Iron (iii) citrate, substantially free of beta-iron hydroxide oxide

Abstract

This invention provides a method for producing high-purity iron(III) citrate substantially free of beta-iron hydroxide oxide, high-purity iron(III) citrate substantially free of beta-iron hydroxide oxide, and medical uses thereof.

1 . High-purity iron(III) citrate substantially free of beta-iron hydroxide oxide, wherein the beta-iron hydroxide oxide content is less than 6% by weight based on the total weight thereof. 
     
     
         2 . The high-purity iron(III) citrate according to  claim 1 , wherein the beta-iron hydroxide oxide content is less than 2.5% by weight. 
     
     
         3 . The high-purity iron(III) citrate according to  claim 1 , wherein the beta-iron hydroxide oxide content is less than 1.0% by weight. 
     
     
         4 . The high-purity iron(III) citrate according to  claim 1 , wherein the molar ratio of iron(III) to citric acid is from 1:0.75 to 1:1.10. 
     
     
         5 . The high-purity iron(III) citrate according to  claim 4 , wherein the molar ratio of iron(III) to citric acid is from 1:0.80 to 1:0.92. 
     
     
         6 . The high-purity iron(III) citrate according to  claim 1 , wherein the percentage of iron(III) citrate dissolved within 15 minutes is 80% or more in dissolution testing conducted with the use of the first fluid of dissolution testing of the Japanese Pharmacopoeia, Fifteenth Edition as a test liquid via the paddle method at 100 rpm in accordance with the Japanese Pharmacopoeia, Fifteenth Edition. 
     
     
         7 . A pharmaceutical composition comprising, as an active ingredient, the high-purity iron(III) citrate according to  claim 1 . 
     
     
         8 . A method of treating hyperphosphatemia, comprising administering the high-purity iron(III) citrate according to  claim 1  to a subject in need thereof. 
     
     
         9 . Powder of the high-purity iron(III) citrate according to  claim 1 , which has an amorphous structure. 
     
     
         10 . Powder of the high-purity iron(III) citrate according to  claim 1 , which has a specific surface area of 20 to 45 m2/g. 
     
     
         11 . Powder of the high-purity iron(III) citrate according to  claim 9 , which has a specific surface area of 20 to 45 m2/g. 
     
     
         12 . A pharmaceutical composition comprising, as an active ingredient, the powder according to  claim 9 . 
     
     
         13 . A method of treating hyperphosphatemia, comprising administering the powder according to  claim 9  to a subject in need thereof. 
     
     
         14 . A method for producing iron(III) citrate comprising:
 a step of forming an iron-containing precipitate comprising bringing ferric chloride into contact with sodium hydroxide for a short period of time at low temperature in an aqueous medium to form an iron-containing precipitate;   a step of generating an aqueous solution of iron(III) citrate comprising bringing citric acid into contact with the iron-containing precipitate in an aqueous medium and generating an aqueous solution of iron(III) citrate via heating; and   a step of precipitating iron(III) citrate comprising bringing the aqueous solution of iron(III) citrate into contact with an organic solvent to precipitate the iron(III) citrate.   
     
     
         15 . The method according to  claim 14 , wherein the step of forming iron-containing precipitate comprises bringing ferric chloride into contact with sodium hydroxide within 2 hours at a liquid temperature of 0° C. to 10° C. 
     
     
         16 . The method according to  claim 14 , wherein the step of generating an aqueous solution of iron(III) citrate comprises bringing citric acid into contact with the iron-containing precipitate at a liquid temperature of 60° C. to 100° C. 
     
     
         17 . The method according to  claim 14 , wherein the iron-containing precipitate is ferrihydride. 
     
     
         18 . Iron(III) citrate produced by the method according to  claim 14 . 
     
     
         19 . A pharmaceutical composition comprising, as an active ingredient, the iron(III) citrate according to  claim 18 . 
     
     
         20 . A method of treating hyperphosphatemia, comprising administering the iron(III) citrate according to  claim 18  to a subject in need thereof. 
     
     
         21 . Powder of the iron(III) citrate according to  claim 18 , which has an amorphous structure. 
     
     
         22 . Powder of the iron(III) citrate according to  claim 18 , which has a specific surface area of 20 to 45 m2/g. 
     
     
         23 . Powder of the iron(III) citrate according to  claim 21 , which has a specific surface area of 20 to 45 m2/g. 
     
     
         24 . A pharmaceutical composition comprising, as an active ingredient, the powder according to  claim 21 . 
     
     
         25 . A method of treating hyperphosphatemia, comprising administering the powder according to  claim 21  to a subject in need thereof. 
     
     
         26 . A method of treating hyperphosphatemia, comprising administering the pharmaceutical composition according to  claim 7  to a subject in need thereof.