Iron BIS-citrate monotartrate and production method thereof, pharmaceutical and / or nutraceutical and / or food compositions comprising it and uses thereof in therapy and nutritional field

Abstract

Complex molecular units of ferrous bis-citrate monot art rate stable over time, which has optimal bioavailability, are obtained through a particular and simple synthesis method, and have the following structural formula M: STRUCTURAL FORMULA M Through a polymerization method, such complex molecular units of iron bis-citrate monotartrate form the monomers of a cyclic polymer structure having the following structural formula P: STRUCTURAL FORMULA P where the iron content per each mole of substance is equal to 50. 20% (w / w), and where the same iron has the dual role of bridging the two acids which move in a cyclic form and binding to the 0- groups of the carboxylic groups by means of dative covalent bonds, resulting in both intramolecular and intermolecular bonds. Such a cyclic polymer structure is usable in pharmaceutical, food, and / or nutraceutical composit ions, in particular in the treatment and prevention of iron deficiency anemias and, in general, all diseases or disorders associated with iron deficiency.

Description

[0001] IRON BIS— CITRATE MONOTARTRATE AND PRODUCTION METHOD THEREOF, PHARMACEUTICAL AND / OR NUTRACEUTICAL AND / OR FOOD COMPOSITIONS COMPRISING IT AND USES THEREOF IN THERAPY AND NUTRITIONAL FIELD

[0002] * * *

[0003] DESCRIPTION

[0004] The present invention relates to a new iron molecule, in particular " ferrous bis-citrate monotartrate", identified by the empirical formula

[0005] C16H16O17Fe8 where citric acid, tartaric acid and elemental iron are bound in complex molecular units, where part of the iron is bridged between the two acids which move in a cyclic form and part of the iron is bound to the O~ groups of the carboxylic groups by means of dative bonds in which the oxygen atom of the carboxylic group donates a pair of electrons to the iron atom so that the donor atom and the acceptor atom are bound to each other in a coordinated manner.

[0006] Through this reaction mechanism, we can also describe how the molecule orients itself in three- dimensional space and create an accurate drawing of the molecule itself, as reported below:

[0007] STRUCTURAL FORMULA M

[0008]

[0009] Iron (II) bis-citrate monotartrate This type of bond can be found in inorganic or bioinorganic metal complexes in which iron acts as the metal center and the carboxylic group acts as the ligand.

[0010] For example, in hemoglobin, a protein present in red blood cells which is responsible for the transport of oxygen in the tissues of the body, the iron atom in the heme group forms dative bonds with carboxylic groups of specific amino acid chains of the protein. This allows hemoglobin to bind and transport oxygen through the blood . The nature of the atoms involved in the dative bond is important. In the specific case, the oxygen atom in the carboxylic group is often an effective donor due to the high electronegativity thereof and the presence of a lone pair of electrons. On the other hand, the iron atom is capable of accepting a pair of electrons by virtue of the electronic structure thereof.

[0011] The invention of such a new complex molecular unit consisting of 2 iron citrate molecules bridged by an iron tartrate molecule with dative bonds, and the related production method, originates from the research conducted by the Applicant on iron absorption, which is known to be an essential mineral for the human body. This research has so far resulted in the identification of a cyclic iron (II) citrate monohydrate with the formula FeC6H6O7.H2O in the form of a ferrous molecule complex with a high iron content, to be used as a dietary supplement of natural or synthetic origin, and the related production method thereof, as a nutritional supplement, and in pharmaceutical and / or nutraceutical and / or food compositions, which have been the subject of Italian patent application no. 102023000027300.

[0012] Following the experiments conducted in such a field, the Applicant has found that complex molecular units consisting of two iron citrate moles and one iron tartrate mole can be effectively produced with a percentage yield of 99.7%, through a method which includes : a) melting together stoichiometric amounts of citric acid and tartaric acid, at a temperature between 150 and 180 °C, preferably at the average melting temperature of 170 °C, at atmospheric pressure; b) placing the solution of the two molten acids in a magnetic stirrer thermoregulated at a temperature which allows the molecules of the two acids to remain molten, preferably 150-155°C, even better 153°C, adding a stoichiometric amount of elemental iron filings; and c) waiting for the formation of a reaction compound which, from a black mix, almost instantaneously turns to a gray-white, consisting of complex molecules of iron bis-citrate and iron monotartrate, with the empirical formula :

[0013] C16H16O17Fe8

[0014] Surprisingly, utilizing the principle of recrystallization, the Applicant has demonstrated that with the addition of pure water, preferably distilled water, at ambient temperature to the gray-white reaction compound, in the amount of 60% by weight of the involved reacting material, (substantially 6 molecules of water against 2 moles of citric acid, 1 mole of tartaric acid, and 1 mole of elemental iron) , an intermolecular bond is generated among the various complex molecular units formed by the molten acids and elemental iron, due to the sudden drop in temperature and the consequent recrystallization of the iron-bound molten acids, leading to the formation of a cyclic polymer structure as shown below:

[0015] STRUCTURAL FORMULA P

[0016] which unlike the unstable ferrous compounds that are easily oxidized in the ferric form upon exposure to the atmosphere, remains stable over time. In essence, the complex molecular units of Iron bis-citrate monotartrate, having the structural formula M, effectively act as monomers representing the structural units of a polymer with structure P, in which iron serves the dual purpose of bridging the two acids which move in a cyclic form and binding to the O~ groups of the carboxylic groups by means of dative covalent bonds, resulting in both intramolecular and intermolecular bonds: thus, always by virtue of the presence of iron, such monomers, to form the polymer. are also bound together by means of one or more dative covalent bonds .

[0017] The Applicant has thus defined an industrial process to achieve the polymerization of complex molecules of Iron bis-citrate monotartrate, which, starting from the reaction compound of the previously shown step c) , includes: d) adding to the reaction compound in the magnetic stirrer, thermoregulated at a temperature of 150-155 °C, pure water, preferably distilled, in a ratio proportional to the reagents in the measurement of 6 molecules of water for every 2 moles of citric acid, 1 mole of tartaric acid, and 1 mole of iron, allowing it to act for 20-40 minutes, preferably 30 minutes, so as to reach a reaction temperature of 85-90 °C, to achieve the formation of a white suspension; e) filtering and collecting such a suspension and bringing it to drying, preferably subjecting it to cryogenic drying or heat drying lyophilization chamber, to obtain a white powder, with a well-bonded molecular structure over time, where multiple units of individual molecules complex with one another to create the polymer structure described by the previous three-dimensional image .

[0018] From laboratory production studies then adapted to industrial scale, it was found that the indicated stoichiometric ratio between iron and the two acids is the only possible one to maximize the production yield of the finished product, which, as mentioned, reaches the extremely significant figure of 99.7% in production yield . In fact, variations in stoichiometric ratios between the three reagents lead to losses in production yield and variation in molecular stability.

[0019] As for the temperature in the second step of the reaction, which begins by adding distilled water to the reaction compound between the two molten acids and the iron filings, a temperature defined between 85-90 °C has been set to support the molecular energy of crystallization in order to accelerate the oxidation and complexation process of the iron powder and the molten acids and to create a well-bonded molecular structure over time.

[0020] A peculiar feature of the invention is the fact that, advantageously, the reaction processing waste, i.e. , the solvent from which the cyclic polymer structure was extracted by filtration, is reused, on an industrial scale, as a reaction catalyst for subsequent productions without the need to resort to melting the acids, adding only iron and acids in the natural state, always at a temperature of 85-90 °C.

[0021] It is significant that the production process through such a circular economy mechanism ensures reaction waste below 0.2%.

[0022] The macromolecule formed by the reaction triggered by the addition of water is filtered through vibrating sieves and then lyophilized so as to remove almost all of the water (the weight of the water in the polymer is equal to 0.87%) .

[0023] Subsequently, by grinding the lyophilized compound, the pure molecule referred to as ferrous bis-citrate monotartrate is obtained, ready to be used in pharmaceutical and supplementary preparations of interest .

[0024] Advantageously, the bis-citrate and ferrous monotartrate is obtained in powder form in which the X- ray crystallographic analysis has led to define the presence of crystals.

[0025] Based on the above, we list below the:

[0026] Objects of the invention

[0027] It is a first object of the invention to provide a complex molecule of ferrous bis-citrate monotartrate stable over time, which has optimal bioavailability, being obtained through a particular and simple synthesis method, having the following structural formula:

[0028] STRUCTURAL FORMULA M where the iron content present for each mole of substance does not exceed 28% of the total weight.

[0029] It is another object of the invention to provide pharmaceutical, food, and / or nutraceutical compositions containing said iron bis-citrate monotartrate in therapy, in particular in the treatment and prevention of iron deficiency anemias and, in general, all diseases or disorders associated with iron deficiency.

[0030] It is another object of the invention to provide a bis-citrate monotartrate, in the form of a cyclic polymer structure consisting of the complex molecular units of said iron bis-citrate monotartrate, which has the following structural formula:

[0031] STRUCTURAL FORMULA P where the iron content for each mole of substance is equal to 50.20% (w / w) .

[0032] It is another object of the invention to provide a therapeutically effective compound containing iron (II) bis-citrate monotartrate having the above-mentioned cyclic polymer structure, to provide a source of iron in the diet and more generally containing iron chemically bound in the ferrous state, which after oral administration is usually used without gastrointestinal disturbances, constipation, or diarrhea.

[0033] It is another object of the invention to provide a method for preparing complex molecular units of ferrous bis-citrate monotartrate where part of the iron is bridged between the two acids, which move in a cyclic form, and part of the iron is bound to the 0~ groups of the carboxylic groups by means of dative bonds.

[0034] It is another object of the invention to provide a method for polymerizing such complex molecular units of ferrous bis-citrate monotartrate by bonding them to one another in a cyclic polymer structure, with entirely new reactivity and well-bonded over time, ensuring stability of at least 36 months.

[0035] It is another object of the invention to provide a method for preparing three-dimensional cyclic structures with specific or polymeric geometries, depending on the components, consisting of complex molecular units in which iron interacts with organic acids, acting as an electron acceptor, coordinating with the oxygen atoms of the carboxylic groups of the same acids through dative bonds, not only intramolecular (i.e. , within the single monomer) but also intermolecular (between different monomers) .

[0036] It is another object of the invention to provide a method for preparing three-dimensional cyclic structures with specific or polymeric geometries, consisting of complex molecular units in which magnesium or zinc can replace iron for the formation of said intermolecular bonds of the monomeric units.

[0037] Background art

[0038] To date, there are no publications, articles, or patent documents regarding the polymerization of iron with organic acids, nor production methods related to the polymerization of metals with acids for pharmaceutical purposes.

[0039] POLYMERIZATION OF THE MOLECULE

[0040] The polymerization of metals with acids is not a standard process in conventional chemistry, as metals conventionally do not form polymers in a manner analogous to organic compounds. However, it is possible to examine some reactions between metals and acids which can lead to the formation of complex structures or composite materials .

[0041] In scientific literature, it is not explained how a polymer can form by means of metal-acid interactions.

[0042] In the present invention, the melting of citric acid and tartaric acid has led to a series of interesting chemical-physical changes. Both these organic acids are compounds loaded with chemical functionalities which can react under heating.

[0043] The following considerations are merely a contribution from the inventor to the understanding of the reaction mechanisms which led to the result claimed here, the properties of which have been demonstrated experimentally .

[0044] The most important property highlighted during the studies conducted by the Applicant on the interaction between citric acid, tartaric acid, and iron is that when mixed and heated, citric acid and tartaric acid in the presence of iron interact by means of an esterification reaction, causing the formation of intramolecular and intermolecular esters.

[0045] It is known that iron forms complexes with citric acid and tartaric acid. For example, iron could coordinate with the oxygen of the carboxylic groups, forming very stable complexes coordinated by electrons and protons in an exchange within the orbitals, resulting in the stabilization of the structure.

[0046] Iron acts as an electron acceptor, coordinating with the oxygen atoms of citric and tartaric acids.

[0047] The unshared electrons (lone pairs) on the oxygen atoms of the carboxylic and hydroxyl groups of the acids can be donated to the empty orbitals of the iron.

[0048] Citric and tartaric acids can lose protons (H+) during the formation of the complex with iron, especially from the carboxylic groups.

[0049] Deprotonation increases the electronic density on the oxygen atoms, facilitating the donation of electrons to iron.

[0050] The d orbitals of iron (3d for Fe2+and Fe3+) can accept electrons from the ligands.

[0051] The empty d orbitals can interact with the lone pairs of the oxygen atoms of citric and tartaric acids.

[0052] The oxygen atoms of the acids have lone pairs in the p orbitals.

[0053] These p orbitals can donate electrons to the d orbitals of iron, forming dative bonds. The coordination between iron and the acids can lead to an energetic stabilization of the system.

[0054] The three-dimensional structure of the complex changes with respect to the individual components, forming specific geometries (for example, polymeric for Fe2+) .

[0055] The interaction between iron, citric acid, and tartaric acid involves the exchange of electrons and protons, leading to the formation of coordinated polymers. The oxygen atoms of the acids donate pairs of electrons to the d orbitals of iron, while the deprotonation of the acids increases the electronic density on the oxygen, facilitating complexat ion . These processes modify the chemical-physical properties of the compounds involved, resulting in the formation of a structure with entirely new reactivity which generates a cyclic polymerization of the compound.

[0056] Therefore, the present invention particularly relates to the production of cyclic polymer structures in which iron, citric acid, and tartaric acid bind in complex monomeric units of ferrous bis-citrate monotartrate . POLYMERIZATION OF THE IRON MOLECULE WITH OTHER MINERALS

[0057] The polymerization process between minerals and ligands, such as citric and tartaric acids, involves different steps, including intermolecular attachment, where the addition of distilled water in the already defined stoichiometric amount allows the aggregation of complex monomeric units of iron citrate and iron tartrate into cyclic polymer structures.

[0058] This provided the impetus to verify the possibility of using another metal to create dative bonds between the different complex units.

[0059] In this step, the Applicant experienced that the use of minerals other than iron can be equally effective in facilitating the reaction. However, the minerals acting as "bridges" must have the ability to accept electrons through the electronic orbitals thereof in space. For example, minerals such as magnesium and zinc have proven to be excellent elements capable of promoting "click" reactions, which allow joining molecular units to form polymer chains.

[0060] A crucial step in this process is represented by the first step of the reaction, in which molten acids are reacted with iron to form monomeric units such as iron citrate or iron tartrate. These monomeric units serve as the base for the construction of polymer chains.

[0061] From the experimental tests performed, it was found possible in the subsequent step to introduce a binding mineral, such as magnesium or zinc, in a stoichiometric ratio of 1 mole of such metals for each monomeric unit, to join the various monomeric units.

[0062] This binder is inserted in a central position of the subunit, facilitating the attachment between the monomeric units. Therefore, the polymer chain which forms will not depend exclusively on iron for the growth thereof, but will also be stabilized and extended by the action of the selected binding mineral. A more versatile and stable polymerization is thus achieved, with the synergistic contribution of both iron and the binding mineral .

[0063] Therefore, the present invention also relates to the particular method of producing a cyclic polymer structure consisting of monomeric units of ferrous biscitrate monotartrate in which the attachment between said monomeric units occurs by virtue of the introduction of a binding mineral having the capacity to accept electrons through the electronic orbitals thereof in space, such as magnesium or zinc.

[0064] Further features and advantages of the present invention will become apparent from the detailed description below, with reference to the accompanying drawings showing the results of the experimental tests performed, in which:

[0065] Figure 1 shows the X-ray diffraction analysis of the ferrous bis-citrate monotartrate obtained according to the method of Example 1, compared with the standard crystalline profiles of iron citrate and iron tartrate, and that of an amorphous form;

[0066] Figure 2 shows the quantification of the molecular elements of the sample of ferrous bis-citrate monotartrate in Fig. 1;

[0067] Figure 3 shows the size of the crystals and the nature thereof in SEM analysis a;

[0068] Figure 4 shows the distribution of the atoms forming the polymer, highlighting the uniform distribution of iron and the quantification thereof at 50%;

[0069] Figure 5 shows the content of intracellular ferritin in response to the treatment with all the tested compounds with respect to the untreated cells at a distance of 1 hour and 3 hours;

[0070] Figure 6 shows the impact of the bioaccessibility fractions of the molecule on the cell viability of the intestinal mucosa; from which it is evident that the bioaccessible fraction of the molecule does not cause any reduction of the intestinal epithelium;

[0071] Figure 7 shows the results of a toxicity test on Caco-2 cells, comparing two molecules indicated as "standard" and "novel" by measuring the percentage of viable cells at various time points: at the time of seeding T=0, at 24 hours, 48 hours, and 72 hours.

[0072] DETAILED DESCRIPTION OF THE INVENTION

[0073] Following prolonged and significant research and development activity, the Applicant has surprisingly found that it is possible to synthesize a new complex iron molecule, the "Iron bis-citrate monotartrate," of formula

[0074] C16H16O17Fe8 which is highly assimilable, through a particular synthesis route.

[0075] The present invention relates to an iron compound in which citric acid, tartaric acid, and elemental iron are bound in complex molecular units, where part of the iron is bridged between the two acids which move in a cyclic form, and part of the iron is bound to the 0~ groups of the carboxylic groups by means of dative bonds.

[0076] Preferably, said iron compound is for use in a treatment method, preferably in a method of therapeutically, preventively or curatively treating iron deficiency anemias and all diseases or disorders associated with iron deficiency in the human body.

[0077] The present invention also relates to a method for preparing said iron compound, characterized in that said iron compound is obtained by direct reaction between elemental iron (0) , preferably in the form of iron filings or powder, and the two citric and tartaric acids in the molten state, in a stoichiometric ratio of 2 :1:1, at a melting temperature between 150 °C and 180 °C, preferably at the average melting temperature of 170 °C.

[0078] Said method is characterized in that said direct reaction between the two molten acids and iron filings preferably occurs in a thermoregulated magnetic stirrer.

[0079] The iron bis-citrate monotartrate thus obtained exhibits high bioavailability, i.e. , is highly assimilable, unlike the majority of iron compounds, which are not only partially absorbed but in many cases have associated non-negligible side effects.

[0080] The present invention also relates to a polymer structure consisting of multiple units of individual molecules of iron bis-citrate monotartrate which complex with one another, as in the underlying three-dimensional image that we will indicate as Structural Formula P:

[0081]

[0082] STRUCTURAL FORMULA P

[0083] According to an aspect thereof, the invention relates to a pharmaceutical and / or nutraceutical and / or food composition, comprising a iron (II) bis-citrate monotartrate having optimal bioavailability, i.e. , it is highly assimilable and has an iron content equal to 50%.

[0084] Preferably, the iron (II) citrate is synthesized by reaction of the ultra-pure (>99.5%) iron (0) filings (or powder) with ultra-pure citric acid (99.9%) in the presence of ultra-pure water. The zero-valent iron is preferably iron filings or powder.

[0085] Substantially, in practice, two molecules of citric acid and one of tartaric acid are melted at the average melting temperature of 170 °C. The solution of the two molten acids is placed inside a magnetic stirrer thermoregulated at a temperature of 153 °C with the addition of one molecule of elemental iron filings. When the formation of a gray-white reaction product, consisting of complex molecules of iron biscitrate monotartrate, is observed, the polymerization step is carried out, which includes the addition of distilled water in the magnetic stirrer in a measurement proportional to the amount of the reactants (substantially 60% by weight of the reagent materials) . Distilled or ultra-pure water, at ambient temperature, is added to the thermoregulated magnetic stirrer at T=153 and allowed to react for about thirty minutes, reaching a temperature of 85-90 °C, which temperature is sufficient to accelerate the oxidation and complexation process of the iron powder and the molten acids until the formation of a white suspension.

[0086] Such a suspension (at 40% H2O) is filtered, collected, and placed in a lyophilization chamber for drying .

[0087] Preferably, the polymer molecule formed by the recrystallization reaction of the acids is filtered through vibrating sieves and then lyophilized so as to remove almost all of the water (remaining water weight 0.87%) .

[0088] By grinding the lyophilized compound, the pure polymer molecule referred to as ferrous bis-citrate monotartrate is obtained, ready to be used in pharmaceutical and supplementary preparations of interest .

[0089] The ferrous bis-citrate monotartrate obtained as described was subjected to analysis to confirm the chemical structure and purity thereof. The stability of the oxidation state of iron (IT) was further verified, repeatedly, by means of a colorimetric assay based on the complex formed with three molecules of 1, 10- phenanthroline and one of iron (II) ion.

[0090] The complexation of the iron (III) ion with Potassium thiocyanate (SCN-) was useful to detect the oxidation state of the iron (III) ion as reported by Lister et al. In this case, the sensitivity of these colorimetric methods (01-0.5 ppm) was sufficient for our purposes. Spectrophotometric analyses were carried out, for quantitative analyses, at the wavelengths of 520 nm and 480 nm, which are the maximum absorption values of the 1 , 10-phenanthroline and Potassium thiocyanate complexes, respectively.

[0091] The results of the analysis confirmed a presence of 50.87 + 2.34% (confirming the EDS analysis data) , i.e. , the absence of iron (III) .

[0092] An X-ray analysis was further conducted to verify if the compound was crystalline or amorphous.

[0093] The crystallographic analysis showed a crystalline form, as shown in Fig. 1. As can be noted, the ferrous biscitrate monotartrate obtained in two repetitions of the method described here (Example 1) shows the same crystalline form, demonstrating the reliability of the synthesis reaction. The crystals were analyzed using microscopy technique: the iron content for each mole of substance is equal to 50.20% (w / w) , which is compatible with the experimental calculation of the theoretical weight of iron, which is 48.20%.

[0094] The invention is hereinafter described in more detail for merely illustrative and in no way limiting purposes . Experimental Part :

[0095] Equipment used

[0096] Static oven THERMOFISHER

[0097] Magnetic stirrer VARIANT Spectrophotometer CARY SEM Microscope BIORAD Incubator THERMOFISHER EXAMPLE 1 Preparation of ferrous bis-citrate monotartrate

[0098] For the molecule (Ferrous bis-citrate monotartrate) , 10.5 grams of citric acid and 6.7 grams of tartaric acid were melted at a temperature of 170 °C. Subsequently, the solution of molten acids was placed in a magnetic stirrer thermoregulated between 140 and 160 °C, specifically at 153 °C, with the addition of 5 grams of elemental iron filings.

[0099] Subsequently, after introducing 300 ml of distilled water into the system, which is left to act for 30 minutes, the temperature of the solution reaches 85-90 °C, with the formation of a white compound.

[0100] At this point, the suspension was filtered and collected, and placed for cryogenic drying or heat drying .

[0101] The percentage yield is 99.7%.

[0102] RESULTS

[0103] Molecular design

[0104] Through the study of the reaction and the results from microscopic and EDS (Electronic Dynamic Station) analyses, the chemical reaction is established whereby the molten acids and elemental iron bond in a molecular complex where the iron is bridged between the two forms of acid, which move in a cyclic form, and the iron is bound to the 0" groups of the carboxylic groups by means of dative covalent bonds.

[0105] Through this reaction mechanism, it was also possible to describe now the molecule orients itself in three-dimensional space and to create an accurate design of the molecule itself . Tn particular, multiple units of individual molecules complex with one another to create a sort of polymer described by the three-dimensional image previously reported as Structural formula P.

[0106] Ferrous bis-citrate monotartrate

[0107] The empirical formula of such a molecule is C16H16O17FE8 having a MOLECULAR WEIGHT of 926.76 g / mol. The experimental calculation of the theoretical weight indicates the following percentages by weight of the single components: % Carbon 20.71 % Oxygen 29.34 % Iron 48.20 % Hydrogen 1.72

[0108] X-RAY CRYSTALLOGRAPHIC ANALYSIS

[0109] X-ray crystallography is a crystallography technigue which, through the diffraction of X-rays, allows obtaining a spectrum so as to reveal the nature of the lattice. In general, this leads to determining the material and molecular structure of a substance. X- rays by powder diffraction are useful for those samples which do not have a sufficient crystal size.

[0110] The X-ray diffraction profiles of the synthesized samples were recorded with an automatic powder diffractometer Empyrean-PANalyt ical , using the Cu Ka radiation filtered with Ni, which corresponds to a wavelength of 1.5418 A.

[0111] The profiles were recorded by means of a continuous scan in the 29 diffraction angle range between 5 and 60° . The result led to the definition of the presence of crystals .

[0112] The crystallographic analyses were performed on 4 types of samples so as to highlight the presence of an innovative compound.

[0113] Sample 1 : Cyclic iron citrate monohydrate of

[0114] IT Pat. App. no. 102023000027300;

[0115] Sample 2: Iron citrate present on the market

[0116] Provider Favaravelli

[0117] Sample 3: Iron bis-citrate monotartrate of the present application;

[0118] Sample 4: Iron tartrate Sigma-Aldric

[0119] CRYSTAL CHARACTERIZATION

[0120] The crystals were analyzed by means of microscopy technique. This technique allows us to verify the size of the crystals and the distribution of the atoms forming the material. For this sophisticated technique, the obtained result allows us to define the atoms composing the crystal and the aggregations thereof with certainty.

[0121] As can be seen, the percentage of iron is 50.20% w / w, which is compatible with the experimental calculation of the theoretical weight of iron, which we have seen to be 48.20%. COLORIMETRIC ASSESSMENT

[0122] To confirm the datum of 50.2% iron, a colorimetric analysis was conducted to determine iron in the 2+ state.

[0123] The colorimetric method based on the complex ion formed with three molecules of 1 , 10-phenanthroline and one of iron (II) ion was used to detect the oxidation state of the iron (II) ion. The complexation of the iron (III) ion with Potassium thiocyanate (SCN-) was useful to detect the oxidation state of the iron (III) ion as reported by Lister et al. In this case, the sensitivity of these colorimetric methods (0.1-0.5 ppm) was sufficient for our purposes. Any color (red) which appears in the solution during the first or the second mentioned test indicates the presence of iron (II) or iron (III) ions, respectively. Spectrophotometric analyses were carried out, for quantitative analyses, at the wavelengths of 520 nm and 480 nm, which are the maximum absorption values of the 1 , 10 --phenanthroline and Potassium thiocyanate complexes, respectively.

[0124] The results of the analysis confirmed a presence of

[0125]

Claims

CLAIMS1) Ferrous bis-citrate monotartrate, identified by the empirical formulaC16H16O17Fe8 wherein citric acid, tartaric acid and elemental iron are bound in complex molecular units, where part of the iron is bridged between the two acids which move in a cyclic form and part of the iron is bound to the 0~ groups of the carboxylic groups by means of dative covalent bonds in which the oxygen atom of the carboxylic group donates a pair of electrons to the iron atom so that the donor atom and the acceptor atom are bound to each other in a coordinated manner, where the amount of iron present does not exceed 28% of the total weight. 2) Ferrous bis-citrate monotartrate according to claim 1, characterized in that the structural formula thereof is as follows:STRUCTURAL FORMULA M3) A process for preparing complex molecules of ferrous bis-citrate monotartrate according to claim 1 or 2, characterized in that the production cycle includes an initial start-up activity comprising the following steps : a) melting together stoichiometric amounts of citric acid and tartaric acid 2:1, at a temperature between 150-180°C, preferably at the average melting temperature of 170°C, at atmospheric pressure; b) placing the solution of the two molten acids in a magnetic stirrer thermoregulated between 140 and 160°C, preferably at 153°C, adding a stoichiometric amount ofelemental iron filings; and c) waiting for the formation of a gray-white reaction compound, consisting of complex molecules having the empirical formula of claim 1 and the structural formula of claim 2.4) A process for preparing complex molecules of ferrous bis-citrate monotartrate according to claim 3, characterized in that it has a percentage yield of 99.7%.5) A process for polymerizing complex molecules of ferrous bis-citrate monotartrate according to claim 1 or 2, characterized in that it includes:1) adding to the gray-white reaction compound obtained in step c) and consisting of complex molecules having the structural formula of claim 2, distilled water in an amount of 60% by weight on the total weight of the reagent material, allowing it to act for 20-40 minutes, preferably 30 minutes, at a reaction temperature between 85-90°C, to trigger the recrystallization of the acids and the formation of a gray-white suspension, so as to generate an intramolecular bond between said various complex molecular units having the structural formula of claim 2, and the formation of a polymer structure having the following structural formula:6) A process according to the preceding claim, characterized in that it includes the further steps of: filtering the suspension, preferably through vibrating sieves to isolate the compound formed by the recrystallization reaction; subjecting said compound to lyophilization so as to remove almost all of the water (remaining water weight 0.87%) ; the n obtaining, by grinding the lyophilized compound, the pure polymer molecule in the form of white crystalline powder ready to be used in the pharmaceutical and supplementary preparations of interest.7) A cyclic polymer structure consisting ofcomplex molecular units of iron bis-citrate monotartrate according to claim 1 or 2 which are mutually bound by means of one or more dative covalent bonds having the following structural formula:where the weight percentages of the components are as follows :8) A process for polymerizing complex molecules of ferrous bis-citrate monotartrate according to claim 5, characterized in that the reaction processing waste,i.e. , the aqueous solvent from which the cyclic polymer structure was extracted by filtration, at the first production cycle, is reused as a reaction catalyst for subsequent productions without the need to resort to melting the acids, adding only elemental iron and acids in the natural state to the aqueous solvent always at the temperature of 85-90°C in the thermoregulated magnetic stirrer, thus reducing the reaction slag to below 0.2%.9) A pharmaceutical and / or nutraceutical and / or food composition, or a food supplement comprising or, alternatively, consisting of ferrous bis-citrate monotartrate, according to claim 1 or 7, with stability of 36 months, and optionally additives, excipients and carriers of acceptable food or pharmaceutical grade.10) A composition according to claim 9, characterized in that it is for oral administration.11) A composition according to any one of claims 9 and 10, characterized in that said composition is for use in a method of therapeutically, preventively or curatively treating iron deficiency anemias and all diseases or disorders associated with iron deficiency.

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