The invention relates to a method of obtaining iron chelate from hydrated iron(III) sulphate. The iron(III) chelate obtained in this way is used in dietary supplements for reducing iron deficiency in the body in humans and treating diseases related to iron deficiency.

Amino acid chelates are generally produced by the reaction between a-amino acids and metal ions with a valency of two or more to form a ring structure. In such a reaction, the positive electric charge of the metal ion can be neutralized by electrons accessible through the carboxyl group or the free amino groups of the amino acid.

The term "chelate" defines the association of a multivalent metal ion with one or more ligands to form a heterocyclic ring structure. According to this definition, chelate formation by neutralizing the positive charges of the metal ion can occur through the formation of an ionic, covalent or coordinate covalent bond. The polyvalent metal ion should be bound to the ligand solely by means of coordination covalent bonds forming the heterocyclic ring.

US Patent No. US7838042 B2 discloses a method of obtaining hypoallergenic metal amino acid chelates and hypoallergenic preparations comprising hypoallergenic metal amino acid chelates. In particular, this patent discloses a method of obtaining iron chelate in which synthetic glycine and calcium oxide are dissolved in water. The synthetic method of producing glycine is based on the reaction of aldehydes with ammonia and hydrogen cyanide, followed by hydrolysis of the resulting a-aminonitriles. The solution of calcium oxide and glycine is mixed until the calcium oxide is completely dissolved. The resulting reaction forms calcium bisglycinate chelate or a complex solution. The iron(II)-comprising ferrous sulphate hydrate is then added to the calcium bisglycinate chelate or the complex solution. Again, the solution is stirred continuously while the ferrous sulphate dissolves and a white precipitate of calcium sulphate is formed. This process creates a chelate of ferrous glycine.

The method known from the above-mentioned patent application has limitations. This process generates a higher yield than theoretical, indicating that the product is contaminated with calcium sulphate. Additionally, there are difficulties in isolating the product in this process. The product created by the above-mentioned the method is glassy, amorphous, difficult to separate. Obtaining it requires filtering the post-reaction mixture by gravity and then concentrating the clarified filtrate and drying it. The obtained product has a vitrified form and is difficult to further use.

In turn, US patent application No. US2007270591 A1 discloses methods of obtaining iron(II) amino acid chelate with a reducing agent associated therewith. The reducing agent can be configured to substantially maintain the iron(II) in its ferrous oxidation state. The iron(II) amino acid chelate according to this method may have a molar ratio of the amino acid ligand to iron(II) of 1:1 to 2:1 and the ratio of reducing agent ligand to iron(II) from 1:1 to 4:1, provided that the combination of amino acid ligands and reducing agent ligands satisfies from 3 to 6 iron(II) coordination positions.

US Patent No. US6710079 B1 describes the composition and method of obtaining amino acid chelates by heating at low to moderate temperatures in a closed environment, the hydration of the metal salt is kept in a closed environment, and serves to provide the necessary moisture to allow binding reactions between electron-rich ligand functional groups and metal ion from the hydrated metal sulphate salt. Additionally, calcium sulphate is formed which can be retained in the end product.

The objective of the present invention is to develop an effective method for the preparation of iron chelate, including the selection of a suitable iron chelator. As part of the research, the following groups of potential complexing agents were analysed in detail: organic carboxylic acids comprising in their structure amino or hydroxyl groups, or amino and hydroxyl groups, and selected amino acids, first of all exogenous. The objective was also to develop such a method of obtaining iron chelate, which would be characterized by simplicity of synthesis, repeatability of the process, ease of scale transfer, maintaining sterility, maintaining chemical purity, avoiding the emission of environmentally harmful waste, the possibility of using typical equipment available on the market in the target production process, low inconvenience of the process for employees and maintaining safety.

A number of experiments were carried out comparing the methods of obtaining chelates based on various amino acids such as: glutamic acid, L-alanine, L- valine, L-proline, L- glutamine, L-leucine and L-methionine. Unexpectedly, it turned out that an optimal method of obtaining iron chelate was found, in which the carrier of the central atom is hydrated ferric sulphate and the ligand is the amino acid L- Alanine as a chelating agent (chelator, coordinator, complexing agent, ligand) iron. The obtained method meets the above-mentioned expectations. The essence of the invention is a method of obtaining iron chelate from hydrated ferric sulphate, which comprises the following steps: a) a solution consisting of alanine and deionized water is prepared at 20°C in a weight ratio of 1: 5.2, then the temperature is increased to 40°C during 45 minutes. b) calcium oxide is then added to the solution with incompletely dissolved alanine with vigorous stirring, the molar ratio of calcium oxide to alanine being at least 1: 2, c) a solution of iron(III) sulphate in water in a weight ratio of 1 : 4.6 is added to the thus obtained mixture, the molar ratio of iron(III) sulphate to alanine being 1:2. d) the reaction mixture is then left for a minimum of 48 h at room temperature until the calcium sulphate precipitates, e) the precipitate formed is filtered off and the iron chelate comprised in the filtrate is concentrated in a vacuum evaporator and dried.

Preferably, in step a) the temperature is increased to 35-65°C, particularly preferably to 40°C.

Preferably, in step b) the molar ratio of calcium oxide to alanine is 1:2. In the case where the molar ratio is less than 1:2, unreacted alanine contaminates the final product.

Preferably, in step d), the solution is left to precipitate for a minimum of 100 h. If the solution is left to precipitate for a minimum of 100 hours, the yield of the process according to the invention is above 85%.

Preferably, in step e), the precipitate is dried at a temperature of at least 60°C.

According to another aspect, the invention also relates to an iron(III) chelate according to the above-mentioned method to reduce iron deficiency in the body in humans and treat diseases related to iron deficiency.

The subject matter of the invention is presented in the following non-limiting embodiments of the protection sought. However, it should be noted that the following information is provided for reference only. Numerous modifications and alternatives to the presented methods can be found by those skilled in the art without departing from the scope of the present invention. The attached claims are intended to cover such modifications.

Embodiment 1 Selection of the chelating agent

In order to select the chelating agent, iron chelate was synthesized with the following chelating agents selected from the group of: glutamic acid, L-alanine, L-valine, L-proline, L- glutamine, L-Ieucine and L-methionine. For each chelator, the synthesis pathway is presented, and Table 8 below provides information on the observed effects of the use of individual chelators.

Glutamic acid. A solution consisting of 10.34 g of glutamic acid and 66 ml of water was prepared. Low solubility of glutamic acid in water, reaching 8.6 mg / ml of water, was observed. 2.0 g of CaO was then added. An exotherm effect was observed upon addition, so it was vigorously stirred until the ingredients were completely dissolved. After a few minutes of stirring, a completely clear solution was obtained. 18.3 g of hydrous iron sulphate was added. A very strong exotherm effect was observed on the addition, therefore, hydrated iron(III) sulphate was added in portions. Stirring was allowed at room temperature for 72h and then it was filtered on a filter paper. The resulting solid precipitate was dried in an oven in a porcelain dish. An attempt was made to dissolve it in water at 50-60°C in about 50 ml, and then 40 ml of ethanol were added. There was turbidity and a red precipitate was dropped out. The whole was dried in a dryer for 72 hours. As a result, 11.2 g of dried chelate was obtained. The ingredients used to obtain the chelate according to this method are summarized in Table 1.

Table 1

L-alanine. A solution consisting of 25.04 g of alanine and 260 ml of deionized water was prepared at 20°C, then after about 10 minutes of stirring with a magnetic stirrer, a solution with incompletely dissolved alanine was obtained, to which 7.99 g of CaO was added. An exotherm effect was observed, so it was stirred vigorously for approx. 45 minutes, and then the temperature was raised to 40°C. A solution of

30.35 g of iron(III) sulfate in 140 ml of water was added to the solution thus obtained. A very strong exotherm effect was observed when adding the iron(III) sulphate solution. Stirring was allowed at room temperature for 2 h and left for 100 h at room temperature. A precipitate of Calcium Sulphate is drops out. The sediment is filtered off. The filtrate, aqueous phase was concentrated on an evaporator. The thick reddish solution was poured into an evaporating dish and dried at 60°C in an oven.

35.4 g of dried chelate was obtained. The ingredients used to obtain the chelate according to this method are summarized in Table 2. Table 2

L-valine. A solution consisting of 16.51 g of valine and 130 ml of water was prepared at 20°C, then after about 10 minutes of stirring with a magnetic stirrer, a solution with incompletely dissolved valine was obtained, to which 4 g of CaO were added. An exotherm effect was observed, so the solution was stirred vigorously for about 30 minutes. A solution of 30.35 g of iron(III) sulphate in water was added to the solution thus obtained. A very strong exothermic effect was observed. Stirring was allowed at room temperature for 2 h and the sediment was drained off. The filtrate was concentrated on an evaporator and poured into an evaporating dish, where it was dried at 60°C. As a result, 33.36 g of dried chelate was obtained. The ingredients used to obtain the chelate according to this method are summarized in Table 3.

Table 3

L-proline. A solution consisting of 16.23 g of L-proline and 130 ml of water was prepared at 20°C, then after about 10 minutes of stirring with a magnetic stirrer, a solution with completely dissolved proline was obtained, to which 4 g of CaO were added. An exothermic effect was observed on the addition of CaO and turbidity appeared. A solution of 30.35 g of iron(III) sulphate in water and 130 ml of water was added in portions to the thus obtained solution due to the formation of an unclear solution. A very strong exothermic effect was observed. Stirring was allowed at room temperature for 0.5 h and the sediment was drained off. The filtrate was concentrated on an evaporator and poured into an evaporating dish, where it was dried at 60°C. 37 g of dried chelate was obtained. The ingredients used to obtain the chelate according to this method are summarized in Table 4. Table 4

L-glutamine. A solution consisting of 20.6 g of L-glutamine and 130 ml of water was prepared at 20°C, then after about 10 minutes of stirring with a magnetic stirrer, a solution with incompletely dissolved L-glutamine was obtained, to which 4 g of CaO were added. An exotherm effect was observed and a significant increase in solubility - the solution was still cloudy but no precipitates were present. A solution of 30.35 g of iron(III) sulphate in water was added in portions to the solution thus obtained. An exotherm effect was observed and the solution turned to a reddish tinge. Stirring was allowed at room temperature for 0.5 h and the sediment was drained off. The filtrate was concentrated on an evaporator and poured into an evaporating dish, where it was dried at 60°C. The ingredients used to obtain the chelate in this process are summarized in Table 5.

Table 5

L-leucine. A solution consisting of 18.5 g of L-leucine and 130 ml of water was prepared at 20°C, then after about 10 minutes of stirring with a magnetic stirrer, a solution with incompletely dissolved L-leucine was obtained, to which 4 g of CaO were added. An exotherm effect was observed and a significant increase in solubility - the solution was still cloudy but no precipitates were present. A solution of 30.35 g of iron(III) sulphate in water was added in portions to the solution thus obtained. An exothermic effect has been observed. Stirring was allowed at room temperature for 0.5 h and the sediment was drained off. The filtrate was concentrated on an evaporator and poured into an evaporating dish, where it was dried at 60°C. 38.70 g of dried chelate was obtained. The ingredients used to obtain the chelate according to this method are summarized in Table 6. Table 6

L-methionine. A solution consisting of 41.88 g of methionine and 130 ml of water was prepared, unfortunately the methionine does not completely dissolve (the water solubility of methionine is about 5%), so an additional 130 ml of water was added, but not fully dissolved methionine was obtained. 7.99 g of CaO was then added to the solution thus obtained. An exothermic effect and an increase in solubility were observed. Complete dissolution of the calcium oxide was observed with intensive stirring for approx. 30 minutes. 39.538 g of iron(III) sulphate was added, the addition of which caused a strong exotherm effect, so it was added in portions. Stirring was allowed at room temperature for 2h and then it was filtered on a filter paper. Then 3.9 g of the filtrate was placed in an open vial in an oven at 60°C. After drying, 0.66 g of a glassy substance remained. The rest of the filtrate in the refrigerator at approx. 5°C does not show a tendency to crystallize. After a week, a muddy sediment drops out of the entire sample, which was decanted and placed in a refrigerator with a glass inoculum. However, the effects were not observed. The ingredients used to obtain the chelate according to this method are summarized in Table 7.

Table 7

Table 8 summarizes the yields of iron chelate production where the source of the central atom was hydrated ferric sulphate with the use of various chelating agents and the observed conditions of the chelate isolation process. Table 8

By analysing the results of the experiments carried out and presented in Table 8, it was surprisingly found that the best conditions for the preparation of iron chelate were achieved using L-alanine as the chelating agent, where the chelate preparation process was characterized by high efficiency and easy chelate separation, and the form of the final product was as expected.

Embodiment 2 Optimization of the chelate preparation method depending on the temperature

Additional experiments were performed to determine the effect on the efficiency of the temperature increase process in step b) of the iron chelate process using alanine as the chelator. Results are given in table 9. Table 9

Unexpectedly, it turned out that increasing the temperature to 35-65% had a positive effect on the efficiency of the chelate production process, reaching the value of over 80%.

Embodiment 3 Optimization of the chelate preparation method depending on the precipitation time

Additional experiments were also carried out to determine the effect of the precipitation time in step e) on the yield of the iron(III) chelate process using alanine as the chelator. The time parameter was estimated for the temperature of 20°C and the obtained results are presented in Table 10.

Table 10

It was unexpectedly found that increasing the precipitation time to lOOh increases the efficiency of the process to over 85%. On the other hand, a satisfactory efficiency of over 80% was achieved in just 48 hours.