Loading and release of water-insoluble drugs

• US 6,306,166 B1
• Filed: 10/14/1998
• Issued: 10/23/2001
• Est. Priority Date: 08/13/1997
• Status: Expired due to Fees

• Current Assignee: Boston Scientific Scimed, Inc. (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Barry, James J., Palasis, Maria
• Primary Examiner(s): KENNEDY, SHARON E
• Application Number:
  US09/172,026
• Time in Patent Office: 1,105 Days
• Field of Search: 604/20, 604/53, 604/96, 604/99, 604/265-266, 604/890.1, 604/892.1, 606/192, 606/194, 623/1.11, 623/1.42, 623/1.43, 623/1.44, 623/1.45, 623/1.46
• US Class Current: 623/1.46
• 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: A61L 2300/222 Steroids, e.g. corticosteroids
• 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 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• 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: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 2025/1075 having a balloon composed of several layers, e.g. by coating or embedding
• CPC Class Codes: A61M 2025/1081 having sheaths or the like for covering the balloon but not forming a permanent part of the balloon, e.g. retractable, dissolvable or tearable sheaths
• CPC Class Codes: A61M 2025/1088 having special surface characteristics depending on material properties or added substances, e.g. for reducing friction
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61M 25/1027 Making of balloon catheters
• CPC Class Codes: A61M 29/02 : Dilators made of swellable material balloon catheters for angioplasty A61M25/104
• CPC Class Codes: C08L 33/08 : Homopolymers or copolymers of acrylic acid esters
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 75/04 : Polyurethanes

Abstract

A medical device, polymer composition, and method for delivering substantially water-insoluble drugs to tissue at desired locations within the body. At least a portion of the exterior surface of the medical device is provided with a polymer coating. Incorporated in the polymer coating is a solution of at least one substantially water-insoluble drug in a volatile organic solvent. The medical device is positioned to a desired target location within the body, whereupon the drug diffuses out of the polymer coating.

Claims

1. A method for preparing a patterned stent having paclitaxel coated thereon comprising the steps of:

providing a polyvinyl aromatic polymer;

providing a patterned stent;

coating at least a portion of the exterior surface of the patterned stent with the polyvinyl aromatic polymer to form a polymer coating; and

applying a drug solution to the polymer, said drug solution comprising paclitaxel dissolved in an organic solvent.

2. The method of claim 1, wherein said organic solvent is selected from the group consisting of ethanol, isopropanol, chloroform, acetone, pentane, hexane, methylene chloride, and mixtures thereof.

3. The method of claim 2, wherein said organic solvent further comprises water.

4. The method of claim 1, wherein said step of applying a drug solution to said polymer includes the step of dipping said polymer into said drug solution.

5. The method of claim 1, wherein said drug solution is applied to said polymer before said polymer is coated onto said patterned stent.

6. The method of claim 1, wherein said drug solution is applied to said polymer after said polymer is coated onto said patterned stent.

7. The method of claim 1, further comprising positioning said patterned stent at a desired location in a body lumen.

8. The method of claim 1, wherein said step of coating comprises applying multiple layers of said polymer to said patterned stent.

9. The method of claim 1, wherein said polyvinyl aromatic polymer is a copolymer.

10. A patterned stent for delivering a substantially water-insoluble drug at a desired location within a body, comprising

a polyvinyl aromatic polymer coating containing paclitaxel provided on at least a portion of said patterned stent.

11. The patterned stent of claim 10, wherein said polymer coating is layered.

12. The patterned stent of claim 10, wherein the at least one water-insoluble drug comprises a combination of paclitaxel and an agent selected from the group consisting of anticoagulants, antimitotics, antithrombogenics, thrombolytics, anti-inflammatory agents, antioxidants, growth factors, modulators of vascular homeostasis, cytocidal agents, and cytostatic agents.

13. The patterned stent of claim 10, wherein the paclitaxel is released from said stent over a time frame effective to inhibit proliferative disease when said stent is positioned at a site of injury to thereby prevent or inhibit undesired cellular proliferation.

14. The patterned stent of claim 13, wherein the time frame is at least about 7 days.

15. The patterned stent of claim 13, wherein the time frame is at least about 28 days.

16. The patterned stent of claim 13, wherein the paclitaxel is released at a rate in the range of from about 0.2 to about 7 μ

g paclitaxel per day.

17. The patterned stent of claim 13, wherein the paclitaxel is released at a rate in the range of from about 0.5 to about 5 μ

g per day.

18. The patterned stent of claim 10, wherein the stent inhibits neointimal proliferation when placed at the site of injury in a blood vessel.

19. The patterned stent of claim 10, wherein said polyvinyl aromatic polymer is a copolymer.

20. A method of preventing or inhibiting proliferative disease at a site of blood vessel injury in a patient comprising implanting a patterned stent comprising an outer coating of polyvinyl aromatic polymer/paclitaxel at the site of injury, wherein the paclitaxel is released from the outer coating at a release rate sufficient to inhibit or prevent cellular proliferation at the site of injury.

21. The method of claim 20, wherein the paclitaxel is released from the outer coating at a release rate of from about 0.2 to about 7 μ

g/day.

22. The method of claim 20, wherein the paclitaxel is released from the outer coating at a release rate and for a period of time sufficient to inhibit or prevent neointima formation at the site of injury.

23. The method of claim 20, wherein the proliferative disease is restenosis.

24. The method of claim 20, wherein the proliferative disease is restenosis.

25. The method of claim 20, wherein said polyvinyl aromatic polymer is a copolymer.

26. A method of preventing or inhibiting proliferative disease in a patient comprising implanting a patterned stent comprising an outer coating of polyvinyl aromatic polymer/paclitaxel at the site of cellular proliferation, wherein the paclitaxel is released from the outer coating at a release rate and for a period of time sufficient to inhibit or prevent cellular proliferation at the site.

27. The method of claim 26, wherein the paclitaxel is released from the outer coating for a period of time from about 7 to about 28 days.

28. The method of claim 26, wherein the paclitaxel is released from the outer coating at a release rate of from about 0.2 to about 7 μ

g/day.

29. The method of claim 26, wherein the paclitaxel is released from the outer coating at a release rate and for a period of time sufficient to inhibit or prevent neointima formation at the site.

30. The method of claim 26, wherein the proliferative disease is restenosis.

31. The method of claim 26, wherein said polyvinyl aromatic polymer is a copolymer.

32. A catheter for delivering substantially water-insoluble drugs to a desired location within a body lumen, said catheter comprising:

a shaft;

an expandable portion mounted on said shaft, said expandable portion including an inflatable balloon and a sheath member extendable over said expandable portion;

a polyvinyl aromatic polymer coating on at least a portion of said expandable portion of said catheter, said polymer coating being impregnated with paclitaxel.

33. The catheter of claim 32 wherein said polymer coating is leyered.

34. The catheter of claim 32 further comprising an agent selected from the group consisting of anticoagulants, antimitotics, antithrombogenics, thrombolytics, anti-inflammatory agents, antioxidants, growth factors, modulators of vascular homeostasis, cytocidal agents and cytostatic agents.

35. The catheter of claim 32 wherein the paclitaxel is released from said catheter over a time frame effective to inhibit proliferative disease when said catheter is positioned at a site of injury to thereby prevent or inhibit undesired cellular proliferation.

36. The catheter of claim 35 wherein the time frame is at least about 7 days.

37. The catheter of claim 35 wherein the time frame is at least about 28 days.

38. The catheter of claim 35 wherein the paclitaxel is released at a rate in the range of from about 0.2 to about 7 μ

g paclitaxel per day.

39. The catheter of claim 35 wherein the paclitaxel is released at a rate in the range of from about 0.5 to about 5 μ

g per day.

40. The catheter of claim 35, wherein the catheter inhibits neointimal proliferation when placed at the site of injury in a blood vessel.

41. The catheter of claim 32, wherein said polyvinyl aromatic polymer is a copolymer.

42. A patterned stent for delivering a substantially water-insoluble drug at a desired location within a body, comprising a polyvinyl aromatic polymer coating containing at least one substantially water-insoluble drug provided on at least a portion of said patterned stent, wherein said substantially water-insoluble drug comprises a combination of paclitaxel and an agent selected from the group consisting of anticoagulants, antimitotics, antithrombogenics, thrombolytics, anti-inflammatory agents, antioxidants, growth factors, modulators of vascular homeostasis, cytocidal agents, and cytostatic agents.

43. The patterned stent of claim 42, wherein said polyvinyl aromatic polymer is a copolymer.