Methods and systems for inhibiting vascular inflammation

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. In one example, the catheters are used to deliver dexamethasone and other anti-inflammatory agents to the peripheral and other vasculature to treat peripheral vascular disease and other conditions.

What is claimed is: 
     
         1 . A method for inhibiting inflammation in a patient's vasculature, said method comprising:
 identifying a patient at risk of or suffering from vascular inflammation;   positioning a catheter within a lumen of a blood vessel of the patient;   advancing a needle radially outwardly from the catheter through the blood vessel wall and into adventitial tissue surrounding the blood vessel;   delivering an anti-inflammatory agent into the adventitial and perivascular tissue in an amount sufficient to inhibit inflammation of the blood vessel.   
     
     
         2 . A method as in  claim 1 , wherein the anti-inflammatory agent is selected from the group consisting of corticosteroids, mineralocorticoids, glucocorticoids, statins and non-steroidal anti-inflammatory drugs (NSAIDs). 
     
     
         3 . A method as in  claim 2 , wherein the anti-inflammatory agent comprises dexamethasone. 
     
     
         4 . A method as in  claim 1 , wherein the needle is advanced so that an aperture of the needle lies beyond an external elastic lamina (EEL) of the blood vessel wall. 
     
     
         5 . A method as in  claim 1 , further comprising confirming advancement of the needle into the adventitial tissue. 
     
     
         6 . A method as in  claim 1 , further comprising delivering a contrast agent into the adventitial and perivascular tissue with the needle advanced into the adventitial tissue surrounding the blood vessel. 
     
     
         7 . A method as in  claim 6 , wherein the delivered contrast agent, when delivered, spreads at least longitudinally along the blood vessel. 
     
     
         8 . A method as in  claim 6 , further comprising visualizing the delivered contrast agent. 
     
     
         9 . A method of  claim 1 , further comprising monitoring a back pressure of the needle when the needle is one or more of advancing into the adventitial tissue or delivering the anti-inflammatory agent. 
     
     
         10 . A method as in  claim 1 , wherein the anti-inflammatory agent, when delivered, spreads at least one of longitudinally or radially along the blood vessel. 
     
     
         11 . A method as in  claim 1 , further comprising repeating the advancing and delivering steps to deliver the anti-inflammatory agent to a plurality of injection sites. 
     
     
         12 . A method as in  claim 1 , wherein the therapeutic agent is fluorescently labeled. 
     
     
         13 . A method as in  claim 1 , further comprising delivering at least one additional pharmaceutical agent into the adventitial and perivascular tissue. 
     
     
         14 . A method as in  claim 13 , wherein the at least one additional pharmaceutical agent comprises one or more of an antineoplastic agent, an antiproliferative agent, a cytostatic agent, an immunosuppressive agent, a different anti-inflammatory agent, an antibiotic agent, an antifungal agent, an antibody, a lipid lowering agent, a calcium channel blocker, an ACE inhibitor, a gene therapy agent, an anti-sense drug, an interfering RNA molecule, a metalloproteinase inhibitor, a growth factor inhibitor, a cell cycle inhibitor, an angiogenesis drug, an anti-angiogenesis drug, or a radiopaque contrast agent. 
     
     
         15 . A method as in  claim 1 , wherein the blood vessel is a peripheral blood vessel. 
     
     
         16 . A method as in  claim 15 , wherein the peripheral blood vessel is selected from the group consisting of iliac arteries, femoral arteries, popliteal arteries, tibial arteries, and peroneal arteries. 
     
     
         17 . A method as in  claim 1 , wherein advancing the needle comprises expanding an expandable element the needle is mounted on. 
     
     
         18 . A method as in  claim 15 , wherein the expandable element comprises an inflatable balloon. 
     
     
         19 . A method as in  claim 15 , wherein the expandable element is expanded to a first expanded configuration before being expanded to a second expanded configuration more expanded than the first. 
     
     
         20 . A method as in  claim 17 , wherein the needle is advanced relative to the expandable element when expanded to the second expanded configuration. 
     
     
         21 . A method as in  claim 1 , wherein the needle is advanced in a direction substantially perpendicular to a central axis of the blood vessel. 
     
     
         22 . A method as in  claim 1 , wherein the anti-inflammatory agent is delivered in an amount sufficient to treat a diffuse vascular disease or a peripheral vascular disease.