Medical device for dispensing medicaments

• US 8,257,305 B2
• Filed: 08/26/2003
• Issued: 09/04/2012
• Est. Priority Date: 09/20/2002
• Status: Active Grant

• Current Assignee: Bayer Intellectual Property GmbH (Bayer AG)
• Original Assignee: Bayer Pharma AG (Bayer AG)
• Inventors: Speck, Ulrich, Scheller, Bruno
• Primary Examiner(s): BOUCHELLE, LAURA A
• Application Number:
  US10/528,577
• Publication Number:
  US 20060020243A1
• Time in Patent Office: 3,297 Days
• Field of Search: 623/1.11, 604/103.02
• US Class Current: 604/103.02
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/412 Tissue-regenerating or healing or proliferative agents
• 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 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 29/08 Materials for coatings
• 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 31/08 Materials for coatings
• 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 2025/1004 Balloons with folds, e.g. folded or multifolded
• CPC Class Codes: A61M 2025/1031 Surface processing of balloon members, e.g. coating or deposition; Mounting additional parts onto the balloon member's surface
• 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 2025/1086 having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves
• CPC Class Codes: A61M 25/0045 multi-layered, e.g. coated coating materials A61L29/08
• 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 25/1002 characterised by balloon shape A61M25/1006, A61M25/1009 take precedence
• CPC Class Codes: A61M 25/1027 Making of balloon catheters
• CPC Class Codes: A61M 25/1038 Wrapping or folding devices for use with balloon catheters
• CPC Class Codes: A61M 25/104 : used for angioplasty
• 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 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system

Abstract

For selective treatment of diseased tissue sections or organ parts, the surface of medical devices entering into contact with areas thereof under pressure is coated with lipophilic substantially water-insoluble medicaments binding to various tissue components with good adherence thereto, said medicaments having an effect thereupon a short time after entering into contact therewith without exerting a harmful influence upon adjacent healthy tissue.

Claims

1. A balloon catheter medical device that releases a drug by immediate release for the selective therapy of specific diseased tissue or an organ part to which said drug will bind, comprising such a drug which is lipophilic, water-insoluble and immediately releasable, adhered to a smooth surface of the balloon of said catheter that comes into contact with the diseased tissue or organ part, which adhered drug when pressed against said tissue or organ part at least for a short time, is immediately released into said tissue or organ part, wherein the concentration of said drug on said surface is up to 5 μ

g/mm².

2. The device according to claim 1, wherein said balloon catheter comprises a stent.

3. The device according to claim 2, wherein a balloon with preformed longitudinal folds is coated with the drug, and the inclination of said folds to refold is not lost after inflation.

4. The device according to claim 2, wherein a balloon is coated with said drug and comprises smooth material to which said drug adheres sufficiently well to resist forces required for folding, essentially without damage.

5. The device according to claim 2, wherein only the area covered by folds is coated with the drug that was dried after application.

6. The device according to claim 1, wherein said balloon catheter does not comprise a stent.

7. The device according to claim 1, wherein the lipophilic drug is an inhibitor of cell proliferation or inflammatory processes, or an antioxidant.

8. The device according to claim 7, wherein the drug used is paclitaxel or other taxane, rapamycin, tacrolimus, a corticoid, a sex hormone, a statin, an epothilone, probucol, a prostacyclin, or an angiogenesis inducer.

9. The device according to claim 7, wherein the lipophilic drug is present as a dry solid or oil on the surface of the device.

10. The device according to claim 9, wherein the dosage form of the drug includes amorphous structures with particle sizes ranging from <

0.1 micron to 5 microns that dissolve quickly due to their large surface area and despite the water-insolubility of the drug.

11. The device according to claim 1, wherein the lipophilic drug is embedded in a readily water-soluble matrix substance to achieve good adhesion to the surface of the device and improve absorption by the tissue.

12. The device according to claim 11, wherein said matrix substance is a low-molecular weight hydrophilic substance with a molecular weight <

5000 D.

13. A medical device of claim 12 wherein said drug is paclitaxel and said device is an angioplasty balloon catheter having a smooth balloon surface.

14. The device according to claim 1, wherein the lipophilic drug is absorbed to particles of or applied to the surface of the device with, a low-molecular weight matrix.

15. The device according to claim 1, having a surface additionally coated with a substance that influences the gliding quality of the device or that prevents blood coagulation.

16. A medical device of claim 1 wherein said drug is paclitaxel and said device is an angioplasty balloon catheter having a smooth balloon surface.

17. A method for producing the device according to claim 1, comprising applying the lipophilic drug in a solution, suspension or emulsion medium using an immersion, spreading, or spraying process or an instrument which delivers a defined volume to the surface of the device to provide a coating and removing excess media and substances that adhere loosely to the surface.

18. The method according to claim 17, wherein the coating process is carried out repeatedly to achieve a reproducible increase of the drug content using the same or a different solution, suspension, or emulsion medium and/or excipient.

19. The method according to claim 18, wherein ethanol, isopropanol, ethyl acetate, diethyl ether, acetone, dimethyl sulfoxide, dimethyl formamide, glycerin, water or a mixture thereof is used as solution, suspension, or emulsion medium.

20. The method according to claim 17, wherein a balloon folded ready for use is used as the drug carrier coated prior to or after sterilization with or without a crimped-on stent.

21. The method according to claim 20, wherein the balloon is coated with the lipophilic drug in unfolded condition and then is folded with a lubricating tool optionally wetted with a biocompatible, gliding agent.

22. The method according to claim 17, wherein a stent is attached prior to or after coating of the balloon.

23. The method according to claim 17, wherein the completely coated device is sterilized using ethylene oxide.

24. A method of treating a vascular disease or circulation disturbance comprising administering a device of claim 1 to affected tissue.

25. A method of opening a passage in the body comprising administering a device of claim 1.

53. The device of claim 1 wherein the lipophilic drug is present as a dry solid on the surface of the device.

54. The device of claim 53 wherein the lipophilic drug is paclitaxel.

55. The device of claim 53 wherein the dried solid also comprises a contrast agent.

56. The device of claim 55 wherein the dried solid comprises paclitaxel and iopromide.

26. A balloon catheter having folds in its balloon, comprising a lipophilic, water-insoluble drug which binds to tissue, said drug being adhered to a smooth balloon surface in a fashion wherein it is immediately released upon coming into contact with said tissue, wherein the balloon area covered with folds is coated with said drug which has been dried after application, and wherein the concentration of said drug on said surface is up to 5 μ

g/mm².

27. The balloon catheter according to claim 26, further comprising a stent, a needle or a guiding wire.

28. The balloon catheter according to claim 26, comprising in its finally folded state a balloon coated with a low-viscosity active agent solution of said drug, by immersing, spraying or applying via a volume measuring device.

29. The balloon catheter according to claim 26, wherein the lipophilic drug is an inhibitor of cell proliferation or an inflammatory process, or an antioxidant.

30. The balloon catheter according to claim 29, wherein the drug is paclitaxel or other taxane, rapamycin, tacrolimus, a corticoid, a sex hormone, a statin, an epothilone, probucol, a prostacyclin or an angiogenesis inducer.

31. The balloon catheter according to claim 29, wherein the lipophilic drug is present as a dry solid or oil on the surface of the balloon.

32. The balloon catheter according to claim 31, wherein the dosage form of the drug comprises amorphous structures with particle sizes ranging from <

0.1 micron to 5 microns that dissolve fast due to their large surface area and despite the water-insolubility of the drug.

33. The balloon catheter according to claim 26, wherein said lipophilic drug is embedded in a readily water-soluble matrix substance to achieve good adhesion to the surface of the balloon and improved absorption by the tissue.

34. The balloon catheter according to claim 33, wherein said matrix substance is a low-molecular weight hydrophilic substance with a molecular weight <

5000 D.

35. A balloon catheter of claim 34 wherein said drug is paclitaxel and said device is an angioplasty balloon catheter having a smooth balloon surface.

36. The balloon catheter according to claim 33, wherein said matrix substance is a contrast agent.

37. The balloon catheter according to claim 36, wherein said substance is an iodinated X-ray contrast agent.

38. The balloon catheter according to claim 37, wherein the drug is paclitaxel and the X-ray contrast agent is iopromide.

39. The balloon catheter according to claim 26, wherein said lipophilic drug is absorbed to a particle or applied to the surface of the device with a low-molecular weight matrix.

40. The balloon catheter according to claim 26, having a surface additionally coated with a substance that influences the glidability of the device or that prevents blood coagulation.

41. A balloon catheter of claim 26 wherein said drug is paclitaxel and said device is an angioplasty balloon catheter having a smooth balloon surface.

42. A method for producing the coated balloon catheter according to claim 26, comprising applying the lipophilic drug in a solution, suspension or emulsion medium using an immersion, spreading, or spraying process or a volume measuring device to the surface of a folded balloon, and removing excess media and substances that adhere loosely to the surface.

43. The method according to claim 42, wherein the coating process is carried out repeatedly to achieve a reproducible increase of the drug content using the same or a different solution, suspension, or emulsion medium and/or excipient.

44. The method according to claim 43, wherein ethanol, isopropanol, ethyl acetate, diethyl ether, acetone, dimethylsulfoxide, dimethylformamide, glycerol, water or a mixture thereof is used as solution, suspension, or emulsion medium.

45. The method according to claim 42, wherein a folded and substantially ready for use balloon is used as the drug carrier coated before or after sterilization with or without a crimped-on stent.

46. The method according to claim 42, wherein a stent is connected to the balloon catheter before or after coating.

47. The method according to claim 42, wherein the finally coated balloon catheter is sterilized using ethylene oxide.

48. A method for the treatment of a vascular disease or a dysfunction of circulation comprising administering a catheter of claim 26.

49. A method for opening a passage in the body comprising administering a catheter of claim 26.

50. A method for tumor treatment comprising administering a catheter of claim 26.

57. The catheter of claim 26 wherein the lipophilic drug is present as a dry solid on the surface of the device.

58. The catheter of claim 57 wherein the lipophilic drug is paclitaxel.

59. The catheter of claim 57 wherein the dried solid also comprises a contrast agent.

60. The catheter of claim 59 wherein the dried solid comprises paclitaxel and iopromide.

51. A balloon catheter medical device that releases a drug by immediate release for the selective therapy of specific diseased tissue or an organ part to which said drug will bind, comprising such a drug which is lipophilic, water-insoluble and immediately releasable, adhered to a surface of the balloon of said catheter that comes into contact with the diseased tissue or organ part, which adhered drug when pressed against said tissue or organ part at least for a short time, is immediately released into said tissue or organ part, wherein the drug is adhered to said surface in a manner resulting in an amount of drug retained on said device of about 10% or less after a time period in which said balloon surface is in contact with said tissue of up to a few minutes, and wherein the concentration of said drug on said surface is up to 5 μ

g/mm².

52. A balloon catheter of claim 51 wherein said drug is paclitaxel and said device is an angioplasty balloon catheter having a smooth balloon surface.