bio-absorbable carrier component, wherein the pre-treatment improves consistency and conformability and enhances the adhesion of the coating comprising the bio-absorbable carrier component.

21. The device of claim 20, wherein the pre-treatment is bio-absorbable.

22. The device of claim 20, wherein the pre-treatment comprises at least one component selected from a group of components comprised of a naturally occurring oil, and an oil composition.

23. The device of claim 20, wherein the pre-treatment comprises fish oil.

24. The device of claim 20, wherein the pre-treatment is modified from its naturally occurring state to a state of increased viscosity in the form of a cross-linked gel.

25. The device of claim 24, wherein the modification of the pre-treatment from its naturally occurring state to the state of increased viscosity occurs prior to application of the pre-treatment on the device.

26. The device of claim 1, wherein the coating inhibits neointimal growth.

27. The device of claim 1, wherein the coating promotes endothelialization.

54. The coated medical device of claim 1, wherein the coating is a flexible, solid-like gel structure.

55. The coated medical device of claim 1, wherein the therapeutic agent remains pharmacologically effective after the coating is cured.

56. The coated medical device of claim 1, wherein the coating is cured without the addition of external crosslinking agents.

28. A coated medical device, comprising:

a pre-treatment provided on the medical device having a first bio-absorbable carrier component; and

a coating disposed on top of the pre-treatment, the coating having a cross-linked second bioabsorbable carrier component at least partially formed of cellular uptake inhibitor and cellular uptake enhancer;

wherein the cellular uptake enhancer comprises one or more fatty acids selected form the group consisting of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and alpha-linolenic acid (ALA);

wherein the coating is cured using at least one of heat and ultraviolet light and further includes a therapeutic agent;

wherein the bio-absorbable carrier component comprises two or more of the fatty acids cross-linked into a substantially random configuration by ester bonds;

wherein the pre-treatment improves consistency and conformability and enhances the adhesion of the coating comprising the second bio-absorbable carrier component; and

wherein the coated medical device is implantable in a patient to effect controlled delivery of the therapeutic agent to the patient.

29. The device of claim 28, wherein the cellular uptake inhibitors comprise alpha-tocopherol.

30. The device of claim 28, wherein the cellular uptake enhancer further comprises myristic acid.

31. The device of claim 28, wherein the content of the first bio-absorbable carrier component and the second bio-absorbable carrier component is substantially the same.

32. The device of claim 28, wherein one or both of the first and second bio-absorbable carrier components comprises at least one component selected from a group of components comprised of a naturally occurring oil, and an oil composition.

33. The device of claim 28, wherein at least one component of the first and second bio-absorbable carrier components further comprises a fish oil.

34. The device of claim 28, wherein at least one component of the first and second bio-absorbable carrier components is modified from its naturally occurring state to a state of increased viscosity in the form of a cross-linked gel.

35. The device of claim 28, wherein at least one component of the first and second bio-absorbable carrier components contains omega-3 fatty acids.

36. The device of claim 28, wherein the therapeutic agent comprises an agent selected from the group consisting of cerivastatin, cilostazol, fluvastatin, lovastatin, paclitaxel, pravastatin, rapamycin, and simvastatin.

37. The device of claim 28, wherein the coating is bio-absorbable.

38. The device of claim 28, wherein the coating inhibits restenosis.

39. The device of claim 28, wherein the coating is prepared by mixing the fatty acids and a solvent.

40. The device of claim 39, wherein the solvent comprises N-Methyl-2-Pyrrolidone (NMP).

41. The device of claim 28, wherein the coating further comprises a compatibilizer and preservative.

42. The device of claim 28, wherein the medical device comprises a stent.

43. The device of claim 42, wherein the stent is formed of a substance selected from the group consisting of stainless steel, Nitinol alloy, nickel alloy, titanium alloy, cobalt-chromium alloy, ceramics, metals, plastics, and polymers.

44. The device of claim 28, wherein the bio-absorbable carrier component is hardened.

45. The device of claim 28, wherein the bio-absorbable carrier component is hardened by mixing the bio-absorbable carrier component with linseed oil.

46. The device of claim 28, wherein the pre-treatment is bio-absorbable.

47. The device of claim 28, wherein the pre-treatment comprises at least one component selected from a group of components comprised of a naturally occurring oil, and an oil composition.

48. The device of claim 28, wherein the pre-treatment comprises fish oil.

49. The device of claim 28, wherein the pre-treatment is modified from its naturally occurring state to a state of increased viscosity in the form of a cross-linked gel.

50. The device of claim 48, wherein the modification of the pre-treatment from its naturally occurring state to the state of increased viscosity occurs prior to application of the pre-treatment on the device.

51. The device of claim 28, wherein the coating inhibits neointimal growth.

52. The device of claim 28, wherein the coating promotes endothelialization.

53. The device of claim 28, wherein the device is sterilized using at least one method of sterilization selected from a group of methods of sterilization comprising ethylene oxide, gamma radiation, e-beam, steam, gas plasma, and vaporized hydrogen peroxide.