Dialysis solutions and methods

Abstract

The present invention provides improved dialysis compositions and methods for dialysis comprising utilizing the disclosed AGE inhibitors, together with methods to reduce dialysis-related complications and disorders.

We claim:  
     
         1 . An improved dialysis solution, wherein the improvement comprises an amount effective to inhibit AGE formation of one or more compounds of the general formula  
       
         
           
           
               
               
           
         
         wherein R 1  is CH 2 NH 2 , CH 2 SH, COOH, CH 2 CH 2 NH 2 , CH 2 CH 2 SH, or CH 2 COOH;  
         R 2  and R 6  is H, OH, SH, NH 2 , C 1-6 alkyl, alkoxy or alkene;  
         R 4  and R 5  are H, C 1-6 alkyl, alkoxy or alkene;  
         Y is N or C, such that when Y is N R 3  is nothing, and when Y is C, R 3  is NO 2  or another electron withdrawing group, and salts thereof.  
       
     
     
         2 . The dialysis solution of  claim 1  further comprising an osmotically active agent that is capable of maintaining the osmotic gradient required to cause transport of water and toxic substances across the peritoneum into the dialysis solution.  
     
     
         3 . The dialysis solution of  claim 2 , wherein the osmotically active agent is selected from the group consisting of ribose, lyxose, xylose, arabinose, glucose, fructose, maltose, lactose, mannose, fructose, and galactose, or polymers thereof, and polyanions.  
     
     
         4 . The dialysis solution of  claim 1  further comprising sodium in a concentration that is less than a sodium plasma concentration in a renal patient who is to receive the solution.  
     
     
         5 . The dialysis solution of any of claims  1 - 4  wherein the compound is pyridoxamine.  
     
     
         6 . An improved method of performing dialysis on a patient wherein the improvement comprises introducing into the dialysis patient a dialysis solution that comprises an amount effective to inhibit AGE formation in the patient of one or more compounds of the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  is CH 2 NH 2 , CH 2 SH, COOH, CH 2 CH 2 NH 2 , CH 2 CH 2 SH, or CH 2 COOH;  
         R 2  and R 6  is H, OH, SH, NH 2 , C 1-6 alkyl, alkoxy or alkene;  
         R 4  and R 5  are H, C 1-6 alkyl, alkoxy or alkene;  
         Y is N or C, such that when Y is N R 3  is nothing, and when Y is C, R 3  is NO 2  or another electron withdrawing group, and salts thereof.  
       
     
     
         7 . A method for decreasing dialysis-related cardiac morbidity and mortality in a dialysis patient, comprising introducing into the patient a dialysis solution that comprises an amount effective to decrease dialysis-related cardiac morbidity and mortality in the patient of one or more compounds of the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  is CH 2 NH 2 , CH 2 SH, COOH, CH 2 CH 2 NH 2 , CH 2 CH 2 SH, or CH 2 COOH;  
         R 2  and R 6  is H, OH, SH, NH 2 , C 1-6 alkyl, alkoxy or alkene;  
         R 4  and R 5  are H, C 1-6 alkyl, alkoxy or alkene;  
         Y is N or C, such that when Y is N R 3  is nothing, and when Y is C, R 3  is NO 2  or another electron withdrawing group, and salts thereof.  
       
     
     
         8 . A method for decreasing dialysis-related amyloidosis in a dialysis patient, comprising introducing into the patient a dialysis solution that comprises an amount effective to decrease dialysis-related amyloidosis in the patient of one or more compounds of the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  is CH 2 NH 2 , CH 2 SH, COOH, CH 2 CH 2 NH 2 , CH 2 CH 2 SH, or CH 2 COOH;  
         R 2  and R 6  is H, OH, SH, NH 2 , C 1-6 alkyl, alkoxy or alkene;  
         R 4  and R 5  are H, C 1-6 alkyl, alkoxy or alkene;  
         Y is N or C, such that when Y is N R 3  is nothing, and when Y is C, R 3  is NO 2  or another electron withdrawing group, and salts thereof.  
       
     
     
         9 . A method for limiting dialysis-related increases in permeability of the peritoneal membrane in a dialysis patient, comprising introducing into the patient a dialysis solution that comprises an amount effective to limit dialysis-related increases in permeability of the peritoneal membrane in the patient of one or more compounds of the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  is CH 2 NH 2 , CH 2 SH, COOH, CH 2 CH 2 NH 2 , CH 2 CH 2 SH, or CH 2 COOH;  
         R 2  and R 6  is H, OH, SH, NH 2 , C 1-6 alkyl, alkoxy or alkene;  
         R 4  and R 5  are H, C 1-6 alkyl, alkoxy or alkene;  
         Y is N or C, such that when Y is N R 3  is nothing, and when Y is C, R 3  is NO 2  or another electron withdrawing group, and salts thereof.  
       
     
     
         10 . A method for inhibiting renal failure progression in a dialysis patient, comprising introducing into the patient a dialysis solution that comprises an amount effective to inhibit renal failure progression in the patient of one or more compounds of the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  is CH 2 NH 2 , CH 2 SH, COOH, CH 2 CH 2 NH 2 , CH 2 CH 2 SH, or CH 2 COOH;  
         R 2  and R 6  is H, OH, SH, NH 2 , C 1-6 alkyl, alkoxy or alkene;  
         R 4  and R 5  are H, C 1-6 alkyl, alkoxy or alkene;  
         Y is N or C, such that when Y is N R 3  is nothing, and when Y is C, R 3  is NO 2  or another electron withdrawing group, and salts thereof.  
       
     
     
         11 . A method for inhibiting ultrafiltration failure and peritoneal membrane destruction in a dialysis patient, comprising introducing into the patient a dialysis solution that comprises an amount effective to inhibit ultrafiltration failure and peritoneal membrane destruction in the patient of one or more compounds of the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  is CH 2 NH 2 , CH 2 SH, COOH, CH 2 CH 2 NH 2 , CH 2 CH 2 SH, or CH 2 COOH;  
         R 2  and R 6  is H, OH, SH, NH 2 , C 1-6 alkyl, alkoxy or alkene;  
         R 4  and R 5  are H, C 1-6 alkyl, alkoxy or alkene;  
         Y is N or C, such that when Y is N R 3  is nothing, and when Y is C, R 3  is NO 2  or another electron withdrawing group, and salts thereof.  
       
     
     
         12 . A method for inhibiting AGE formation in a dialysis patient comprising administering to the patient a dialysis solution comprising an amount effective to inhibit AGE formation of one or more compounds of the general formula:  
       
         
           
           
               
               
           
         
         wherein R 1  is CH 2 NH 2 , CH 2 SH, COOH, CH 2 CH 2 NH 2 , CH 2 CH 2 SH, or CH 2 COOH;  
         R 2  and R 6  is H, OH, SH, NH 2 , C 1-6 alkyl, alkoxy or alkene;  
         R 4  and R 5  are H, C 1-6 alkyl, alkoxy or alkene;  
         Y is N or C, such that when Y is N R 3  is nothing, and when Y is C, R 3  is NO 2  or another electron withdrawing group, and salts thereof.  
       
     
     
         13 . The method of any of claims  6 - 12  wherein the compound is pyridoxamine.