Resorbable polymeric device for localized drug delivery

• US 20050177118A1
• Filed: 02/12/2005
• Published: 08/11/2005
• Est. Priority Date: 05/13/1994
• Status: Active Grant

• Current Assignee: Kensey Nash Corporation (DSM-Firmenich AG)
• Original Assignee: Kensey Nash Corporation (DSM-Firmenich AG)
• Inventors: Hoganson, David M., Goldman, Scott M., Bradica, Gino, Brekke, John H.
• Granted Patent: US 8,795,242 B2
• Time in Patent Office: Days
• US Class Current: 604/288.10
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/16 Blood plasma; Blood serum umbilical cord blood A61K35/51
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/15 Depsipeptides; Derivatives thereof
• CPC Class Codes: A61L 2430/20 for reconstruction of the heart, e.g. heart valves
• CPC Class Codes: A61L 27/3641 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/507 for artificial blood vessels apparatus for applying cells on a blood vessel prosthesis A61F2/062
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body

Abstract

An implantable device for facilitating the healing of voids in bone, cartilage and soft tissue is disclosed. A preferred embodiment includes a cartilage region comprising a polyelectrolytic complex joined with a subchondral bone region. The cartilage region, of this embodiment, enhances the environment for chondrocytes to grow articular cartilage; while the subchondral bone region enhances the environment for cells which migrate into that region'"'"'s macrostructure and which differentiate into osteoblasts. Another embodiment is arranged for the local delivery of therapeutic agent. A preferred embodiment is a porous resorbable implant, wherein the therapy delivery may be localized in nature, rather than systemic, such that higher doses at the target site may be allowed than would be tolerable by the body systemically.

Claims

1. An implantable device comprising a structure suitable for the local delivery of at least one therapeutic agent to targeted tissue selected from the group consisting of the heart, veins, arteries and combinations thereof, said device comprising a customizable structure having open pores, and a separate structure which resides within said open pores, wherein said at least one therapeutic agent is released from said device over a finite period of time.

2. The implantable device of claim 1, wherein said at least one therapeutic agent supports the natural function of the heart amidst the delivery of another therapy comprising surgery on the heart, lungs, esophagus, mediastinum, arteries or veins.

3. The device of claim 1 wherein said structure having open pores is covered at least partially by a non-porous membrane.

4. The device of claim 3 wherein said device further comprises a plurality of faces, wherein, upon implantation, a first face is placed adjacent said targeted tissue, and wherein said non-porous membrane is not located on said first face.

5. The device of claim 1 wherein said device is arranged to be retained on said targeted tissue by contraction of the construct.

6. The device of claim 5 wherein said device contracts in contact with a fluid after being placed in contact with said targeted tissue.

7. The device of claim 1 wherein said at least one therapeutic agent is at least one selected from the group consisting of molecular oxygen, taxol, rapamycin, dexamethasone, anti-inflammatory drugs, radiotherapeutic drugs, chemotherapeutic agents, cytotoxic drugs, cytostatic drugs, and combinations thereof.

8. The device of claim 1 wherein said device further comprises a plurality of layers comprising at least a first layer, a second layer, and a third layer, wherein said first layer is arranged to be in contact with said target tissue, and said third layer is arranged on an opposite surface of the device, with said second layer being arranged between said first and third layers.

9. The device of claims 8 wherein said implantable device is arranged to prevent the formation of adhesions between the target tissue and at least one surrounding structure.

10. The device of claim 8 wherein said at least one surrounding structure is selected from the group consisting of a sternum and a chest wall.

11. The device of claim 8 wherein said first layer is releasably attached to at least one of said second and third layers.

12. The device of claim 8 wherein said second layer comprises hylauronic acid.

13. A device for implant in a living being, said device comprising:

a porous construct arranged to deliver at least one therapeutic agent to target tissue; and

a delivery tube comprising a proximal end, a distal end, and an internal lumen extending therebetween, wherein said distal end of said delivery tube is releasably attached to said porous construct, and said proximal end of said delivery tube is arranged to accept an introduction of an additional amount of said at least one therapeutic agent for transport through said internal lumen to said porous construct.

14. The device of claim 13, wherein said proximal end of said delivery tube extends out of the living being and is accessible for adding an additional therapeutic agent.

15. The device of claim 13, wherein said proximal end of said delivery tube is releasably attached to a port arranged subcutaneously in said living being, and available for the subcutaneous addition of an additional therapeutic agent.

16. The device of claim 13 wherein said at least one therapeutic agent reduces inflammation in said targeted tissue.

17. The device of claim 13 wherein said porous construct comprises a first region and a second region, wherein said first region is arranged to contact said target tissue and deliver said at least one therapeutic agent thereto.

18. The device of claim 17, wherein said second region does not contact said target tissue, and prevents the delivery of said at least one therapeutic agent therefrom.

19. The device of claim 13 wherein said delivery tube is releasably attached to said porous construct by a filament.

20. The device of claim 15 wherein said delivery tube is releasably attached to said port by a filament.

21. The device of claim 20, wherein said delivery tube is arranged to be released from said port by severing said filament at said port.

22. The device of claim 19 wherein said delivery tube is arranged to be released from said porous construct by severing said filament at a location outside the living being.

23. The device of claim 13 wherein said delivery tube is arranged to be removed from said porous construct and removed from said living being without displacing said porous construct from said target tissue.

24. The device of claim 13 wherein at least a portion of said porous construct comprises an open porous arrangement, whereby therapeutic agents delivered to said construct will disperse said portion via capillary action.

25. The device of claim 24 wherein said device is arranged to be placed on a non-planar target tissue, and provide even distribution of therapeutic agent through said open porous arrangement.

26. The device of claim 13 wherein said porous construct comprises a plurality of porous regions comprising varying average pore sizes, wherein a region having a larger average pore size is arranged to deliver a greater amount of said at least one therapeutic agent than a region having a smaller average pore size.

27. The device of claim 13 wherein said device is arranged to be retained on said target tissue by contraction of the construct.

28. The device of claim 27, wherein said device contracts in contact with a fluid after being placed in contact with said targeted tissue.

29. The device of claim 13 wherein said at least one therapeutic agent is at least one selected from the group consisting of molecular oxygen, taxol, rapamycin, dexamethasone, anti-inflammatory drugs, radiotherapeutic drugs, chemotherapeutic agents, cytotoxic drugs, cytostatic drugs, and combinations thereof.

30. A method for the prevention of postoperative atrial fibrillation comprising the steps of:

a. providing an implantable device comprising a resorbable porous construct comprising a first structure having open pores, and a second structure within the pores of said first structure, said porous construct being arranged to administer at least one therapeutic agent from the porous construct to a target tissue to limit inflammation in the target tissue; and

b. contacting said porous construct with said target tissue comprising at least one selected from the group of heart, vena cava, pulmonary veins and combinations thereof, whereupon said at least one therapeutic agent is delivered to said target tissue.

31. The method of claim 30 wherein said contacting of said porous construct to said targeted tissue is arranged to cause said porous construct to contract and adhere to said target tissue.

32. The method of claim 30 wherein said at least one therapeutic agent is a steroid to prevent atrial fibrillation.

33. The method of claim 30 wherein said at least one therapeutic agent is at least one selected from the group consisting of molecular oxygen, taxol, rapamycin, dexamethasone, anti-inflammatory drugs, radiotherapeutic drugs, chemotherapeutic agents, cytotoxic drugs, cytostatic drugs, and combinations thereof.

34. The method of claim 30 wherein said at least one therapeutic agent is administered with an additional agent which limits systemic absorption of said at least one therapeutic agent.

35. The method of claim 30 further comprising the steps of:

c. performing an operation;

d. removing said construct

e. contacting a second porous construct against said target tissue, said second porous construct being arranged to deliver a different dosage of said at least one therapeutic agent to target tissue.

36. The method of claim 30 wherein said implantable device further comprises a delivery tube comprising a proximal end, a distal end, and an internal lumen extending therebetween, wherein said distal end of said delivery tube is releasably attached to said porous construct, and said proximal end of said delivery tube is arranged to accept an introduction of an additional amount of said at least one therapeutic agent for transport through said internal lumen to said porous construct.

37. The method of claim 36. wherein the method further comprises the steps of:

c. monitoring said living being for response to said delivery of at least one therapeutic agent;

d. in response to said monitoring step, delivering a different dosage of said at least one therapeutic agent through said delivery tube for delivery to said target tissue through said porous construct; and

e. removing said delivery tube from said living being.

42. The method of claim 36, wherein the method further comprises the steps of:

c. monitoring said living being for response to said delivery of at least one therapeutic agent;

d. in response to said monitoring step, delivering through said delivery tube for delivery to said target tissue through said porous construct one or more therapeutic agents that are different from said at least one therapeutic agent; and

e. removing said delivery tube from said living being.

38. A method for treating cancer within a patient comprising the steps of:

a. providing an implantable device comprising a resorbable porous construct comprising a first structure having open pores, and a second structure within the pores of said first structure, said porous construct being arranged to administer at least one therapeutic agent from said porous construct to a target tissue; and

b. contacting said porous construct with said target tissue whereupon said at least one therapeutic agent is delivered to said target tissue, wherein said at least one therapeutic agent comprises at least one selected from the group consisting of chemotherapeutic drugs, radiotherapeutic drugs, and molecular oxygen.

39. The method of claim 38 wherein said implantable device further comprises a delivery tube comprising a proximal end, a distal end, and an internal lumen extending therebetween, wherein said distal end of said delivery tube is releasably attached to said porous construct, and said proximal end of said delivery tube is arranged to accept an introduction of an additional amount of said at least one therapeutic agent for transport through said internal lumen to said porous construct.

40. The method of claim 39 wherein the method further comprises the steps of:

c. monitoring said living being for response to said delivery of at least one therapeutic agent;

d. in response to said monitoring step, delivering through said delivery tube for delivery to said target tissue through said porous construct a different dosage of said at least one therapeutic agent; and

e. removing said delivery tube from said living being.

41. The method of claim 38 wherein said at least one therapeutic agent is administered with an additional agent which limits systemic absorption of said at least one therapeutic agent.

43. The method of claim 39 wherein the method further comprises the steps of:

c. monitoring said living being for response to said delivery of at least one therapeutic agent;

d. in response to said monitoring step, delivering through said delivery tube for delivery to said target tissue through said porous construct one or more therapeutic agents that are different from said at least one therapeutic agent; and

e. removing said delivery tube from said living being.