DRUG-ELUTING GRAFT

• US 20080319425A1
• Filed: 06/20/2007
• Published: 12/25/2008
• Est. Priority Date: 06/20/2007
• Status: Active Grant

• Current Assignee: Oregon Health & Science University
• Original Assignee: Oregon Health & Science University
• Inventors: Hanson, Stephen R.
• Granted Patent: US 8,721,711 B2
• Time in Patent Office: Days
• US Class Current: 604/891.1
• CPC Class Codes: A61F 2/064 with special features to facilitate anastomotic coupling anastomosis of natural blood vessels A61B17/11
• CPC Class Codes: A61F 2250/0068 the pharmaceutical product being in a reservoir
• CPC Class Codes: A61M 1/3655 Arterio-venous shunts or fistulae

Abstract

Embodiments of the present invention provide a device for the local delivery of a substance into a natural tissue conduit in the mammalian body, having a first element capable of contacting the lumen of the conduit and a second element which overlays first element, a reservoir being formed between the first element and the second element, the interior of the reservoir being capable of fluid communication with the conduit such that a substance placed in the reservoir is delivered into the conduit. In embodiments, the first element may be fully or partially microporous or a separate intermediate microporous membrane may be provided. Also provided are methods of mixing or moving a drug within a reservoir using various mixing elements. Also provided are methods of locally delivering a substance into a natural tissue conduit in the mammalian body utilizing a device in accordance with embodiments of the present invention.

Claims

1. A device for the local delivery of a substance into a natural tissue conduit in a mammalian body, comprising:

a first biocompatible element that is configured to be affixed to the conduit and having a first surface, an opposite second surface, and an intermediate macroporous portion that communicates the second surface with the first surface;

a second microporous element that overlays the second surface of the first element; and

a third element comprised of a substantially non-porous biocompatible material that overlays the second element, a reservoir having an interior being formed between the second element and the third element, the interior of the reservoir being capable of fluid communication with the conduit via the second microporous element and the macroporous portion of the first element such that, when in use, a substance in the reservoir may be delivered into the conduit.

2. The device of claim 1, wherein, when in use, the first surface of the macroporous portion is configured to be placed in fluid communication with the lumen of the conduit.

3. The device of claim 1, wherein the first element is configured as a patch which, when in use, overlies a portion of the conduit.

4. The device of claim 1, wherein the first element further comprises an elongated tubular segment having a substantially non-compliant, hollow body portion which is open at both ends, wherein the first surface is the luminal surface of the tubular segment, and wherein the tubular segment is capable of being affixed to the natural tissue conduit at both of the ends of the tubular segment.

5. The device of claim 1, further comprising a tube in communication at its first end with the reservoir and at its second end with a remote source of the substance.

6. The device of claim 5, further comprising a pump connected to the second end of the tube for delivering the substance to the reservoir and for creating pressure within the reservoir that exceeds by a sufficient amount the intraluminal pressure of the natural tissue conduit, thereby controlling a rate of delivery of the substance.

7. The device of claim 5, further comprising an additional tube in communication at its first end with the reservoir and at its second end with a remote source of an additional substance, wherein the reservoir is divided to prevent mixing of the substances prior to delivery of the substances to the conduit.

8. The device of claim 7, further comprising a pump connected to the second end of the tube for delivering the additional substance to the reservoir and for creating pressure within the reservoir that exceeds by a sufficient amount the intraluminal pressure of the natural tissue conduit, thereby controlling a rate of delivery of the substance.

9. The device of claim 1, wherein the substance is a drug-containing solution.

10. The device of claim 1, wherein the substance is an antiproliferative drug.

11. The device of claim 1, wherein the microporous element has pores sized to restrict movement of the substance through the pores of the microporous element when pressure within the reservoir is above the intraluminal pressure of the natural tissue conduit.

12. The device of claim 1, wherein the microporous element has pores having an average pore size of approximately 10 nm to 1000 nm.

13. The device of claim 1, wherein the macroporous element has pores having an average pore size or internodal distance greater than approximately 10 μ

m.

14. The device of claim 1, further comprising one or more mixing elements disposed within the reservoir.

15. The device of claim 1, wherein the one or more mixing elements are beads.

16. The device of claim 1, wherein the one or more mixing elements comprise a nonstick material or a magnetic material.

17. A device for the local delivery of a substance into a natural tissue conduit in a body, comprising:

a first element comprised of a biocompatible material that is configured to be affixed to the conduit and has a first surface, an opposite second surface, and an intermediate portion having at least a portion thereof that is microporous that communicates the second surface with the first surface, wherein the first surface of the intermediate portion is configured to contact the lumen of the conduit; and

a second element comprised of a substantially non-porous biocompatible material that overlays the second surface of the first element, a reservoir having an interior being formed between the first element and the second element, the interior of the reservoir being capable of fluid communication with the conduit via the microporous portion such that, when in use, a substance in the reservoir is delivered into the conduit.

18. The device of claim 17, wherein the microporous portion has pores having an average pore size of approximately 10 nm to 1000 nm.

19. The device of claim 17, further comprising one or more mixing elements disposed within the reservoir.

20. A device for the local delivery of a substance into a natural tissue conduit in a mammalian body, comprising:

a first element comprised of a biocompatible material that is configured to be affixed to the conduit and has a first surface, an opposite second surface, and an intermediate porous portion that communicates the second surface with the first surface;

a second element comprised of a substantially non-porous biocompatible material that overlays the first element, a reservoir having an interior being formed between the first element and the second element, the interior of the reservoir having one or more mixing elements and being capable of fluid communication with the conduit via the porous portion of the first element such that, when in use, a substance in the reservoir is delivered into the conduit.

21. The device of claim 20, wherein the intermediate porous portion is macroporous.

22. The device of claim 20, further comprising a microporous element that resides between the second surface of the first element and the second element.

23. A method of locally delivering a substance into a natural tissue conduit in a mammalian body, comprising:

forming a device comprising a first element comprised of a biocompatible material that is configured to be affixed to the conduit having a first surface, an opposite second surface, and an intermediate macroporous portion that communicates the second surface with the first surface, wherein the first surface of the macroporous portion is configured to contact the lumen of the conduit, and a second microporous element that overlays the second surface of the first element; and

a third element comprised of a substantially non-porous biocompatible material that overlays the second element, a reservoir having an interior being formed between the third element and the second element, the interior of the reservoir being capable of fluid communication with the conduit via the macroporous portion and the microporous element such that, when in use, a substance placed in the reservoir is delivered into the conduit;

affixing the device to the natural tissue conduit such that the first surface of the macroporous portion contacts the lumen of the conduit and such that the interior of the reservoir is in fluid communication with the conduit via the microporous second element and the macroporous portion of the first element; and

placing a substance in the reservoir.

24. The method of claim 23, wherein said device further comprises a pump coupled to the reservoir, and wherein said pump is set to deliver the substance into the conduit at a low infusion rate.

25. The method of claim 23, further comprising at least partially filling the reservoir with the substance prior to affixing the device to the natural tissue conduit.