Methods and kits for volumetric distribution of pharmaceutical agents via the vascular adventitia and microcirculation

• US 8,708,995 B2
• Filed: 05/28/2010
• Issued: 04/29/2014
• Est. Priority Date: 01/22/2002
• Status: Active Grant

• Current Assignee: Mercator MedSystems, Inc.
• Original Assignee: Mercator MedSystems, Inc.
• Inventors: Seward, Kirk Patrick, Barr, Lynn Mateel, Wilber, Judith Carol, Cafferata, Robert
• Primary Examiner(s): MENDEZ, MANUEL A
• Application Number:
  US12/790,541
• Publication Number:
  US 20100305546A1
• Time in Patent Office: 1,432 Days
• Field of Search: 604506- 8, 604/510, 604/511, 604/93.01, 604/95.01, 604/116, 604/117, 604/103.02, 604/164.01, 604/528, 604/529, 604/532, 600/424, 600/431, 600433- 5
• US Class Current: 604/508
• 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 2300/422 Anti-atherosclerotic agents
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61M 2005/1588 having means for monitoring, controlling or visual inspection, e.g. for patency check, avoiding extravasation
• CPC Class Codes: A61M 2025/0057 Catheters delivering medicament other than through a conventional lumen, e.g. porous walls or hydrogel coatings
• CPC Class Codes: A61M 2025/0093 wherein at least one needle is a microneedle
• CPC Class Codes: A61M 2025/0096 being laterally outward extensions or tools, e.g. hooks or fibres
• CPC Class Codes: A61M 2025/1086 having a special balloon surface topography, e.g. pores, protuberances, spikes or grooves
• CPC Class Codes: A61M 25/0043 characterised by structural features
• CPC Class Codes: A61M 25/0084 being one or more injection needles
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61M 37/0015 by using microneedles
• CPC Class Codes: A61M 5/158 Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body

Abstract

Methods and kits for delivering pharmaceutical agents to the adventitia and other regions outside the external elastic lamina (EEL) surrounding a blood vessel utilize a catheter having a needle. The needle is positioned in up to 5 mm beyond the EEL and delivers an amount of pharmaceutical agent sufficient to circumferentially permeate around the blood vessel and, in many cases, extend longitudinally and radially along the blood vessel. Confirmation that a delivery aperture of the needle lies beyond the EEL may be required before delivering the pharmaceutical agent.

Claims

1. An improved method for injecting a pharmaceutical agent into the adventitial tissue of a living host using a needle positioned from a lumen of a blood vessel, wherein the improvement comprises penetrating the needle radially outwardly from the blood vessel lumen through a blood vessel wall and an external elastic lamina (EEL) and into adventitial tissue surrounding the lumen, injecting a fluid through the needle, monitoring backpressure to confirm that a delivery aperture of the needle has penetrated through the blood vessel wall and beyond the external elastic lamina of the blood vessel and into the adventitial tissue, and observing the backpressure lower as the delivery aperture of the needle passes through the EEL and into the adventitial tissue, wherein such a lowering of the backpressure confirms entry of the delivery aperture of the needle into the adventitial tissue.

2. A method as in claim 1, wherein the injected fluid comprises a non-active agent and the pharmaceutical agent is delivered only after confirming that the delivery aperture of the needle is in the adventitial tissue.

3. A method as in claim 2, wherein the non-active agent comprises saline.

4. A method as in claim 1, wherein the fluid is the pharmaceutical agent.

5. A method as in claim 4, wherein pharmaceutical agent comprises a small molecule drug, a protein, or a gene.

6. A method as in claim 5, wherein the agent has a maximum dimension of 200 nm or below.

7. A method as in claim 1, wherein the delivery aperture of the needle is positioned at a distance less than 5 mm beyond the EEL.

8. A method as in claim 1, wherein the blood vessel is a coronary blood vessel.

9. A method as in claim 8, wherein the coronary blood vessel is an artery.

10. A method as in claim 9, wherein the artery is at risk of hyperplasia.

11. A method as in claim 9, wherein the artery has regions of vulnerable plaque.

12. A method as in claim 1, wherein the living host is suffering from congestive heart failure or a cardiac arrhythmia.

13. A method as in claim 1, wherein the blood vessel is a cerebral blood vessel and the adventitial tissue is in the brain of the host.

14. A method as in claim 1, wherein the blood vessel is a hepatic blood vessel and the adventitial tissue is in the liver of the host.

15. A method as in claim 1, wherein the pharmaceutical agent is being delivered to treat a neoplastic disease in the adventitial tissue.

16. An improved method for injecting a pharmaceutical agent into the adventitial tissue of a living host using a needle positioned from a lumen of a blood vessel, wherein the method comprises positioning the needle by deploying the needle radially outwardly from the blood vessel lumen into a blood vessel wall, confirming that placement of a delivery aperture of the needle is beyond the external elastic lamina (EEL) of the blood vessel wall and is in the adventitial tissue by injecting a fluid through the needle following needle positioning and monitoring backpressure during injection, wherein placement of the delivery aperture is confirmed to be in adventitial tissue when the backpressure during injection is lower than the backpressure that would exist during injection when the delivery aperture placement is in the blood vessel wall.

17. A method as in claim 16, wherein the injected fluid comprises a non-active agent and the pharmaceutical agent is delivered only after confirming that the delivery aperture of the needle is in the adventitial tissue.

18. A method as in claim 17, wherein the non-active agent comprises saline.

19. A method as in claim 16, wherein the fluid is the pharmaceutical agent.

20. A method as in claim 19, wherein pharmaceutical agent comprises a small molecule drug, a protein, or a gene.

21. A method as in claim 20, wherein the agent has a maximum dimension of 200 nm or below.

22. A method as in claim 16, wherein the delivery aperture of the needle is positioned at a distance less than 5 mm beyond the EEL.