Use of collagenase to facilitate guide wire crossing in total arterial occlusions

Abstract

The use of a collagenase containing formulation for degrading collagen within an occlusive atherosclerotic plaque in a chronic fibrotic occlusion, chronically occluded animal tube or cavity. A medical-related apparatus is provided comprising a medical-related device having provided thereto a therapeutic amount of a collagen degrading composition comprising a proteiolytic enzyme containing formulation. A method is provided for treating chronically occluded animal tubes and cavities by administering a therapeutic effective amount of a proteolytic enzyme-containing formulation adjacent to an occluding atherosclerotic plaque, waiting for a pre-angioplasty waiting period, followed by crossing the plaque with an angioplasty guide wire.

1 - 32 . (cancelled)  
     
     
         33 . A method of degrading collagen within an occlusive atherosclerotic plaque in a chronically occluded animal tube or cavity, the method comprising administering a therapeutic effective amount of a proteolytic enzyme containing formulation adjacent the plaque.  
     
     
         34 . The method of  claim 33 , wherein said collagenase containing formulation is an infusion preparation and the method further comprises retaining the formulation adjacent to the plaque during a formulation exposure waiting period.  
     
     
         35 . A method of degrading collagen within an occlusive atherosclerotic plaque in a chronically occluded animal tube or cavity, the method comprising administering a therapeutic effective amount of a proteolytic enzyme containing formulation into the plaque.  
     
     
         36 . The method of  claim 35 , wherein said collagenase containing formulation is an infusion preparation and the method further comprises retaining the formulation in the plaque during a formulation exposure waiting period.  
     
     
         37 . The method of  claim 34 , wherein said infusion preparation is formulated for administration of a dosage of from about 50 μg to about 2000 μg of type 1A collagenase.  
     
     
         38 . The method of  claim 36 , wherein said infusion preparation is formulated for administration of a dosage of from about 50 μg to about 2000 μg of type 1A collagenase.  
     
     
         39 . The method of  claim 34 , wherein said infusion preparation is formulated for administration of a dosage of from about 150 μg to 500 μg of collagenase.  
     
     
         40 . The method of  claim 36 , wherein said infusion preparation is formulated for administration of a dosage of from about 150 μg to 500 μg of collagenase.  
     
     
         41 . A medical-related apparatus for degrading collagen within an occlusive atherosclerotic plaque in a chronically occluded animal tube or cavity comprising a medical-related device having a therapeutic amount of a collagen degrading composition comprising a proteolytic enzyme containing formulation.  
     
     
         42 . The medical-related apparatus of  claim 41 , wherein the composition is provided on the apparatus.  
     
     
         43 . The medical-related apparatus of  claim 41 , wherein the composition is provided with the apparatus.  
     
     
         44 . The medical-related apparatus of  claim 41 , wherein the composition is provided through the apparatus.  
     
     
         45 . The medical-related apparatus according to  claim 41 , wherein the proteolytic enzyme containing formulation comprises a proteolytic enzyme selected from the group consisting of matrix metalloproteinases, serine elastases, trypsin, neutral protease, chymotrypsin, aspartase, cysteinase and clostripain, and human purified matrix degrading enzymes.  
     
     
         46 . The medical-related apparatus according to  claim 41 , wherein the proteolytic enzyme containing formulation comprises collagenase.  
     
     
         47 . The medical-related apparatus according to  claim 41 , wherein the medical related device is selected from the group consisting of needles, cannulae, catheters, occlusive balloon catheters, and guidewires.  
     
     
         48 . A kit for for the prevention or treatment of an atherosclerotic plaque in a chronically occluded animal tube or cavity comprising a medical-related device and a therapeutic amount of a collagen degrading composition comprising a proteolytic enzyme containing formulation.  
     
     
         49 . The kit of  claim 48 , wherein the composition is provided on the apparatus.  
     
     
         50 . The kit of  claim 48 , wherein the composition is provided with the apparatus.  
     
     
         51 . The kit of  claim 48 , wherein the composition is provided through the apparatus.  
     
     
         52 . The kit of  claim 48 , wherein the proteolytic enzyme containing formulation comprises a proteolytic enzyme selected from the group consisting of matrix metalloproteinases, serine elastases, trypsin, neutral protease, chymotrypsin, aspartase, cysteinase and clostripain, and human purified matrix degrading enzymes.  
     
     
         53 . The kit according to  claim 48 , wherein the proteolytic enzyme containing formulation comprises collagenase.  
     
     
         54 . The kit according to  claim 48 , wherein the medical related device is selected from the group consisting of needles, cannulae, catheters, occlusive balloon catheters, and guidewires.  
     
     
         55 . A method of use of a medical-related apparatus for administering a collagen degrading composition within an occlusive atherosclerotic plaque in a chronically occluded animal tube or cavity, the method comprising loading the apparatus with the composition for said administration.  
     
     
         56 . A method of treating chronically occluded animal tubes and cavities comprising the steps of: 
 administering a therapeutic effective amount of a proteolytic enzyme containing formulation adjacent an occluding atherosclerotic plaque;    waiting for a pre-angioplasty waiting period; and,    crossing the plaque with an angioplasty guide wire.    
     
     
         57 . The method of  claim 56  wherein the duration of the pre-angioplasty waiting period is between about 1 hour and about 108 hours.  
     
     
         58 . The method of  claim 57  wherein the duration of the pre-angioplasty waiting period is between about 12 hours and about 86 hours.  
     
     
         59 . The method of  claim 58  wherein the duration of the pre-angioplasty waiting period is between about 24 hours and about 72 hours.  
     
     
         60 . The method of  claim 56  wherein the duration of the pre-angioplasty waiting period is about 24 hours.  
     
     
         61 . The method of  claim 56  wherein the step of administering a therapeutic effective amount of a proteolytic enzyme containing formulation comprises the steps of: 
 advancing an over-the-wire angioplasty balloon catheter on a guide wire into the occluded tube or cavity using fluoroscopic guidance;    inflating the balloon at low pressure;    removing the guide wire;    infusing a proteolytic enzyme formulation into the tube or cavity lumen;    waiting for a formulation exposure waiting period; and,    removing the angioplasty equipment.    
     
     
         62 . The method of  claim 56  wherein the proteolytic enzyme containing formulation is infused into the tube or cavity lumen adjacent to the occlusion.  
     
     
         63 . The method of  claim 61  wherein the proteolytic enzyme containing formulation is infused directly into the occlusion.  
     
     
         64 . The method of  claim 61  wherein the infusion of the proteolytic enzyme containing formulation is through the wire port of an angioplasty catheter.  
     
     
         65 . The method of  claim 61  wherein the infusion of the proteolytic enzyme containing formulation is through an infusion needle.  
     
     
         66 . The method of  claim 61  wherein the infusion of the proteolytic enzyme containing formulation is through a catheter.  
     
     
         67 . The method of  claim 61  wherein the balloon is inflated to a pressure in the range of about 1-5 atmospheres.  
     
     
         68 . The method of  claim 61  wherein the balloon is inflated to a pressure of about 4 atmospheres.  
     
     
         69 . The method of  claim 61  wherein the proteolytic enzyme containing formulation is infused under low pressure.  
     
     
         70 . The method of  claim 61  wherein the proteolytic enzyme containing formulation is infused under a pressure in the range of about 0.5 atmospheres to 3.5 atmospheres.  
     
     
         71 . The method of  claim 70  wherein the proteolytic enzyme containing formulation is infused under a pressure in the range of about 1 to 2 atmospheres.  
     
     
         72 . The method of  claim 61  wherein the formulation exposure waiting period is at least about 10 minutes.  
     
     
         73 . The method of  claim 72  wherein the formulation exposure waiting period is between about 20 minutes and about 100 minutes.  
     
     
         74 . The method of  claim 73  wherein the formulation exposure waiting period is between about 50 minutes and about 80 minutes.  
     
     
         75 . The method of  claim 74  wherein the formulation exposure waiting period is between about 60 minutes.  
     
     
         76 . The method  claim 75  wherein the proteolytic enzyme containing formulation comprises a proteolytic enzyme selected from the group consisting of matrix metalloproteinases, serine elastases, trypsin, neutral protease, chymotrypsin, aspartase, cysteinase and clostripain, and human purified matrix degrading enzymes.  
     
     
         77 . The method  claim 76  wherein the proteolytic enzyme containing formulation comprises a matrix metalloproteinase selected from the group consisting of collagenase, type 1A collagenase, gelatinases, and stromelysin, and human purified matrix degrading enzymes.  
     
     
         78 . The method  claim 77  wherein the proteolytic enzyme containing formulation comprises collagenase containing formulation.  
     
     
         79 . The method  claim 78  wherein the effective therapeutic amount of proteolytic enzyme containing formulation comprises 50-2000 μg of type IA Collagenase.  
     
     
         80 . The method  claim 78  wherein the effective therapeutic amount of proteolytic enzyme containing formulation comprises a dosage of from about 150 μg to 500 μg of collagenase.