DRUG-ELUTING MEDICAL DEVICES

• US 20110091515A1
• Filed: 06/11/2009
• Published: 04/21/2011
• Est. Priority Date: 06/12/2008
• Status: Abandoned Application

• Current Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Original Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Inventors: Kloog, Yoel, Zilberman, Meital, Kraitzer, Amir, Elsner, Jonathan
• Application Number:
  US12/997,611
• Publication Number:
  US 20110091515A1
• Time in Patent Office: Days
• US Class Current: 424/409
• CPC Class Codes: A61L 15/26 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 15/425 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 15/64 specially adapted to be resorbable inside the body
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/406 Antibiotics
• 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 2300/62 Encapsulated active agents, e.g. emulsified droplets
• 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 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/022 Metals or alloys
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/146 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 1/02 : Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Composite structures composed of a device as a core structure, being a medical device or article, and a porous polymeric coat and designed capable of encapsulating bioactive agents while retaining the activity of these agents are disclosed. Further disclosed are processes of preparing such composite structures.

Claims

1-25. -25. (canceled)

26. A composite structure comprising a device and at least one polymeric porous coat coating at least a part of said device and encapsulating at least one bioactive agent, said coat being capable of encapsulating said at least one bioactive agent while retaining an activity of said bioactive agent and/or capable of releasing said bioactive agent in a pre-determined release rate, with the proviso that said device is not a fiber and further with the proviso that when said device is comprised of fibrous elements, said coat is not coating said fibrous elements at the contact point of intercrossing junctions of said fibrous elements in said device, such that said fibrous elements are in contact with each other in each of said junctions.

27. The composite structure of claim 26, wherein said device is a medical device.

28. The composite structure of claim 27, wherein said device is a medical device selected from the group consisting of a mesh, a suture mesh, a wound dressing, a stent, a skin patch, a bandage, a suture anchor, a screw, a pin, a tack, a rod, an angioplastic plug, a plate, a clip, a ring, a needle, a tube, a dental implant, an orthopedic implant, a guided tissue matrix, an aortic aneurysm graft device, an atrioventricular shunt, a catheter, a heart valve, a hemodialysis catheter, a bone-fracture healing device, a bone replacement device, a joint replacement device, a tissue regeneration device, a tumor targeting and destruction device, a periodontal device, a hernia repair device, a hemodialysis graft, an indwelling arterial catheter, an indwelling venous catheter, a pacemaker casing, a pacemaker lead, a patent foramen ovale septal closure device, a vascular stent, a tracheal stent, an esophageal stent, a urethral stent, a rectal stent, a stent graft, a synthetic vascular graft, a vascular aneurysm occluder, a vascular clip, a vascular prosthetic filter, a vascular sheath, a drug delivery port and a venous valve.

29. The composite structure of claim 27, wherein said device is biodegradable.

30. The composite structure of claim 26, wherein said device has a mesh structure.

31. The composite structure of claim 27, wherein said device has a mesh structure.

32. The composite structure of claim 30, wherein said mesh structure has a form selected from the group consisting of a sheet, a tube, a sphere, a box and a cylinder.

33. The composite structure of claim 26, wherein said at least one bioactive agent is selected from the group consisting of a hydrophilic agent and a hydrophobic agent.

34. The composite structure of claim 26, wherein said at least one bioactive agent is selected from a group consisting of a macro-biomolecule and a small organic molecule.

35. The composite structure of claim 26, wherein said polymeric coat is characterized by an average pore diameter that ranges from about 1 nm to about 1 mm.

36. The composite structure of claim 35, wherein said average pore diameter ranges from about 1 nm to about 50 μ

m.

37. The composite structure of claim 35, wherein said average pore diameter ranges from about 100 nm to about 200 μ

m.

38. The composite structure of claim 26, wherein said polymeric coat is characterized by a pore density that ranges from about 5% of void volume per coat volume to about 95% of void volume per coat volume.

39. The composite structure of claim 26, wherein a thickness of said polymeric coat ranges from about 0.1 μ

m to about 2000 μ

m.

40. The composite structure of claim 26, wherein said polymeric coat comprises a polymer selected from the group consisting of an aliphatic polyester made of glycolide (glycolic acid), lactide (lactic acid), caprolactone, p-dioxanone, trimethylene carbonate, hydroxybutyrate, and/or hydroxyvalerate;

a polypeptide made of natural and modified amino acids;

a polyether made of at least one natural and modified saccharide;

a polydepsipeptide;

a biodegradable nylon co-polyamide;

a polydihydropyran, a polyphosphazene, a poly(ortho-ester), a poly(cyanoacrylate), a polyanhydride, poly(glycolic acid), poly(lactic acid), polydioxanone (PDS), poly(alkylene succinate), poly(hydroxybutyrate), polybutylene diglycolate), poly(epsilon-caprolactone), and any copolymer thereof.

41. The composite structure of claim 26, being prepared by contacting said device and an emulsion containing an aqueous solution and an organic solution, said organic solution containing at least one second polymer and said emulsion further containing said at least one bioactive agent either within said aqueous solution or within said organic solution, to thereby obtain said device having a layer of said emulsion applied on at least a part thereof, and by freeze-drying said device having said layer applied thereon.

42. The composite structure of claim 26, wherein said device is a stent device and said at least one bioactive agent comprises a bioactive agent selected from the group consisting of paclitaxel, sirolimus, everolimus, zotarolimus and a farnesyl derivative having the general Formula I:

43. The composite structure of claim 42, wherein said farnesyl derivative is farnesylthiosalicylate (FTS) or fluoro-FTS.

44. The composite structure of claim 42, wherein said stent device is a bare stainless steel stent device.

45. The composite structure of claims 42, wherein a concentration of said bioactive agent ranges from about 0.1 weight percent to about 10 weight percent of the total weight of said polymeric porous coat.

46. The composite structure of claim 42, wherein said polymeric porous coat comprises poly(DL-lactic-co-glycolic acid).

47. The composite structure of claim 26, wherein said device is a mesh device and said bioactive agent is an antimicrobial agent, the composite structure being a drug-eluting mesh.

48. The composite structure of claim 47, wherein said antimicrobial agent is selected from the group consisting of gentamicin, ceftazidime and mafenide.

49. The composite structure of claim 47, wherein a concentration of said bioactive agent ranges from about 0.1 weight percent to about 10 weight percent of the total weight of said polymeric porous coat.

50. The composite structure of claim 42, wherein said polymeric porous coat comprises poly(DL-lactic-co-glycolic acid).

51. A drug-eluting stent, comprising a stent device and a polymeric porous coat coating at least a part of said stent device and encapsulating a bioactive agent, said bioactive agent is selected from the group consisting of paclitaxel, sirolimus, everolimus, zotarolimus and a farnesyl derivative having the general Formula I:

52. The drug-eluting stent of claim 51, wherein said farnesyl derivative is farnesylthiosalicylate (FTS) or fluoro-FTS.

53. The drug-eluting stent of claim 51, wherein said stent device is a bare stainless steel stent device.

54. The drug-eluting stent of claim 51, wherein a concentration of said bioactive agent ranges from about 0.1 weight percent to about 10 weight percent of the total weight of said polymeric porous coat.

55. The drug-eluting stent of claim 51, wherein said polymeric porous coat comprises poly(DL-lactic-co-glycolic acid).

56. A drug-eluting mesh, comprising a mesh device and a polymeric porous coat coating at least a part of said mesh device and encapsulating a bioactive agent, said bioactive agent is an antimicrobial agent.

57. The drug-eluting mesh of claim 56, wherein said antimicrobial agent is selected from the group consisting of gentamicin, ceftazidime and mafenide.

58. The drug-eluting mesh of claim 56, wherein a concentration of said bioactive agent ranges from about 0.1 weight percent to about 10 weight percent of the total weight of said polymeric porous coat.

59. The drug-eluting mesh of claim 56, wherein said polymeric porous coat comprises poly(DL-lactic-co-glycolic acid).

60. A process of preparing a composite structure which comprises a device and a porous polymeric coat coating at least a part of said device, wherein the coat comprises at least one bioactive agent encapsulated therein and/or applied thereon, the process comprising:

contacting said device and an emulsion containing an aqueous solution and an organic solution, said organic solution containing at least one second polymer and said emulsion further containing said at least one bioactive agent either within said aqueous solution or within said organic solution, to thereby obtain said device having a layer of said emulsion applied on at least a part thereof; and

freeze-drying said device having said layer applied thereon, thereby obtaining the composite structure;

with the proviso that said device is not a fiber and further with the proviso that when said device is comprised of fibrous elements, said layer of said emulsion is not applied on said fibrous elements at the contact point of intercrossing junctions of said fibrous elements in said device, such that said fibrous elements are in contact with each other in each of said junctions.

61. The process of claim 60, further comprising, prior to said freeze-drying, removing excess of said emulsion, thereby substantially clearing the openings, crevices, grooves and/or crannies in said device.

62. The process of claim 60, wherein said device is medical device.

63. The process of claim 62, wherein said medical device is selected from the group consisting of a mesh, a suture mesh, a wound dressing, a stent, a skin patch, a bandage, a suture anchor, a screw, a pin, a tack, a rod, an angioplastic plug, a plate, a clip, a ring, a needle, a tube, a dental implant, an orthopedic implant, a guided tissue matrix, an aortic aneurysm graft device, an atrioventricular shunt, a catheter, a heart valve, a hemodialysis catheter, a bone-fracture healing device, a bone replacement device, a joint replacement device, a tissue regeneration device, a tumor targeting and destruction device, a periodontal device, a hernia repair device, a hemodialysis graft, an indwelling arterial catheter, an indwelling venous catheter, a pacemaker casing, a pacemaker lead, a patent foramen ovale septal closure device, a vascular stent, a tracheal stent, an esophageal stent, a urethral stent, a rectal stent, a stent graft, a synthetic vascular graft, a vascular aneurysm occluder, a vascular clip, a vascular prosthetic filter, a vascular sheath, a drug delivery port and a venous valve.