Drug eluting graft constructs and methods

Patent metadata

Field	Value
Publication number	US-11065368-B2
Application number	US-201414210903-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

Abstract

The present invention provides, in certain aspects, medical graft products that incorporate multiple drug depots in and/or on the products. One such product is a sheet graft construct, for example for tissue support that includes a sheet graft material with a plurality of drug depots. The drug depots can be hardened deposits formed directly onto the sheet graft material and/or can be capable of eluting a drug for a minimum of 72 hours.

First claim

What is claimed is:

1. An implantable device, comprising:
a sheet graft material having a top side and a bottom side;
a plurality of drug depots attached to the sheet graft material;
wherein the sheet graft material has a porous matrix formed by a network of fibers, the porous matrix having pores formed between the fibers of the network;
wherein the drug depots each comprise solid deposits including a polymeric carrier and at least one drug, the solid deposits each including a first portion infiltrating pores of the porous matrix and a second portion external of the porous matrix;
wherein the sheet graft material has a thickness extending between the top surface and the bottom surface;
wherein the first portions of the drug depots extend only partially through the thickness of the sheet graft material;
wherein each said drug depot covers a corresponding depot-bearing portion of the sheet graft material;
wherein each said depot-bearing portion of the sheet graft material is thinner than depot-free portions of the sheet graft material occurring between the depot-bearing portions;
wherein each said depot-bearing portion of the sheet graft material is denser than the depot-free portions of the sheet graft material occurring between the depot-bearing portions;
wherein the drug depots include 5 or more drug depots each having a top surface with a surface area of about 50 mm 2 to about 500 mm 2 ;
wherein the first portions of the drug depots and the fibers form a hybrid matrix region including fibers entrained within the matrix of the first portions of the drug depots.

2. The implantable device of claim 1 , wherein the sheet graft material comprises an extracellular matrix sheet material.

3. The implantable device of claim 1 , wherein the drug is an antibiotic agent.

4. The implantable device of claim 1 , wherein the drug is gentamycin.

5. The implantable device of claim 1 , wherein the depots are capable of eluting the drug over a period of time greater than about 72 hours when the device is immersed in 66.7 mM phosphate buffered saline at 37° C.

6. The implantable device of claim 1 , wherein the depots are attached to the top side of the sheet graft material, and wherein the depots in combination cover less than about 50% of the surface area of the top side of the sheet material.

7. The implantable device of claim 1 , having from 5 to about 80 of said drug depots attached to the sheet graft.

8. The implantable device of claim 1 , wherein:
each depot-bearing portion has a surface area constituting about 0.5% to about 15% of the surface area of the top surface of the sheet graft material.

9. The implantable device of claim 1 , wherein:
the 5 or more drug depots each having a top surface with a surface area of about 50 mm 2 to about 500 mm 2 are in the form of wafers having a circular, ovoid, or polygonal shape.

10. The implantable device of claim 1 , wherein:
each said depot-bearing portion of the sheet graft material is selectively compressed and thereby less porous and denser than depot-free portions of the sheet graft material occurring between the depot-bearing portions.

11. The implantable device of claim 1 , wherein:
the drug depots are formed by a process including:
depositing a flowable material including a carrier polymer and the at least one drug onto the top side of the sheet graft material so as to form a plurality of deposited material portions; and
hardening the deposited material portions.

12. The implantable device of claim 1 , wherein:
the sheet graft material comprises one or more membranous tissue layers harvested from a source tissue of a warm-blooded vertebrate animal and decellularized, and wherein the network of fibers comprises a network of collagen fibers that retains an inherent network structure from the source tissue.

13. The implantable device of claim 12 , wherein the one or more membranous tissue layers is effective when implanted in a subject to become infiltrated with cells of the subject.

14. The implantable device of claim 12 , wherein the one or more membranous tissue layers is effective when implanted in a subject to become replaced by tissue of the subject.

15. An implantable device, comprising:
a graft material having a porous matrix formed by a network of fibers, the porous matrix having pores formed between the fibers of the network;
a plurality of drug depots including a polymeric carrier and a drug, the drug depots including a first portion infiltrating pores of the porous matrix and a second portion external of the porous matrix, wherein the first portion extends only partially through a thickness of the porous matrix, and wherein the first portion and fibers of the network of fibers form a hybrid matrix region including fibers entrained within material of the first portion;
wherein the drug depots include 5 or more drug depots each having a top surface with a surface area of at least 50 mm 2 ; and
wherein the depots are capable of eluting the drug over a period of time greater than about 72 hours when the device is immersed in 66.7 mM phosphate buffered saline at 37° C.

16. The implantable device of claim 15 , wherein the graft material comprises an extracellular matrix material.

17. The implantable device of claim 15 , wherein the drug is an antibiotic agent.

18. The implantable device of any one of claim 17 , wherein the drug is gentamycin.

19. The implantable device of claim 15 , wherein from 5 to about 80 of said drug depots incorporate at least 80% of a total dose of the drug on the device.

20. An implantable device, comprising:
a sheet graft material having a top side and a bottom side;
a plurality of drug depots attached to the sheet graft material, the drug depots including a polymeric carrier and a drug; and
wherein from 5 to 80 of said drug depots incorporate at least 80% of a total dose of the drug on the device;
wherein 5 or more of the drug depots each have a top surface with a surface area of at least 50 mm 2 ;
wherein, the sheet graft material has a porous matrix formed by a network of fibers, the porous matrix having pores formed between the fibers of the network;
the drug depots comprise solid deposits including a first portion infiltrating pores of the porous matrix and a second portion external of the porous matrix;
wherein the first portions of the drug depots and the fibers form a hybrid matrix region including fibers entrained within the matrix of the first portions of the drug depots.

21. The implantable device of claim 20 , wherein:
the first portions of the drug depots extend only partially through the thickness of the sheet graft material.

22. The implantable device at claim 20 , wherein the drug is gentamycin.

Assignees

• Cook Medical Technologies Llc
• Cook Biotech Inc

Inventors

• Peck Rhonda
• Shah Bhavin
• Patel Umesh H
• Gearhart Krista
• Charlebois Steven
• Milner Keith
• Rodenberg Eric J

Classifications

• A61L27/3633

  Extracellular matrix [ECM] · CPC title

• A61L31/005

  Ingredients of undetermined constitution or reaction products thereof · CPC title

• A61L2300/406

  Antibiotics · CPC title

• A61L31/146 Primary

  Porous materials, e.g. foams or sponges · CPC title

• A61L2300/414

  Growth factors · CPC title