Iron amino acid compounds, method for preparing iron amino acid compounds, compositions containing iron amino acid compounds, and uses thereof

Abstract

The invention describes hydrosoluble iron (III) oxyhydroxide complexes prepared from different sources of iron, amino acids and carboxylic acids. The iron (III) complexes have no undesirable residual taste and can be used as supplementation forms for the prevention or treatment of iron deficiency anemia in humans or animals and pharmaceutical or food compositions containing them.

What is claimed is: 
     
         1 . An iron amino acid compound having a molecular formula: 
       
         
           
           
               
               
           
         
         Where: 
         R is —H or the side chain of an essential or nonessential amino acid selected from the group consisting of alanine, phenylalanine, leucine, isoleucine, proline, hydroxyproline, arginine, methionine, aspartic acid, glutamic acid, valine, threonine, isothreanine, histidine, tryptophan, serine, glutamine, and mixtures thereof; 
         R 1  is H or —OH; 
         R 2  is —H or —CH 2 COOH; 
         R 3  is —H or —OH; 
         R 4  is H; 
         K is equal to 0 or 1; wherein
 If k is equal to zero, q is between 1 and 3; 
 If k is equal to 1, q is between 0 and 3; 
 
         X is —Na, —K, —Ca, —Mg or —NH 4 ; 
         Y is between 0 and 20; 
         The molar ratio of m:n ranges from 1:0.5 to 1:10; 
         The molar ratio of m:p ranges from 1:0.1 to 1:1; and 
         The molar ratio m:h ranges from 0.001 to 5.0. 
       
     
     
         2 . The iron amino acid compound according to  claim 1 , wherein the molecular formula 
       
         
           
           
               
               
           
         
         Represents carboxylic acids selected from the group consisting of citric, oxalic, tartaric, malic, succinic, adipic, and fumaric. 
       
     
     
         3 . Process for obtaining iron amino acid compounds, comprising:
 (i) reaction of a source of iron (III) with an amino acid, an organic acid and a base in aqueous solution;   (ii) separating the iron (III) amino acid complex obtained in solid form or as an aqueous solution; and   (iii) drying the solvent used for obtaining the iron (III) amino acid complex.   
     
     
         4 . Process according to  claim 3 , wherein the stoichiometric ratio between the iron source and the selected amino acid is not less than 1:0.5, and preferably not greater than 1:10, respectively, the stoichiometric ratio between the iron source and the selected organic acid varied between 1:0.1 and 1:1 and the stoichiometric ratio of the iron source and the base varied from 1:0.001 and 1:5.0. 
     
     
         5 . Process according to  claim 3 , wherein the iron source is selected from ferric hypophosphite, ferric albuminate, ferric chloride, ferrous chloride, ferric sulfate, ferrous sulfate, ammonium ferric sulfate, ammonium ferrous sulfate, ferric citrate, ammonium ferric citrate, ferrous gluconate, ferrous iodide, ferrous lactate, ferrous fumarate, ferric triglycinate, ferrous bisglycinate, ferrous aspartate glycinate, ferric nitrate, ferric aspartate, ferric phosphate, ferrous hydroxide, ferric hydroxide, ferrous oxide, ferric oxide, metallic iron, ferric ascorbate, ferrous formate, ferrous acetate, ferrous malate, ferrous glutamate, iron glycine sulphate and soluble ferric pyrophosphate, ferric subsulfate, sodium ferric citrate, iron sodium edetate, ferric formate, ammonium ferric oxalate, ferric oxalate of potassium, ferric oxalate, sodium peptonate ferric hydroxides, and other forms of iron, and their respective combinations. 
     
     
         6 . Process according to  claim 3 , wherein the amino acid being selected from glycine, L-lysine, L-alanine, L-phenylalanine, L-leucine, L-isoleucine, L-proline, L-hydroxyproline, L-arginine, L-ornithine, L-methionine, L-aspartic acid, L-glutamic acid, L-valine, L-threonine, L-isothreonine, L-histidine, L-tryptophan, L-serine, L-glutamine, L-citrulline, or also mixtures thereof or their enantiomeric forms, and preferably glycine. 
     
     
         7 . Process according to  claim 3 , wherein the organic acid is selected from citric, oxalic, tartaric, malic, succinic, adipic, fumaric and, preferably, citric acid. 
     
     
         8 . Process according to  claim 3 , wherein base is selected from potassium hydroxide, sodium hydroxide, calcium oxide, calcium hydroxide, calcium carbonate, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, potassium phosphate or calcium alkali, magnesium oxide, magnesium hydroxide, magnesium carbonate, ammonium hydroxide, or any one of their combinations. 
     
     
         9 . Process according to  claim 3 , wherein the reaction in reaction times ranges from 10 min to 5 h, depending on the iron source, amino acid, selected organic acid or base. 
     
     
         10 . Process according to  claim 3 , wherein the separation is by ultrafiltration processes, nanofiltration dialysis of the reaction medium and subsequent concentration by evaporation, until a solution is obtained with the desired complex concentrations; through a filtering process or adding a solvent in which the iron (III) complex is insoluble. 
     
     
         11 . Process according to  claim 3 , wherein drying is under reduced pressure performed in rotary dryers, in greenhouses with or without ventilation, spray dryers or flash dryers. 
     
     
         12 . A pharmaceutical composition comprising a compound according to  claim 1  and at least one pharmaceutically acceptable carrier. 
     
     
         13 . A nutritional composition comprising a compound according to  claim 1  and at least one nutritionally acceptable carrier. 
     
     
         14 . The composition according to  claim 12 , comprising at least two sources of iron. 
     
     
         15 . The composition according to  claim 14 , wherein a second source of iron is selected from the group consisting of ferric hypophosphite, ferric albuminate, ferric chloride, ferrous chloride, ferric sulfate, ferrous sulfate, ammonium ferric sulfate, ammonium ferrous sulfate, ferric citrate, ammonium ferric citrate, ferrous gluconate, ferrous iodide, ferrous lactate, ferrous fumarate, ferric triglycinate, ferrous bisglycinate, ferrous aspartate glycinate, ferric nitrate, ferric aspartate, ferric phosphate, ferrous hydroxide, ferric hydroxide, ferrous oxide, ferric oxide, metallic iron, ferric ascorbate, ferrous formate, ferrous acetate, ferrous malate, ferrous glutamate, iron glycine sulphate and soluble ferric pyrophosphate, ferric subsulfate, sodium ferric citrate, iron sodium edetate, ferric formate, ammonium ferric oxalate, ferric oxalate of potassium, ferric oxalate, sodium peptonate ferric hydroxides, and mixtures thereof in any proportions. 
     
     
         16 . The composition according to  claim 12 , wherein the carrier is selected from the group consisting of maltodextrins, starch, calcium sulfate, magnesium sulfate, calcium carbonate, cellulose derivatives, lactose and its derivatives, water, mixtures of water and another carrier selected from solutions of sorbitol, xylitol, glucose, sucrose, and other saccharides, alcohol, propylene glycol, mixtures for puddings, cake mix, bread, cereals, soups, sauces, cereal bars, chewy candies, hard candies, chewing gum, cheese, curd, jams, yogurts, fruit concentrates for the preparation of juices, yoghurts and milk drinks, syrups, carbonated and noncarbonated beverages selected from soft drinks, juices, flavored waters, nectar type drinks, mixed drinks, milk drinks, powder mixes for preparation of drinks, preparations of effervescent powder, chocolate powder, tea, coffee, and hot drinks obtained by fermentation. 
     
     
         17 . The composition according to  claim 12 , wherein the sweetener is selected from the group consisting of sucrose, sorbitol, xylitol, fructose, glucose, sucralose, aspartame, acesulfame potassium, saccharin, cyclamate, thaumatin, steviosides, rebaudiosides, neohesperidin dihydrochalcone, alitame, and mixtures thereof in any proportions. 
     
     
         18 . A method of preventing and/or treating iron deficiencies in man and animals comprising producing a medicine comprising the composition according to  claim 12 , wherein the composition comprises:
 Iron from 0.01 to 200 mg/g of the composition from one or more sources of iron, whereby at least one source of iron is an amino acid complex;   0.0 to 99% w/w of a nutrient;   0.001 to 99% w/w of a pharmaceutically or nutritionally acceptable inert carrier;   0.0 to 99% w/w sweetener;   0.001 to 20% w/w flavoring agents;   0.001 to 1% w/w colorants;   0.0 to 20% w/w of at least one additive selected from the group consisting of anti-humectants, humectants, antioxidants, thickeners, stabilizers, sequestrants, lubricants, preservatives, acidity regulators, and combinations thereof.   
     
     
         19 . A method of preventing and/or treating iron deficiencies in man and animals comprising producing a nutritional supplement comprising the composition according to  claim 13 , wherein the composition comprises:
 Iron from 0.01 to 200 mg/g of the composition from one or more sources of iron, whereby at least one source of iron is an amino acid complex;   0.0 to 99% w/w of a nutrient;   0.001 to 99% w/w of a pharmaceutically or nutritionally acceptable inert carrier;   0.0 to 99% w/w sweetener;   0.001 to 20% w/w flavoring agents;   0.001 to 1% w/w colorants;   0.0 to 20% w/w of at least one additive selected from the group consisting of anti-humectants, humectants, antioxidants, thickeners, stabilizers, sequestrants, lubricants, preservatives, acidity regulators, and combinations thereof.   
     
     
         20 . The iron amino acid compound according to  claim 1 , wherein R is —H. 
     
     
         21 . The iron amino acid compound according to  claim 2 , wherein the molecular formula 
       
         
           
           
               
               
           
         
         Represents citric acid.