Apparatus and methods for preventing or treating failure of hemodialysis vascular access and other vascular grafts

• US 6,726,923 B2
• Filed: 01/16/2002
• Issued: 04/27/2004
• Est. Priority Date: 01/16/2001
• Status: Expired due to Term

• Current Assignee: Vascular Therapies, Inc.
• Original Assignee: Vascular Therapies, LLC
• Inventors: Nikolaychik, Victor V., Iyer, Sriram S., Kipshidze, Nicholas N.
• Primary Examiner(s): Travers, Russell
• Assistant Examiner(s): SHARAREH, SHAHNAM J
• Application Number:
  US10/051,708
• Publication Number:
  US 20030113359A1
• Time in Patent Office: 832 Days
• Field of Search: 424/422, 424/423, 424/426, 424/444, 424/443, 514/56, 514/291
• US Class Current: 424/443
• CPC Class Codes: A61K 31/122 having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/395 having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/204 with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
• CPC Class Codes: A61L 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• 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 27/20 Polysaccharides
• CPC Class Codes: A61L 27/225 Fibrin; Fibrinogen
• CPC Class Codes: A61L 27/44 having a macromolecular matrix
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 1/16 with membranes
• CPC Class Codes: A61M 1/3655 Arterio-venous shunts or fistulae
• CPC Class Codes: A61M 2039/0258 for vascular access, e.g. blood stream access
• CPC Class Codes: A61M 2039/0261 Means for anchoring port to the body, or ports having a special shape or being made of a specific material to allow easy implantation/integration in the body
• CPC Class Codes: A61M 2202/0468 non-physiological
• CPC Class Codes: A61M 2202/0478 : Heparin
• CPC Class Codes: A61M 39/0247 : Semi-permanent or permanent transcutaneous or percutaneous access sites to the inside of the body peritoneal dialysis catheters A61M1/285; tracheostomy devices A61M16/0465; measuring pressure within the body A61B5/03; colostomy devices A61F5/445; gastrotomy feeding tubes A61J15/0015; means for fixing a feeding tube outside of the body A61J15/0053
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• 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 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/08 : Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

This invention is a prosthetic device generally placed on the outside surface of the vessel or graft which then elutes antiproliferative drugs or agents from a drug-eluting matrix material. Methods of perivascular antiproliferative drug administration also are disclosed.

Claims

1. A method of prophylactically treating vasculoproliferative disease in a vascular structure following the construction of an arterio-venous graft, an arterial-arterial graft or an arterio-venous fistula, the method comprising applying locally and external to the vascular structure, perivascularly, a therapeutic agent-eluting sleeve, the sleeve comprising a biocompatible matrix material imbibed with rapamycin thereby enabling delivery of an antiproliferative effective amount of rapamnycin to the vascular structure.

9. A method according to claims 1-8 wherein the graft comprises synthetic or biologic materials.

14. A method according to claims 1-8 and 10-13 wherein the sleeve is substantially circumvascular.

15. A method according to claims 1-8 and 10-13 wherein a combination of rapamycin and heparin is administered to the vascular structure.

16. A method according to claim 15 wherein the amounts of rapamycin and heparin are sufficient to exhibit a synergistic effect in treating vasculoproliferative disease.

17. A method according to claim 15 wherein the amount of rapamycin is about 2 micrograms/cm² to about 10.0 mgs/cm² and the amount of heparin is about 70 units/cm² to about 20,000 units/cm² before contacting the sleeve to the vascular structure.

18. A method according to claims 1-8 and 10-13 wherein a combination of rapamycin analogue(s) and heparin is administered to the vascular structure.

19. A method according to claim 18 wherein the amounts of rapamycin analogues and heparin are sufficient to exhibit a synergistic effect in treating vasculoproliferative disease.

20. A method according to claims 1-8 and 10-13 wherein the biocompatabile matrix is biodegradable.

21. A method according to claims 1-8 and 10-13 wherein the biocompatabile matrix is non-biodegradable.

22. A method according to claims 1-8 and 10-13 wherein the biocompatible biodegradable matrix is collagen.

23. A method according to claim 22 wherein the collagen is Type I Bovine collagen.

24. A method according to claim 22 wherein the collagen is selected from the group consisting of Type I, Type II, Type III, Type IV, Type XI, and mixtures thereof.

25. A method according to claim 22 wherein the collagen is manufactured using recombinant techniques.

26. A method according to claims 1-8 and 10-13 wherein the biocompatabile matrix comprises a combination of biodegradable and non-biodegradable materials.

27. A method according to claims 1-8 and 10-13 wherein the sleeve comprises a rapamycin imbibed inner matrix layer and an external support skeletal layer.

28. A method according to claim 27 wherein the inner matrix layer comprises collagen and the external support skeletal layer comprises polytetrafluoro-ethylene (PTFE).

29. A method according to claims 1-8 and 10-13 wherein the sleeve comprises a rapamycin analogue-imbibed inner matrix layer and an external support skeletal layer.

30. A method according to claim 29 wherein the inner matrix layer comprises collagen, and the external support skeletal layer is polytetrafluroethylene (PTFE).

31. A method according to claims 1-8 and 10-13 wherein the amount of rapamycin is about 2 micrograms/cm² to about 10.0 mgs/cm² before contacting the sleeve to the vascular structure.

32. A method according to claims 1-8 and 10-13 wherein the matrix material is further imbibed with dexamethasone.

33. A method according to claims 1-8 and 10-13 wherein the vascular structure is an artery, vein, graft, or anastamotic site.

34. A method according to claims 1-8 and 10-13 wherein the matrix material is selected from the group consisting of collagen, fibrin, chitosan and mixtures thereof.

35. A method according to claims 1-8 and 10-13 wherein rapamycin is administered to the vascular structure.

36. A method according to claims 1-8 and 10-13 wherein a rapamycin analogue is administered to the vascular structure.

2. A method of prophylactically treating vasculoproliferative disease in a vascular structure following the construction of an arterio-venous graft, an arterial-arterial graft or an arterio-venous fistula, the method comprising applying localy and external to the vascular structure, perivascularly, a therapeutic agent-eluting sleeve, the sleeve comprising a biocompatible matrix material imbibed with analogue(s) of rapamycin thereby enabling delivery of an antiproliferative effective amount of rapamycin analogue(s) to the vascular structure.

3. A method of treating established vasculoproliferative disease in a vascular structure following the construction of an arterio-venous graft, an arterial-arterial graft or an arterio-venous fistula, the method comprising applying locally and external to the vascular structure, perivascularly, a therapeutic agent-eluting sleeve, the sleeve comprising a biocompatible matrix material imbibed with Rapamycin thereby enabling delivery of an antiproliferative effective amount of rapamycin to the vascular structure.

4. A method of treating established vasculoproliferative disease in a vascular structure following the construction of an arterio-venous graft, an arterial-arterial graft or an arterio-venous fistula, the method comprising applying locally and external to the vascular structure, perivascularly, a therapeutic agent-eluting sleeve, the sleeve comprising a biocompatible matrix material imbibed with rapamycin analogue(s) thereby enabling delivery of an antiproliferative effective amount of rapamycin analogue(s) to the vascular structure.

5. A method of prophylactically treating vasculoproliferative disease in vascular structures including at least one anastamotic site wherein the vasculoproliferative disease includes tissue encroaching on the lumen of the vascular structure following the construction of arterio-venous grafts, arterial-arterial grafts or arterio-venous fistulae, the method comprising applying locally and external to the vascular structure, perivascularly, adjacent to the site of anastamosis, a therapeutic agent-eluting sleeve, the sleeve comprising a biocompatible matrix material imbibed with rapamycin thereby enabling delivery of an antiproliferative effective amount of rapamycin to the vascular structure.

6. A method of prophylactically treating vasculoproliferative disease in vascular structures including at least one anastamotic site wherein the vasculoproliferative disease includes tissue encroaching on the lumen of the vascular structure following the construction of arterio-venous grafts, arterial-arterial grafts or arterio-venous fistulae, the method comprising applying locally and external to the vascular structure, perivascularly, adjacent to the site of anastamosis a therapeutic agent-eluting sleeve, the sleeve comprising a biocompatible matrix material imbibed with rapamycin analogue(s) thereby enabling delivery of an antiproliferative effective amount of rapamycin analogue(s) to the vascular structure.

7. A method of treating established vasculoproliferative disease in vascular structures including at least one anastamotic site wherein the vasculoproliferative disease includes tissue encroaching on the lumen of the vascular structure following the construction of arterio-venous grafts, arterial-arterial grafts or aterio-venous fistulae, the method comprising applying locally and external to the vascular structure, perivascularly, adjacent to the site of anastamosis, a therapeutic agent-eluting sleeve, the sleeve comprising a biocompatible matrix material imbibed with rapamycin thereby enabling delivery of an antiproliferative effective amount of rapamycin to the vascular structure.

8. A method of treating established vasculoproliferative disease in vascular structures including at least one anastamotic site wherein the vasculoproliferative disease includes tissue encroaching on the lumen of the vascular structure following the construction of arterio-venous grafts, arterial-arterial grafts or arterio-venous fistulae, the method comprising applying locally and external to the vascular structure, perivascularly, adjacent to the site of anastamosis, a therapeutic agent-eluting sleeve, the sleeve comprising a biocompatible matrix material imbibed with rapamycin analogue(s) thereby enabling delivery of an antiproliferative effective amount of rapamycin analogue(s) to the vascular structure.

10. A method of prophylactically treating vasculoproliferative disease in one or more vascular structures comprising:

providing an implantable antiproliferative agent-eluting perivascular sleeve comprising a biocompatible matrix material imbibed with rapamycin; and

contacting external to the vascular structure perivascularaly and locally with the sleeve wherein an antiproliferative effective amount of rapamiycin is administered to the vascular structure.

11. A method of prophylactically treating vasculoproliferative disease in one or more vascular structures comprising:

providing an implantable antiproliferative agent-eluting perivascular sleeve comprising a biocompatible matrix material imbibed with rapamycin analogue(s); and

contacting external to the vascular structure perivascularaly and locally with the sleeve wherein an antiproliferative effective amount of rapamycin analogue(s) is administered to the vascular structure.

12. A method of treating established vasculoproliferative disease in one or more vascular structures comprising;

providing an implantable antiproliferative agent-eluting perivascular sleeve comprising a biocompatible matrix material imbibed with rapamycin; and

contacting external to the vascular structure pelivascularly and locally with the sleeve wherein an antiproliferative effective amount of rapamycin is admnistered to the vascular structure.

13. A method of treating established vasculoproliferative disease in one or more vascular structures comprising:

providing an implantable antiproliferative agent-eluting perivascular sleeve comprising a biocompatible matrix material imbibed with rapamycin analogue(s); and

contacting external to the vascular structure perivascularly and locally with the sleeve wherein an antiproliferative effective amount of rapamycin analogue(s) is administered to the vascular structure.