Aqueous iron carbohydrate complexes, their production and medicaments containing them
A water soluble iron carbohydrate complex obtainable from an aqueous solution of iron(III) salt and an aqueous solution of the oxidation product of one or more maltrodextrins using an aqueous hypochlorite solution at a pH-value within the alkaline range, where, when one maltodextrin is applied, its dextrose equivalent lies between 5 and 20, and when a mixture of several maltodextrins is applied, the dextrose equivalent of the mixture lies between 5 and 20 and the dextrose equivalent of each individual maltodextrin contained in the mixture lies between 2 and 40, a process for its production and a medicament for the treatment and prophylaxis of iron deficiency conditions.
1. An iron (III) carboxymaltodextrin complex which has a weight average molecular weight in the range of from 118 kDa to 271 kDa as measured by gel permeation chromatography, and is obtained from the oxidation of maltodextrin, wherein when one maltodextrin is present its dextrose equivalent lies between 5 and 20, and when a mixture of several maltodextrins is present, the dextrose equivalent of the mixture lies between 5 and 20 and the dextrose equivalent of each individual maltodextrin contained in the mixture lies between 2 and 40, and iron is present in an amount ranging from 20% to 35% by weight, relative to said iron (III) carboxymaltodextrin complex measured complexometrically.
2. The iron (III) carboxymaltodextrin complex of claim 1 , wherein the oxidized maltodextrin is obtained by oxidation of maltodextrin in an aqueous hypochlorite solution.
3. The iron (III) carboxymaltodextrin complex of claim 1 , wherein from about 80% to about 100% of an aldehyde group per molecule of maltodextrin is oxidized.
4. The iron (III) carboxymaltodextrin complex of claim 1 , wherein from about 90% to about 100% of an aldehyde group per molecule of maltodextrin is oxidized.
5. The iron (III) carboxymaltodextrin complex of claim 2 , wherein a concentration of the hypochlorite solution is from 13% to 16% by weight, calculated as active chlorine.
6. A medicament comprising the iron (III) carboxymaltodextrin complex of claim 1 and at least one pharmaceutically acceptable carrier, excipient, or additive, wherein said medicament is an aqueous solution of said iron (III) carboxymaltodextrin complex.
7. The medicament comprising the iron (III) carboxymaltodextrin complex of claim 6 , wherein said iron (III) carboxymaltodextrin complex is present in said aqueous solution in an amount of from 1% to 20% by weight, based on a total weight of the aqueous solution.
8. The medicament comprising the iron (III) carboxymaltodextrin complex of claim 6 , wherein the oxidized maltodextrin is obtained by oxidation of maltodextrin in an aqueous hypochlorite solution.
9. The medicament comprising the iron (III) carboxymaltodextrin complex of claim 6 , wherein from about 80% to about 100% of an aldehyde group per molecule of maltodextrin is oxidized.
10. The medicament comprising the iron (III) carboxymaltodextrin complex of claim 6 , wherein from about 90% to about 100% of an aldehyde group per molecule of maltodextrin is oxidized.
11. The medicament comprising the iron (III) carboxymaltodextrin complex of claim 8 , wherein a concentration of the hypochlorite solution is from 13% to 16% by weight, calculated as active chlorine.
12. The medicament comprising the iron (III) carboxymaltodextrin complex of claim 8 , wherein said iron (III) carboxymaltodextrin complex is present in said aqueous solution in an amount of from 1% to 20% by weight, based on a total weight of the aqueous solution.
13. The medicament comprising the iron (III) carboxymaltodextrin complex of claim 6 , wherein the aqueous solution has been sterilized at a temperature of 121° C. and above.
14. The medicament of claim 6 , wherein the aqueous solution has been sterilized at a temperature of 121° C. and above at a contact time of 15 minutes.
15. The medicament of claim 7 , wherein the aqueous solution has been sterilized (i) at a temperature of 121° C. at a contact time of 15 minutes; or (ii) at a temperature of above 121° C. at a contact time of 15 minutes.
16. The medicament of claim 8 , wherein the aqueous solution has been sterilized at a temperature of 121° C. and above.
17. The medicament of claim 8 , wherein the aqueous solution has been sterilized at a temperature of 121° C. and above at a contact time of 15 minutes.
18. The medicament of claim 9 , wherein the aqueous solution has been sterilized at a temperature of 121° C. and above.
19. The medicament of claim 10 , wherein the aqueous solution has been sterilized (i) at a temperature of 121° C. at a contact time of 15 minutes or less; or (ii) at a temperature of 121° C. and above at a contact time of 15 minutes.
20. The medicament of claim 13 for parenteral administration to a subject in need thereof in the form of a single dose of 500 mg to 1000 mg of iron.
21. The medicament of claim 6 , wherein the iron (III) carboxymaltodextrin complex has a weight average molecular weight of from about 118 kDa to about 189 kDa.
22. The medicament of claim 6 for parenteral administration to a subject in need thereof in the form of a single dose of 500 mg to 1000 mg of iron.
23. The medicament of claim 18 for parenteral administration to a subject in need thereof in the form of a single dose of 500 mg to 1000 mg of iron.
24. The medicament of claim 6 , wherein the iron (III) carboxymaltodextrin complex has a weight average molecular weight of: about 141,000 Da, or about 140,000 Da, or about 189,000 Da, or about 178,000 Da, or about 137,000 Da, or about 170,000 Da.
25. The medicament of claim 12 , wherein the iron (III) carboxymaltodextrin complex has a weight average molecular weight of: about 141,000 Da, or about 140,000 Da, or about 189,000 Da, or about 178,000 Da, or about 137,000 Da, or about 170,000 Da.
26. The medicament of claim 18 , wherein the iron (III) carboxymaltodextrin complex has a weight average molecular weight of: about 141,000 Da, or about 140,000 Da, or about 189,000 Da, or about 178,000 Da, or about 137,000 Da, or about 170,000 Da.
27. A method for treating an iron deficiency condition in a subject in need thereof, the method comprising administering to the subject in need thereof a pharmaceutically effective amount of a medicament of claim 6 , wherein the iron deficiency condition is anemia.
28. The method of claim 27 , wherein said medicament is administered (i) intravenously; (ii) by injection; or (iii) by infusion.
29. A method for treating an iron deficiency condition in a subject in need thereof, the method comprising administering to the subject in need thereof a pharmaceutically effective amount of a medicament of claim 22 , wherein the iron deficiency condition is anemia and wherein said medicament is administered (i) intravenously; (ii) by injection; or (iii) by infusion.