US2007141042A1PendingUtilityA1

Methods for the treatment and prevention of diseases of biological conduits

53
Individually held — no corporate assignee on recordPriority: Feb 20, 2003Filed: Feb 27, 2004Published: Jun 21, 2007
Est. expiryFeb 20, 2023(expired)· nominal 20-yr term from priority
Inventors:Nicholas FrananoCharles P. Romano
A61K 38/4833A61P 9/08A61P 7/00A61P 43/00A61K 38/4826A61K 38/195A61K 38/488A61K 38/4886A61P 9/10A61K 38/484A61P 9/00A61K 38/486
53
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Claims

Abstract

Methods are described for dilating biological conduits by removing elastin and remodeling collagens in the wall of the conduit. Methods include the use of agents that increase the release of endogenous elastase and collagenase in the wall of the conduit, either by cells that are normally present in the wall of the conduit or by inflammatory cells that are attracted to the conduit, thereby providing additional conduit dilation. Methods also include the use of agents that increase conduit wall permeability and expose elastin and collagen fibers. Methods also include removing components of the extracellular matrix of arteries and veins leading to an inhibition of intimal hyperplasia in the wall of the vessels by decreasing biomechanical stimuli directed toward the cells in the wall of the vessel. Methods further include the use of agent that degrade micro fibers, in addition to elastin, in order to decrease the resynthesis of elastin. Methods also include the use of agent that stabilize the diameter of aneurysmal arteries by blocking cell surface receptors in the wall of the aneurysmal artery that are important in the recruitment of inflammatory cells.

Claims

exact text as granted — not AI-modified
1 . A method of increasing the external diameter of at least a segment of a biological conduit, said method comprising: 
 administering to said segment in a human subject in need thereof, via a parenteral route, a composition comprising an agent that increases the local concentration of one or more endogenous elastases or collagenases, wherein said agent is not an elastase or collagenase, in an amount effective to increase the external diameter of said segment, and wherein said increase is sustained for a duration of at least 24 hours after it is achieved,    thereby increasing the external diameter of at least a segment of a biological conduit.    
   
   
       2 . (canceled)  
   
   
       3 . The method of  claim 1 , wherein said agent stimulates the local synthesis or release of one or more endogenous elastases or collagenases.  
   
   
       4 - 6 . (canceled)  
   
   
       7 . The method of  claim 1  or  3 , wherein the biological conduit is an artery or vein, or an arterial or venous vascular graft.  
   
   
       8 - 14 . (canceled)  
   
   
       15 . The method of any one of  claim 1  or  3 , wherein said biological conduit is obstructed or susceptible to obstruction due to compliance mismatch between an artery and vein, an artery and a venous vascular graft, an artery and a synthetic graft, or a vein and a synthetic graft.  
   
   
       16 . The method of  claim 15 , wherein said compliance mismatch is between an artery and a vein connected by an anastomosis.  
   
   
       17 . The method of  claim 15 , wherein the compliance mismatch is between an artery and a venous vascular graft connected by an anastomosis.  
   
   
       18 . The method of  claim 15 , wherein the compliance mismatch is between an artery and a synthetic graft connected by an anastomosis.  
   
   
       19 . The method of  claim 15 , wherein the compliance mismatch is between an vein and a synthetic graft connected by an anastomosis.  
   
   
       20 . The method of  claim 18 , wherein the synthetic graft comprises poly tetrafluoroethylene (“PTFE”) or Dacron.  
   
   
       21 . The method of  claim 19 , wherein the synthetic graft comprises PTFE or Dacron.  
   
   
       22 . The method of  claim 15 , wherein the composition is administered to the venous vascular graft.  
   
   
       24 . The method of  claim 15 , wherein the composition is administered to both the artery or vein, and the arterial or venous vascular graft.  
   
   
       25 . The method of any one of  claim 1  or  3 , wherein said biological conduit is obstructed or susceptible to obstruction.  
   
   
       26 . The method of  claim 25 , wherein said biological conduit is obstructed or susceptible to obstruction due to intimal hyperplasia.  
   
   
       27 - 32 . (canceled)  
   
   
       33 . The method of any one of  claim 1  or  3 , wherein said composition is administered directly to said biological conduit.  
   
   
       34 . The method of  claim 33 , wherein said composition is administered by a catheter.  
   
   
       35 . The method of  claim 33 , wherein said composition is administered to a surgically exposed segment of the biological conduit within the human subject.  
   
   
       36 . The method of  claim 35 , wherein said composition is administered by a catheter.  
   
   
       37 . The method of  claim 34 , wherein the composition is delivered into the lumen of the biological conduit.  
   
   
       38 . The method of  claim 35 , wherein the composition is delivered into the lumen of the biological conduit.  
   
   
       39 . The method of  claim 34 , wherein the composition is applied to the external surface of the biological conduit.  
   
   
       40 . The method of  claim 35 , wherein the composition is applied to the external surface of the biological conduit.  
   
   
       41 . The method of any one of  claim 1  or  3 , wherein said composition is administered directly to a segment of the artery or vein or venous vascular graft.  
   
   
       42 . The method of  claim 41 , wherein the composition is delivered into the lumen of the artery or vein, or venous vascular graft.  
   
   
       43 . The method of  claim 41 , wherein the composition is applied to the external surface of the of the artery or vein or the venous vascular graft.  
   
   
       44 . The method of any one of  claim 1  or  3 , wherein said composition is administered percutaneously into a tissue comprising said biological conduit.  
   
   
       45 . The method of  claim 44 , wherein the biological conduit is a coronary artery or a vein bypass graft connected to a coronary artery.  
   
   
       46 . The method of  claim 45 , wherein the composition is administered percutaneously into the pericardial space.  
   
   
       47 . The method of any one of  claim 1  or  3 , wherein the method further comprises the step of pressurizing the lumen of the biological conduit concurrently with administering the composition to the biological conduit.  
   
   
       48 . The method of  claim 47 , wherein the lumen of the biological conduit is pressurized by mechanical action.  
   
   
       49 . The method of  claim 47 , wherein the lumen of the biological conduit is pressurized with a balloon catheter.  
   
   
       50 . The method of  claim 47 , wherein the administration of the composition and the pressurizing are performed by the same device.  
   
   
       51 - 64 . (canceled)  
   
   
       65 . The method of  claim 1 , wherein the biological conduit is a ureter, bronchus, bile duct, or pancreatic duct.  
   
   
       66 . The method of  claim 1 , wherein the external diameter is increased by 5% to 500%.  
   
   
       67 . The method of  claim 66 , wherein the external diameter is increased by 5% to 25%, by 25% to 50%, by 50% to 100%, by 100% to 200%, by 200% to 400%, or by 400% to 500%.  
   
   
       68 . The method of  claim 66 , wherein the external diameter is increased by 10% to 400%, by 25% to 300%, or by 50% to 200%.  
   
   
       69 - 86 . (canceled)

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