Multiple drug delivery from a balloon and a prosthesis

• US 8,057,813 B2
• Filed: 03/18/2005
• Issued: 11/15/2011
• Est. Priority Date: 03/19/2004
• Status: Active Grant

• Current Assignee: Abbott Laboratories Incorporated
• Original Assignee: Abbott Laboratories Incorporated
• Inventors: von Oepen, Randolf, Burke, Sandra E., Toner, John L., Cromack, Keith R.
• Primary Examiner(s): Wax; Robert A
• Assistant Examiner(s): BARHAM, BETHANY P
• Application Number:
  US11/084,172
• Publication Number:
  US 20050246009A1
• Time in Patent Office: 2,433 Days
• Field of Search: 623/1.11, 623/1.42, 427/2.21, 424/422, 606/108
• US Class Current: 424/422
• CPC Class Codes: A61F 2/86 Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
• CPC Class Codes: A61F 2/91 made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
• CPC Class Codes: A61F 2/915 with bands having a meander structure, adjacent bands being connected to each other
• CPC Class Codes: A61F 2/958 Inflatable balloons for placing stents or stent-grafts
• CPC Class Codes: A61F 2002/91525 within the whole structure different bands showing different meander characteristics, e.g. frequency or amplitude
• CPC Class Codes: A61F 2002/91533 characterised by the phase between adjacent bands
• CPC Class Codes: A61F 2002/91575 connected peak to trough
• CPC Class Codes: A61F 2002/91591 Locking connectors, e.g. using male-female connections
• CPC Class Codes: A61F 2250/0067 Means for introducing or releasing pharmaceutical products into the body
• CPC Class Codes: A61F 2310/0097 Coating or prosthesis-covering structure made of pharmaceutical products, e.g. antibiotics
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• 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: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

Disclosed is an interventional device for delivery of therapeutic agents from an angioplasty balloon and from a prosthesis such as an intraluminal stent. The invention also relates to the method of loading the beneficial agents onto the balloon and the device, as well as the method of delivery of the agents from separate surfaces. The invention also relates to an interventional device having a prosthesis surface that is loaded with a first beneficial agent, and a balloon surface loaded with a second beneficial agent. The invention also relates to a method of loading multiple beneficial agents onto the prosthesis surfaces and the balloon surfaces, and to a method of manufacturing an interventional device for the delivery of a first beneficial agent and a second beneficial agent from separate surfaces.

Claims

1. A system for delivering beneficial agents, comprising:

a balloon having an outer surface, at least a portion of the outer surface of the balloon having a continuous coating of a therapeutically effective amount of a first beneficial agent; and

a prosthesis that can be delivered or implanted having a surface that is at least partially coated with a therapeutically effective amount of a second beneficial agent,

wherein the first beneficial agent is different from the second beneficial agent with respect to hydrophobicity and at least the coating of the first beneficial agent has a varied local areal density as a measure of beneficial agent per unit local surface area, and wherein the system is useful for the treatment and prevention of a vascular disease.

2. A system according to claim 1, wherein the balloon is an angioplasty balloon.

3. A system according to claim 1, wherein the prosthesis is a stent.

4. A system according to claim 3, wherein the stent is crimped onto the balloon.

5. A system according to claim 1, wherein the prosthesis is at least partially retained on the balloon by the coating on the balloon.

6. A system according to claim 3, wherein the stent is a self-expanding stent.

7. A system according to claim 1, wherein the coating on the balloon further comprises a carrier for the first beneficial agent.

8. A system according to claim 7, wherein the carrier is selected from the group consisting of complex sugars (mannitol), starches (cellulose), collagens, and polymeric materials.

9. A system according to claim 1, wherein the coating on the prosthesis further comprises a carrier for the second beneficial agent.

10. A system according to claim 9, wherein the carrier for the second beneficial agent is selected from a group consisting of phosphorylcholine, polycaprolactone, poly-D,L-lactic acid, poly-L-lactic acid, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolic acid-cotrimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates, fibrin, fibrinogen, cellulose, starch, collagen, Parylene®

, Parylast®

, polyurethane, polycarbonate urethanes, polyethylene, polyethylene terephthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicone polysiloxanes, substituted polysiloxanes, polyethylene oxide, polybutylene terephthalate-co-PEG, PCL-co-PEG, PLA-co-PEG, polyacrylates, polyvinyl pyrrolidone, polyacrylamide, thermoplastic elastomers, polyolefin elastomers, EPDM rubbers, polyamide elastomers, biostable plastic, acrylic polymers, nylon, polyesters, epoxies and derivatives, and combinations thereof.

11. A system according to claim 1 wherein the second beneficial agent is not coated on the balloon.

12. A system according to claim 1, wherein a surface of the prosthesis is loaded with therapeutically effective amounts of more than one beneficial agent.

13. A system according to claim 1, wherein the first beneficial agent and the second beneficial agent are individually selected from the group consisting of antitlirombotics, anticoagulants, antiplatelet agents, anti-lipid agents, thrombolytics, antiproliferatives, anti-inflammatories, 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, antiallergic substances, viral vectors, nucleic acids, monoclonal antibodies, antisense compounds, oligonucleotides, cell permeation enhancers, radiopaque agent markers, HMG CoA reductase inhibitors, pro-drugs and combinations thereof.

14. A system according to claim 13, wherein the HMG CoA reductase inhibitors are selected from the group consisting of atorvastatin, simvastatin, pravastatin, lovastatin, cerivastatin, and fluvastatin.

15. A system according to claim 1, wherein the first and second beneficial agents are individually selected from the group consisting of indomethacin, phenyl salicylate, vinblastine, ABT-627 (atrasentan), ABT-578, testosterone, progesterone, paclitaxel, taxanes, cyclosporin A, vincristine, carvedilol, vindesine, dipyridamole, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexol, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, iotrolan, rapamycin, rapamycin derivatives, pimecrolimus, everolimus, fenofibrate, carvedilol, taxoteres, tacrolimus, peroxisomal proliferator activated receptor y (PPAR-γ

) agonists, paricalcitol, butylated hydroxytoluene, butylated hydroxyanisole, vitamin E, danazol, probucol, tocopherols, tocotrienols and pro-drugs, analogs, derivatives, and combinations thereof.

16. A system according to claim 15, wherein the PPAR-γ

agonist is a thiazolidinedione.

17. A system according to claim 1, wherein the first and second beneficial agents are a nucleic acid that encodes a pharmaceutically useful peptide or an anti-sense oligonucleotide used to control a gene of interest in a cell of a patient.

18. A system according to claim 1, further comprising additional prostheses.

19. A system according claim 1, wherein the coating on the balloon forms a pattern, wherein the pattern is not based solely on folds, indentations, or depressions formed into the surface of the balloon.

20. A system according to claim 1, wherein the coating on the balloon extends beyond said prosthesis.

21. A system according to claim 3, wherein the coated balloon is adapted to be delivered after the stent is implanted to accomplish final sizing of the stent.

22. A system according to claim 1, wherein the first beneficial agent can be transferred from the coating on the balloon into the coating on the prosthesis.

23. A system according to claim 1, wherein the coating on the prosthesis comprises a barrier that prevents transfer of the first beneficial agent from the coating on the balloon into the coating on the prosthesis or of the second beneficial agent from the coating on the prosthesis into the coating on the balloon.

24. A system according to claim 23, wherein the barrier is polymeric.

25. A system according to claim 24, wherein the polymeric component is selected from a group consisting of phosphorylcholine, polycaprolactone, poly-D, L-Lactic acid, poly-L-Lactic acid, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates, fibrin, fibrinogen, cellulose, starch, collagen, Parylene®

, Parylast®

, polyurethane, polycarbonate urethanes, polyethylene, polyethylene terephthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicone polysiloxanes, substituted polysiloxanes, polyethylene oxide, polybutylene terephthalate co-PEG, PCL-co-PEG, PLA-co-PEG, polyacrylates, polyvinyl pyrrolidone, polyacrylamide, thermoplastic elastomers, polyolefin elastomers, EPDM rubbers, polyamide elastomers, biostable plastic, acrylic polymers, nylon, polyesters, epoxies and derivatives, and combinations thereof.

26. A system according to claim 22, wherein the first beneficial agent is adapted to be delivered from the coating on the prosthesis into a target site.

27. A system according to claim 1, wherein the coating on the balloon contains multiple beneficial agents.

28. A system according to claim 1, wherein the coating on the prosthesis contains multiple beneficial agents.

29. A system according to claim 1, wherein the second beneficial agent is more hydrophobic than the first beneficial agent.

30. A system of claim 1, wherein the outer surface of the balloon is coated with a pattern of droplets of the first beneficial agent.

40. A system according to claim 1, wherein the varied local areal density includes a varied coating thickness.

41. A system according to claim 1, wherein the varied local areal density includes a coating pattern.

42. A system according to claim 1, wherein the varied local areal density includes a uniform coating having a varied loading of beneficial agent.

31. A system for delivering beneficial agents, comprising:

a balloon having an outer surface, at least a portion of the outer surface of the balloon having a continuous coating of a therapeutically effective amount of a first beneficial agent, the continuous coating comprising a first carrier adapted to release the first beneficial agent at a first release rate; and

a prosthesis capable of being implanted, the prosthesis including a coating containing a second carrier adapted to release a therapeutically effective amount of a second beneficial agent at a second release rate different from the first release rate,

wherein at least the first beneficial agent has a varied local areal density as a measure of beneficial agent per unit local surface area.

32. A system of claim 31, wherein the prosthesis is a stent capable of expanding or being expanded, and the stent is mounted on the balloon.

33. A system of claim 31, wherein the first carrier and the second carrier have different diffusivity.

34. A system of claim 31, wherein the first and second carriers have different affinity.

35. A system of claim 31, wherein the coating on the balloon includes a pattern of droplets of the first carrier.

36. A system for delivering beneficial agents, comprising:

a balloon including a plurality of balloon areas covered by a continuous first coating of a therapeutically effective amount of a first beneficial agent, the plurality of balloon areas having local areal densities of the first continuous coating that are different from each other; and

a prosthesis capable of being implanted, the prosthesis including a plurality of prosthesis areas covered by a second coating containing a therapeutically effective amount of a second beneficial agent, the plurality of prosthesis areas having local areal densities of the second coating that are different from each other, wherein areal density is amount of beneficial agent per unit local surface area.

37. A system of claim 36, wherein the prosthesis is a stent capable of expanding or being expanded, and the stent is mounted on the balloon.

38. A system of claim 36, wherein a distal end and a proximal end of the balloon each have a local areal density of the first coating that is less than a local area density of a medial area of the balloon located between the distal end and the proximal end.

39. A system of claim 36, wherein the balloon is covered by a pattern of droplets of the first coating.