Method of selecting phosphate binder and its uses thereof

Abstract

A method of selecting or determining a candidate compound suitable for use as a phosphate binder is disclosed. The candidate compound includes ferric compounds, ferric compound complexes, and their derivatives, salts, analogs, and metabolites. The effectiveness of the candidate compound as a phosphate binder is evaluated by a method, comprising measuring and correlating reduction of phosphate concentration in solution and reduction of phosphate absorption in cells.

1 - 34 . (canceled) 
     
     
         35 . A method to determine whether a candidate compound is capable of binding phosphate, comprising the steps of:
 a) contacting the candidate compound with phosphate in a variety of buffers or solutions, and measuring the reduction of phosphate concentration;   b) contacting the candidate compound with phosphate in a solution containing Caco-2 cells, and measuring the reduction of phosphate absorption in said cells as compared to the absence of said compound; and   
       wherein a candidate compound that reduces both the phosphate concentration in the absence of Caco-2 cells, and phosphate absorption in the Caco-2 cells is a phosphate binder. 
     
     
         36 . The method of  claim 35 , wherein the buffers or solutions are simulated gastrointestinal fluids. 
     
     
         37 . The method of  claim 35 , wherein ferric citrate is used as a standard for a phosphate binder. 
     
     
         38 . The method of  claim 35 , wherein measuring reduction of phosphate concentration in a variety of buffers or solutions comprises determining the Langmuir adsorption isotherm in said buffers or solutions. 
     
     
         39 . The method of  claim 35 , wherein measuring reduction of phosphate concentration or phosphate absorption comprises equilibrium binding experiments or kinetic experiments. 
     
     
         40 . A method for preventing, treating or stabilizing phosphate imbalance in a subject, comprising administrating to said subject an amount of ferric trimaltol effective for preventing, treating or stabilizing phosphate imbalance. 
     
     
         41 . The method of  claim 40 , wherein the amount of ferric trimaltol is 3-6 grams per day. 
     
     
         42 . The method of  claim 40 , wherein the subject suffers from hyperphosphatemia. 
     
     
         43 . The method of  claim 40 , wherein the subject suffers from metabolic acidosis. 
     
     
         44 . The method of  claim 40 , wherein the subject is a chronic kidney disease patient. 
     
     
         45 . A method for preventing, treating or stabilizing phosphate imbalance in a subject, comprising administrating to said subject an amount of ferric bicarbonate effective for preventing, treating or stabilizing phosphate imbalance. 
     
     
         46 . The method of  claim 45 , wherein the amount of ferric bicarbonate is 3-6 grams per day. 
     
     
         47 . The method of  claim 45 , wherein the subject suffers from hyperphosphatemia. 
     
     
         48 . The method of  claim 45 , wherein the subject suffers from metabolic acidosis. 
     
     
         49 . The method of  claim 45 , wherein the subject is a chronic kidney disease patient. 
     
     
         50 . A method for preventing, treating or stabilizing phosphate imbalance in a subject, comprising administrating to said subject an amount of ferric carbonate effective for preventing, treating or stabilizing phosphate imbalance. 
     
     
         51 . The method of  claim 50 , wherein the amount of ferric carbonate is 3-6 grams per day. 
     
     
         52 . The method of  claim 50 , wherein the subject suffers from hyperphosphatemia. 
     
     
         53 . The method of  claim 50 , wherein the subject suffers from metabolic acidosis. 
     
     
         54 . The method of  claim 50 , wherein the subject is a chronic kidney disease patient.