Iron complex compounds for theraputic use

Abstract

The present invention relates to iron complex compounds for therapeutic use which are low in arsenic, chromium, lead, cadmium, mercury and/or aluminum, compositions thereof and processes for preparing said iron complex compounds.

1 - 15 . (canceled) 
     
     
         16 . A process for preparing an iron carbohydrate complex compound comprising the steps of
 (i) obtaining an iron preparation by
 a. decomposing iron pentacarbonyl; 
 b. recrystallization of an iron salt from an aqueous solution thereof 
 c. extracting an aqueous iron salt solution with an organic solvent and recovering the iron salt by stripping the organic solvent; 
 d. precipitation at an anode during electrolysis of an aqueous iron salt solution; 
 e. contacting an aqueous iron salt solution with a base so as to form a precipitate of iron hydroxide and separating the precipitate from the liquid by filtration or centrifugation; or 
 f. distillation of ferric chloride from a mixture comprising ferric chloride and non-volatile impurities, wherein 
   the iron preparation comprises iron in a form selected from a water-soluble iron salt, an iron hydroxide or an iron oxide-hydroxide,   the amount of arsenic in the iron preparation does not exceed 4.5 μg per g of iron, and   the amount of lead in the iron preparation does not exceed 1.5 μg per g of iron; and   (ii) reacting the iron preparation with a ligand in the presence of water so as to form the iron carbohydrate complex compound, and   (iii) recovering said iron carbohydrate complex compound.   
     
     
         17 . The process of  claim 16 , wherein recrystallization in step (i)(b) is recrystallization of ferric nitrate from an aqueous solution containing nitric acid. 
     
     
         18 . The process of  claim 16 , wherein the aqueous iron salt solution of step (i)(c) is obtained during the processing of an iron-containing nickel ore. 
     
     
         19 . The process of  claim 16 , wherein the organic solvent is an alcohol having about 4-20 carbon atoms or an organic solutions of an amine salt. 
     
     
         20 . The process of  claim 16 , wherein the aqueous solution in step (i)(d) comprises iron chloride or iron sulfate. 
     
     
         21 . The process of  claim 16 , wherein the base in step (i)(e) is selected from sodium hydroxide and sodium carbonate. 
     
     
         22 . The process of  claim 16 , wherein step (ii) comprises heating said iron preparation and ligand in the presence of water to boiling. 
     
     
         23 . The process of  claim 16 , wherein the amount of iron in the iron carbohydrate complex compound, determined for dry matter, is from 10 to 50 wt-%. 
     
     
         24 . The process of  claim 16 , further comprising (iv) formulating said iron carbohydrate complex compound for parenteral administration. 
     
     
         25 . The process of  claim 24 , wherein the concentration of iron in the formulation is from 25 to 300 mg/ml. 
     
     
         26 . The process of  claim 25 , wherein said formulation is for subcutaneous injection, intramuscular injection, intravenous injection, or intravenous infusion. 
     
     
         27 . The process of  claim 16 , wherein
 the amount of cadmium in the iron preparation does not exceed 0.6 μg per g of iron, and   the amount of mercury in the iron preparation does not exceed 0.9 μg per g of iron.   
     
     
         28 . The process of  claim 16 , wherein
 the amount of chromium in the iron preparation does not exceed 330 μg per g of iron.   
     
     
         29 . The process of  claim 16 , wherein
 the amount of aluminum in the iron preparation does not exceed 200 μg per g of iron.   
     
     
         30 . The process of  claim 16 , wherein the amount of arsenic in the iron complex compound does not exceed 1.5 μg per g of iron; the amount of lead in the iron complex compound does not exceed 0.5 μg per g of iron; the amount of cadmium in the iron complex compound does not exceed 0.4 μg per g of iron; the amount of mercury in the iron complex compound does not exceed 0.3 μg per g of iron; the amount of chromium in the iron complex compound does not exceed 100 μg per g of iron; and/or the amount of aluminum in the iron complex compound does not exceed 25 μg per g of iron. 
     
     
         31 . The process of  claim 16 , wherein the iron carbohydrate complex compound is selected from iron carboxymaltose, iron polyglucose sorbitol carboxymethyl ether complex, iron dextran, iron hydrogenated dextran, iron sucrose, iron gluconate, iron polymaltose, iron hydrogenated oligosaccharides such as iron hydrogenated oligoisomaltose, iron hydroxyethyl starch, iron dextran glucoheptonic acid and a mixture of two or more thereof. 
     
     
         32 . The process of  claim 31 , wherein said iron carbohydrate complex compound is iron hydrogenated oligoisomaltose. 
     
     
         33 . The process of  claim 31 , wherein said iron carbohydrate complex compound is iron dextran or iron hydrogenated dextran. 
     
     
         34 . The process of  claim 31 , wherein said iron carbohydrate complex compound is iron carboxymaltose. 
     
     
         35 . An iron carbohydrate complex compound, wherein
 the amount of arsenic in the iron complex compound does not exceed 4.5 μg per g iron, and   the amount of lead in the iron complex compound does not exceed 1.5 μg per g iron.   
     
     
         36 . The iron carbohydrate complex compound of  claim 35 , wherein
 the amount of cadmium in the iron complex compound does not exceed 0.6 μg per g of iron, and   the amount of mercury in the iron complex compound does not exceed 0.9 μg per g of iron.   
     
     
         37 . The iron carbohydrate complex compound of  claim 35  or  claim 36 , wherein
 the amount of chromium in the iron complex compound does not exceed 330 μg per g of iron. 
 
     
     
         38 . The iron carbohydrate complex compound of  claim 35 ,  36 , or  37 , wherein the amount of aluminum in the iron complex compound does not exceed 200 μg per g iron. 
     
     
         39 . The iron carbohydrate complex compound of  claim 35 , wherein the amount of arsenic in the iron complex compound does not exceed 1.5 μg per g of iron; the amount of lead in the iron complex compound does not exceed 0.5 μg per g of iron; the amount of cadmium in the iron complex compound does not exceed 0.4 μg per g of iron; the amount of mercury in the iron complex compound does not exceed 0.3 μg per g of iron; the amount of chromium in the iron complex compound does not exceed 100 μg per g of iron; and/or the amount of aluminum in the iron complex compound does not exceed 25 μg per g of iron. 
     
     
         40 . The iron carbohydrate complex compound of  claim 35  or  39 , wherein the iron carbohydrate complex compound is selected from iron carboxymaltose, iron polyglucose sorbitol carboxymethyl ether complex, iron dextran, iron hydrogenated dextran, iron sucrose, iron gluconate, iron polymaltose, iron hydrogenated oligosaccharides such as iron hydrogenated oligoisomaltose, iron hydroxyethyl starch, iron dextran glucoheptonic acid and a mixture of two or more thereof. 
     
     
         41 . The iron carbohydrate complex compound of  claim 35  or  39 , which is iron hydrogenated oligoisomaltose. 
     
     
         42 . The iron carbohydrate complex compound of  claim 41 , wherein said iron hydrogenated oligoisomaltose has the formula:
 {FeO (1-3X) (OH) (1+3X) (C 6 H 5 O 7   3− ) X }, (H 2 O) T , (C 6 H 10 O 6 ) R (—C 6 H 10 O 5 —) Z (C 6 H 13 O 5 ) R , (NaCl) Y  wherein X is about 0.031, T is about 0.25, R is about 0.14, Z is about 0.49, and Y is about 0.14.   
     
     
         43 . The iron carbohydrate complex compound of  claim 41 , wherein the iron hydrogenated oligoisomaltose is ferric derisomaltose. 
     
     
         44 . The iron carbohydrate complex compound of  claim 35  or  39 , which is iron dextran or iron hydrogenated dextran. 
     
     
         45 . The iron carbohydrate complex compound of  claim 35  or  39 , which is iron carboxymaltose. 
     
     
         46 . The iron carbohydrate complex compound of  claim 35  or  39 , wherein the amount of iron in the iron carbohydrate complex compound, determined for dry matter, is from 10 to 50 wt-%. 
     
     
         47 . The iron carbohydrate complex compound of  claim 35  or  39 , which is formulated for parenteral administration. 
     
     
         48 . The iron carbohydrate complex compound of  claim 47 , wherein the concentration of iron in the formulation is from 25 to 300 mg/ml. 
     
     
         49 . The iron carbohydrate complex compound of  claim 48 , wherein said formulation is for subcutaneous injection, intramuscular injection, intravenous injection, or intravenous infusion.