Medical device having a hydration inhibitor

• US 7,445,792 B2
• Filed: 03/09/2004
• Issued: 11/04/2008
• Est. Priority Date: 03/10/2003
• Status: Expired due to Fees

• Current Assignee: Abbott Laboratories
• Original Assignee: Abbott Laboratories
• Inventors: Toner, John L., Cromack, Keith R.
• Primary Examiner(s): Kennedy; Sharon E.
• Application Number:
  US10/796,243
• Publication Number:
  US 20040180039A1
• Time in Patent Office: 1,701 Days
• Field of Search: 424/422, 424/93.2, 424/426, 424/423, 623/1.15, 623/1.46
• US Class Current: 424/423
• CPC Class Codes: A61M 31/002 Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50

Abstract

A medical device having a hydration inhibitor for controlled delivery of a beneficial agent and methods of manufacturing of the same. The medical device includes an interventional component loaded with a beneficial agent having a first Log P value, the beneficial agent being associated with a hydration inhibitor to control the elution rate of at least part of the beneficial agent, the hydration inhibitor having a second Log P value which is greater than the first Log P value.

Claims

1. A medical device comprising:

an interventional component to be deployed in a patient;

a beneficial agent to be delivered from the interventional component, the beneficial agent loaded on at least a portion of the interventional component and having a first Log P value; and

an effective amount of a hydration inhibitor associated with the beneficial agent to control delivery of the beneficial agent from the interventional component, the hydration inhibitor having a second Log P value, the second Log P value being greater than the first Log P value, wherein the effective amount of the hydration inhibitor is an amount sufficient to shift the liquid-solid contact angle of the beneficial agent in association with the hydration inhibitor to at least 50 degrees.

2. The device according to claim 1, wherein the beneficial agent is selected from a group consisting of antithrombotics, 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, oligionucleotides, cell permeation enhancers, pro-drugs and combinations thereof.

3. The device according to claim 2, wherein the beneficial agent is selected from the group of indomethacin, phenyl salicylate, B-estradiol, vinblastine, ABT-627, testosterone, progesterone, paclitaxel, cyclosporin A, vincristine, carvedilol, vindesine, dipyridamole, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexol, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, iotrolan and pro-drugs, analogs, derivatives, or combinations thereof.

4. The device according to claim 2, wherein the beneficial agent is a nucleic acid that encodes a pharmaceutically useful peptide or an anti-sense oligo-nucleotide used to control a gene of interest in a cell of the patient.

5. The device according to claim 1, wherein the hydration inhibitor is selected from a group consisting of beneficial agents, polymeric materials, markers, additives, and combinations thereof.

6. The device according to claim 1, wherein the hydration inhibitor is a second beneficial agent.

7. The device according to claim 6, wherein the second beneficial agent is selected from a group consisting of antioxidants, antithrombotics, 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, oligionucleotides, cell permeation enhancers, radiopaque agents markers and combinations thereof.

8. The device according to claim 7, wherein the second beneficial agent is selected from a group consisting of paclitaxel, rapamycin, rapamycin derivatives, pimecrolimus, everolimus, fenofibrate, carvedilol, taxoteres, tacrolimus, butylated hydroxytoluene, butylated hydroxyanisole, vitamin E, danazol, probucol, tocopherols, tocotrienols, ABT-578, ABT-627 and analogs, derivatives, or combinations thereof.

9. The device according to claim 6, wherein the hydration inhibitor is associated with the first beneficial agent as a layer of the second beneficial agent at least partially covering the first beneficial agent.

10. The device according to claim 9, further comprising an outer layer of a third beneficial agent, the third beneficial agent having a third Log P value.

11. The device according to claim 10, wherein the third Log P value is less than the second Log P value.

12. The device according to claim 10, wherein the third beneficial agent is the same as the first beneficial agent.

13. The device according to claim 6, wherein the hydration inhibitor is associated with the first beneficial agent as a mixture of the second beneficial agent with the first beneficial agent.

14. The device according to claim 1, wherein the hydration inhibitor is associated with the beneficial agent as a mixture of the hydration inhibitor and the beneficial agent.

15. The device according to claim 14, wherein the hydration inhibitor is an additive.

16. The device according to claim 15, wherein the additive is selected from a group consisting of nitrophenyl octyl ether, bisethylhexyl sebacate, diisododecylphthalate, N-methylpyrrolidone, linolenic acid, linoleic acid, stearic acid, oleic acid, and combinations thereof.

17. The device according to claim 14, wherein the hydration inhibitor is a polymeric material.

18. The device according to claim 17, wherein the polymeric material 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 terapthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicone polysiloxanes, substituted polysiloxanes, polyethylene oxide, polybutylene terepthalate-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 or combination thereof.

19. The device according to claim 14, wherein the polymeric material has a zwitterionic pendant group.

20. The device according to claim 1, further comprising a layer of polymeric material on at least a portion of a surface of the interventional component, the beneficial agent at least partially loaded onto the layer of polymeric material.

21. The device according to claim 20, wherein the layer of polymeric material has a zwitterionic pendant group.

22. The device according to claim 21, wherein the layer of polymeric material has a phosphoryl choline pendant group.

23. The device according to claim 20, wherein the hydration inhibitor controls delivery of the beneficial agent from the layer of polymeric material.

24. The device according to claim 1, wherein the interventional component is selected from the group consisting of a stent, graft, stent-graft, valve, filter, coil, staple, suture, guidewire, catheter, and catheter balloon.

25. The device according to claim 1, wherein the first Log P value is at least about 0.5 units less than the second Log P value.

26. A method of manufacturing a medical device, the method comprising the steps of:

providing an interventional component to be deployed in a patient;

loading a beneficial agent on the interventional component for delivery therefrom, the beneficial agent having a first Log P value; and

associating an effective amount of a hydration inhibitor with the beneficial agent to control delivery of the beneficial agent from the interventional component, the hydration inhibitor having a second Log P value, the second Log P value being greater than the first Log P value, wherein the effective amount of the hydration inhibitor is an amount sufficient to shift the liquid-solid contact angle of the beneficial agent in association with the hydration inhibitor to at least 50 degrees.

27. The method according to claim 26, wherein the beneficial agent loaded by the loading step is selected from a group consisting of antithrombotics, 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, oligionucleotides, cell permeation enhancers, pro-drugs and combinations thereof.

28. The method according to claim 27, wherein the beneficial agent loaded by the loading step is a nucleic acid, wherein the nucleic acid encodes a pharmaceutically useful peptide or an anti-sense oligo-nucleotide used to control a gene of interest in a cell of the patient.

29. The method according to claim 27, wherein the beneficial agent loaded by the loading step is selected from a group consisting indomethacin, phenyl salicylate, B-estradiol, vinblastine, ABT-627, testosterone, progesterone, paclitaxel, cyclosporin A, vincristine, carvedilol, vindesine, dipyridamole, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexol, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, iotrolan and pro-drugs, analogs, derivatives, or combinations thereof.

30. The method according to claim 26, wherein the hydration inhibitor associated by the associating step is selected from a group consisting of beneficial agents, polymeric materials, markers, additives, and combinations thereof.

31. The method according to claim 26, wherein the hydration inhibitor associated by the associating step is a second beneficial agent.

32. The method according to claim 31, wherein the second beneficial agent is selected from a group consisting of antioxidants, antithrombotics, 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, oligionucleotides, cell permeation enhancers, radiopaque agents markers and combinations thereof.

33. The method according to claim 32, wherein the second beneficial agent is selected from a group consisting of paclitaxel, rapamycin, rapamycin derivatives, pimecrolimus, everolimus, fenofibrate, carvedilol, taxoteres, tacrolimus, butylated hydroxytoluene, butylated hydroxyanisole, vitamin E, danazol, probucol, tocopherols, tocotrienols, ABT-578, ABT-627 and analogs, derivatives, or combinations thereof.

34. The method according to claim 26, wherein the associating step includes applying the second beneficial agent as a layer to at least partially cover the first beneficial agent.

35. The method according to claim 34, further comprising the step of applying a third layer of a third beneficial agent on at least a portion of the interventional component, the third beneficial agent having a third Log P value.

36. The method according to claim 35, wherein the third Log P value is greater than the second Log P value.

37. The method according to claim 35, wherein the third Log P value is the same as the first Log P value.

38. The method according to claim 34, wherein the associating step includes forming a mixture of the second beneficial agent with the first beneficial agent.

39. The method according to claim 26, wherein the associating step includes forming a mixture of the hydration inhibitor and the beneficial agent.

40. The method according to claim 39, wherein the hydration inhibitor associated by the associating step is an additive.

41. The method according to claim 40, wherein the additive is selected from a group consisting of nitrophenyl octyl ether, bisethylhexyl sebacate, diisododecylphthalate, N-methylpyrrolidone, linolenic acid, linoleic acid, stearic acid, oleic acid, and combinations thereof.

42. The method according to claim 39, wherein the hydration inhibitor associated by the association step is a polymeric material.

43. The method according to claim 42, wherein the polymeric material 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 terapthalate, ethylene vinyl acetate, ethylene vinyl alcohol, silicone polysiloxanes, substituted polysiloxanes, polyethylene oxide, polybutylene terepthalate-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 or combination thereof.

44. The method according to claim 42, wherein the polymeric material has a zwitterionic pendant group.

45. The method according to claim 26, further comprising the step of applying a layer of polymeric material on at least a portion of a surface of the interventional component, and further wherein the loading step includes loading the beneficial agent at least partially onto the layer of polymeric material.

46. The method according to claim 45, wherein the layer of polymeric material applied by the applying step has a zwitterionic pendant group.

47. The method according to claim 46, wherein the layer of polymeric material applied by the applying step has a phosphoryl choline pendant group.

48. The method according to claim 45, wherein the hydration inhibitor associated by the associating step controls delivery of the beneficial agent from the layer of polymeric material.

49. The method according to claim 26, wherein the interventional component is selected from the group consisting of a stent, graft, stent-graft, valve, filter, coil, staple, suture, guidewire, catheter, and catheter balloon.

50. The method according to claim 26, wherein the first Log P value of the beneficial agent loaded by the loading step is at least about 0.5 units less than the second Log P value of the hydration inhibitor associated by the associating step.

51. The method according to claim 26, wherein the liquid-solid contact angle of the beneficial agent in association with the hydration inhibitor is at least about 70°

.

52. A medical device comprising:

an interventional component to be deployed in a patient;

a beneficial agent to be delivered from the interventional component, the beneficial agent loaded on at least a portion of the interventional component and having a first Log P value; and

an effective amount of a hydration inhibitor associated with the beneficial agent to enhance the stability of the moisture sensitive beneficial agent to be delivered from the interventional component, the hydration inhibitor having a second Log P value, the second Log P value being greater than the first Log P value, wherein the effective amount of the hydration inhibitor is an amount sufficient to shift the liquid-solid contact angle of the beneficial agent in association with the hydration inhibitor to at least 50 degrees.

53. The device according to claim 52, wherein the beneficial agent is selected from a group consisting of antithrombotics, 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, oligionucleotides, cell permeation enhancers, pro-drugs and combinations thereof.

54. The device according to claim 53, wherein the beneficial agent is selected from the group of indomethacin, phenyl salicylate, β

-estradiol, vinblastine, ABT-627, testosterone, progesterone, paclitaxel, cyclosporin A, vincristine, carvedilol, vindesine, dipyridamole, methotrexate, folic acid, thrombospondin mimetics, estradiol, dexamethasone, metrizamide, iopamidol, iohexol, iopromide, iobitridol, iomeprol, iopentol, ioversol, ioxilan, iodixanol, iotrolan and pro-drugs, analogs, derivatives, or combinations thereof.

55. The device according to claim 53, wherein the beneficial agent is a nucleic acid that encodes a pharmaceutically useful peptide or an anti-sense oligo-nucleotide used to control a gene of interest in a cell of the patient.

56. The device according to claim 52, wherein the hydration inhibitor is selected from a group consisting of beneficial agents, polymeric materials, markers, additives, and combinations thereof.

57. The device according to claim 52, wherein the hydration inhibitor is a second beneficial agent.

58. The device according to claim 57, wherein the second beneficial agent is selected from a group consisting of antioxidants, antithrombotics, 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 agents markers and combinations thereof.

59. The device according to claim 58, wherein the second beneficial agent is selected from a group consisting of paclitaxel, rapamycin, rapamycin derivatives, pimecrolimus, everolimus, fenofibrate, carvedilol, taxoteres, tacrolimus, butylated hydroxytoluene, butylated hydroxyanisole, vitamin E, danazol, probucol, tocopherols, tocotrienols, ABT-578, ABT-627 and analogs, derivatives, or combinations thereof.