Treatment of ophthalmic disorders using urea and urea derivatives

Abstract

Methods for treating disorders of the eye and/or disorders of a nerve in a human or veterinary patient by delivering to the patient a therapeutically effective amount of a compound selected from the group of; urea, urea derivatives, thiourea, thiourea derivatives, guanidine, guanidine derivatives and compounds having General Formula I as set forth herein. For ophthalmic applications, the compound may be delivered by intravitreal injection such that the compound causes vitreal liquefaction, posterior vitreoretinal detachment and other affects.

What is claimed is:  
     
         1 . A method for treating an ophthalmological disorder, said method comprising the step of: 
 A. contacting with the vitreous body of an eye of the patient a therapeutic amount of a compound selected from the group consisting of: 
 urea;  
 urea derivatives;  
 thiourea;  
 thiourea derivatives;  
 guanidine;  
 guanidine derivatives; and,  
 compounds having the general formula:  
                     
 Wherein:  
   R is hydrogen, C 1 -C 8  alkyl, C 3 -C 8  cycloalkyl, C 1 l-C 6  alkylphenyl or hydroxyl protecting group;    R 1  and R 2  are each independently hydrogen, C 1 -C 6  alkyl, C 3 -C 8  cycloalky, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, C 2 -C 6  alkenyl, C 2 -C 6  alkenyl, —S(O)q(C 1 -C 6  alkenyl) or                          Wherein A is —CH 2 —, —O—, —S—, —S(O)— or —S(O) 2 —: W 1  and W 2  are each independently hydrogen, halo, hydroxyl, C 1 -C 4  alkyl, C 1 -C 4  alkoxy,, C 1 -C 4  alkylthio,, C 2 -C 4  alkenyl, or, C 2 -C 4  alkynyl;    R 3  is hydrogen,, C 1 -C 8  alkyl,, C 3 -C 8  cycloalkyl, or, C 1 -C 6  alkylphenyl;    X is O, S, or NR 4 ;    R 4  is hydrogen,, C 1 -C 6  alkyl,, C 1 -C 4  alkylphenyl or, C 1 -C 6  alkoxy;    R 5  is hydrogen,, C 3 -C 8  cycloalkyl or C 1 -C 8  alkyl;                          Wherein Z 1  and Z 2  are each independently hydrogen, C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl, C 1 -C 6  alkoxy, hydroxyl, C 2 -C 4  alkenyl, C 2 -C 6  alkyl, C 1 -C 6 alkythio, halo, trifluoromethyl or —NR 6 R 7 ;    R 6  and R 7  are each independently hydrogen, C 3 -C 8  cycloalkyl, C 1 -C 6  alkyl, C 1 -C 4  alkylphenyl;    n is 1 to 6 all inclusive;    m and p are each independently 0 to 6, both inclusive;    q is 0, 1 or 2; and pharmaceutical salts thereof.    
     
     
         2 . A method according to  claim 1  wherein the compound is injected intravitreally.  
     
     
         3 . A method according to  claim 1  wherein the method is carried out to treat a retinal tear.  
     
     
         4 . A method according to  claim 3  further comprising the step of: 
 B performing a retinopexy procedure after administration of the compound in Step A.  
 
     
     
         5 . A method according to  claim 4  wherein Step B is performed approximately 3 days after Step A.  
     
     
         6 . A method according to  claim 1  wherein the method is carried out to cause vitreal liquefaction and collapse.  
     
     
         7 . A method according to  claim 1  wherein the method is carried out to cause posterior vitreo-retinal detachment and collapse.  
     
     
         8 . A method according to  claim 1  wherein the method is carried out to treat a macular hole.  
     
     
         9 . A method according to  claim 1  wherein the method is carried out to treat vitreous hemorrhage.  
     
     
         10 . A method according to  claim 9  wherein the method is carried out to accelerate the clearance of hemorrhagic blood from the vitreous humor.  
     
     
         11 . A method according to  claim 1  wherein the method is carried out as an adjunct to virectomy.  
     
     
         12 . A method according to  claim 11  further comprising the step of: 
 B. performing a vitrectomy after performance of Step A.  
 
     
     
         13 . A method according to  claim 12  wherein Step B is carried out at least 1 day after Step A.  
     
     
         14 . A method according to  claim 1  wherein the method is carried out to treat macular edema.  
     
     
         15 . A method according to  claim 1  wherein the method is carried out to treat optic nerve damage.  
     
     
         16 . A method according to  claim 1  wherein the method is carried out to treat optic neuropathy.  
     
     
         17 . A method according to  claim 1  wherein the method is carried out to treat rubeosis.  
     
     
         18 . A method according to  claim 1  wherein the method is carried out to treat neovascular glaucoma.  
     
     
         19 . A method according to  claim 1  wherein the method is carried out to treat diabetic retinopathy.  
     
     
         20 . A method according to  claim 1  further comprising the step of: 
 B. contacting with the vitreous humor a therapeutic amount of a nonsteroidal antiinflamatory agent.  
 
     
     
         21 . A method according to  claim 20  wherein Steps A and B are carried out concurrently by administering a solution containing a compound according to  claim 1  in combination with an nonsteroidal antiinflamatory agent.  
     
     
         22 . A method for preventing or treating a disorder of a nerve, said method comprising the step of: 
 A. contacting with the nerve a therapeutically effective amount of a compound selected from the group consisting of: 
 urea;  
 urea derivatives;  
 thiourea;  
 thiourea derivatives;  
 guanidine;  
 guanidine derivatives; and,  
 compounds having the general formula:  
                     
 Wherein:  
   R is hydrogen, C 1 -C 8  alkyl, C 3 -C 8  cycloalkyl, C 1 -C 6  alkylphenyl or hydroxyl protecting group;    R 1  and R 2  are each independently hydrogen, C 1 -C 6  alkyl, C 3 -C 8  cycloalky, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, C 2 -C 6 alkenyl, C 2 -C 6  alkenyl, —S(O)q(C 1 -C 6  alkenyl) or                          Wherein A is —CH 2 —, —O—, —S—, —S(O)— or —S(O) 2 —: W 1  and W 2  are each independently hydrogen, halo, hydroxyl, C 1 -C 4  alkyl, C 1 -C 4  alkoxy,, C 1 -C 4  alkylthio,, C 2 -C 4  alkenyl, or, C 2 -C 4  alkynyl;    R 3  is hydrogen,, C 1 -C 8 alkyl,, C 3 -C 8 cycloalkyl, or, C 1 -C 6 alkylphenyl;    X is O, S, or NR 4 ;    R 4  is hydrogen,, C 1 -C 6  alkyl,, C 1 -C 4 alkylphenyl or, C 1 -C 6  alkoxy;    R 5  is hydrogen,, C 3 -C 8  cycloalkyl or C 1 -C 8  alkyl;    Y is                          Wherein Z 1  and Z 2  are each independently hydrogen, C 1 -C 6  alkyl, C 3 -C 8  cycloalkyl, C 1 -C 6  alkoxy, hydroxyl, C 2 -C 4  alkenyl, C 2 -C 6  alkyl, C 1 -C 6 alkythio, halo, trifluoromethyl or —NR 6 R 7 ;    R 6  and R 7  are each independently hydrogen, C 3 -C 8  cycloalkyl, C 1 -C 6  alkyl, C 1 -C 4  alkylphenyl;    n is 1 to 6 all inclusive;    m and p are each independently 0 to 6, both inclusive;    q is 0, 1 or 2; and pharmaceutical salts thereof.    
     
     
         23 . A method according to  claim 22  wherein the method is carried out for the purpose of treating a disorder of the optic nerve.  
     
     
         24 . A method according to  claim 23  wherein the compound is delivered in Step A by intravitreal injection.  
     
     
         25 . A method according to  claim 22  wherein the method is carried out to treat a disorder of the spinal chord or brain.  
     
     
         26 . A method according to  claim 25  wherein the compound is delivered in Step A by intrathecal injection.  
     
     
         27 . A method according to  claim 22  wherein the method is carried out to treat a disorder of a peripheral nerve.  
     
     
         28 . A method according to  claim 27  wherein the compound is delivered in Step A by injection into or adjacent to the peripheral nerve.