IRON (III) CITRATE, SUBSTANTIALLY FREE OF BETA-IRON HYDROXIDE OXIDE
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.