Coatings with tunable molecular architecture for drug-coated balloon

• US 8,951,595 B2
• Filed: 12/11/2009
• Issued: 02/10/2015
• 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: Stankus, John, Trollsas, Mikael, Hossainy, Syed, Pacetti, Stephen, Ngo, Michael
• Primary Examiner(s): Yuan, Dah-Wei D.
• Assistant Examiner(s): BOWMAN, ANDREW J
• Application Number:
  US12/636,079
• Publication Number:
  US 20110143014A1
• Time in Patent Office: 1,887 Days
• Field of Search: 424/425, 424/423, 424/400, 424/78.17, 424/486, 623/1.2, 623/1.17, 623/1.11, 623/1.12, 623/1.16, 623/1.42, 427/2.1, 427/2.3, 427/155, 427/259, 427/264, 427/272, 427/336, 604/161, 514/291
• 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 an outer surface of a balloon of a balloon catheter, the method comprising:

selecting a first therapeutic agent;

selecting a first excipient;

modifying the first excipient, wherein modifying the first excipient comprises modification to two or more properties of the first excipient selected from the group consisting of polymer chain spacing, hydrophilicity, molecular charge, cyclic chain density, aliphatic chain length, functional group density, molecular weight, glass transition temperature, and crystallinity percentage;

selecting a second therapeutic agent;

selecting a second excipient;

modifying the second excipient, wherein modifying the second excipient comprises modification to at least one property of the excipient selected from the group consisting of polymer chain spacing, hydrophilicity, molecular charge, cyclic chain density, aliphatic chain length, functional group density, molecular weight, glass transition temperature, and crystallinity percentage;

blending the first therapeutic agent and the first excipient and the second therapeutic agent and the second excipient to define a coating; and

applying the coating to the outer surface of the balloon, wherein the first therapeutic agent and the first excipient have a weight ratio of about 20;

1 to about 1;

20, and further wherein the coating enables transfer of a therapeutically effective amount of the therapeutic agent to a body lumen within less than one hour.

2. The method of claim 1, further including:

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

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

1 to about 1;

20.

4. The method of claim 1, wherein the first therapeutic agent and the first excipient have a weight ratio of about 2:

1 to about 1;

2.

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

6. The method of claim 1, wherein the first 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 balloon by direct fluid application.

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

10. The method of claim 1, wherein the first excipient is a polymer having a polydispersity index from about 1.05 to about 10.

11. The method of claim 10, further including:

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

12. The method of claim 10, wherein the first therapeutic agent is zotarolimus.

13. The method of claim 10, wherein the first excipient is poly(vinylpyrrolidone).

14. The method of claim 11, wherein the plasticizer is glycerol.

15. The method of claim 1, wherein the coating has a dissolution time of about 10 seconds to about 1 hour.

16. The method of claim 1, further including:

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

17. The method of claim 1, wherein the first therapeutic agent is the same as the second therapeutic agent.

18. The method of claim 15, wherein the first excipient is poly(vinylpyrrolidone).

19. The method of claim 16, wherein the plasticizer is glycerol.

20. The method of claim 15, wherein the therapeutically effective amount is transferred in less than 5 minutes.

21. The method of claim 15, wherein the therapeutically effective amount is transferred in 30 seconds or less.

27. The method of claim 1, wherein modifying the first excipient occurs prior to blending the first therapeutic agent and the first excipient and the second therapeutic agent and the second excipient to define the coating.

28. The method of claim 1, wherein the first excipient is positively charged.

29. The method of claim 1, wherein the first excipient is negatively charged.

30. The method of claim 1, wherein the first excipient includes cyclic and aliphatic carbon chains, and further wherein modifying the first excipient includes adjusting cyclic chain to aliphatic chain ratio.

31. The method of claim 30, wherein the adjusted ratio results in reduced coating elasticity.

32. The method of claim 30, wherein the adjusted ratio results in reduced release rate of the first therapeutic agent from the coating.

33. The method of claim 1, wherein the first excipient is poly(ester amide) polymer.

34. The method of claim 1, wherein modifying the first excipient includes grafting a low molecular weight polyethylene glycol molecule to the first excipient, and further wherein the modified first excipient exhibits increased adhesion to a vessel wall.

35. The method of claim 1, wherein the modified first excipient has increased crystallinity.

36. The method of claim 35, wherein the first excipient is poly(L-lactide-co-caprolactone) polyester, and the crystallinity of the first excipient is modified by adjusting the content of L-lactide.

37. The method of claim 36, wherein the content of L-lactide is increased and the first excipient exhibits greater storage stability.

40. The method of claim 1, wherein the coating has a fast dissolution time after balloon inflation of one minute or less.

41. The method of claim 1, wherein the coating has a soluble dissolution time after balloon inflation of one minute to one hour.

22. A method of tuning the solubility of a coating for a medical device balloon of a balloon catheter, the method comprising:

selecting a first therapeutic agent;

selecting a first excipient;

modifying the first excipient, wherein modifying the first excipient comprises modification to two or more properties of the excipient selected from the group consisting of polymer chain spacing, hydrophilicity, molecular charge, cyclic chain density, aliphatic chain length, functional group density, molecular weight, glass transition temperature, and crystallinity percentage;

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

selecting a second therapeutic agent;

selecting a second excipient;

modifying the second excipient, wherein modifying the second excipient comprises modification to at least one property of the excipient selected from the group consisting of polymer chain spacing, hydrophilicity, molecular charge, cyclic chain density, aliphatic chain length, functional group density, molecular weight, glass transition temperature, and crystallinity percentage;

blending the second therapeutic 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 an outer surface of the balloon, the different dissolution rates defining a tunable solubility.

23. The method of claim 22, wherein the first excipient is a polymer having a molecular weight of less than about 35 kDalton.

24. The method of claim 22, wherein the second excipient is a polymer having a molecular weight greater than about 100 kDalton.

25. The method of claim 22, wherein the first excipient is poly(vinylpyrrolidone) or poly(ethylene glycol).

26. The method of claim 22, wherein the second excipient is poly(vinylpyrrolidone) or poly(ethylene glycol).

38. The method of claim 22, wherein the first excipient is polyvinylpyrrolidone.

39. The method of claim 22, wherein the second excipient is polyethylene glycol.