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

• US 7,744,584 B2
• Filed: 10/21/2003
• Issued: 06/29/2010
• 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, Cafferata, Robert, Wilber, Judith Carol
• Primary Examiner(s): Sirmons; Kevin C
• Assistant Examiner(s): WITCZAK, CATHERINE
• Application Number:
  US10/691,119
• Publication Number:
  US 20040138643A1
• Time in Patent Office: 2,443 Days
• Field of Search: 604/507, 604/508, 604506- 8, 604/264, 604/528, 604/511, 604/93.01, 604/95.01, 604/116, 604/117, 604/103.02, 604/164.01, 604/529, 604/532, 604/510, 600/424, 600/431, 600433- 5
• US Class Current: 604/510
• 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 method for injecting a pharmaceutical agent into the tissue of a living host, the method comprising:

positioning a catheter longitudinally within a lumen of a blood vessel;

advancing a needle radially outwardly from the catheter through the blood vessel wall and past an external elastic lamina (EEL) to a distance such that a delivery aperture of the needle will be positioned at a distance from the inner wall of the blood vessel in a range from 10% to 75% of the mean luminal diameter of the vessel;

confirming that the delivery aperture of the needle has radially penetrated into adventitial tissue beyond the external elastic lamina (EEL) of the blood vessel, wherein confirming comprises injecting contrast media through the needle aperture and observing whether (a) the media spreads 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 needle aperture has not reached the adventitial tissue; and

injecting the pharmaceutical agent through the needle into the tissue if it has been confirmed that the aperture of the needle is positioned in adventitial tissue beyond the external elastic lamina (EEL).

2. A method as in claim 1, wherein the needle is positioned so that a penetration distance of the delivery aperture of the needle beyond the EEL does not exceed 5 mm.

3. A method as set in claim 2, wherein the agent distributes longitudinally along the blood vessel over a distance of at least 1 cm and radially by a distance of at least 1 cm or within a time period no greater than 60 minutes.

4. A method as in claim 3, wherein the concentrations of agent at all locations spaced at least 2 cm from the delivery site are at least 10% of the concentration at the delivery site.

5. A method as in claim 2, wherein the agent distributes via the lymphatic system surrounding the target.

6. A method as in claim 2, wherein the aperture of the needle is positioned at a distance less than 5 mm beyond the EEL.

7. A method as in claim 6, wherein pharmaceutical agent comprises a small molecule drug, a protein, or a gene.

8. A method as in claim 7, wherein the agent has a maximum dimension of 200 nm or below.

9. A method as in claim 2, wherein the blood vessel is a coronary blood vessel.

10. A method as in claim 7, wherein the coronary blood vessel is an artery.

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

12. A method as in claim 10, wherein the coronary artery has regions of vulnerable plaque.

13. A method as in claim 2, wherein the patient is suffering from congestive heart failure or a cardiac arrhythmia.

14. A method as in claim 2, wherein the blood vessel is a cerebral blood vessel and the tissue is in the brain of the host.

15. A method as in claim 2, wherein the blood vessel is a hepatic blood vessel and the tissue is in the liver of the host.

16. A method as in claim 2, wherein the agent is being delivered to treat a neoplastic disease in the tissue.