Use of hyaluronidase in the manufacture of an ophthalmic preparation for liquefying vitreous humor in the treatment of eye disorders

Abstract

An enzymatic method is provided for treating ophthalmic disorders of the mammalian eye. Prevention of neovascularization and the increased rate of clearance from the vitreous of materials toxic to retina is accomplished by administering an amount of hyaluronidase effective to liquefy the vitreous humor of the treated eye without causing toxic damage to the eye. Liquefaction of the vitreous humor increases the rate of liquid exchange from the vitreal chamber. This increase in exchange removes those materials and conditions whose presence causes ophthalmological and retinal damage.

1 . A method for inducing liquefaction of a vitreous humor to prevent a disorder of a mammalian eye comprising the step of contacting with said vitreous humor of said mammalian eye an amount of hyaluronidase effective to liquefy said vitreous humor whereby said disorder is prevented without causing toxic damage to said mammalian eye.  
     
     
         2 . The method of  claim 1  wherein said method is carried out for the purpose of treating proliferative diabetic retinopathy.  
     
     
         3 . The method of  claim 1  wherein said method is carried out for the purpose of treating age-related macular degeneration.  
     
     
         4 . The method of  claim 1  wherein said method is carried out for the purpose of treating amblyopia.  
     
     
         5 . The method of  claim 1  wherein said method is carried out for the purpose of treating retinitis pigmentosa.  
     
     
         6 . The method of  claim 1  wherein said method is carried out for the purpose of treating macular holes.  
     
     
         7 . The method of  claim 1  wherein said method is carried out for the purpose of treating macular exudates.  
     
     
         8 . The method of  claim 1  wherein said method is carried out for the purpose of treating cystoid macular edema.  
     
     
         9 . The method of  claim 1  wherein said hyaluronidase is in a liquid solution, and wherein the step of contacting of said enzyme with the vitreous humor comprises: injecting said liquid solution into the vitreous humor.  
     
     
         10 . The method of  claim 1  wherein said hyaluronidase is contacted with the vitreous in the absence of thimerosal.  
     
     
         11 . The method of  claim 1  wherein said hyaluronidase is contacted with the vitreous humor at a dose of 5-200 International Units.  
     
     
         12 . The method of  claim 1  wherein said hyaluronidase is contacted with the vitreous humor at a dose of 1 International Units.  
     
     
         13 . The method of  claim 1  wherein said hyaluronidase is administered in multiple doses.  
     
     
         14 . The method of  claim 13  wherein a single intravitreal injection has an injectate volume of less than 100:1.  
     
     
         15 . The method of  claim 1  wherein said hyaluronidase is devoid of hyaluronic acid lysing activity having a molecular weight above approximately 100,000 when determined by 10% SDS PAGE electrophoresis.  
     
     
         16 . The method of  claim 1  wherein said hyaluronidase is devoid of gelatinolytic activity having a molecular weight between approximately 60,000-100,000 when determined by 10% SDS PAGE electrophoresis.  
     
     
         17 . The method of  claim 1  wherein said hyaluronidase enzyme is devoid of caseinolytic activity having a molecular weight above approximately 45,000 when determined by 10% SDS PAGE electrophoresis.  
     
     
         18 . The method of  claim 1  wherein said hyaluronidase is devoid of hyaluronidase matter having a molecular weight above approximately 100,000 when determined by 4-20% SDS PAGE electrophoresis.  
     
     
         19 . The method of  claim 1  wherein said hyaluronidase is devoid of hyaluronidase matter having a molecular weight between approximately 50,000-60,000 when determined by 4-20% SDS PAGE electrophoresis.  
     
     
         20 . The method of  claim 1  wherein said hyaluronidase is devoid of hyaluronidase matter having a molecular weight below approximately 20,000 when determined by 4-20% SDS PAGE electrophoresis.  
     
     
         21 . The method of  claim 1  wherein said hyaluronidase is prepared in a solution for injection which is free of thimerosal and which has the formulation: said hyaluronidase up to 8,000 IU; lactose at 5.0-130.0 mg; and phosphate at 0.01-100.0 mmoles.  
     
     
         22 . The method of  claim 1  wherein said hyaluronidase is prepared in a solution for injection which is free of thimerosal and which has the formulation: said hyaluronidase at 6,500 IU; lactose at 5.0 mg; and phosphate at 0.02 mmoles.  
     
     
         23 . The method of  claim 1  wherein said hyaluronidase is prepared in a solution for injection which is free of thimerosal and which has the formulation: said hyaluronidase at 500-1,000 IU; lactose at 5.0-10.0 mg; and phosphate at 0.01-10.0 mmoles.  
     
     
         24 . A method for treating a disorder of a mammalian eye comprising the step of: contacting with a vitreous humor of said mammalian eye an amount of hyaluronidase effective to treat said disorder without causing toxic damage to said mammalian eye.  
     
     
         25 . The method of  claim 24  wherein said vitreous humor is free of hemorrhagic blood that permits viewing of a retina of said mammalian eye.  
     
     
         26 . The method of  claim 24  wherein said contacting step is practiced in the absence of vitrectomy.