COATINGS WITH TUNABLE MOLECULAR ARCHITECTURE FOR DRUG-COATED BALLOON

• US 20110143014A1
• Filed: 12/11/2009
• Published: 06/16/2011
• Est. Priority Date: 12/11/2009
• Status: Active Grant

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories Incorporated)
• Inventors: Ngo, Michael, Pacetti, Stephen, Hossainy, Syed, Stankus, John, Trollsas, Mikael
• Granted Patent: US 8,951,595 B2
• Time in Patent Office: Days
• US Class Current: 427/2.14
• CPC Class Codes: A61F 2/958 Inflatable balloons for placing stents or stent-grafts
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61L 2300/204 with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
• 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 2300/606 Coatings
• CPC Class Codes: A61L 2420/02 Methods for coating medical devices
• CPC Class Codes: A61L 2420/06 Coatings containing a mixture of two or more compounds
• 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: 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 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 25/1029 Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril

Abstract

A drug delivery balloon is provided, the a balloon having an outer surface, and a tunable coating disposed on at least a length of the balloon surface. The tunable coating includes a first therapeutic agent and a first excipient, and can include a second therapeutic agent and a second excipient. The first and second therapeutic agents have different dissolution rates during balloon inflation and therefore provide a coating that is tunable.

Claims

1. A method of coating a medical device having an outer surface, the method comprising:

selecting a cytostatic therapeutic agent;

selecting at least one excipient;

blending the cytostatic agent and excipient to define a coating; and

applying the coating to the outer surface of the medical device, wherein the cytostatic therapeutic agent and the at least one excipient have a weight ratio of about 20;

1 to about 1;

20, and further wherein the coating provides increased efficiency of therapeutic transfer to a body lumen.

2. The method of claim 1, further including:

blending a plasticizer with the cytostatic therapeutic agent and the excipient.

3. The method of claim 2, wherein the excipient to plasticizer weight ratio is from about 20:

1 to about 1;

20.

4. The method of claim 1, wherein the cytostatic therapeutic agent and the at least one excipient has a weight ratio of about 2:

1 to about 1;

2.

5. The method of claim 1, wherein the cytostatic therapeutic agent is zotarolimus.

6. The method of claim 1, wherein the excipient is poly(vinylpyrrolidone).

7. The method of claim 2, wherein the plasticizer is glycerol.

8. The method of claim 1, wherein the coating is applied to the outer surface of the medical device by direct fluid application.

9. The method of claim 1, further including applying heat to the coated medical device to dry the coating.

10. The method of claim 1, wherein the medical device is a balloon catheter.

11. A method of coating a medical device having an outer surface, the method comprising:

selecting a cytostatic therapeutic agent;

selecting at least one polymeric excipient;

blending the cytostatic therapeutic agent and at least one polymeric excipient to define a coating; and

applying the coating to at least one length of the outer surface of the medical device, wherein the at least one polymeric excipient has a polydispersity index from about 1.05 to about 10 and provides increased efficiency of therapeutic transfer to a body lumen.

12. The method of claim 11, further including:

blending a plasticizer with the cytostatic therapeutic agent and excipient.

13. The method of claim 11, wherein cytostatic therapeutic agent is zotarolimus.

14. The method of claim 11, wherein the excipient is poly(vinylpyrrolidone).

15. The method of claim 12, wherein the plasticizer is glycerol.

16. The method of claim 11, wherein the medical device is a balloon catheter.

17. A method of coating a medical device having an outer surface, the method comprising:

selecting a cytostatic therapeutic agent;

selecting at least one excipient;

blending the cytostatic therapeutic agent and at least one excipient to define a coating;

applying the coating to at least one length of the outer surface of the medical device; and

inserting or implanting the coated medical device in a body lumen, wherein the coating has a dissolution rate of about 10 seconds to about 1 hour and provides an increased efficiency of therapeutic transfer to a body lumen.

18. The method of claim 17, further including:

blending a plasticizer with the cytostatic therapeutic agent and excipient.

19. The method of claim 17, wherein cytostatic therapeutic agent is zotarolimus.

20. The method of claim 17, wherein the excipient is poly(vinylpyrrolidone).

21. The method of claim 18, wherein the plasticizer is glycerol.

22. The method of claim 17, wherein the therapeutic transfer to the body lumen occurs in less than 5 minutes.

23. The method of claim 17, wherein the therapeutic transfer to the body lumen occurs in 30 seconds or less.

24. The method of claim 17, wherein the medical device is a balloon catheter

25. A method of tuning the solubility of a coating for a medical device, the method comprising:

selecting a first cytostatic therapeutic agent;

selecting a first excipient;

blending the first cytostatic agent and the first excipient to define a first coating, the first coating having a first dissolution rate;

selecting a second cytostatic therapeutic agent;

selecting a second excipient;

blending the second cytostatic agent and second excipient to define a second coating, the second coating having a second dissolution rate;

wherein the first and second dissolution rates are different; and

applying the first and second coatings to at least one length of the outer surface of the medical device, the different dissolution rates defining a tunable solubility.

26. The method of claim 25, wherein the first excipient is a polymer having a molecular weight of less than about 35 kDalton.

27. The method of claim 25, wherein the second excipient is a polymer having a molecular weight greater than about 100 kDalton.

28. The method of claim 25, wherein the first excipient is poly(vinylpyrrolidone) or poly(ethylene glycol).

29. The method of claim 25, wherein the second excipient is poly(vinylpyrrolidone) or poly(ethylene glycol).

30. The method of claim 25, wherein the medical device is a balloon catheter

31. A method of coating a medical device, the method comprising:

selecting a therapeutic agent;

selecting at least one excipient;

modifying the excipient;

blending the therapeutic agent and the charged excipient to define a coating; and

applying the modified excipient to an expandable member, wherein the coating provides desired delivery kinetics.

32. The method of claim 31, further including charging the excipient with a positive charge.

33. The method of claim 31, further including charging the excipient with a negative charge.

34. The method of claim 31, wherein the excipient includes cyclic and aliphatic carbon chains, and further wherein the excipient is modified by adjusting cyclic chain to aliphatic chain ratio.

35. The method of claim 34, wherein the adjusted ratio results in reduced elasticity.

36. The method of claim 34, wherein the modified excipient includes a therapeutic agent and further wherein the adjusted ratio results in reduced release rate of the therapeutic agent.

37. The method of claim 31, wherein the excipient is poly(ester amide) polymer.

38. The method of claim 31, wherein the excipient is modified by grafting a low molecular weight polyethylene glycol molecule to the excipient, and further wherein modified excipient exhibits increased adhesion to a vessel wall.

39. The method of claim 31, wherein the modified excipient has increased crystallinity.

40. The method of claim 39, wherein the excipient is poly(L-lactide-co-caprolactone) polyester, and the crystallinity of the excipient is modified by adjusting the content of L-lactide.

41. The method of claim 40, wherein the content of L-lactide is increased and the excipient exhibits greater storage stability.

42. The method of claim 31, wherein the coating is applied to a balloon.