Pharmaceutical Compositions and Methods for Digesting Atherosclerotic Plaques

Abstract

Disclosed are pharmaceutical compositions and methods for digesting atherosclerotic plaques in a patient in need thereof. The compositions include and the methods utilize a mixture of collagenases for digesting plaques and optionally may include or utilize additional agents such as cyclodextrins, chelating agents, and tissue plasminogen activator.

1 . A pharmaceutical composition comprising:
 (a) a mixture comprising each of collagenase type I, collagenase type III, collagenase type IV, and collagenase type V; and   (b) a carrier.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the collagenases are present in the composition at concentrations that are sufficient for digesting a human arterial plaque and reducing mass of the human arterial plaque by at least 30% after the sample is contacted with the composition for no more than about 30 minutes. 
     
     
         3 . The pharmaceutical composition of  claim 1 , comprising each of collagenase type I, collagenase type III, collagenase type IV, and collagenase type V at a concentration of at least 0.5 mg/ml. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the mixture of consists of collagenase type I, collagenase type III, collagenase type IV, and collagenase type V. 
     
     
         5 . The pharmaceutical composition of  claim 1 , further comprising a cyclodextrin at a concentration of 5-25 mM. 
     
     
         6 . The pharmaceutical composition of  claim 1 , further comprising a chelating agent at a concentration of 0.75-1.25 mg/ml. 
     
     
         7 . The pharmaceutical composition of  claim 1 , further comprising tissue plasminogen activator at a concentration of 0.75-1.25 mg/ml. 
     
     
         8 . The pharmaceutical composition of  claim 1 , further comprising cholesterol esterase at a concentration of 0.1-10 units/ml. 
     
     
         9 . The pharmaceutical composition of  claim 1 , further comprising lipoprotein lipase at a concentration of 30-10,000 units/ml. 
     
     
         10 . The pharmaceutical composition of  claim 1 , further comprising apolipoprotein CII at a concentration of 1-20 units/ml. 
     
     
         11 . The pharmaceutical composition of  claim 1 , further comprising phospholipase A2. 
     
     
         12 . The pharmaceutical composition of  claim 1 , further comprising pepsin at a concentration of 1-50 mg/ml. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the composition has a pH of about 7.2-7.6. 
     
     
         14 . A method for digesting a human arterial plaque in a patient, the method comprising contacting the plaque with the pharmaceutical composition of  claim 1 . 
     
     
         15 . The method of  claim 14 , wherein the composition is administered to the patient via a double-balloon catheter 
     
     
         16 . The method of  claim 14 , wherein the composition is contacted with the human arterial plaque for no more than about 10 minutes. 
     
     
         17 . The method of  claim 14 , further comprising applying ultrasonic energy to the plaque.