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

• US 9,061,098 B2
• Filed: 03/11/2014
• Issued: 06/23/2015
• Est. Priority Date: 01/22/2002
• Status: Expired due to Term

• 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:
  US14/203,942
• Publication Number:
  US 20140303569A1
• Time in Patent Office: 469 Days
• Field of Search: 604/522, 604/41, 604506-509, 604/96.01, 604/97.01, 604/97.02, 604/98.01, 604/99.01, 604/103.01, 604/103.02, 604/103.07, 604/103.08, 604/104, 604/271, 604/272, 604/913, 600/431, 606/159, 606/170, 606/185, 606/190, 606/191, 606/194, 606/195
• US Class Current: 1/1
• 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. A kit for delivering a pharmaceutical agent to a patient suffering from or at risk of vascular disease, said kit comprising:

a catheter having a needle which can be advanced from a blood vessel lumen through a wall of the blood vessel to position an aperture of the needle beyond an external elastic lamina (EEL) of the wall by a distance not exceeding 5 mm; and

instructions for use setting forth a method comprising;

positioning the needle through the wall so that the aperture of the needle is positioned beyond the EEL by a distance not exceeding 5 mm;

confirming that placement of the aperture is beyond the EEL and is in adventitial tissue surrounding the blood vessel lumen; and

delivering an amount of the pharmaceutical agent from the aperture so that the agent distributes both longitudinally and radially from the injection site.

2. The kit of claim 1, wherein confirming that placement of the aperture is beyond the EEL and is in adventitial tissue comprises injecting a fluid through the needle following needle positioning and monitoring backpressure during injection, wherein placement of the aperture is confirmed to be in the 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.

3. The kit of claim 1, wherein confirming that placement of the aperture is beyond the EEL comprises injecting contrast media through the aperture and observing whether (a) the media spread longitudinally along the outside of the vessel wall indicating that the aperture is in adventitial tissue or (b) the media is constrained within the wall of the blood vessel indicating that the aperture has not reached the adventitial tissue.

4. A kit 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.

5. A kit as in claim 4, wherein the non-active agent comprises saline.

6. A kit as in claim 1, wherein the fluid is in the pharmaceutical agent.

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

8. A kit as in claim 1, wherein the pharmaceutical agent comprises a small molecule drug, a protein, or a gene.

9. A kit as in claim 1, wherein the pharmaceutical agent has a maximum dimension of 200 nm or below.

10. A kit as in claim 1, wherein positioning the needle through the wall comprises penetrating the needle radially outwardly from the blood vessel lumen through the blood vessel wall and the EEL and into the adventitial tissue.

11. A kit as in claim 1, wherein the method further comprises observing the backpressure lower as the aperture of the needle passes through the EEL and into the adventitial tissue, wherein such a lowering of the backpressure confirms entry of the aperture into the adventitial tissue.

12. A kit as in claim 1, further comprising means coupled to the needle for detecting when the aperture of the needle has advanced beyond the EEL.

13. A kit as in claim 12, wherein the means for detecting when the aperture has advanced beyond the EEL comprises one or more of a temperature sensor attached to the needle near the aperture, an electrical impedance sensor attached to the needle near the aperture, a pH sensor attached to the needle near the aperture, or an insertion force sensor coupled to the needle.

14. A kit as in claim 1, wherein the blood vessel is a coronary blood vessel.

15. A kit as in claim 14, wherein the coronary blood vessel is an artery.

16. A kit as in claim 15, wherein the artery is at risk of hyperplasia or has regions of vulnerable plaque.

17. A kit as in claim 1, wherein the patient is suffering from congestive heart failure or a cardiac arrhythmia.

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

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

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