Cyclic iron (II) citrate monohydrate and production method thereof, pharmaceutical and / or nutraceutical and / or food compositions comprising it and uses thereof in therapy and in the nutritional field

Abstract

In an iron (II) citrate monohydrate, identified by the formula FeC6H6O7-H2O ( Ferrous citrate monohydrate or iron citrate (II) monohydrate), obtained according to a particular production method, citric acid and elemental iron are bound in a molecular complex where the iron is agglomerated in the citrate which moves to a cyclic form and the iron is bound to the O groups of the carboxylic groups 1 and 3 through ionic bonds, forming two enantiomers, D and L (R and S), both perfectly water-soluble and highly assimilable by the human body. Formula (L) & Formula (D). With a different absorption mechanism from traditional iron molecules, said iron citrate monohydrate is usable in pharmaceutical and / or nutraceutical and / or food compositions, in particular in the treatment and prevention of iron deficiency anemias and in general of all diseases and disorders associated with iron deficiency. The effectiveness is proven by several examples.

Description

The present invention relates to an iron (II) citrate, in particular an iron (II) citrate monohydrate, identified by the formula FeC6H6O7-H2O (Ferrous citrate monohydrate or iron (II) citrate monohydrate), characterized in that unlike the known type, the pH thereof is 2.5 and the molecular structure thereof is not linear, but cyclic, which is distributed in the three directions of space defining what is referred to as the crystalline lattice, citric acid and elemental iron are bound in a molecular complex where the iron is agglomerated in the citrate which moves to a cyclic form and iron is bound to the O~ groups of the carboxylic groups 1 and 3 through dative bonds, forming two enantiomers, D and L (R and S), both perfectly water-soluble and highly assimilable by the human body. The present invention further relates to the particular production method of said Iron Citrate monohydrate in the form of a ferrous molecule complex, which leads the molecule itself to a different absorption mechanism than traditional iron molecules, which method provides for said iron (II) citrate being obtained by direct reaction between zero valent iron, preferably in the form of iron filings or powder, and citric acid in a 1:1 stoichiometric ratio in water, initially starting the reaction in the presence of a starter catalyst such as Fe++ produced in the laboratory, which in water forms ferrous hydroxide Fe(OH)2, in an amount between 5000 and 15,000 ppm., and using, for subsequent productions, always as a catalyst, the reaction processing waste of the zero valent iron and citric acid, or the aqueous solution containing citric iron in an equal amount between 5000 ppm and 15,000 ppm, preferably 10,000 ppm, thus reducing, in a perspective of circular economy, the presence of waste to 0.05%. The invention further relates to pharmaceutical and / or nutraceutical and / or food compositions comprising said iron (II) citrate monohydrate and the uses thereof in therapy and in the food industry (as food or food supplement) , in particular in the treatment and prevention of iron deficiency anemias and in general of all diseases and disorders associated with iron deficiency. By virtue of the experimentally proven solubility thereof in water, the invention further relates to the direct use of said iron (II) citrate monohydrate, in the form of a dry powder, as an additive to be dissolved in water or aqueous solutions, like any salt or sugar. Scope of the invention Iron is an indispensable mineral for the human body. Iron is a trace element necessary for the human body, as it is a fundamental constituent of hemoglobin, myoglobin and several iron-dependent enzymes. Iron performs several functions, such as the transport of oxygen to tissues (hemoglobin), the transfer of electrons in the respiratory chain (transferrin) and the involvement thereof in important enzymatic systems such as the synthesis and degradation of biogenic amines (including the neurotransmitters dopamine and serotonin) and the metabolic degradation of xenobiotics (cytochrome p450 and b5). Given the importance thereof for the human body and since iron is an essential element which is introduced exclusively with the diet, it is continuously recovered and reused by the body, by virtue of the slow and fast-release reserves thereof. In healthy individuals, losses are very limited and, for this reason, the daily requirement requires a minimum exogenous intake which can be met through diet; furthermore, in the absence of exogenous iron for prolonged periods, the body resorts to the consumption of reserve iron stored in ferritin and hemosiderin. In healthy subjects and in baseline conditions, the total iron content in the body is about 4-5 grams, of which about 65% is present in the hemoglobin molecule, while 10% is contained in myoglobin. The remaining amount is mainly represented by storage iron (ferritin and hemosiderin) and by minimal amounts contained in enzymes and cytochromes or associated with transferrin (transport protein). Therefore, the human body maintains the balance between all the forms in which iron is present through control of the iron reserve, the modulation of absorption according to needs and the recovery thereof through the catabolism of erythrocytes. Iron absorption depends on essentially three main factors: the amount of iron introduced into the body through the diet, the release of the iron contained in food by digestive processes and the bioavailability thereof so that it can be absorbed by the mucosa of the small intestine, and the conditions of the intestinal lumen which greatly influence the final availability thereof. Iron is contained in discrete amounts in both foods of animal origin (offal, egg yolk, meat, including fishery products: oysters and clams are particularly rich) and in those of vegetable origin (legumes such as lentils and peas, nuts, asparagus, brewer's yeast, endive, green radicchio and nuts). Iron absorption greatly depends on the food in which it is contained and on the form in which it is found (inorganic or organic) . In general, the absorption of iron present in foods of plant origin is quite low, about 10%; for meats it is about 30%, for soybeans 20%, for fish 15% and for eggs 10%; this highlights that to take account of iron absorption, it is necessary to know the bioavailability as well as the content of the element itself in foods. Currently, research on the absorption of iron through food is still limited and incomplete and the number of subjects studied is modest, considering the multiplicity of factors involved in the assimilation process of the metal. Furthermore, iron metabolism is not completely known, as there are no foods and / or formulations capable of restoring the correct metabolism of iron in the body, while supplementation, in subjects with iron deficiency, serves exclusively to partially compensate for the amount of iron circulating in the body for short periods. The indications reported for the intake of iron in the diet are based on the losses and amounts necessary for growth and to form reserves, also taking into account the bioavailability of this nutrient in the diet itself. A lack of iron is responsible for iron deficiency anemia, a widespread disease in European countries and on several continents, especially in Africa where poor nutrition and malnutrition lead to an increase in people suffering from anemia. Approximately 30% of women of childbearing age and adolescents experience this dysfunction due to depletion of iron reserves, following massive blood loss during menstruation. Such a deficiency also has negative repercussions on other biological systems and mechanisms such as thermoregulation, the immune system and brain neurotransmission systems. Clinically, iron deficiency anemia presents with asthenia, pallor, tachypnea, and tachycardia. In such situations, some signs, such as difficulty concentrating and fatigue, can already be found in the incipient phases of the actual deficiency; the simple control of blood parameters may or may not confirm iron deficiency. Complicating the picture of the diagnosis, it should be noted that it is somewhat difficult to establish the adequacy of the iron values, since there is no single parameter indicative of possible deficiency and this only further complicates the control of iron supplementation. From an immune system perspective, iron deficiency is accompanied by atrophy of lymphatic tissue and a reduction in the activity of macrophages. Excessive iron intake can instead promote bacterial proliferation in malnourished subjects or in the course of infections, although there are no known cases of acute poisoning in adults, as the accumulation diseases are exclusively genetic in nature (hemochromatosis). When calculating iron intake in the diet, it is also important to distinguish the two forms thereof: heme iron (organic form) and non-heme iron (inorganic form), the bioavailability of which is very different and greatly affects the assessment of the potential absorption of iron in the diet. Heme iron, a fundamental constituent for the functioning of hemoglobin and necessary for the formation of red blood cells, is present in the hemoproteins of fish, meat and eggs, and is what our body is best able to absorb from food. The absorption thereof is around 25% and does not depend on the composition of the diet, as it is absorbed as such as a porphyrin complex without interference from other nutrients. The oxidation state of iron in the porphyrin complex is 2 + , which is the form which makes hemoglobin active in oxygen transport. The absorption of non-heme iron is closely related to both the composition of the diet and the state of individual nutrition. The latter is found in grains and vegetables, and being absorbed in smaller amounts, it must be converted to organic form in order to be used later. Furthermore, the oxidized form of ferric iron (Fe3+) is not active in hemoglobin and the body must first transform it into ferrous iron (Fe2+) before it can be used in hemoglobin synthesis. Some dietary constituents, such as phytates (found in the bran of grains and spinach), tannins (found in tea and coffee) and polyphenols (found in olive oil), have the ability to inhibit the absorption of non-heme iron. Experimental tests show that many other compounds, such as ascorbic acid (Vitamin C) and certain foods, such as meat and fish, can even increase the absorption thereof. Therefore, to have greater absorption of the iron contained in vegetables, it is advisable to combine such vegetables, in the same meal, with foods rich in vitamin C: for example, lemon juice can be used as a condiment, or drink orange juice in combination with grains and vegetables. The vitamin C and heme iron contained in foods of animal origin increase the absorption of non-heme iron by 50%. The percentage of non-heme iron absorbed ranges from 2 to 13%. Iron absorption takes place in the intestine at the level of the duodenum and in the first stretch of fasting. The pH of the duodenum favors the absorption of iron in the ferrous state, the latter being much more soluble than ferric iron, providing a greater opportunity for chelation and a higher exposure of the mucosa to solubilized forms, before precipitation occurs . Hemic (organic) iron is absorbed by a different mechanism with respect to inorganic (non-hemic) iron. According to some research, once the heme is detached from the globin to which it is bound, it is recovered from mucosal cells; according to other research, the protein part is removed within the mucosal epithelium. In any case, the released iron is transferred to the plasma in a form which can be bound to transferrin, a protein capable of transporting the iron absorbed by the intestine, that released from the storage sites, and that resulting from the catabolism of hemoglobin. In cases of proven iron deficiency, diet alone, even if based on foods with a high iron content, may be insufficient to resolve the deficiency thereof and it is therefore necessary to resort to targeted products with a high iron content, referred to as food supplements for such a reason. In the most serious cases, where the deficiency becomes dangerous for the body, it is necessary to resort to intravenous injections of iron-based pharmaceutical preparations to quickly restore the amounts required by the body. Among the first attempts made by man to overcome such a deficiency, which date back to the last century, mention should be made of the preparation of "iron water" and "nailed apple" or "iron apple". Nowadays it is possible to turn to the administration of supplements, of natural or synthetic origin, as nutritional supplements in the event of poor introduction with the diet or an increased need by the body. In general, they should however be taken on an empty stomach to avoid decreasing the absorption thereof . One of the best known drugs for the martial therapy of iron deficiency anemias and anemias from acute or chronic blood loss is Ferrograd®, a slow-release tablet drug of ferrous sulfate, the one tablet per day administration of which should be sufficient to cover the daily requirement for this element, even in more demanding subjects. Unfortunately, taking Ferrograd® as a drug is not free of contraindications. Among the side effects which are found, and which are common to all drugs and preparations used as iron supplements, mention should be made of diarrhea, constipation, nausea, abdominal pain, dark stools, allergic reactions; rare cases of gastric intolerance and acute iron intoxication have also been found. Ironbased supplements and drugs are also not recommended for those suffering from hemochromatosis and hemolytic anemia, diseases associated with a reduction in the number of red blood cells and hemoglobin not related to iron deficiency. The most commonly used oral preparation (and the oldest) for iron supplementation is ferrous sulfate, despite being an inorganic compound. As is known, metals are more easily assimilated when taken in organic form, i.e., when the metal is bound to organic molecules, such as citrate, fumarate, gluconate, pyruvate, malate, lactate, etc. In inorganic salts, the mineral is instead free and can be found together with much smaller inorganic compounds such as potassium chloride, magnesium sulfate and sodium chloride, which can interfere with iron assimilation. In addition to ensuring better efficacy, organic salts reduce the possibility that the unassimilated mineral overloads the body's elimination mechanisms. In fact, some of these inorganic salts are not assimilated and used, but directly eliminated right after ingestion, creating the conditions for possible body fatigue, as the excess iron not used properly by the body can have a pro-oxidant effect and can potentially damage cells. Despite such knowledge, as mentioned, ferrous sulfate continues to be a compound widely used for iron supplementation, having been the first compound developed for such a purpose. A growing awareness of the relationship between health and diet and a low propensity to change individual eating habits have led to the development of a new category of enriched products which aim to increase the nutritional value of foods, keeping the organoleptic characteristics thereof unchanged. Using food as a vehicle to increase the intake of certain nutrients is a method which has already been tried for a decade: for example, the enrichment of cooking salt with iodine or the enrichment of flour with iron. Other products enriched with minerals and vitamins recently introduced on the market are dairy products, baby products and fruit juices. An important feature of enriched food products lies in the bioavailability of the mineral component once the product is ingested. Prior art As mentioned, the use of iron (II) citrate (also referred to as ferrous citrate) as a supplement is known, but there is still no complete and precise characterization of this compound in the literature to date, nor of the weight of the preparation method on the features of the compound, and it does not appear in the catalogs of chemical products of the most important international companies. Already in Hermann Kammerer's article "Beitrrage zur Kenntnise der Citonsaure" in JUSTUS LIEBIGS ANNALEN DER CHEMIE, VERLAG CHEMIE GMBH, DE Vol. 170, no. 1-2, January 1, 1873 , pages 176-190, a compound with formula FeC6H6O7»H2O is disclosed, obtained by contacting iron and citric acid, without however providing any indication regarding the use of a specific stoichiometric ratio of iron powder and citric acid such as that of 1:1 disclosed herein, nor the use of a water solution enriched with Fe++ for the preparation thereof, nor information regarding the features of the molecular structure thereof and a physical property thereof such as solubility in water. US3091626 discloses a complicated method for preparing iron (II) citrate which includes the reaction of double salts (sodium citrate and ferrous chloride) and subsequent isolation from the ferrous citrate solution, but the molecular structure of which is not cyclic. Furthermore, the author of the aforesaid patent highlights that it is not possible to prepare ferrous citrate from metallic iron and citric acid dissolved in aqueous solution. Even if it does not describe ferrous citrate using the same name "ferrous citrate monohydrate", WO 2021 / 034800 A2 discloses a product, having the same empirical formula, C6H8O8Fe, but obtained through a process which does not allow obtaining a compound in which iron is complexed forming the innovative structure of the present application. In October 2022, CAS number 2831338-40-8 was issued by the American Chemical Society, which identifies an iron salt having formula FEC6H8O7-H2O (Ferrous citrate monohydrate or iron (II) citrate monohydrate), the structural formula of which is shown below: * HjO , where it is clearly seen that we are in the presence of hydroxyl groups as such. Otherwise, in the iron (II) citrate of the present invention, all the hydroxyl groups are deprotonated, thus having a net negative charge, which forms bonds with the positive charges present in Fe(II), thus creating a cyclization of the molecule and the complexation thereof. h2o The document: NAVIGLIO DANIELE ET AL. "Iron (II) Citrate Complex as a Food Supplement: Synthesis, Characterization and Complex Stability". NUTRIENS, Vol.10, no.11, November 1,   2016, page 1647, XPO93174639, that for brevity we will indicate below as DN, describes a crystalline iron (II) citrate complex having the formula FeCeHeOvlbO and the use thereof as a food supplement for treating iron deficiencies. Furthermore, DN also describes a method for preparing said iron (II) citrate complex, which includes adding citric acid monohydrate to water, heating and adding iron filings when the temperature has reached 90 degrees C. The precipitate formed was filtered and lyophilized. Such a crystalline citrate complex reveals the presence of the COO~ group as a whole (page 8) and that the iron is practically completely present as iron (II) (page 7) . The structure FeCeHeOvfbO is never indicated as cyclic. The Applicant took charge of carrying out comparative tests with the compound DN so as to demonstrate both the different form of the crystalline iron (II) citrate monohydrate of the present application, and the inventive activity deriving from the surprising effects which clearly originate from the different features distinguishing the iron citrate monohydrate of the present application with respect to DN. COMPARATIVE TESTS AND ARGUMENTS The first feature to be underlined is that the document DN, in section 2.5, indicates the formation of a ferrous citrate having pH 6.5. (Iron citrate (50 mg) was added to 100 ml of ultrapure water. The pH value (6.5) of the solution was modified using NaOH (0.1 M) or HC1 (0.1 M) . The pH range evaluated was from 2 to 12. The complex stability was assessed using the spectrophotometric techniques described in Section 2. 4) . Differently, the present patent application discloses the formation of a cyclic ferrous citrate compound having pH 2.5 (see page 58 of the present patent application; . It is known that, chemically, the pH of a solution molecule significantly influences the structure and function of biological molecules: in particular, two molecules with the same crude formula, but present in solutions with different pHs, can behave differently from the biological perspective due to differences in the ionization of functional groups present in the molecule. The pH difference primarily influences the threedimensional shape of the molecule. For example, in proteins, the charge on ionizable groups causes different folds or influences the interaction with other molecules accordingly, as reported in the fundamental text "LehnInger 11 s principles of biochemistry". Each biological molecule has different shapes at different pHs and the biological function thereof depends on the pH. We can cite practical examples such as: Enzymes and Proteins: The function of proteins, in particular enzymes, depends on the three-dimensional structure thereof, which in turn is influenced by the ionization of the side groups. Therefore, at different pHs, the same protein has a different shape and, therefore, a different biological activity. Enzymatic Activity: Many enzymes have an optimal pH at which they work best. Outside this pH range, the activity thereof can decrease or be completely abolished. In light of the above, the molecule synthesized in DN with pH 6.5 and the molecule of the present patent application, with pH 2.5, are two chemically different molecules . A complete comparative crystallographic analysis was then followed to support the claimed polymorphism and the unexpected properties of the crystalline form thereof with respect to the document DN. We anticipate the results with respect to the Experimental Part here, where the results of the different tests carried out are reported, given the probative value thereof which confirms the presence of innovative properties of the product described, specifically with respect to DN. The description will be better followed by referring to the accompanying drawings, in which: Figure la shows the X-ray diffraction analysis on a first sample A, repeated on a second sample B, of the iron (II) citrate disclosed in the prior art document DN; Fig. lb shows the crystallographic analysis of the iron (II) citrate molecule of the present invention, obtained according to the procedure of Example 1; Fig. 1c shows the three graphs A(and B) and C in comparison, which highlights how the characteristic pattern of points of A (and B) and of the sample C are very different; Fig. 2 shows the microscopic images of the crystals of the iron citrate sample in Fig. lb of the invention; Fig. 2a shows the % amount of atoms forming the material of the crystals themselves; Fig. 3 is an EDS layered image, showing how the iron is distributed in the central part of the crystal; Fig. 4 shows the thermogravimetric analysis of iron (II) citrate obtained according to the procedure of Example 1; Figs. 5a and 5b show the results of the solubility test of the Iron citrate monohydrate according to the invention, where by dissolving samples at a concentration of 5000 ppm and 10,000 ppm at room temperature m distilled water and subjecting them to mechanical stirring for 1 hour and 3 hours, respectively, clear and transparent solutions are always obtained; Fig. 6 is a histogram showing the bioaccessible fraction and the excreted fraction of iron expressed as a percentage (%) of the total amount of iron measured at the end of the (complete) digestive process: as can be seen, gastric juices have no impact on the molecule which passes inertly through the stomach; Fig. 7 is a histogram showing the impact of the bioaccessible fractions of the formulation on the viability of the intestinal mucosa: the bioaccessible fraction of the formulation does not cause any reduction of the cellular viability of the intestinal epithelium; Fig. 8 is a histogram showing the absorption of iron in the intestinal epithelium after 1 hour and after 3 hours: to assess the amount of iron, expressed as cell pg / g, absorbed by intestinal epithelial cells, iron was quantified in the apical (fraction applied on the epithelium), basolateral (fraction absorbed), and intracellular fractions; after 1 hour of exposure the amount of iron measured in the intracellular compartment is 70.60 + 14.52 ; after 3 hours it is 95.62 ± 6.75; Fig. 9 is a histogram showing the levels of intestinal ferritin following exposure of the intestinal epithelium to the formulation for 1 hour and 3 hours, where the results are expressed as a mean standard deviation: ferritin was chosen as an indicator of the intracellular iron content, since it is involved in the micronutrient storage process and the expression thereof depends on the intracellular iron level: for the molecule tested, a significant increase in ferritin expression was evidenced with respect to the control FD, which reaches a plateau already after 1 hour of exposure of the intestinal epithelium, about 65.15 protein pg / g; Fig. 10 is the flow diagram of the preparation process of iron citrate iron monohydrate according to the present invention. COMPARATIVE ANALYSIS ON X-RAY CRYSTALLOGRAPHY X-ray crystallography is a fundamental technique for determining the atomic and molecular structure of a crystal. This technique exploits the diffraction of X-rays by atoms in the crystal. Diffracted X-rays form a characteristic pattern of spots (reflections) on a detector. The position and intensity of these reflections contain information on the distances between the atomic planes and the orientation of the atoms in the crystal. The crystallographic analysis reported in DN, on sample A and the repetition thereof on sample B, is shown in Fig. la. The crystallographic analysis of the molecule of the present patent application, sample C, in the same scale as DN, is shown in Fig. lb. In Fig. 1c, the two graphs A and C are compared (graph B is a duplicate of graph A) where it is noted how the characteristic patterns of points are different. For ease of comparison, below we report the detected data of the peaks, diffraction angle and intensity of sample A of DN and sample C of the present patent application: 5 Peak S amp1e A Diffraction Angle (°) Intensity *10A4 Peak S amp1e C Diffraction Angle (°) Intensity *10A4 1 10 2.75 1 12 2.45 2 14 2.25 2 15 1.63 3 16 3.00 3 18 2.78 4 19 1.25 4 19 0.97 5 20 0.90 5 20 1.58 6 21 0.60 6 22 1.20 7 23 0.90 7 24 0.72 8 24 0.60 8 27 1.2 9 25 0.50 9 29 0.87 10 27 1.10 10 30 1.12 11 31 0.57 11 34 1.32 12 33 0.74 12 37 0.89 13 34 0.32 13 40 1.62 14 40 0.47 14 42 0.89 15 43 0.89 15 44 0.75 16 45 0.49 16 59 1.09 17 50 1.14 18 52 0.84 19 54 1.06 20 57 0.78 21 60 0.72 22 64 0.70 23 66 0.86 24 68 0.73 25 70 0.73 It is well known that when X-ray diffraction patterns show peaks at separate distances, the samples have differences in the crystalline structures thereof. 5        In particular in the present case, the Crystalline Structure differences are capable of indicating the following aspects: a) Different Crystalline Phases If the diffraction peaks of the samples are at 10 different angular positions (20), this defines that the samples belong to different crystalline phases defined by two different chemical compounds or two different aggregates which are extremely different. Each crystalline phase has a unique diffraction pattern 15 thereof. Different distances between the peaks indicate that the samples have different lattice parameters. This means that the unit cell sizes of the crystals in the samples are not equal. b) Chemical Composition Different peak positions can reflect variations in the chemical composition of the samples, which can alter the interplanar distances within the crystal. c) Lattice Deformations: Internal stresses or deformations in the crystalline lattice can give rise to variations in the positions of the diffraction peaks. Differences in these voltages can cause peaks to appear at separate distances . It should also be noted that comparing the peaks and the various intensities confirms that with regard to : d) Peak Intensity: • Sample A and sample C have peaks of different intensity, e) Peak Definition • The peaks of sample A and sample C are sharp and well defined f) Peak Positions • The positions of the main peaks are different from Sample A and C, indicating that the samples have different crystalline structures g) Number of Peaks • Samples A and B show a similar number of peaks, suggesting comparable structural complexity, while sample C has a higher number of peaks and in different positions. • Sample C has significant peaks in the 50-70° region, which samples A and B do not have We want to draw attention to the fact that peaks in the 50-70° region in an X-ray diffraction pattern can provide important information about the crystalline structure of the analyzed sample. Peaks at high diffraction angles (50-70°) correspond to very small interplanar distances, according to Bragg's law: nX=2dsin(0)n\lambda = 2d \sin(\theta)nX=2dsin(0), where d is the interplanar distance, X\ lambdaX is the wavelength of the X-rays,   and 0\theta0 is the diffraction angle.   Since   sin(0)\sin(\theta)sin(0) increases with the angle, peaks at 50-70° indicate that the corresponding crystalline planes are very close to each other. The presence of peaks in this region indicates the crystalline order at the atomic level, revealing finer details of the sample structure. By comparing the peaks observed in the 50-70° region with the reference data of the diffraction patterns of DI, it is possible to identify the crystalline phases present in the sample. Each crystalline material has a characteristic diffraction pattern which is used as a "fingerprint" for the identification thereof. h) Identification of impurities If the sample is a mixture of iron with other substances, the peaks in this region can slightly differ in positions and intensities due to the presence of other elements and variations in the crystalline structure. This can help identify the composition of the molecular mixture and the distribution of the elements . Peaks in the 50-70° region in an X-ray diffraction pattern are indicative of crystalline planes with small interplanar distances and provide important details about the atomic structure of the sample. These peaks are crucial for crystalline phase identification, crystalline structure determination, and quantitative analysis of sample components. Confirming this, the document DN does not three-dimensionally define the mapping of the atoms forming the crystal, making no reference to further elements (atoms) which could have aggregated during the experimental reaction procedure, while the subject of the Applicant's application indicates an innovative production method, different from DN, where the use of the catalyst not only reduces the reaction time but acts as a protection for the cyclic aggregation of ferrous citrate monohydrate, avoiding the presence of impurities . As can be seen from Figure 3 of the present patent application, the atoms which have been detected within the crystal are attributable only to Carbon, Hydrogen, Oxygen and Iron. There are no traces of further cations or anions which could interfere with the pH of the molecule and the cyclic three-dimensional molecular structure. In addition, it should be underlined that the reaction rate of the reagents in a final product not only depends on the purity of the reagents but also on the molecular interactions. In DN, the following step is indicated by the author: "As confirmed by the diffraction of monocrystalline X-rays, the structure of the compound can be described as a pseudo three-dimensional octahedral structure consisting of coordinated polyhedral iron chains". This means that the author of the article indicates that, although the compound may have a threedimensional arrangement of atoms, the structure is dominated by units which repeat along a main dimension (often along a specific axis or direction) . In other words, the crystalline lattice shows a kind of limited three-dimensionality, but with a mainly two-dimensional organization along an axis or a plane not forming a well-defined three-dimensional compound. Furthermore, the document DN clearly indicates how the iron is positioned in the center of the structure. In chemistry, an octahedral coordination refers to the arrangement of atoms around a central atom (in this specific case, the iron atom) . In this geometry, the central atom (iron) is surrounded by six atoms or groups (ligands) arranged so that the angles therebetween are about 90 degrees. Instead, as can be verified from Figure 3 of the present patent application, the iron atoms are positioned on the right side of the crystal bound with a strong dative bond to the O~ groups of the various molecular carboxyl groups. OBSERVATION OF POLYMORPHS It is known that the polymorphs of a substance have the same chemical composition, but different arrangement of atoms in space, which leads to different physical, chemical and biological properties. The polymorphs of a substance can have different properties, such as: • Melting points: Different temperatures at which each polymorph passes from the solid to the liquid state . • Solubility: The rate and amount at which each polymorph dissolves in a solvent. • Stability: Some polymorphs can be more stable than others at certain temperatures and pressures. Considering that the document DN previously disclosed that the iron citrate monohydrate closest to the present invention is a linear structure with different pH and differences in the crystal and taking into account that the iron citrate monohydrate described is coordinated by a strong dative bond while the iron citrate of DN is coordinated by ionic attractions, it should be borne in mind that a dative (or coordination) bond is formed when an atom (typically a transition metal such as iron) accepts a pair of electrons from a ligand (in this case, citrate) . In the case of an iron citrate complex with dative bond, as regards the: • Structure: The iron is coordinated by citrate atoms through dative bonds, creating a complex structure having a specific geometry; while as regards the • Solution: In solution, the complex can partially dissociate, but often retains the complex configuration thereof to some extent (as demonstrated by p. 41-43 of the present patent application), depending on the strength of the coordination bond and the solution pH. Differently, a two-dimensional linear iron citrate salt has a structure in which the iron and citrate ions are bound ionically or through simpler covalent bonds, without significant complexation. In particular, with regard to the • Structure: The iron is simply bound to the citrate anions in a less complex form, potentially as a linear chain, while as regards the • Solution: In solution, this type of salt dissociates completely into the constituent ions thereof (Fe2+ and citrate), with a lower tendency to form complex structures with respect to complexes with dative bond. In terms of "equality" in solution, there are some fundamental differences to consider: State of Dissociation: Complex with Dative Bond: the iron and citrate ions do not dissociate completely and the salt maintains part of the complex structure thereof in solution. Linear Complex: the salt tends to dissociate completely into Fe2+ ions and citrate in solution. Chemical and Physical Properties: The chemical and physical properties of complexes with dative bond significantly differ from linear salts due to the difference in electron configuration and geometric structure (underlined in the crystallographic analysis) Interactions in solution, such as solubility, reactivity, and interaction with other ions or molecules, can vary between the two. Stability in Solution: The stability of a complex with dative bond is influenced by factors such as pH and ion concentration, and this leads to it remaining intact under certain conditions (as shown in the Stability studies reported on pages 43 to 45 of the present patent application). On the other hand, a dissociated linear salt does not have structural stability to maintain, being completely dissociated in solution. (Atkins-Jones principles of chemistry) Absorption differences An iron citrate complex with dative bond in solution is not equal to a linear iron citrate salt in solution. Although both contain the same elements (iron and citrate) , the structure, behavior in solution, and chemical and physical properties thereof differ. Furthermore, the absorption of the two molecules by humans will certainly be biochemically different. In fact, the molecule of the present invention, since it has a pH of 2.5 in solution and, as previously demonstrated, does not dissociate into free Fe, resists the acidic pH of the stomach 1-3 passed to the intestine in the form of a complex. With the molecule of DN instead having a pH of 6.5 and given the previous dissociation conditions, the passage from Fe2+ (ferrous iron) to Fe3+ (ferric iron) in the stomach is a redox process influenced by the chemical conditions and the acidic environment of the gastrointestinal tract. Here is how it occurs: The stomach has a very acidic pH, typically between 1 and 3, due to the presence of hydrochloric acid (HC1). The acidic environment favors redox reactions, in particular the oxidation of ferrous iron (Fe2 + ) to ferric iron (Fe3 + ) . Ferrous iron (Fe2 + ) can be oxidized to ferric iron (Fe3 + ) in the presence of oxidants, such as dissolved oxygen or other oxidizing agents present in the stomach. The chemical composition is as follows: 4Fe2++O2+4H+^4Fe3++2H2O Hydrochloric acid (HC1) not only maintains the acidic pH but also provides protons (H+) necessary for the reaction. We can therefore conclude that the molecule of the present patent application differs from that disclosed by DN in that it is different for the pH, for the geometric structure thereof, for the structural stability linked to the dative bond thereof, for the absorption speed by the patient, and for the absence of impurities, allowing to solve a series of objective technical problems that those skilled in the art in the specific field could have requested to solve at the filing date of the present patent application. Objects of the invention It is a first object of the invention to provide pharmaceutical and / or nutraceutical and / or food compositions comprising an iron (IT) citrate, a molecule which is chemically defined as a "neutral complex" in which iron 2+ is strongly bound to the citrate ion, which has a high bioavailability, being obtained through a particular and simple synthesis procedure which allows obtaining iron citrate monohydrate in the form of crystals with a non-linear, but cyclic, molecular structure, which has allowed us to define with certainty, through microscopy techniques described below, the atoms forming the crystal and the aggregations thereof. It is another object of the invention to provide the use of said food and / or nutraceutical compositions of the invention in therapy, in particular in the treatment and prevention of iron deficiency anemias and in general of all the diseases or disorders associated with iron deficiency. It is another object of the invention to provide the use of said compositions of the invention in the nutritional field, as food supplements. It is a further object of the invention to provide the use of iron (II) citrate, prepared as described herein, as an active ingredient of pharmaceutical and / or nutraceutical and / or food compositions. DETAILED DESCRIPTION OF THE INVENTION The Applicant, after long and intensive research and development activity, surprisingly found that it is possible to synthesize a highly assimilable iron (II) citrate through a particular synthesis route. Therefore, the present invention firstly relates to an iron (II) complex having the chemical formula FeC6H6O7 -H2O -ferrous citrate monohydrate or iron (II) citrate monohydrate-, the non-linear structural formula of which is as follows: " V . ; -h2o where citric acid and elemental iron are bound in a molecular complex where the iron is agglomerated in the citrate which moves to a cyclic form and the iron is bound to the Cr groups of the carboxyl groups 1 and 3 through dative bonds. Through this reaction mechanism, we can also describe how the molecule orients itself in threedimensional space to create a drawing of the molecule itself that we will indicate for brevity as CFG, which spatially can take a dextrorotatory or levorotatory shape in space, forming the D and L ( R or S ) enantiomers as previously reported. STRUCTURAL FORMULA OF FeC6H6O7. H2O H2O . H2O Preferably, said iron (II) citrate is for use in a treatment method, preferably in a therapeutic, preventive or curative treatment method, of iron deficiency anemias and of all diseases or disorders associated with iron deficiency. The present invention secondly relates to the method of preparing an iron (II) complex, having a structural formula as indicated above, characterized in that said iron (II) citrate is obtained by direct reaction between zero valent iron, preferably in the form of fine-grained iron filings or powder, and pure citric acid  of  pharmaceutical  grade, in  a  1:1 stoichiometric ratio in the presence of water, reacting iron filings  at  a temperature  from 40°C  (1  Atm pressure) to the boiling temperature of the reaction mixture, preferably at a temperature below 95°C, even more preferably below 90°C, so as to speed up the oxidation and complexation process of the iron powder and citric acid, thus creating a firm molecular structure over time. According to a peculiar feature of the invention, the first reaction between zero valent iron and citric acid is carried out in water in the presence of a starter consisting of Fe(II) produced in the laboratory, so as to form the compound Fe(OH)2 at a concentration such as to saturate the reaction liquid (H2O). This presence is then replaced in the subsequent production steps by production waste, substantially the aqueous solvent with ferrous citrate, which is around 1.40%. It is a further advantageous feature of the invention that through a circular economy mechanism, the production process ensures chemical reaction waste below 0.05%. The present invention also relates to a pharmaceutical, or nutraceutical, or food composition, or a food supplement comprising a mixture comprising or, alternatively, consisting of an iron (II) complex with chemical formula FeC6H6O7 -H2O, ferrous citrate monohydrate or iron (II) citrate monohydrate having a structure formula as indicated above CFG and, optionally, additives, excipients and carriers of acceptable food or pharmaceutical grade. Preferably, said composition is characterized in that it comprises from 1 to 500 mg of iron (II) citrate monohydrate, preferably from 5 to 200 mg, for example from 10 to 100 mg. Preferably, said composition is characterized in that it is for oral administration. Preferably, said composition is for use in a treatment method, preferably in a therapeutic, preventive or curative treatment method of iron deficiency anemias and of all diseases or disorders associated with iron deficiency. According to an aspect thereof, the invention relates to a pharmaceutical and / or nutraceutical and / or food composition (here also only "composition") comprising an iron (II) citrate having an optimal bioavailability, being obtained through a particular and simple synthesis method and at least one physiologically acceptable excipient and / or carrier. According to an embodiment, said iron (II) citrate is obtainable and / or obtained by direct reaction between zero valent iron and citric acid, preferably in a 1:1 stoichiometric ratio. The iron (II) citrate thus produced has a high bioavailability, i.e., it is highly assimilable, unlike most of the known and commercially available iron salts, which are not only partially absorbed but in many cases have associated non-negligible side effects. In particular, the iron (II) citrate included in the compositions according to the invention is synthesized by direct reaction between zero valent iron and citric acid, preferably in a 1:1 stoichiometric ratio, in aqueous solution, preferably with water saturated in Iron (II) where all the products used are strictly tested for "food grade". From laboratory production studies, then adapted on pilot plants, this stoichiometric ratio proved to be the only one possible to maximize the production yield of finished product up to 98.32% in production yield. Variations in stoichiometric ratios lead to losses in production yield and variation in molecular stability. In fact, 1:2 and 1:3 ratios of filings and citric acid and vice versa were tested, but the results were disappointing in terms of production yield and not of formation of the raw material. Preferably, the iron (II) citrate is synthesized by reaction of the filings (or powder) of very pure iron (>99.5%) with very pure anhydrous citric acid (>99.9%), in a heated reactor, in the presence of water saturated with iron (II) in the form of FE++ catalyst, which pushes to maximize production yields and, not creating waste products, generates a circular economy. Preferably, and only for the first production, a starter consisting of iron (II) produced in the laboratory which forms iron (II) hydroxide (ferrous hydroxide) is used as a reaction catalyst in water. With reference to the flow diagram in Fig. 10, the resulting iron (II) citrate, isolated from the reaction mixture by filtration, preferably through vibrating sieves, is pearly greyish-white in colored, and is subjected to freeze-drying, so as to remove almost all water (remaining water weight 1.87%) . By grinding the freeze-dried compound, the pure Iron citrate monohydrate molecule is then obtained, ready to be used in the pharmaceutical supplementation preparations of interest. Advantageously, according to a feature of the invention, the reaction processing waste, i.e., the solvent in which traces (1.40%) of iron citrate monohydrate are present, is reused as a reaction catalyst for subsequent productions without the need to use the starter. Thereby, through a circular economy mechanism, the production process ensures chemical reaction waste below 0.05%. Preferably, the citric acid employed in the reaction is either citric acid anhydrous or citric acid monohydrate . The iron (II) citrate obtained as described was subjected to analysis to confirm the chemical structure and purity thereof, in particular to thermogravimetric analysis. The stability of the iron oxidation state was also verified, repeatedly, by means of a colorimetric assay with the addition of 1,10-ortho-phenanthroline, to ascertain that the iron oxidation state was constantly (II) and counter-tested with potassium thiocyanate to see the presence of Fe+++. The stability of the oxidation state is of fundamental importance for the bioavailability of iron, since, as mentioned, the conversion of iron (II) to iron (III) leads to a poor assimilation of the metal, as it is not directly used by the body. Clinical tests were therefore carried out with the aim of evaluating the bioaccessibility and intestinal absorption of the iron released by the Iron citrate formulation. As shown above, the crystallographic analysis showed a mainly crystalline form, as shown in Figure lb. As can be noted, the iron (II) citrate obtained through the process described herein (Example 1) shows the same crystalline form, demonstrating the reliability of the synthesis reaction. Furthermore, the molecular formula of the obtained crystalline white compound is FeC6H6O7.H2O, i.e., a water molecule is contained in the crystalline lattice of the compound, whereby the synthesized substance is ferrous citrate monohydrate. The iron content for each mole of substance is 21.0% (w / w). A detailed description of the synthesis procedure and analytical techniques are given in the Experimental Part below. Iron (II) citrate prepared as described herein can be used as a food supplement and / or as an additive in food products. Such a supplement and such food products can be used in the treatment and prevention of iron deficiency anemias and in general of all diseases and disorders associated with iron deficiency. Preferably, the iron (II) citrate prepared as described herein is contained in pharmaceutical and / or nutraceutical and / or food compositions. Ferrous citrate is contained in the table of substances allowed by the Ministry of Health for human nutrition. The use of the iron (II) citrate prepared as described herein as an active ingredient of pharmaceutical and / or nutraceutical and / or food compositions is a further subject of the invention. Such compositions can be administered through any suitable route of administration; preferably the compositions of the invention are suitable for oral administration. According to a preferred embodiment, the compositions of the invention are oral or buccal, solid, semi-solid, gel or liquid compositions and can contain conventional physiologically acceptable excipients and / or carriers, as well as food additives and nutraceuticals. The compositions of the invention can be in the form of tablets, hard capsules, soft capsules, capsules, granules, fine granules, powders, tablets, syrups, emulsions, suspensions and solutions suitable for oral administration. Other suitable food, nutraceutical and / or pharmaceutical forms can in any case be used and fall within the scope of protection of the invention. Such compositions can be taken alone or with water or, especially when in the form of powders or granules, can be mixed with other foods, for example with yogurt, creams, gels and the like. Alternatively, the compositions of the invention can be in ready-to-use drinkable form, for example in the form of drinking sachets, of the "stick pack" type, in this case preferably in the form of a cream or gel. The types of excipients, carriers, food, nutraceutical and / or pharmaceutical additives used for the preparation of the compositions of the invention, the ratios of contents of the additives to the active ingredients and the methods of preparing the food, nutraceutical and / or pharmaceutical composition can be appropriately chosen by the skilled formulator. By way of example, organic or inorganic substances, or solid or liquid substances can be used as excipients and carriers, as long as they are edible, physiologically acceptable, and compatible with all other components of the composition. As mentioned, those skilled in the art are perfectly able to select the most suitable vehicles and excipients for preparing the composition. Examples of excipients used for preparing solid food, nutraceutical and / or pharmaceutical compositions include for example lactose, sucrose, starch, talc, cellulose, dextrin, kaolin, calcium carbonate, stearic acid or magnesium stearate, lactose, polyethylene glycol, mannitol, sorbitol, chelating agents, anticaking agents, sweetening agents, preserving agents and flavoring agents. For the preparation of liquid compositions for oral administration, a conventional inert diluent such as water or an oil, for example a vegetable oil, can be used. The liquid composition can contain in addition to the inert diluent, auxiliaries such as wetting agents, suspending agents, sweeteners, flavorings, colorings and preservatives. The liquid composition can be enclosed in capsules of an absorbable material, such as gelatin. The sweeteners can be one or more natural sugars, of reduced choice, for example sucrose, dextrose, xylitol, mannitol or sorbitol, or a synthesis product, for example sodium saccharin, aspartame, acesulfame k or sucralose. If necessary, acidifying agents can also be added, as long as they are compatible with the components of the composition. Flavoring agents are food-, nutraceutically-and / or pharmaceutically-acceptable flavors and flavors of synthetic oils or natural oils, the latter extracted from plants, flowers, fruits and combinations thereof, for example cinnamon, mint, anise, and citrus leaves, bitter almonds, citrus fruits, in particular orange and / or lemon, lime, vanilla, chocolate and grapefruit oils. Chocolate, vanilla or eucalyptus flavors and fruit essences can also be used advantageously, in particular apple, pear, peach, strawberry, apricot, orange, lemon and grape. The composition of the invention can also be in controlled release form or in immediate release / controlled release mixed form. The preparation of such forms is well known to those skilled in the pharmaceutical art. Controlled release forms, for example extended release, are known in the art and include for example the use of excipients and vehicles including retarding materials such as polymers and copolymers of acrylic and methacrylic acid; cellulose derivatives such as hydroxypropyl methylcellulose, hydroxyethyl cellulose, hydroxypropyl ethylcellulose, hydroxypropyl cellulose, methylcellulose, ethylcellulose or sodium carboxymethyl cellulose; gums; waxes; glycerides or aliphatic alcohols or mixtures thereof. The composition of the invention can be multi-dose (e.g., when in liquid form) or in dosage unit form. Each dosage unit can contain from 1 to 500 mg of iron (II) citrate monohydrate, preferably from 5 to 200 mg, for example from 10 to 100 mg, as 50 mg, considering that only 21.0% (w / w) is assimilable iron. The composition of the invention can be administered once or more times a day, preferably once or twice a day. The dosage and daily dose can naturally vary as a function of age, sex and state of health, diet and eating habits of the subject to be treated, as well as the severity of the iron deficiency and the type of therapy, preventive or curative. The doctor will decide the correct dosage of the formulation based on the patient's physiological state. If desired or necessary, the composition of the invention can also contain further active ingredients, for example of natural origin, useful for the prevention and treatment of the nerve diseases described herein. The invention further relates to the use of the compositions described herein in therapy, in particular in the treatment and prevention of iron deficiency anemias and in general of all diseases or disorders associated with iron deficiency. The invention further relates to the use of the compositions described herein in the nutritional field, as food supplements. The invention further relates to a method for the treatment and prevention of iron deficiency anemias and in general of all diseases or disorders associated with iron deficiency, which comprises administering to a subject in need thereof an effective amount of a composition as described herein. In clinical tests, the compositions of the invention showed that the iron (IT) citrate contained therein is highly assimilable and did not show relevant side effects. The invention is hereinafter described in more detail for purely illustrative, and in no way limiting, purposes . EXPERIMENTAL PART The studies carried out start from the formation of the molecule and the preparation method thereof to move on to in vitro analyses on the bioaccessibility and intestinal absorption of the iron released by the Iron Citrate formulation, up to the evaluation of toxicity in test subjects. Then the clinical trial performed on consenting patients is described, which allowed analyzing the representative parameters of the states of anemia due to iron deficiency and verifying the effectiveness of the treatment with iron citrate monohydrate according to the invention. EXPERIMENTAL PROTOCOLS High purity reagents and solvents were used. The water was produced by a milli-Q generator (Millipore, Bedford, MA, USA). Analytical scale series B 204 S (Mettler-Toledo, Germany), freeze dryer mod. Heto Lyolab 3000 (Analytical De Mori, Milan, Italy). UV-Vis spectrophotometer, mod UV-1601 (Shimadzu, Tokyo, Japan), quartz cuvettes with 1.00 cm optical path were used. An automatic powder diffractometer Panalytical Empyrean Powder (Santa Barbara, CA, USA) and the thermogravimetric analyzer TGA400 Perkin Elmer (Norwalk, CT, USA) were used. The first reaction was carried out in water in the presence of a starter consisting of an iron (IT) base obtained in the laboratory. FORMATION OF THE FERROUS CITRATE MONOHYDRATE MOLECULE. The idea of developing organic ferrous iron complexes comes from the traditional administration of the "iron apple" or "Nai apple" which our ancestors used on individuals with various degrees of iron deficiency. Several rusty nails were inserted into an apple and left in contact for about 12-24 hours. After extraction, the apple would appear blackened and would be administered to the anemic subject. The chemical transformation of metallic iron into ionic iron occurs in the apple due to complexed iron compounds which are highly assimilated by the human body. From this popular intuition, the spontaneous process of the "Nail Apple" has been recreated according to the present invention, under stable laboratory conditions. In practice according to the present invention, the citric acid dissolved in iron (11)-enriched water is reacted with zero valent iron (metallic iron, for example iron filings or powder), in a stoichiometric ratio equal to 1:1, heating at a suitable temperature, for example between 40°C and the boiling temperature of the mixture, preferably around 90°C in order to speed up the oxidation and complexation process of the iron and citric acid powder, creating a firm molecular structure over time. PREPARATION OF IRON (II) CITRATE Pharmaceutical grade pure anhydrous citric acid (400 g) was added to 1000 mL of Fe++ enriched water in the amount of 10, 000 ppm, and the solution was heated in a reactor under magnetic stirring. The iron filings (100 grams) were added when the temperature of the solution reached 90°C, the reaction was stopped when the filings completely disappeared and there was a change in color from gray to white; the mixture was then cooled to room temperature after the complete reaction of the iron. In relation to the stoichiometric ratio, iron powder and citric acid are mixed together in a 1:1 ratio. Advantageously, for the first production, a starter consisting of iron (II)) produced in the laboratory is used as a reaction catalyst, which is transformed into iron (II) hydroxide in the aqueous solution. The precipitated pearly gray salt was washed with water and filtered under vacuum with a paper filter; finally, the residue was freeze-dried after freezing at -20°C. THERMOGRAVIMETRIC ANALYSIS Thermogravimetric analysis (TGA) was conducted for iron citrate monohydrate (~ 100 mg) at a temperature range of 30°C to 900°C. The data are shown as the average of three independent replicates in Figure 4. From the data obtained, the iron percentage in the reaction product was 21.1% ± 0.4 (w / w) , since it is in agreement with the theoretical calculated for FeCeHeO? •H2O, as demonstrated by the graph in Fig. 4. DETERMINATION OF THE IRON OXIDATION STATE The colorimetric method based on the complex ion formed by three molecules of 1,10-phenanthroline and one of iron (IT) ion was used to detect the oxidation state of the iron (IT) ion (Fortune, W.B.; Mellon, M.G. Determination of iron with ophenanthroline: A spectrophotometric study. Ind. Eng. Chern. Anal. Ed. 1938, 10, 60-64) . The complexation of the iron (ITT) ion with thiocyanate (SCFF) was useful in detecting the oxidation state of the iron (III) ion (Lister, M.W.; Rivington, D.E. Some measurements on the iron (111) -thiocyanate system in aqueous solution. Can. J. Chern. 1955, 33, 1572-1590) . Any color (red) that appears in the solution, during the first or second test mentioned here, 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 thiocyanate complexes, respectively. For the spectrophotometric dosing of iron, the required solutions were prepared from ammonium iron (II) sulfate [ (NH4) 2Fe (SO4) 2X6H2O] of analytical grade, 1, 10-phenanthroline, potassium thiocyanate (KSCN), hydroxylamine hydrochloride (NH2OH HC1), sodium acetate (NaAc) and 99.999% H2SO4 (Aldrich product no. 339741). The results showed the presence of iron (II) ion and the absence of iron (III) ion. COMPLEX STABILITY Iron citrate (50 mg) was added to 100 mL of water to effect dissolution. The pH value (2.5) of the solution was modified using NaOH (0.1 M) or HC1 (0.1 M). The pH range evaluated was between 2 and 12. The complex stability was evaluated by the spectrophotometric techniques described above. CRYSTALLOGRAPHIC ANALYSIS: X-RAY DIFFRACTOMETRY As previously illustrated, x-ray crystallography is a crystallography technique which uses x-ray diffraction to obtain a spectrum to reveal lattice matter. Typically this leads to determining the material and molecular structure of a substance. The X-ray diffraction profiles of the synthesized samples were recorded with an automatic powder diffractometer, using Ni-filtered Cu K-alpha radiation, which corresponds to a wavelength of 1.5418 A. The profiles were recorded using a continuous scan in the range of diffraction angle 20 between 5 and 60 . (FIG.1) As already mentioned, the result led to the definition of the presence of crystals. CRYSTAL CHARACTERIZATION The crystals were analyzed using microscopic techniques. These techniques allow us to verify the size of the crystals and the distribution of the atoms forming the material. With this sophisticated technique, the results obtained allow us to accurately determine the atoms forming it and the percentage thereof (Figs. 2 and 2a) . EDS LAYERED IMAGE 1 Fig. 3 shows that the iron is distributed in the central part of the crystal. This allows us to say that the molecule closes in a ring to form molecular complexes, where the iron is bound through dative bonds. This chemical structure is an innovative structure where the iron is complexed and not in free form. PREPARATION OF IRON (II) CITRATE MONOHYDRATE CAPSULES. Capsules were prepared containing 50 mg of iron (II) citrate (iron equal to about 21% (w / w), thus 10 mg of highly assimilable iron) and about 300 mg of starch. The method followed for preparing the capsules was as follows: the iron (II) citrate was mixed uniformly with the starch until a homogeneous powder was obtained and then the capsules were filled. SOLUBILITY TEST OF THE IRON CITRATE MONOHYDRATE COMPOUND A dry sample with a moisture content of 1.8% was dissolved in distilled water at a concentration of 5000 ppm and 10,000 ppm at room temperature under constant stirring for 1 hour and for 3 hours. The sample in the 5,000 ppm solution completely dissolved after 1 hour, while the sample in the 10,000 ppm solution completely dissolved after 3 hours. This is demonstrated by the photographs in Figs. 5a and 5b, where the clarity of water is always the same. STUDY ON THE CONTENT OF FREE IRON AND COMPLEXED IRON Two samples were prepared for analysis in triplicate by dissolving 500 mg for each of the following compounds in 100 ml of distilled water. Weight (MG)Water (ML) Iron citrate          500                  100 Monohydrate Standard FE2+           500                  100 After magnetic stirring for one hour, the assay was performed using orthophenanthroline to verify the presence of Fe2+. ASS .509 Iron citrate 0.2100 Monohydrate Standard FE2+0,3809 Ammonium hydroxide was then added to the stock solutions of the samples until a pH of 10.67 was reached, generating an alkaline environment for the formation of Fe2+ iron hydroxide. Fe2+ hydroxide is predominant in the standard and not in the iron citrate monohydrate. After 5 hours, the samples were filtered through filter paper. The supernatant was acidified to pH 2.45 with citric acid. With the following absorbance: S amp1e 50 9 Iron citrate 0, 0384 monohydrate FE2+ standard 0,3684 Comparing the absorbance before and after the reaction with 24% ammonium hydroxide, it was observed that: Sample (PRE) Sample (POST) Iron citrate       0.2100 0.0384 monohydrate FE2+ standard       0,3809 0,3684 The percentage of free iron capable of transforming into iron hydroxide (Fe(OH)2) is as follows for each sample: % Free Iron % Complexed Iron Iron citrate       18,28 81,72 Monohydrate FE2+ standard       96,71 3,29 It can be affirmed that iron citrate monohydrate is a complex of ferrous molecules in which the complexed iron is not attacked by a basic agent such as ammonium hydroxide (24%) . For this reason, iron citrate monohydrate is an innovative molecule in which the fixed position of citric acid pushes the molecule towards a different rapid absorption mechanism with respect to traditional iron molecules. PRODUCT SHELF LIFE STUDY The product shelf life study was carried out according to two methods: 1) In vitro, accelerating degradation kinetics at increasing temperatures; 2) In vivo storage of the sample and collection every month for the duration of 18 months. The analysis included two factors:    a) microbiological analysis and b) ferrous iron content using the dosage of orthophenanthroline and countertest with potassium thiocyanate for FE+++. The results of the test are presented below. IN VITRO ANALYSIS The analysis involved the dissolution of 100 mg of iron citrate monohydrate in 100 ml of distilled water, thus creating a ferrous iron solution with a concentration of 210 ppm. The microbiological parameters and the total content of ferrous iron (Fe2+) were then analyzed at time 0. The results were as follows: Enterobacteriaceae (CFU / g)Ferrous iron (mg / L) TIME 0        <100                  208.98 ±0.13 The first results were recorded and the solution was incubated at a temperature of 37 °C for a duration of 4 weeks, thus accelerating the degradation kinetics of the molecules. Furthermore, 37 °C is the optimal temperature for the growth of Enterobacteriaceae (a family of microorganisms belonging to the class of pathogenic microorganisms). Samples were collected every 7 days to construct a kinetic degradation profile of the molecules. TABLE 1 Enterobacteriaceae (CFU / g)Ferrous iron (mg / L) TIME 0 <100 2 0 9,98 ± 0.13 TIME 7 <100 209.88 ± 0.35 TIME 14 <100 209.91 ± 0.15 TIME 21 <100 207.91 ± 0.91 TIME 28 <100 208.11 ± 0.19 As observed by the experiment, there was no growth of pathogenic microorganisms and the iron content remained substantially unchanged. IN VIVO ANALYSIS An analysis of the iron content in the Fe2+ oxidation state was carried out on a specific production batch, as well as a microbiological analysis (in particular aimed at the Enterobacteriaceae family). After 12 and 24 months, the analysis was repeated on the same production batch, keeping the standards unchanged. TABLE 2 Enterobacteriaceae (CFU / g)Ferrous iron (mg / L) TIME 0 <100 2 0 9,98 ± 0.13 TIME 12 <100 209.28 ± 0.65 TIME 18 <100 208.91 ± 0.82 TIME 24 <100 208.91 ± 0.82 MOLECULAR TOXICITY Molecular toxicity was evaluated through a GLP study (acute oral toxicity of ic (Ischemic accidents in rats), carried out by the Biogem Institute (Ariano Irpino), AV, Italy) . In vivo analyses were carried out on laboratory rats. LD50 (Lethal Dose 50): represents the amount of a substance, per unit of body weight, expressed in mg / kg, capable of causing the death of 50% of the experimental population. The study involved a case series of three subjects per group, administering increasing amounts of the compound in milligrams. The results of the study showed the safety of the molecule even at high doses. No changes in the normal health and behavioral conditions of the reference ID were observed, neither on the day of administration nor on the following days, throughout the duration of the experiment. TABLE 3 Injuries Animal 10,RK Animal 10,LK Animal 11 RK Animal 11LK Animal 12,RK Animal 12,LK lymphocyte interstitial infiltration 0 / 4 0 / 4 1 / 4 0 / 4 0 / 4 0 / 4 Rk= Right Kidney; LK= Left Kidney; 0= No Injury; 1= Minimal; 2=slight 3= Moderate; 4= Marked In conclusion, the aim of the study was to evaluate the potential toxic effects on target organs of Iron Citrate Monohydrate in laboratory mice. No adverse effects on health or mortality were observed in any of the 12 rats examined. Furthermore, no macroscopic damage was recorded during the autopsy. EVALUATION OF BIOACCESSIBILITY AND BIOAVAILABILITY OF THE IRON CITRATE MONOHYDRATE MOLECULE The post-mineralization substance was analyzed with respect to the data obtained in section 1.3. The presence of molecular iron, measuring 20.30% + 0.30, was also confirmed here. This confirms the data represented by TGA. The digestive process involved the use of 50 mg of material, corresponding to 10 mg of iron, subjected to gastric digestion. This digestion process is designed to simulate the human digestive process and is based on the use of fluids which simulate the physiological secretions typical of digestion. Three independent replicates were prepared and analyzed by ICP-MS for each sample. Bioaccessibility refers to the amount of active ingredients released from the formulation into the gastrointestinal tract and available for intestinal absorption. Digestion has no impact on the iron content in the formulation. As can be seen from the graph in Fig. 6, gastric juices have no effect on the molecule, which crosses the stomach inertly. Before evaluating the bioavailability of iron, the impact of the bioaccessible fractions of the formulation on the cellular viability of the intestinal mucosa was evaluated (Fig. 7) . Caco-2 monolayers were exposed to increasing amounts of the formulation for 3 hours. Dose-response analysis revealed that the bioaccessible fraction of the formulation does not cause any reduction in the cellular viability of the intestinal epithelium. Referring to Fig. 8, to assess iron absorption, intestinal epithelia were exposed to the bioaccessible fraction of the formulation for 1 and 3 hours. At the end of incubation, iron was quantified in the apical fraction, basolateral fraction and intracellular fraction to assess the amount of iron absorbed by intestinal epithelial cells. The results show that the basolateral fraction absorbs about 7 pg of iron, in addition to the fraction present within the cells, which amounts to 95.62 pg / g of cells. Iron absorption was also assessed by determining ferritin levels. Ferritin was chosen as an indicator of intracellular iron content since it is involved in the micronutrient storage process and the expression thereof depends on the intracellular level of iron. For the molecule tested, a significant increase in ferritin expression was observed with respect to the control (FD), reaching, as seen in Fig. 9, a plateau after only 1 hour of exposure of the intestinal epithelium, approximately 65.15 pg / g of protein. Therefore, the studies demonstrate an in vitro absorption of the molecule of 83.78%, a bioaccessibility of 98.45% and a positive impact on intestinal epithelial cells. ADMINISTRATION TO CONSENTING PATIENTS Capsules prepared according to the method described above were used to carry out in vivo tests on consenting subjects. The administration involved taking 1-2 capsules per day, on an empty stomach. In all cases, no side effects were detected and the subjects experienced less asthenia and a widespread state of well-being in the first days of treatment. Blood tests before and after iron citrate administration showed the increase m bound blood parameters . LIVE STUDIES OF PARAMETERS REPRESENTATIVE OF IRON DEFICIENCY ANEMIA STATES The in vivo absorption study of the Ferro Citrate Monohydrate molecule involved 30 patients, of whom only 11 were included in the study as they had hemoglobin values below 12 g / dL and parameter values below those of serum iron (70-170 mg / dL) and ferritin (50-150 g / dL) . The study had a duration of 30 days with a total administration of 315 mg of active ingredient, equivalent to 10.5 mg of iron in the Fe2 + oxidation state per day. Patients underwent blood tests at an approved clinical site. Three samples were taken for each patient. Recruitment sampling 15-day control sampling 30-day control sampling The aim of this test was to verify the trend of the increasing values of hemoglobin, serum iron and ferritin in the blood. Furthermore, parameters such as MCH (mean corpuscular hemoglobin) and the total number and size of red blood cells were considered. Patients signed a private document and were instructed on the conduct of the study. Subjects were recruited based on specific parameter values, i.e., hemoglobin deficiency below the reference range (12-16 pg / dL), serum iron (70-170 pg / dL9 and ferritin (50-150 ng / dL) values. Patients showed mean parameter values indicative of a moderately severe anemic condition. TABLE 4 PATIENT Hemoglobin (g / dL) Ferritin (ng / mL) Serum       iron (pg / dL) AO 2 9.5 26.2 56 AO 3 8.9 17.1 32 AO 4 11.9 26.2 56 AO 5 11.1 18.1 48 AO 6 10.3 32.1 31 AO 8 11.2 18.2 48 AO 9 9.5 7.2 12 A10 11.3 18.5 25.1 All 9.2 16.2 14.8 Al 2 11.8 17.2 56 Al 3 10.9 24.2 45 After a treatment, which we reiterate consisted of a daily dose of 10.5 mg for a duration of 30 days of iron in the Fe2+ oxidation state, the analyses were repeated at 15 5 days, corresponding to a total administration of 157 mg of active ingredient, with the following parameter values: TABLE 5 Patient Hemoglobin (g / dL) Ferritin (ng / dL) Serum        iron (pg / dL) A0 2 10.2 30.8 67 A0 3 11.4 38.2 54 A0 4 13.5 32.1 67 A0 5 12.8 22.4 56 A0 6 12.4 42 58 A0 8 12.8 24.6 56 A0 9 10.2 14.5 26 A10 12.5 24.2 34.6 All 11.1 20,1 28.2 Al 2 12.7 20.2 68 Al 3 11.4 28.1 52 and at 30 days, following a total administration of active ingredient for an amount of 315 mg of Iron. The results are given in the following Table: TABLE 6 5 Hemoglobin, ferritin and serum iron values, 30 days Patient Hemoglobin (g / dL) Ferritin (ng / mL) Serum        iron (pg / dL) A0 2 12.4 32.7 71 A0 3 13.9 57.1 81 A0 4 14.1 55.4 75 A0 5 13.4 38.2 68 A0 6 14.2 49 75 A0 8 13.1 26.6 67 A0 9 12.4 16 32 A10 14.2 26.3 42 All 12.8 24.2 34 Al 2 13.4 22 75 Al 3 12.5 32.1 67 HEMOGLOBIN PARAMETER ANALYSIS The iron contained in hemoglobin binds to oxygen to transport it through the body. Oxygen transport is 10 therefore the most important function of hemoglobin and therefore of red blood cells. The World Health Organization (WHO) defines ANEMIA as a reduction in the level of hemoglobin below 12 g / dL . A subsequent classification defines the severity thereof and subdivides it into: mild degree (Hb between 12 g / dL and 10 g / dL9) moderate degree (Hb between lOg / dL and 8 g / dL), severe degree (<8 g / dL) (2.3) The analysis of hemoglobin parameter values in patients treated with the ferrous citrate molecule demonstrates a mean increase in hemoglobin of 1.4g / dL within 15 days and a mean change of 2.8 g / dL within 30 days . Starting from an average hemoglobin level of 11.26 g / dL, over 15 days hemoglobin increased to a value of 12.78 g / dL. These data indicate that a treatment with only 158.5 mg of ferrous iron is sufficient to restore a passive, albeit mild, state of hemoglobin. As shown in Table 7 below, patients A04, A05, A06, A08, A10, and Al2. TABLE 7 PATIENT Hemoglobin (g / dL) Hemoglobin (g / dL) Hemoglobin g / dL Time 0)           Time 15 days     Time 30 days A0 2 9.5 10.2 12.4 A0 3 8.9 11.4 13.9 A0 4 11.9 13.5 14.1 A0 5 11.1 12.8 13.4 A0 6 10.3 12.4 14.2 A0 8 11.2 12.8 13.1 A0 9 9.5 10.2 12.4 A10 11.3 12.5 14.2 All 9.2 11.1 12.8 Al 2 11.8 12.7 13.4 Al 3 10.9 11.4 12.5 On the other hand, a 30-day treatment, with the intake of 315 mg of Ferrous Iron, is sufficient to fill significant gaps in hemoglobin deficiency. Patient A03 is an exceptional case. The initial hemoglobin value for patient A03 was 8.9 g / dL. The final hemoglobin value after treatment is 13.9 g / g / dL, which means that a severe state of hemoglobin deficiency has been overcome, which even exceeded the minimum reference value of 8%. But what is most surprising is the low amount of molecule needed to obtain these results. These data contradict the scientific literature, as demonstrated by a study published by Schrier et al. in Blood 2015 where it is stated that the absorption of 1500-3000 mg of iron is necessary to correct established iron deficiency anemia. Administering an iron therapy, the average absorption of which is about 10% of the iron administered, it can be said that with the intake of 100 mg of iron per day, of which only 10 mg are absorbed, it takes 1 month to absorb 300 mg, 4 months to absorb 1000 mg, and even 8-12 months to bring hemoglobin deficiency levels back to the values of the reference parameters for moderate anemia: therefore, the difference between the literature data and those demonstrated by this experimental study shows that a 10-fold lower amount is already sufficient to correct established iron deficiency anemia. Considering the baseline of 12g / dL, we can confirm that at day 15, 54.54% of patients in the study were able to correct established anemia. Even more interesting is that after 30 days of treatment, 100% of patients managed to return to baseline values of the parameter . FERRITIN PARAMETER ANALYSIS Ferritin is the main iron storage protein within cells. Therefore, the concentration thereof in the blood reflects the extent of iron stores in the body. In clinical practice, the measurement of plasma ferritin (ferritin concentration) is useful to assess the amount of iron available in the body as a whole. An abnormal level of ferritin in the blood can be an indicator of an underlying disease or a specific condition, such as deficiencies responsible for anemia . Ferritin is a spherical protein complex and represents the main iron storage protein within the cell. It accumulates excess iron in a soluble and nontoxic form, transporting it to the areas where it is needed. Excess iron can be toxic to cells due to the ability thereof to generate reactive species which can directly damage DNA and proteins. Therefore, ferritin functions in cellular detoxification by limiting the formation of reactive oxygen species and mitigating the damaging effects thereof on cellular structures. Thereby, it acts as a cushion against excess iron by sequestering it. Small amounts of ferritin are also secreted into the blood, where it acts as an iron transporter. TABLE 8 below shows the ferritin values in ng / dL, at time 0, at 15 days and at 30 days. TABLE 8 Patient Ferritin Time 0 (ng / dL) Ferritin Time 15 days. (ng / dL) Ferritin Time    3 0   days (ng / dL) AO 2 26.2 30.8 32.7 AO 3 17.1 38.2 57.1 AO 4 26.2 32.1 55.4 AO 5 18.1 22.4 13.4 AO 6 32.1 42 49 AO 8 18.2 24.6 25.6 AO 9 7.2 14.5 16 A10 18.5 24.2 26.3 All 16.2 20,1 24.2 Al 2 17.2 20.2 22 Al 3 24.2 28.1 32.1 From the results obtained, it is interesting to note that ferritin, which quantifies the amount of iron stored and ready to be used by the body, increased in all patients by an average of 42%. 5        These results are also consistent with the increase in hemoglobin, since starting from a pathological condition, iron tends to be incorporated into the section of the body which needs it most and then deposited as storage iron, binding to ferritin. 10       SERUM IRON PARAMETER ANALYSIS The test measures iron levels (serum iron), i.e., the concentration of iron circulating in the blood which is not bound to hemoglobin (referred to as "transport iron"). Based on the values obtained, the 15 doctor will assess whether the levels fall within the normal range. In a healthy adult individual there are about 3-5 grams of total iron, of which: one part is found in red blood cells (iron bound to hemoglobin) one portion is stored as a reserve in the body (iron bound to ferritin and hemosiderin) One part represents the "transport iron" (iron bound to transferrin) which is transported by the liver and intestine to the tissues in need thereof through the blood. In conclusion, since the amount of free iron in the blood is negligible, serum iron effectively measures transferrin-bound iron. Low iron levels can cause anemia and are generally due to situations of deficiency (reduced intake with diet or increased need) or poor absorption. Furthermore, low iron levels may indicate significant or prolonged bleeding, pregnancy, rapid growth (in children), infectious disease, neoplasm, or acute myocardial infarction. TABLE 9 Patient Serum iron time 0 (gg / dL) Serum iron time 15 (gg / dL) Serum iron time 30 (gg / dL) A0 2 56 67 71 A0 3 32 54 81 A0 4 56 67 75 A0 5 48 56 68 A0 6 31 58 75 A0 8 48 56 67 A0 9 12 26 32 A10 25.1 34.6 42 All 14.8 28.2 34 Al 2 56 68 75 Al 3 45 52 67 The iron levels, which represent the bound iron circulating in the blood, showed a significant increase when comparing the values at time 0 with those at time 30. An increase of 38.30% from baseline occurred, resulting in complete restoration of baseline conditions for 4 out of 11 patients and almost complete restoration for 3 patients. This indicates that sufficient iron was introduced to allow bound iron to circulate in the blood for 63.63% of the total patients. TOTAL ABSORPTION OF THE IRON CITRATE MONOHYDRATE MOLECULE The absorption of iron citrate follows the following mechanism: Iron is mainly absorbed in the duodenum, then in the proximal section of the small intestine. Enterocytes directly absorb heme iron, while as far as inorganic forms are concerned, the mineral is absorbed exclusively in a bivalent form. During transit in the stomach, the acidity of the gastric environment promotes the reduction of Fe3+ to Fe2 + and together with pepsin releases the iron bound to proteins. As a result, when the synthesis and secretion of gastric juices is altered (e.g., by the use of proton pump inhibitor drugs), iron absorption is substantially reduced. However, at the brush border level of enterocytes, there is a protein - referred to as duodenal cytochrome b (Dcytb) - capable of reducing trivalent iron to bivalent iron, allowing the absorption thereof. Tn the ferrous state, the mineral is then transported across the apical membrane of the enterocyte using the bivalent iron transporter (DMT1). In a hypothetical classification of bioavailability, we would therefore have Heme iron in first place, followed by the inorganic form Fe2+ and a little further back by the non-heme form Fe3+. Some substances in the diet, such as citric acid, promote iron absorption by keeping it in the Fe2+ form. On the other hand, dietary fiber has an opposite effect, and some anti-nutrients (tannins) of vegetable origin. To empirically calculate the absorption of iron citrate, we tested the value of iron present in subjects pre-treatment and posttreatment with predetermined doses of the compound. The difference in pre- and post-intake levels also considering physiological losses led to defining the % absorption of the compound Ferro Citrate Monohydrate, and with significant increases in hemoglobin, Serum iron and Ferritin. As described by the study protocol of Brittenham GM et al. Hematology 2013. TABLE 10 SS334>tt3 ’Si AMt? (sWA MS :       MS I Z.9      1 -iS 5144     io 13 403 :       515      j       5       s 40 : 51$ 227       _ib 4-04 ( « ) Mpr MS' 2.3S       ■" r 405 )        315        i       2,3       ) 2© 231 MS 46$         3--^ S / W ■        3^5        :       <3^       ; 44 MS MS 2S5        _     ' ' )        MS        )                   | IS <4 41$____________ j____________MS___________j___________Z3___________| ________________ MS 41$ ;       MS       )      2.5      ( 15..^ 7,6 . 515 S22         .       -. ••. 4W :       MS I                1 19,2 U $ lf>S         £' 412 :        SIS’        i        1,6        | 1$ <6 MS 41? :          535          :                      ! 22 7,9 ["PAZIENTE" = PATIENT "FERRO ASSUNTO" = IRON TAKEN "DELTA EMOGLOBINA" = DELTA HEMOGLOBIN "DELTA SIDEREMIA" = DELTA SERUM IRON "DELTA FERRITINA" = DELTA FERRITIN "Ferro assorbito" = Iron absorbed "% ASSORBITA" = ABSORBED % "MEDIA" = MEAN] The iron absorbed by the ongoing experimentation is incredibly equal to 91.9%, an impressive figure considering that the average iron absorbed through other types of molecules stands at 15-20%, as reported in the second edition of the book published in December 2022 with the title Nutritional Anemia. STUDY EVALUATING SIDE EFFECTS Side effects were evaluated by completing product evaluation questionnaires, during the study period indicated in section 1.8. The product evaluation questionnaire was completed during recruitment and in the final phase at a Medical Center. Statistical analysis was performed using an intention-to-treat modified analysis, all participants who were randomized received a dose of study drug and participated in at least one post-baseline visit and were then included in the analysis. Two-tailed P values less than 0.05 were predefined as statistically significant. Side effects were evaluated by completing product evaluation questionnaires, during the study period. The product evaluation questionnaire was completed during recruitment and in the final phase at the same Medical Center. The questionnaire evaluated the pre-treatment physiological state and the posttreatment physiological state with six specific questions, and a comparative approval question regarding the supplements previously used. Out of 11 patients selected in the study, 8 questionnaires were considered because the statistical requirements were met. WELL-BEING STATUS PRE-INTAKE QUESTION The overall rating was 1.25 points on a scale 010, where 0 is the minimum and 10 is the maximum. WELL-BEING STATUS POST-INTAKE QUESTION The overall rating was 7.13 punN on a scale of 010 where 0 is the minimum and 10 is the maximum, a percentage increase from initial conditions of 470.4%. SYMPTOM PRE-TREATMENT SELF-ASSESSMENT QUESTION The overall assessment was 5.23 points on a scale of 0-10 where 0 is the minimum of symptoms and 10 is the maximum of the typical symptoms of anemia. SYMPTOM POST-TREATMENT SELF-ASSESSMENT QUESTION The overall assessment was 1.88 points on a scale of 0-10 where 0 is the minimum of symptoms and 10 is the maximum of the typical symptoms of anemia, with a decrease in the typical symptoms of anemia-related diseases of 64%. QUESTION: INDICATE SIDE EFFECTS WITH THE USE OF THE IRON-BASED DRUG / SUPPLEMENT USED UP TO NOW. The overall rating was 4.99 points on a scale of 0-10 where 0 is the minimum of symptoms and 10 is the maximum of symptoms induced by the iron drug / supplement. QUESTION: INDICATE SIDE EFFECTS WITH THE USE OF THE ACTIVE INGREDIENT IRON CITRATE MONOHYDRATE The overall rating was 0.32 points on a scale of 0-10 where 0 is the minimum of symptoms and 10 is the maximum of symptoms induced by the iron drug / supplement. Less than 1% of patients experienced side effects after administration of the active ingredient. This evaluation of side effects was more than expected, given that the iron not absorbed by the active ingredient Iron Citrate Monohydrate stands at 10% of 315 mg total taken, or 31.5 mg. The supplement formulations which the patients used a month before the study were formulations with iron sulfate where doses of 9.6 grams per treatment are used (treatment duration 4 months), as the amount not absorbed from the literature data of iron sulfate stands at 85%, the unabsorbed amount is, therefore, equal to 8.16 grams of iron sulfate; from this amount it seems almost obvious that those who use iron sulfate supplements have common and uncommon side effects . Given the high bioavailability and a 64-fold lower amount of unabsorbed molecule at the same treatment, iron citrate is strictly logical in a concept of a supplement with low / no side effects on patients. In fact, when asked: "How satisfying is the product with respect to supplements used in the past?" the average response was 8.35 points out of 10 where 10 is the maximum satisfaction of the product iron citrate monohydrate. STATISTICAL ANALYSIS Statistical analysis was performed using an intention-to-treat modified analysis, all participants who were randomized received a dose of study drug and participated m at least one post-baseline visit and were then included in the analysis. We used mixed-effects linear models to compare the primary and secondary efficacy endpoints between the randomization groups,   using compound symmetry to account for repeated measurements within each participant. In these models, randomization group, time, and group-by-time terms were analyzed as fixed effects and participants were analyzed as random effects. The primary outcome was the difference in mean change from baseline in each outcome variable at the end of the treatment period (30 days). We also examined differences in the rate of change of each analyte at all time points by testing the statistical significance of group-by-time interaction terms in the model. In the latter models, when there was a significant effect of time, we located the significant changes individually at the post-baseline time points by comparing them with baseline values in the mixed linear models. The proportion of participants who had an adverse event at any time after the baseline visit was compared between randomization groups using Fisher's exact test. Two-tailed P values less than 0.05 were predefined as statistically significant. From what has been disclosed so far, the importance of this molecular complex with a dative bond of cyclic iron (II) citrate monohydrate emerges, which leads the molecule itself to a different absorption mechanism than traditional iron molecules which allows it to reach 91.9%, free of toxicity, with low or no side effects, water-soluble, to be used in the treatment and prevention of iron deficiency anemias and in general of all diseases and disorders associated with iron deficiency.

Claims

CLAIMS :1) An iron (II) citrate, in particular an iron (II) citrate monohydrate, identified by the formula FeC6H6O7 -H2O (Ferrous citrate monohydrate or iron (II) citrate monohydrate), characterized in that it has pH 2.5 and that its molecular structure is not linear, but cyclic, in which citric acid and elemental iron are bound in a molecular complex with dative bond6.     »''T'"       4k / so-         . H2O0'where iron is agglomerated in the citrate which moves to a cyclic form and iron is bound to the O~ groups of the carboxyl groups 1 and 3 through dative bonds, forming the following two enantiomers, D and L (R and S) which are both water-soluble:L                        Dby providing the molecule itself with an enhanced absorption mechanism by the human organism, different from traditional iron molecules.2)   A method of preparing an iron (II) crystal,having a structural formula like that in claim 1,characterized in that said iron (II) crystal is obtained by direct reaction between zero valent iron, preferably in the form of fine-grained iron filings or powder, and pure pharmaceutical grade citric acid, in a stoichiometric ratio 1:1 in the presence of water, said direct reaction between zero valent iron and citric acid being carried out at a temperature between 40°C (1 Atm pressure) and the boiling temperature of the reaction mixture, preferably at a temperature lower than 95°C, even more preferably lower than 90°C, so as to speed up the oxidation and complexation process of the iron powder and citric acid, thus creating a molecular structure well bonded over time.3) The method according to the preceding claim, characterized in that it includes the further steps of: isolating the resulting iron (II) citrate from the reaction mixture by filtration, preferably through vibrating sieves, obtaining a pearly greyish-white colored compound;subjecting said compound to freeze-drying, so as to remove almost all of the water (remaining water weight 1.87%), andthen obtaining, by grinding the freeze-dried compound, the pure molecule of Iron citrate monohydrate in the form of a dry crystalline powder ready to be used in the pharmaceutical preparations of interest.4) The preparation method according to claim 3, characterized in that the reaction processing waste, i.e., the aqueous solvent enriched with Fe2+, is reused as a reaction catalyst for subsequent productions without the need to use the starter, thus reducingreaction waste below 0.05%.5) The preparation method according to claim 3 onwards, characterized in that the iron content for each mole of substance obtained is equal to 21.0% (w / w).6) The iron (IT) citrate monohydrate, according to claim 1 or 2, in the form of a dry crystalline powder, as an additive to be dissolved directly in water or in aqueous solutions, for use in the treatment and prevention of iron deficiency anemias and in general of all diseases and disorders associated with iron deficiency.7) A pharmaceutical and / or nutraceutical and / or food composition comprising iron (IT) citrate monohydrate according to claim 1 or 2, and optionally additives, excipients and carriers of food or pharmaceutically acceptable grade, to be used in therapy and in the food industry (as a food or food supplement), in particular in the treatment and prevention of iron deficiency anemias and in general of all diseases and disorders associated with iron deficiency.8) A composition according to claim 7 for oral or parenteral administration, characterized in that it comprises from 1 to 500 mg of iron (IT) citrate monohydrate, preferably from 5 to 200 mg, for example from 10 to 100 mg.9) A composition according to claim 7, characterized in that the average in vivo absorption of iron released by the same formulation on patients is equal to 91.9%, which value is at least four timeshigher than the average of iron absorbed through other types of iron molecules, which stands at 15-20%.

Images