Anchorage devices comprising an active pharmaceutical ingredient

• US 9,585,988 B2
• Filed: 11/10/2011
• Issued: 03/07/2017
• Est. Priority Date: 11/12/2010
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: TYRX, INC. (Medtronic Plc)
• Inventors: McJames, William, Do, Frank, Pulapura, Satish, Ge, Qing
• Primary Examiner(s): Bertram, Eric D.
• Application Number:
  US13/293,816
• Publication Number:
  US 20120185004A1
• Time in Patent Office: 1,944 Days
• Field of Search: 607/3
• US Class Current: 1/1
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 31/08 Materials for coatings
• 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: A61N 1/059 Anchoring means

Abstract

An anchorage device comprising a mesh substrate coupled to an implantable medical device is disclosed, where the mesh substrate has a coating comprising a polymer, and the mesh further comprises at least one active pharmaceutical ingredient. The active pharmaceutical agent is designed to elute from the mesh over time. The mesh substrate can be configured to reduce the mass of the anchorage device such that tissue in-growth and/or scar tissue formation at the treatment site is reduced. In some embodiments, the mesh substrate can be formed with a mesh having a low areal density. In some embodiments, the mesh substrate can include one or more apertures or pores to reduce the mass of the substrate.

Claims

1. An anchorage device comprising a mesh substrate coupled to an implantable medical device, said mesh substrate comprising two sheets that define a pocket, said implantable medical device being positioned in said pocket, said mesh substrate having a coating comprising a polymer and at least one active pharmaceutical ingredient;

wherein said mesh substrate comprises pores ranging in size between about 5 mm to about 10 mm,

wherein said mesh substrate comprises one or more apertures,

wherein said apertures are larger than said pores,

wherein one of said sheets is formed with a non-biodegradable material and one of said sheets is formed with a biodegradable material, and

wherein said sheet that is formed with said non-biodegradable material has no pores.

2. The anchorage device of claim 1, wherein said active pharmaceutical ingredient is selected from the group consisting of anesthetics, antibiotics, anti-inflammatory agents, procoagulant agents, fibrosis-inhibiting agents, anti-scarring agents, leukotriene inhibitors/antagonists, cell growth inhibitors and mixtures thereof.

3. The anchorage device of claim 1, wherein said active pharmaceutical ingredient is an antibiotic.

4. A method of preventing, mitigating, or treating a bacterial infection comprising implanting the anchorage device of claim 3.

5. The method of claim 3, wherein said antibiotic is effective against S. aureus, S. epidermidis, E. coli, MRSA, A. baumanii, E. aerogenes, P. mirabilis, S. capitis, and S. sclefeifreii.

6. The anchorage device of claim 1, wherein said antibiotic is selected from the group consisting of rifampin and minocycline and mixtures thereof.

7. The anchorage device of claim 1, wherein said polymer is selected from the group consisting of polylactic acid, polyglycolic acid, poly(L-lactide), poly(D,L-lactide)polyglycolic acid[polyglycolide], poly(L-lactide-co-D,L-lactide), poly(L-lactide-co-glycolide), poly(D, L-lactide-co-glycolide), poly(glycolide-co-trimethylene carbonate), poly(D,L-lactide-co-caprolactone), poly(glycolide-co-caprolactone), polyethylene oxide, polydioxanone, polypropylene fumarate, poly(ethyl glutamate-co-glutamic acid), poly(tert-butyloxy-carbonylmethyl glutamate), polycaprolactone, polycaprolactone co-butylacrylate, polyhydroxybutyrate, copolymers of polyhydroxybutyrate, poly(phosphazene), poly(phosphate ester), poly(amino acid), polydepsipeptides, maleic anhydride copolymers, polyiminocarbonates, poly[(97.5% dimethyl-trimethylene carbonate)-co-(2.5% trimethylene carbonate)], poly(orthoesters), tyrosine-derived polyarylates, tyrosine-derived polycarbonates, tyrosine-derived polyiminocarbonates, tyrosine-derived polyphosphonates, polyethylene oxide, polyethylene glycol, polyalkylene oxides, hydroxypropylmethylcellulose, polysaccharides such as hyaluronic acid, chitosan and regenerate cellulose.

8. The anchorage device of claim 1, wherein said polymer is a polyarylate.

9. The anchorage device of claim 1, wherein said polymer is a member of the P22-xx family.

10. The anchorage device of claim 9, wherein said polymer comprises 10-30% DT.

11. The anchorage device of claim 1, wherein said active pharmaceutical ingredient is released from said coating over about a 24 hour time period.

12. The anchorage device of claim 1, wherein said polymer is a polyarylate and said active pharmaceutical ingredient is selected from an antibiotic.

13. The anchorage device of claim 12, wherein said polymer is selected from the group consisting of a tyrosine-derived polyarylate and said antibiotic is selected from the group consisting of rifampin, minocycline, or mixtures thereof.

14. The anchorage device of claim 1, wherein said implantable medical device is a cardiovascular implantable electronic device and wherein said active pharmaceutical ingredient is an antibiotic.

15. The anchorage device of claim 14, wherein said antibiotic achieves a level equal or exceeding a minimum inhibitory concentration of said antibiotic for methicillin-resistant Staphylococcus aureus on both sides of said cardiovascular implantable electronic device for at least about 24 hours after implantation of said cardiovascular implantable electronic device.

16. The anchorage device of claim 14, wherein said antibiotic achieves a level equal or exceeding a minimum inhibitory concentration of said antibiotic for methicillin-resistant Staphylococcus aureus on both sides of said cardiovascular implantable electronic device for at least about hours after implantation of said cardiovascular implantable electronic device.

17. The anchorage device of claim 1, wherein said mesh covers only a portion of said implantable medical device.

18. The anchorage device of claim 1, wherein said mesh is formed by knitting.

19. The anchorage device of claim 1, wherein said mesh has a low areal density.

20. The anchorage device of claim 1, wherein an amount of said active pharmaceutical ingredient in said coating ranges from between about 5% to about 30% by total weight of said coating.

21. The anchorage device of claim 1, wherein said coating has a thickness ranging from about 5 μ

m to about 200 μ

m.

22. The anchorage device of claim 1, wherein said one or more apertures are covered or coated with a polymer.

23. The anchorage device of claim 1, wherein said one or more apertures allow for tissue ingrowth.

24. The anchorage device of claim 1, wherein said active pharmaceutical ingredient is a combination of rifampin and minocycline.

25. The anchorage device of claim 1, wherein said anchorage device is entirely resorbable.

26. The anchorage device of claim 1, wherein said mesh substrate is resorbable.

27. The anchorage device of claim 1, wherein said polymer comprises a resorbable material.

28. The anchorage device of claim 27, wherein said resorbable material comprises a resorbable polyarylate.

29. The anchorage device of claim 27, wherein said resorbable material is selected from a group consisting of:

BTE glutarate, DTM glutarate, DT propylamide glutarate, DT glycineamide glutarate, BTE succinate, BTM succinate, BTE succinate PEG, BTM succinate PEG, DTM succinate PEG, DTM succinate, DT N-hydroxysuccinimide succinate, DT glucosamine succinate, DT glucosamine glutarate, DT PEG ester succinate, DT PEG amide succinate, DT PEG ester glutarate, DT PEG ester succinate, DTMB P(Desaminotyrsoyl tyrosine methylparaben ester-glutarate), and DTPP P(Desaminotyrsoyl tyrosine propylparaben ester-glutarate).

30. The anchorage device of claim 27, wherein said resorbable material is a fully resorbable terpolymer of glycolic acid 6-hydroxycaproic acid and 1,3 propanediol.

31. The anchorage device of claim 1, wherein said mesh substrate comprises filaments that define said pores therebetween.

32. The anchorage device of claim 1, wherein a portion of said implantable medical device extends outside of said pocket.

33. The anchorage device of claim 1, wherein said pocket is defined as an area about 1 inch around said implantable medical device in all dimensions.

34. The anchorage device of claim 1, wherein a portion of a side along said perimeter is not sealed such that an opening is defined though which said implantable medical device can be inserted into said pocket.

35. An anchorage device comprising a mesh substrate coupled to an implantable medical device, said mesh substrate comprising two sheets that define a pocket, said implantable medical device being positioned in said pocket, said mesh substrate comprising a plurality of filaments that define pores therebetween, said mesh substrate having a coating comprising a polymer and at least one active pharmaceutical ingredient;

wherein said mesh substrate comprises one or more apertures wherein said apertures are larger than said pores,

wherein one of said sheets is formed with a non-resorbable material and one of said sheets is formed with a resorbable material, and

wherein said sheet that is formed with said non-resorbable material has no pores.

36. The anchorage device of claim 35, wherein a portion of said implantable medical device extends outside of said pocket.

37. The anchorage device of claim 35, wherein said pocket is defined as an area about 1 inch around said implantable medical device in all dimensions.

38. The anchorage device of claim 35, wherein a portion of a side along said perimeter is not sealed such that an opening is defined though which said implantable medical device can be inserted into said pocket.

39. An anchorage device comprising:

a mesh substrate coupled to an implantable medical device, said mesh substrate having a coating comprising a polymer and at least one active pharmaceutical ingredient,

wherein said mesh substrate comprises two sheets that are sealed along a portion of a perimeter of said mesh substrate to define a pocket, said implantable medical device being positioned in said pocket,

wherein said mesh substrate comprises one or more pores and one or more apertures, said apertures being larger than said pores,

wherein one of said sheets is formed with a non-biodegradable material or a non-resorbable material and one of said sheets is formed with a biodegradable material or a resorbable material, and

wherein said sheet that is formed with said non-biodegradable material or said non-resorbable material has no pores.

40. The anchorage device of claim 39, wherein a portion of a side along said perimeter is not sealed such that an opening is defined though which said implantable medical device can be inserted into said pocket.

41. The anchorage device of claim 39, wherein said sheets are ultrasonically sealed along said portion of said perimeter.

42. The anchorage device of claim 39, wherein said apertures are formed in each of said sheets.

43. The anchorage device of claim 39, wherein said apertures are formed in only one of said sheets.

44. The anchorage device of claim 39, wherein said coating covers said apertures.

45. The anchorage device of claim 39, wherein said pocket has a substantially toroidal or donut shape.

46. The anchorage device of claim 39, further comprises a layer of film embedded between said sheets.

47. The anchorage device of claim 39, wherein said polymer is a tyrosine-derived polyarylate.

48. The anchorage device of claim 39, wherein said at least one active pharmaceutical ingredient is a combination of rifampin and minocycline.

49. The anchorage device of claim 39, wherein said coating has a thickness ranging from about 5 μ

m to about 200 μ

m.

50. The anchorage device of claim 39, wherein said coating has a thickness of about 10 μ

m.