Delivery of Highly Lipophilic Agents Via Medical Devices

• US 20090216317A1
• Filed: 03/22/2006
• Published: 08/27/2009
• Est. Priority Date: 03/23/2005
• Status: Abandoned Application

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories), Abbott Laboratories
• Original Assignee: Abbott Laboratories
• Inventors: Krasula, Richard W., Burke, Sandra E., Toner, John L., Cromack, Keith R., Schwartz, Lewis B.
• Application Number:
  US11/886,815
• Publication Number:
  US 20090216317A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61F 2/04 Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts A61F2/18, A61F2/20 take precedence; devices, other than stent-grafts, providing patency to, or preventing collapsing of, tubular structures of the body other than stent-grafts, e.g. stents A61F2/82; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95
• 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 2002/044 Oesophagi or esophagi or gullets
• CPC Class Codes: A61F 2002/047 Urethrae
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 2300/216 with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• 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 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

An apparatus and system for delivering a lipophilic agent associated with a medical device including: a medical device, a first lipophilic agent capable of penetrating a body lumen, wherein the transfer coefficients of the first lipophilic agent is by an amount that is statistically significant of at least approximately 5,000, wherein the first lipophilic agent is associated with the medical device, wherein the first lipophilic agent/medical device is placed adjacent to said body lumen, and wherein a therapeutically effective amount of the first lipophilic agent is delivered to a desired area within a subject. Furthermore, the invention relates to a method for improving patency in a subject involving placement of a medical device in a body lumen for treating and/or preventing adjacent diseases or maintaining patency of the body lumen.

Claims

1. A system for delivering a lipophilic agent, comprising:

a medical device;

a first lipophilic agent capable of penetrating a body lumen, wherein the transfer coefficient of said first lipophilic agent is by an amount of at least approximately 5,000 (ug/mL)<sup>−

1</sup>, wherein said first lipophilic agent is associated with said medical device, wherein said first lipophilic agent/medical device is placed adjacent to said body lumen; and

wherein a therapeutically effective amount of said first lipophilic agent is delivered to a desired area within a subject.

2. The system according to claim 1, further comprising at least one pharmaceutically acceptable carrier or excipient, wherein said medical device is associated with said pharmaceutically acceptable carrier or excipient.

3. The system according to claim 2, wherein said pharmaceutically acceptable carrier or excipient is a polymer.

4. The system according to claim 2, wherein said pharmaceutically acceptable carrier or excipient is an agent.

5. The system according to claim 1, wherein said body lumen comprises at least one of a vessel wall, a coronary artery, esophageal lumen, and a urethra.

6. The system according to claim 1, wherein said first lipophilic agent/medical device is placed adjacent to said body lumen including coronary arteries, wherein a therapeutically effective amount of said first lipophilic agent is delivered into said coronary arteries and diffused into the pericardial sac in said drug delivery system.

7. The system according to claim 6, wherein said system provides substantially uniform dug delivery of said lipophilic agent to the myocardium.

8. The system according to claim 6, wherein said system is useful for the treatment and/or prevention of vascular diseases in a subject.

9. The system according to claim 3, wherein said delivery mechanism of said first lipophilic agent includes polymer hydration followed by dissolution of said first lipophilic agent, and wherein said first lipophilic agent is thereafter delivered into said body lumen.

10. The system according to claim 3, wherein said delivery mechanism of said first lipophilic agent includes a lipophilic agent/polymer matrix which controls the elution rate of said first lipophilic agent to said body lumen.

11. The system according to claim 1, further comprises at least one second lipophilic agent.

12. The system according to claim 1, further comprises at least one lipophilic prodrug.

13. The system according to claim 1, further comprises at least one lipophilic penetration enhancer.

14. The system according to claim 13, wherein said lipophilic penetration enhancer is a pharmaceutical agent.

15. The system according to claim 1, wherein the concentration of said first lipophilic agent delivered into said body lumen is a therapeutically effective amount.

16. The system according to claim 11, wherein the concentration of said second lipophilic agent in combination with said first lipophilic agent is delivered into said body lumen in a therapeutically effective amount.

17. The system according to claim 1, wherein said first lipophilic agent is zotarolimus having the structures as follows,

18. The system according to claim 1, further comprises at least one beneficial agent.

19. The system according to claim 1, wherein said first lipophilic agent includes partition coefficients greater than 20,000 P.

20. The system according to claim 1, wherein said first lipophilic agent includes partition coefficients greater than 20,000 P and said lipophilic agent having solubilities of less than about 30 ug/ml.

21. The system according to claim 1, wherein said first lipophilic agent includes a LogP at least approximately 4.3.

22. The system according to claim 1, wherein said system comprises a first lipophilic agent having transfer coefficients of at least approximately 10,000 (μ

g/mL)<sup>−

1</sup>.

23. The system according to claim 1, wherein said system comprises a first lipophilic agent having transfer coefficients of at least approximately 15,000 (μ

g/mL)<sup>−

1</sup>.

24. The system according to claim 1, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 15 μ

g/g to about 150 μ

g/g over a period of up to about 5 days.

25. The system according to claim 1, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 15 μ

g/g to about 80 μ

g/g over a period from about 5 days to up to about 15 days.

26. The system according to claim 1, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 5 μ

g/g to about 60 μ

g/g over a period from 15 days up to about 28 days.

27. The system according to claim 1, wherein said first lipophilic agent reaches therapeutically significant concentrations in targeted areas in said subject comprising at least one of the distal myocardium, the unstent myocardium, in said subjacent myocardium, in unstented and distal coronary arteries, and maintains those concentrations throughout a 28 day period.

28. The system according to claim 1, wherein said medical device is permanently or temporarily implanted into a subject.

29. The system according to claim 1, wherein said first lipophilic agent is in amorphous form.

30. The system according to claim 1, further comprises a beneficial agent including at least one of antithrombotics, anticoagulants, antiplatelets agents, anti-lipid agents, thrombolytics, antiproliferatives, antiinflammatories, agents that inhibit hyperplasia, smooth muscle cell inhibitors, antibiotics, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters, antimitotics, antifibrins, antioxidants, antineoplastics, agents that promote endothelial cell recovery, matrix metalloproteinase inhibitors, antineoplastics, antimetabolites, antiallergic substances, viral vectors, nucleic acids, monoclonal antibodies, inhibitors of tyrosine kinase, antisense compounds, oligionucleotides, cell permeation enhancers, and any combinations thereof.

31. The system according to claim 1, further comprises a beneficial agent including at least one of hypoglycemic agents, hypolipidemic agents, proteins, nucleic acids, agents useful for erythropoiesis stimulation, angiogenesis agents, antiulcer/antireflux agents, and antinauseants/antiemetics, PPAR-alpha agonists, and any combinations thereof.

32. The system according to claim 1, further comprises a beneficial agent including at least one of sodium heparin, LMW heparins, heparoids, hirudin, argatroban, forskolin, vapriprost, prostacyclin and prostacylin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), glycoprotein Iib/Iia (platelet membrane receptor antagonist antibody), recombinant hirudin, thrombin inhibitors, indomethacin, phenyl salicylate, β

-estradiol, vinblastine, ABT-627 (astrasentan), testosterone, progesterone, paclitaxel, methotrexate, fotemustine, RPR-101511A, cyclosporin A, vincristine, carvediol, vindesine, dipyridamole, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexyl, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, iotrolan and pro-drugs, analogs, derivatives, and any combinations thereof.

33. The system according to claim 1, wherein said medical device is an endovascular medical device.

34. The system according to claim 1, wherein said medical device includes intracoronary medical devices selected from the group consisting of stents, drug delivery catheters, grafts, and drug delivery balloons utilized in subjects'"'"' vasculature.

35. The system according to claim 1, wherein said medical device includes a stent selected from the group consisting of peripheral stents, peripheral coronary stents, degradable coronary stents, non-degradable coronary stents, self-expanding stents, balloon-expanded stents, and esophageal stents.

36. The system according to claim 1, wherein said medical device is selected from the group consisting of arterio-venous grafts, by-pass grafts, penile implants, vascular implants and grafts, intravenous catheters, small diameter grafts, artificial lung catheters, electrophysiology catheters, bone pins, suture anchors, blood pressure and stent graft catheters, breast implants, benign prostatic hyperplasia and prostate cancer implants, bone repair/augmentation devices, breast implants, orthopedic joint implants, dental implants, implanted drug infusion tubes, oncological implants, pain management implants, neurological catheters, central venous access catheters, catheter cuff, vascular access catheters, urological catheters/implants, atherectomy catheters, clot extraction catheters, PTA catheters, PTCA catheters, stylets (vascular and non-vascular), drug infusion catheters, angiographic catheters, hemodialysis catheters, neurovascular balloon catheters, thoracic cavity suction drainage catheters, electrophysiology catheters, stroke therapy catheters, abscess drainage catheters, biliary drainage products, dialysis catheters, central venous access catheters, and parental feeding catheters.

37. The system according to claim 1, wherein said medical device is selected from the group consisting of pacemakers, vascular grafts, sphincter devices, urethral devices, bladder devices, renal devices, gastroenteral and anastomotic devices, vertebral disks, hemostatic barriers, clamps, surgical staples/sutures/screws/plates/wires/clips, glucose sensors, blood oxygenator tubing, blood oxygenator membranes, blood bags, birth control/IUDs and associated pregnancy control devices, cartilage repair devices, orthopedic fracture repairs, tissue adhesives, tissue sealants, tissue scaffolds, CSF shunts, dental fracture repair devices, intravitreal drug delivery devices, nerve regeneration conduits, electrostimulation leads, spinal/orthopedic repair devices, wound dressings, embolic protection filters, abdominal aortic aneurysm grafts and devices, neuro aneurysm treatment coils, hemodialysis devices, uterine bleeding patches, anastomotic closures, in vitro diagnostics, aneurysm exclusion devices, neuropatches, vena cava filters, urinary dilators, endoscopic surgical and wound drainings, surgical tissue extractors, transition sheaths and dialators, coronary and peripheral guidewires, circulatory support systems, tympanostomy vent tubes, cerebro-spinal fluid shunts, defibrillator leads, percutaneous closure devices, drainage tubes, bronchial tubes, vascular coils, vascular protection devices, vascular intervention devices including vascular filters and distal support devices and emboli filter/entrapment aids, AV access grafts, surgical tampons, drug delivery capsule and cardiac valves.

38. The system according to claim 1, wherein said medical device is selected from the group consisting of atrial septal defect closures, electro-stimulation leads for cardiac rhythm management, tissue and mechanical prosthetic heart valves and rings, arterial-venous shunts, valve annuloplasty devices, mitral valve repair devices, left ventricle assist devices, left atrial appendage filters, cardiac sensors, pacemaker electrodes and leads.

39. The system according to claim 11, wherein said second lipophilic agent is at least one of zotarolimus having the following structures;

40. The system according to claim 1, wherein said lipophilic agent is continuously delivered to the epicardium and/or pericardial sac.

41. A method for improving patency in a subject involving placement of a medical device in a body lumen for treating and/or preventing adjacent diseases or maintaining patency of the body lumen, comprising:

providing a medical device in a body lumen;

providing a first lipophilic agent capable of penetrating a body lumen, wherein the transfer coefficient of said first lipophilic agent is by an amount of at least approximately 5,000 (ug/mL)<sup>−

1</sup>, wherein said first lipophilic agent is associated with said medical device;

placing said first lipophilic agent/medical device adjacent to a body lumen; and

delivering a therapeutically effective amount of said first lipophilic agent to a desired area within a subject.

42. The method according to claim 41, further comprising at least one pharmaceutically acceptable carrier or excipient, wherein said medical device is associated with said pharmaceutically acceptable carrier or excipient.

43. The method according to claim 42, wherein said pharmaceutically acceptable carrier or excipient is a polymer.

44. The method according to claim 42, wherein said pharmaceutically acceptable carrier or excipient is an agent.

45. The method according to claim 41, wherein said body lumen comprises at least one of a vessel wall, a coronary artery, esophageal lumen, and a urethra.

46. The method according to claim 41, wherein said first lipophilic agent/medical device is placed adjacent to said body lumen including coronary arteries, wherein a therapeutically effective amount of said first lipophilic agent is delivered into said coronary arteries and diffused into the pericardial sac in said method.

47. The method according to claim 48, wherein said method provides substantially uniform dug delivery of said lipophilic agent to the myocardium.

48. The method according to claim 41, wherein said method is useful for the treatment and/or prevention of vascular diseases in subject.

49. The method according to claim 43, wherein said delivery mechanism of said first lipophilic agent includes polymer hydration followed by dissolution of said first lipophilic agent, and wherein said first lipophilic agent is thereafter delivered into said body lumen.

50. The method according to claim 43, wherein said delivery mechanism of said first lipophilic agent includes a lipophilic agent/polymer matrix which controls the elution rate of said first lipophilic agent to said body lumen.

51. The method according to claim 41, further comprises at least one second lipophilic agent.

52. The method according to claim 41, further comprises at least one lipophilic prodrug.

53. The method according to claim 41, further comprises at least one lipophilic penetration enhancer.

54. The method according to claim 53, wherein said lipophilic penetration enhancer is a pharmaceutical agent.

55. The method according to claim 41, wherein the concentration of said first lipophilic agent delivered into said body lumen is a therapeutically effective amount.

56. The method according to claim 51, wherein the concentration of said second lipophilic agent in combination with said first lipophilic agent is delivered into said body lumen in a therapeutically effective amount.

57. The method according to claim 41, wherein said first lipophilic agent is zotarolimus.

58. The method according to claim 41, further comprises at least one beneficial agent.

59. The method according to claim 41, wherein said first lipophilic agent includes partition coefficients greater than 20,000 P.

60. The method according to claim 41, wherein said first lipophilic agent includes partition coefficients greater than 20,000 P and said lipophilic agent having a solubilities of less than about 30 ug/ml.

61. The method according to claim 41, wherein said first lipophilic agent includes a LogP at least approximately 4.3.

62. The method according to claim 41, wherein said method comprises a first lipophilic agent having solubilities of at least approximately 15 μ

g/mL.

63. The method according to claim 41, wherein said method comprises a first lipophilic agent having transfer coefficients of at least approximately 10,000 (μ

g/mL)<sup>−

1</sup>.

64. The method according to claim 41, wherein said method comprises a first lipophilic agent having transfer coefficients of at least approximately 15,000 (μ

g/mL)<sup>−

1</sup>.

65. The method according to claim 41, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 15 μ

g/g to about 150 μ

g/g over a period of up to about 5 days.

66. The method according to claim 41, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 15 μ

g/g to about 80 μ

g/g over a period from about 5 days to up to about 15 days.

67. The method according to claim 41, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 5 μ

g/g to about 60 μ

g/g over a period from 15 days up to about 28 days.

68. The method according to claim 41, wherein said first lipophilic agent reaches therapeutically significant concentrations in targeted areas in said subject comprising at least one of the distal myocardium, the unstent myocardium, in said subjacent myocardium, in unstented and distal coronary arteries, and maintains those concentrations throughout a 28 day period.

69. The method according to claim 41, wherein said medical device is permanently or temporarily implanted into a subjects'"'"' body.

70. The method according to claim 41, wherein said first lipophilic agent is in amorphous form.

71. The method according to claim 41, further comprises a beneficial agent including at least one of antithrombotics, anticoagulants, antiplatelets agents, anti-lipid agents, thrombolytics, antiproliferatives, antiinflammatories, agents that inhibit hyperplasia, smooth muscle cell inhibitors, antibiotics, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters, antimitotics, antifibrins, antioxidants, antineoplastics, agents that promote endothelial cell recovery, matrix metalloproteinase inhibitors, antineoplastics, antimetabolites, antiallergic substances, viral vectors, nucleic acids, monoclonal antibodies, inhibitors of tyrosine kinase, antisense compounds, oligionucleotides, cell permeation enhancers, and any combinations thereof.

72. The method according to claim 41, further comprises a beneficial agent including at least one of hypoglycemic agents, hypolipidemic agents, proteins, nucleic acids, agents useful for erythropoiesis stimulation, angiogenesis agents, antiulcer/antireflux agents, and antinauseants/antiemetics, PPAR-alpha agonists, and any combinations thereof.

73. The method according to claim 41, further comprises a beneficial agent including at least one of sodium heparin, LMW heparins, heparoids, hirudin, argatroban, forskolin, vapriprost, prostacyclin and prostacylin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), glycoprotein Iib/Iia (platelet membrane receptor antagonist antibody), recombinant hirudin, thrombin inhibitors, indomethacin, phenyl salicylate, β

-estradiol, vinblastine, ABT-627 (astrasentan), testosterone, progesterone, paclitaxel, methotrexate, fotemustine, RPR-101511A, cyclosporin A, vincristine, carvediol, vindesine, dipyridamole, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexyl, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, iotrolan and pro-drugs, analogs, derivatives, and any combinations thereof.

74. The method according to claim 41, wherein said medical device is an endovascular medical device.

75. The method according to claim 44, wherein said medical device includes intracoronary medical devices selected from the group consisting of stents, drug delivery catheters, grafts, and drug delivery balloons utilized in a subjects'"'"' vasculature.

76. The method according to claim 41, wherein said medical device includes a stent selected from the group consisting of peripheral stents, peripheral coronary stents, degradable coronary stents, non-degradable coronary stents, self-expanding stents, balloon-expanded stents, and esophageal stents.

77. The method according to claim 41, wherein said medical device is selected from the group consisting of arterio-venous grafts, by-pass grafts, penile implants, vascular implants and grafts, intravenous catheters, small diameter grafts, artificial lung catheters, electrophysiology catheters, bone pins, suture anchors, blood pressure and stent graft catheters, breast implants, benign prostatic hyperplasia and prostate cancer implants, bone repair/augmentation devices, breast implants, orthopedic joint implants, dental implants, implanted drug infusion tubes, oncological implants, pain management implants, neurological catheters, central venous access catheters, catheter cuff, vascular access catheters, urological catheters/implants, atherectomy catheters, clot extraction catheters, PTA catheters, PTCA catheters, stylets (vascular and non-vascular), drug infusion catheters, angiographic catheters, hemodialysis catheters, neurovascular balloon catheters, thoracic cavity suction drainage catheters, electrophysiology catheters, stroke therapy catheters, abscess drainage catheters, biliary drainage products, dialysis catheters, central venous access catheters, and parental feeding catheters.

78. The method according to claim 41, wherein said medical device is selected from the group consisting of pacemakers, vascular grafts, sphincter devices, urethral devices, bladder devices, renal devices, gastroenteral and anastomotic devices, vertebral disks, hemostatic barriers, clamps, surgical staples/sutures/screws/plates/wires/clips, glucose sensors, blood oxygenator tubing, blood oxygenator membranes, blood bags, birth control/IUDs and associated pregnancy control devices, cartilage repair devices, orthopedic fracture repairs, tissue adhesives, tissue sealants, tissue scaffolds, CSF shunts, dental fracture repair devices, intravitreal drug delivery devices, nerve regeneration conduits, electrostimulation leads, spinal/orthopedic repair devices, wound dressings, embolic protection filters, abdominal aortic aneurysm grafts and devices, neuro aneurysm treatment coils, hemodialysis devices, uterine bleeding patches, anastomotic closures, in vitro diagnostics, aneurysm exclusion devices, neuropatches, vena cava filters, urinary dilators, endoscopic surgical and wound drainings, surgical tissue extractors, transition sheaths and dialators, coronary and peripheral guidewires, circulatory support systems, tympanostomy vent tubes, cerebro-spinal fluid shunts, defibrillator leads, percutaneous closure devices, drainage tubes, bronchial tubes, vascular coils, vascular protection devices, vascular intervention devices including vascular filters and distal support devices and emboli filter/entrapment aids, AV access grafts, surgical tampons, drug delivery capsule and cardiac valves.

79. The method according to claim 41, wherein said medical device is selected from the group consisting of atrial septal defect closures, electro-stimulation leads for cardiac rhythm management, tissue and mechanical prosthetic heart valves and rings, arterial-venous shunts, valve annuloplasty devices, mitral valve repair devices, left ventricle assist devices, left atrial appendage filters, cardiac sensors, pacemaker electrodes and leads.

80. The method according to claim 51, wherein said second lipophilic agent is at least one of zotarolimus having the following structures;

81. The method according to claim 68, wherein delivering said lipophilic agent delivered to the epicardium and/or pericardial sac is continuous.

82. A medical device, comprising:

a therapeutically effective amount of a first lipophilic agent associated with said medical device, wherein said first lipophilic agent is capable of penetrating a body lumen, wherein the transfer coefficient of said first lipophilic agent is by an amount of at least approximately 5,000 (ug/mL)<sup>−

1</sup>; and

wherein said first lipophilic agent/medical device is capable of being placed adjacent to a body lumen of a subject and deliver a therapeutically effective amount of said first lipophilic agent to a desired area in a subject.

83. The device according to claim 82, further comprising at least one pharmaceutically acceptable carrier or excipient, wherein said medical device is associated with said pharmaceutically acceptable carrier or excipient.

84. The device according to claim 83, wherein said pharmaceutically acceptable carrier or excipient is associated with said medical device in the form of a coating.

85. The device according to claim 83, wherein said pharmaceutically acceptable carrier or excipient is a polymer.

86. The device according to claim 83, wherein said pharmaceutically acceptable carrier or excipient is an agent.

87. The device according to claim 83, wherein said pharmaceutically acceptable carrier or excipient comprises at least one of the following properties including biodegradable, biocompatible and synthetic.

88. The device according to claim 82, wherein said body lumen comprises at least one of a vessel wall, a coronary artery, esophageal lumen, and a urethra.

89. The device according to claim 82, wherein said first lipophilic agent/medical device is placed adjacent to said body lumen including coronary arteries, wherein a therapeutically effective amount of said first lipophilic agent is delivered into said coronary arteries and diffused into the pericardial sac in a drug delivery system.

90. The device according to claim 89, wherein said first lipophilic agent and/or said medical device provides substantially uniform dug delivery of said lipophilic agent to the myocardium.

91. The device according to claim 89, wherein said first lipophilic agent is useful for the treatment and/or prevention of vascular diseases in a subject.

92. The device according to claim 85, wherein said delivery mechanism of said first lipophilic agent includes polymer hydration followed by dissolution of said first lipophilic agent, and wherein said first lipophilic agent is thereafter delivered into said body lumen.

93. The device according to claim 85, wherein said delivery mechanism of said first lipophilic agent includes a lipophilic agent/polymer matrix which controls the elution rate of said first lipophilic agent to said body lumen.

94. The device according to claim 82, further comprises at least one second lipophilic agent.

95. The device according to claim 82, further comprises at least one lipophilic prodrug.

96. The device according to claim 82, further comprises at least one lipophilic penetration enhancer.

97. The device according to claim 96, wherein said lipophilic penetration enhancer is a pharmaceutical agent.

98. The device according to claim 82, wherein the concentration of said first lipophilic agent delivered into said body lumen is a therapeutically effective amount.

99. The device according to claim 94, wherein the concentration of said second lipophilic agent in combination with said first lipophilic agent is delivered into said body lumen in a therapeutically effective amount.

100. The device according to claim 82, wherein said first lipophilic agent is zotarolimus.

101. The device according to claim 82, further comprises at least one beneficial agent.

102. The device according to claim 82, wherein said first lipophilic agent includes partition coefficients greater than 20,000 P.

103. The device according to claim 82, wherein said first lipophilic agent includes partition coefficients greater than 20,000 P and said lipophilic agent having solubilities of less than about 30 ug/ml.

104. The device according to claim 82, wherein said first lipophilic agent includes a LogP at least approximately 4.3.

105. The device according to claim 82, wherein said system comprises a first lipophilic agent having solubilities of at least approximately 15 μ

g/mL.

106. The device according to claim 82, wherein said system comprises a first lipophilic agent having transfer coefficients of at least approximately 10,000 (μ

g/mL)<sup>−

1</sup>.

107. The device according to claim 82, wherein said system comprises a first lipophilic agent having transfer coefficients of at least approximately 15,000 (μ

g/mL)<sup>−

1</sup>.

108. The device according to claim 82, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 15 μ

g/g to about 150 μ

g/g over a period of up to about 5 days.

109. The device according to claim 82, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 15 μ

g/g to about 80 μ

g/g over a period from about 5 days to up to about 15 days.

110. The device according to claim 82, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 5 μ

g/g to about 60 μ

g/g over a period from 15 days up to about 28 days.

111. The device according to claim 82, wherein said first lipophilic agent reaches therapeutically significant concentrations in targeted areas in said subject comprising at least one of the distal myocardium, the unstent myocardium, in said subjacent myocardium, in unstented and distal coronary arteries, and maintains those concentrations throughout a 28 day period.

112. The device according to claim 82, wherein said medical device is permanently or temporarily implanted into a subjects'"'"' body.

113. The device according to claim 82, wherein said first lipophilic agent is in amorphous form.

114. The device according to claim 82, further comprises a beneficial agent including at least one of antithrombotics, anticoagulants, antiplatelets agents, anti-lipid agents, thrombolytics, antiproliferatives, antiinflammatories, agents that inhibit hyperplasia, smooth muscle cell inhibitors, antibiotics, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters, antimitotics, antifibrins, antioxidants, antineoplastics, agents that promote endothelial cell recovery, matrix metalloproteinase inhibitors, antineoplastics, antimetabolites, antiallergic substances, viral vectors, nucleic acids, monoclonal antibodies, inhibitors of tyrosine kinase, antisense compounds, oligionucleotides, cell permeation enhancers, and any combinations thereof.

115. The device according to claim 82, further comprises a beneficial agent including at least one of hypoglycemic agents, hypolipidemic agents, proteins, nucleic acids, agents useful for erythropoiesis stimulation, angiogenesis agents, antiulcer/antireflux agents, and antinauseants/antiemetics, PPAR-alpha agonists, and any combinations thereof.

116. The device according to claim 82, further comprises a beneficial agent including at least one of sodium heparin, LMW heparins, heparoids, hirudin, argatroban, forskolin, vapriprost, prostacyclin and prostacylin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), glycoprotein Iib/Iia (platelet membrane receptor antagonist antibody), recombinant hirudin, thrombin inhibitors, indomethacin, phenyl salicylate, β

-estradiol, vinblastine, ABT-627 (astrasentan), testosterone, progesterone, paclitaxel, methotrexate, fotemustine, RPR-101511A, cyclosporin A, vincristine, carvediol, vindesine, dipyridamole, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexyl, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, iotrolan and pro-drugs, analogs, derivatives, and any combinations thereof.

117. The device according to claim 82, wherein said medical device is an endovascular medical device.

118. The device according to claim 82, wherein said medical device includes intracoronary medical devices selected from the group consisting of stents, drug delivery catheters, grafts, and drug delivery balloons utilized in a subjects'"'"' vasculature.

119. The device according to claim 82, wherein said medical device includes a stent selected from the group consisting of peripheral stents, peripheral coronary stents, degradable coronary stents, non-degradable coronary stents, self-expanding stents, balloon-expanded stents, and esophageal stents.

120. The device according to claim 82, wherein said medical device is selected from the group consisting of arterio-venous grafts, by-pass grafts, penile implants, vascular implants and grafts, intravenous catheters, small diameter grafts, artificial lung catheters, electrophysiology catheters, bone pins, suture anchors, blood pressure and stent graft catheters, breast implants, benign prostatic hyperplasia and prostate cancer implants, bone repair/augmentation devices, breast implants, orthopedic joint implants, dental implants, implanted drug infusion tubes, oncological implants, pain management implants, neurological catheters, central venous access catheters, catheter cuff, vascular access catheters, urological catheters/implants, atherectomy catheters, clot extraction catheters, PTA catheters, PTCA catheters, stylets (vascular and non-vascular), drug infusion catheters, angiographic catheters, hemodialysis catheters, neurovascular balloon catheters, thoracic cavity suction drainage catheters, electrophysiology catheters, stroke therapy catheters, abscess drainage catheters, biliary drainage products, dialysis catheters, central venous access catheters, and parental feeding catheters.

121. The device according to claim 82, wherein said medical device is selected from the group consisting of pacemakers, vascular grafts, sphincter devices, urethral devices, bladder devices, renal devices, gastroenteral and anastomotic devices, vertebral disks, hemostatic barriers, clamps, surgical staples/sutures/screws/plates/wires/clips, glucose sensors, blood oxygenator tubing, blood oxygenator membranes, blood bags, birth control/IUDs and associated pregnancy control devices, cartilage repair devices, orthopedic fracture repairs, tissue adhesives, tissue sealants, tissue scaffolds, CSF shunts, dental fracture repair devices, intravitreal drug delivery devices, nerve regeneration conduits, electrostimulation leads, spinal/orthopedic repair devices, wound dressings, embolic protection filters, abdominal aortic aneurysm grafts and devices, neuro aneurysm treatment coils, hemodialysis devices, uterine bleeding patches, anastomotic closures, in vitro diagnostics, aneurysm exclusion devices, neuropatches, vena cava filters, urinary dilators, endoscopic surgical and wound drainings, surgical tissue extractors, transition sheaths and dialators, coronary and peripheral guidewires, circulatory support systems, tympanostomy vent tubes, cerebro-spinal fluid shunts, defibrillator leads, percutaneous closure devices, drainage tubes, bronchial tubes, vascular coils, vascular protection devices, vascular intervention devices including vascular filters and distal support devices and emboli filter/entrapment aids, AV access grafts, surgical tampons, drug delivery capsule and cardiac valves.

122. The device according to claim 82, wherein said medical device is selected from the group consisting of atrial septal defect closures, electro-stimulation leads for cardiac rhythm management, tissue and mechanical prosthetic heart valves and rings, arterial-venous shunts, valve annuloplasty devices, mitral valve repair devices, left ventricle assist devices, left atrial appendage filters, cardiac sensors, pacemaker electrodes and leads.

123. The device according to claim 94, wherein said second lipophilic agent is at least one of zotarolimus having the following structures;

124. The device according to claim 89, wherein said lipophilic agent is continuously delivered to the epicardium and/or pericardial sac.

125. A stent, comprising:

a therapeutically effective amount of a first lipophilic agent associated with said stent, wherein said first lipophilic agent is capable of penetrating a body lumen, wherein the transfer coefficient of said first lipophilic agent is by an amount of at least approximately 5,000 (ug/mL)<sup>−

1</sup>; and

wherein said first lipophilic agent/stent is capable of being placed adjacent to a body lumen of a subject and deliver a therapeutically effective amount of said first lipophilic agent to a desired area in a subject.

126. The stent according to claim 125, further comprising at least one pharmaceutically acceptable carrier or excipient, wherein said stent is associated with said pharmaceutically acceptable carrier or excipient.

127. The stent according to claim 126, wherein said pharmaceutically acceptable carrier or excipient is associated with said stent in the form of a coating.

128. The stent according to claim 126, wherein said pharmaceutically acceptable carrier or excipient is a polymer.

129. The stent according to claim 126, wherein said pharmaceutically acceptable carrier or excipient is an agent.

130. The stent according to claim 126, wherein said pharmaceutically acceptable carrier or excipient comprises at least one of the following properties including biodegradable, biocompatible and synthetic.

131. The stent according to claim 125, wherein said body lumen comprises at least one of a vessel wall, a coronary artery, esophageal lumen, and a urethra.

132. The stent according to claim 125, wherein said first lipophilic agent/stent is placed adjacent to said body lumen including coronary arteries, wherein a therapeutically effective amount of said first lipophilic agent is delivered into said coronary arteries and diffused into the pericardial sac in a drug delivery system.

133. The stent according to claim 132, wherein said first lipophilic agent and/or said stent provides substantially uniform dug delivery of said lipophilic agent to the myocardium.

134. The stent according to claim 132, wherein said first lipophilic agent is useful for the treatment and/or prevention of vascular diseases in subject.

135. The stent according to claim 128, wherein said delivery mechanism of said first lipophilic agent includes polymer hydration followed by dissolution of said first lipophilic agent, and wherein said first lipophilic agent is thereafter delivered into said body lumen.

136. The stent according to claim 128, wherein said delivery mechanism of said first lipophilic agent includes a lipophilic agent/polymer matrix which controls the elution rate of said first lipophilic agent to said body lumen.

137. The stent according to claim 125, further comprises at least one second lipophilic agent.

138. The stent according to claim 125, further comprises at least one lipophilic prodrug.

139. The stent according to claim 125, further comprises at least one lipophilic penetration enhancer.

140. The stent according to claim 139, wherein said lipophilic penetration enhancer is a pharmaceutical agent.

141. The stent according to claim 125, wherein the concentration of said first lipophilic agent delivered into said body lumen is a therapeutically effective amount.

142. The stent according to claim 137, wherein the concentration of said second lipophilic agent in combination with said first lipophilic agent is delivered into said body lumen in a therapeutically effective amount.

143. The stent according to claim 125, wherein said first lipophilic agent is zotarolimus.

144. The stent according to claim 125, further comprises at least one beneficial agent.

145. The stent according to claim 125, wherein said first lipophilic agent includes partition coefficients greater than 20,000 P.

146. The stent according to claim 125, wherein said first lipophilic agent includes partition coefficients greater than 20,000 P and said lipophilic agent having solubilities of less than about 30 ug/ml.

147. The stent according to claim 125, wherein said first lipophilic agent includes a LogP at least approximately 4.3.

148. The stent according to claim 125, wherein said stent comprises a first lipophilic agent having solubilities of at least approximately 15 μ

g/mL.

149. The stent according to claim 125, wherein said stent comprises a first lipophilic agent having transfer coefficients of at least approximately 10,000 (μ

g/mL)<sup>−

1</sup>.

150. The stent according to claim 125, wherein said stent comprises a first lipophilic agent having transfer coefficients of at least approximately 15,000 (μ

g/mL)<sup>−

1</sup>.

151. The stent according to claim 125, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 15 μ

g/g to about 150 μ

g/g over a period of up to about 5 days.

152. The stent according to claim 125, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 15 μ

g/g to about 80 μ

g/g over a period from about 5 days to up to about 15 days.

153. The stent according to claim 125, wherein the dosage delivery of said first lipophilic agent into said body lumen ranges from about 5 μ

g/g to about 60 μ

g/g over a period from 15 days up to about 28 days.

154. The stent according to claim 125, wherein said first lipophilic agent reaches therapeutically significant concentrations in targeted areas in said subject comprising at least one of the distal myocardium, the unstent myocardium, in said subjacent myocardium, in unstented and distal coronary arteries, and maintains those concentrations throughout a 28 day period.

155. The stent according to claim 125, wherein said stent is permanently or temporarily implanted into a subjects'"'"' body.

156. The stent according to claim 125, wherein said first lipophilic agent is in amorphous form.

157. The stent according to claim 125, further comprises a beneficial agent including at least one of antithrombotics, anticoagulants, antiplatelets agents, anti-lipid agents, thrombolytics, antiproliferatives, antiinflammatories, agents that inhibit hyperplasia, smooth muscle cell inhibitors, antibiotics, growth factor inhibitors, cell adhesion inhibitors, cell adhesion promoters, antimitotics, antifibrins, antioxidants, antineoplastics, agents that promote endothelial cell recovery, matrix metalloproteinase inhibitors, antineoplastics, antimetabolites, antiallergic substances, viral vectors, nucleic acids, monoclonal antibodies, inhibitors of tyrosine kinase, antisense compounds, oligionucleotides, cell permeation enhancers, and any combinations thereof.

158. The stent according to claim 125, further comprises a beneficial agent including at least one of hypoglycemic agents, hypolipidemic agents, proteins, nucleic acids, agents useful for erythropoiesis stimulation, angiogenesis agents, antiulcer/antireflux agents, and antinauseants/antiemetics, PPAR-alpha agonists, and any combinations thereof.

159. The stent according to claim 125, further comprises a beneficial agent including at least one of sodium heparin, LMW heparins, heparoids, hirudin, argatroban, forskolin, vapriprost, prostacyclin and prostacylin analogues, dextran, D-phe-pro-arg-chloromethylketone (synthetic antithrombin), glycoprotein lib/Iia (platelet membrane receptor antagonist antibody), recombinant hirudin, thrombin inhibitors, indomethacin, phenyl salicylate, β

-estradiol, vinblastine, ABT-627 (astrasentan), testosterone, progesterone, paclitaxel, methotrexate, fotemustine, RPR-101511A, cyclosporin A, vincristine, carvediol, vindesine, dipyridamole, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexyl, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, iotrolan and pro-drugs, analogs, derivatives, and any combinations thereof.

160. The stent according to claim 125, wherein said stent includes a stent selected from the group consisting of peripheral stents, peripheral coronary stents, degradable coronary stents, non-degradable coronary stents, self-expanding stents, balloon-expanded stents, and esophageal stents.

161. The stent according to claim 137, wherein said second lipophilic agent is at least one of zotarolimus having the following structures;

162. The stent according to claim 132, wherein said lipophilic agent is continuously delivered to the epicardium and/or pericardial sac.