US2006034822A1PendingUtilityA1

Hyaluronidase preparation for ophthalmic administration and enzymatic methods for accelerating clearance of hemorrhagic blood from the vitreous body of the eye

63
Assignee: KARAGEOZIAN HAMPAR LPriority: Nov 22, 1995Filed: Aug 15, 2005Published: Feb 16, 2006
Est. expiryNov 22, 2015(expired)· nominal 20-yr term from priority
A61K 31/7016A61P 27/00A61P 27/02A61K 38/47A61K 38/43
63
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Claims

Abstract

A thimerosal-free hyaluronidase preparation wherein the preferred hyaluronidase enzyme is devoid of molecular weight fractions below 40,000 MW, between 60-70,000 MW and above 100,000 MW. Also disclosed is a method for accelerating the clearance of hemorrhagic blood from the vitreous humor of the eye, said method comprising the step of contacting at least one hemorrhage-clearing enzyme (e.g., a β-glucuronidase, matrix metalloproteinase, chondroitinase, chondroitin sulfatase or protein kinase) with the vitreous humor in an amount which is effective to cause accelerated clearance of blood therefrom.

Claims

exact text as granted — not AI-modified
1 . A method for accelerating the clearance of hemorrhagic blood from the vitreous humor of a mammalian eye, said method comprising the step of: 
 contacting with said vitreous humor an amount of an enzyme which is active to accelerate the clearance of hemorrhagic blood from the vitreous humor.    
   
   
       2 . The method of  claim 1  wherein said enzyme is selected from the group consisting of: 
 hyaluronidase;    keratinase;    chondroitinase AC;    chondroitinase B;    chondroitinase ABC;    chondroitin 4 sulfatase;    chondroitin 6 sulfatase;    matrix metalloproteinase-1;    matrix metalloproteinase-2;    matrix metalloproteinase-3;    matrix metalloproteinase-9;    streptokinase;    urokinase; and,    combinations thereof.    
   
   
       3 . The method of  claim 1  wherein said enzyme is a β-glucuronidase enzyme.  
   
   
       4 . The method of  claim 1  wherein said enzyme is a matrix metalloproteinase enzyme.  
   
   
       5 . The method of  claim 1  wherein said enzyme is a protein kinase enzyme.  
   
   
       6 . The method of  claim 1  wherein said enzyme is a chondroitin sulfatase enzyme.  
   
   
       7 . The method of  claim 1  wherein said enzyme is in liquid solution, and wherein the step of contacting of said enzyme with the vitreous humor comprises: 
 injecting said liquid solution into the vitreous humor.    
   
   
       8 . The method of  claim 1  wherein said enzyme is hyaluronidase.  
   
   
       9 . The method of  claim 8  wherein said amount of said hyaluronidase enzyme is 10-300 International Units.  
   
   
       10 . The method of  claim 1  wherein said enzyme is administered in a single intravitreal injection.  
   
   
       11 . The method of  claim 10  herein the single intravitreal injection has an injectate volume of less than 50 μl.  
   
   
       12 . The method of  claim 8  wherein said hyaluronidase enzyme is devoid of molecular weight fractions above 100,000 MW.  
   
   
       13 . The method of  claim 8  wherein said hyaluronidase is devoid of hyaluronidase molecular weight fractions below 40,000 MW.  
   
   
       14 . The method of  claim 8  wherein said hyaluronidase is devoid of molecular weight fractions between 60,000-70,000 MW.  
   
   
       15 . The method of  claim 8  wherein said hyaluronidase is devoid of molecular weight fractions above 100,000 MW below 40,000 MW and between 60,000-70,000 MW.  
   
   
       16 . The method of  claim 8  wherein hyaluronidase enzyme is devoid of gelatinolytic hyaluronidase having molecular weights between approximately 60,000-100,000 MW.  
   
   
       17 . The method of  claim 8  wherein said hyaluronidase enzyme is devoid of caseinolytic hyaluronidase having molecular weight above approximately 45,000 MW.  
   
   
       18 . The method of  claim 8  wherein said hyaluronidase enzyme is devoid of hyaluronic acid lysing hyaluronidase having molecular weights above approximately 100,000 MW.  
   
   
       19 . The method of  claim 1  wherein said method further comprises: 
 contacting said enzyme with said vitreous humor in the absence of thimerosal.    
   
   
       20 . The method of  claim 8  wherein said hyaluronidase enzyme is prepared in a solution for injection which is free of thimerosal and which has the general formulation:  
     
       
         
               
               
               
             
                   
                   
               
                   
                   
               
                   
                 Hyaluronidase (ACS) 
                 0-8000 I.U.; 
               
                   
                 Lactose, USP 
                 13.3 mg; and 
               
                   
                 Phosphate, USP 
                 5 mmoles; 
               
                   
                   
               
                   
                   
               
           
              
              
             
             
              
              
              
              
              
             
          
         
       
     
     and, wherein the hyaluronidase enzyme is devoid of molecular weight fractions below 40,000.  
   
   
       21 . The method of  claim 20  wherein said solution for injection has the following specific formulation:  
     
       
         
               
               
               
             
                   
                   
               
                   
                   
               
                   
                 Hyaluronidase (ACS) 
                 7,200 I.U.; 
               
                   
                 Lactose, USP 
                 13.3 mg; and 
               
                   
                 Phosphate, USP 
                 5 mmoles. 
               
                   
                   
               
                   
                   
               
           
              
              
             
             
              
              
              
              
              
             
          
         
       
     
   
   
       22 . The method of  claim 20  wherein said solution for injection is dissolved in balanced salt solution.  
   
   
       23 . A hyaluronidase preparation for ophthalmic administration, said preparation being free of thimerosal and free of hyaluronidase which is less than 40,000 MW.  
   
   
       24 . The preparation of  claim 23  wherein said preparation is further free of hyaluronidase having molecular weights between 60,000-70,000 MW.  
   
   
       25 . The preparation of  claim 23  wherein said preparation is further free of hyaluronidase having a molecular weight in excess of 100,000 MW.  
   
   
       26 . The preparation of  claim 23  wherein said preparation is further devoid of hyaluronic acid lysing hyaluronidase having molecular weight above approximately 100,000 MW.  
   
   
       27 . The preparation of  claim 23  wherein said preparation is further devoid of caseinolytic hyaluronidase having molecular weight above approximately 45,000 MW.  
   
   
       28 . The preparation of  claim 23  wherein said preparation is further devoid of gelatinolytic hyaluronidase having molecular weight between approximately 60,000-100,000 MW.  
   
   
       29 . The preparation of  claim 23  wherein said preparation is a solution for injection having the following general formulation:  
     
       
         
               
               
               
             
                   
                   
               
                   
                   
               
                   
                 Hyaluronidase (ACS) 
                 0-8000 I.U.; 
               
                   
                 Lactose, USP 
                 13.3-133.3 mg; and 
               
                   
                 Phosphate, USP 
                 5-200 mmoles; 
               
                   
                   
               
                   
                   
               
           
              
              
             
             
              
              
              
              
              
             
          
         
       
       and, wherein the hyaluronidase enzyme is devoid of molecular weight fractions below 40,000.  
     
   
   
       30 . The preparation of  claim 29  wherein the amount of hyaluronidase (ACS) in said formulation is 7,200 I.U.  
   
   
       31 . The preparation of  claim 29  wherein the components of said formulation are dissolved in balanced salt solution.

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