Iron ammonium citrate organic acid complex, method for producing the same, and applications

Abstract

The present invention relates to an ammonium iron citrate organic acid complex or a salt thereof, and a method for producing the same; further, to compositions containing the ammonium iron citrate organic acid complex or a salt thereof, and to the application of the complex as an animal feed additive and a food additive; and further, to the application of the ammonium iron citrate organic acid complex or a salt thereof in the manufacture of drugs for the prevention and treatment of diarrhea in farmed animals.

Description

Technical Field

[0001] The present invention relates to an ammonium iron citrate organic acid complex or a salt thereof and a method for producing the same, and further relates to a composition containing the ammonium iron citrate organic acid complex or a salt thereof and the application of the complex as an animal feed additive and a food additive, and further relates to the application of the ammonium iron citrate organic acid complex or a salt thereof in the production of drugs for preventing and treating diarrhea in farmed animals.

Background Art

[0002] Ammonium iron citrate is also called ferric ammonium citrate and ammonium ferric 2-hydroxy-1,2,3-propanetricarboxylate, and is a double salt of ferric citrate and ammonium citrate. It is an organic non-hemoglobin iron complex or iron salt composed of naturally occurring substances (iron, citric acid, and ammonia), and plays an important role in the fields of food and animal farming.

[0003] In food or drugs, ammonium iron citrate is used as an iron source for treating iron element deficiency, as a food additive for enhancing the nutrition of bread or as a dietary iron supplement, and is applied to the production of composite sweetener-containing products and salt as an anti-caking agent.

[0004] In the field of animal farming, ammonium iron citrate is used to reduce the production of H2S in the rumen, used as a nutritional component in health foods for dogs and cats, promotes the growth of dogs and cats, supplements various trace elements and vitamins necessary for their growth, makes the hair coat clean, enhances the immune function of the body, balances nutrition, regulates estrus, increases the number of fetuses, promotes the health of the reproductive system, etc. Furthermore, as a composite mineral of poultry feed additive, it supplements the demand of poultry for mineral elements and promotes the growth and development of poultry.

[0005] However, as described in CN113234107A, ammonium iron citrate is highly hygroscopic, easily degrades under light exposure, and must be stored away from light and at low temperatures. When directly applied to products such as food, feed, or pharmaceuticals, it leads to unstable product quality, susceptibility to moisture absorption, and deterioration, making it unsuitable for practical applications in the animal farming sector. [Overview of the project]

[0006] To address the technical challenges associated with ammonium iron citrate, such as its high susceptibility to deliquescent properties, its tendency to degrade under light irradiation, and the need for storage away from light and at low temperatures, the present invention provides an ammonium iron citrate organic acid complex or salt thereof that is less susceptible to moisture absorption and degradation, and has improved stability.

[0007] The present invention further provides a method for producing an iron ammonium citrate organic acid complex or a salt thereof.

[0008] The present invention further provides feed compositions, food compositions, and medicinal compositions containing an iron ammonium citrate organic acid complex or a salt thereof.

[0009] The present invention further provides applications of iron ammonium citrate organic acid complexes or salts thereof as animal feed additives or food additives, or applications in the manufacture of animal feed additives or food additives.

[0010] The present invention further provides applications of iron ammonium citrate organic acid complexes or salts thereof in the manufacture of drugs for the prevention and treatment of diarrhea in animals.

[0011] In order to achieve the above objectives of the present invention, the following technical solutions are particularly adopted.

[0012] The present invention provides an ammonium iron citrate organic acid complex and a salt thereof, comprising ammonium iron citrate and an organic acid.

[0013] In some technical proposals, the iron ammonium citrate organic acid complex or a salt thereof further comprises at least one solvent capable of solvating the iron ammonium citrate and the organic acid.

[0014] In another aspect, the present invention further provides a method for producing the above-mentioned iron ammonium citrate organic acid complex or a salt thereof, wherein the method is Step (1) involves dissolving an organic acid or its salt in a solvent to obtain a solution of the organic acid or its salt, Step (2) involves dissolving ammonium iron citrate in a solvent to obtain a solution of ammonium iron citrate, Step (3) involves adding the ammonium iron citrate solution to the organic acid or its salt solution to obtain a reaction mixture, and stirring it at a reaction or heating temperature of 25-60°C for 1-4 hours. Step (4) involves stirring the reaction solution after step (3) at room temperature for 4 to 15 hours, The process includes step (4), filtering the reaction solution after step (4), concentrating and drying the filtrate to obtain an ammonium iron citrate organic acid complex or a salt thereof containing ammonium iron citrate and an organic acid.

[0015] The present invention further provides a composition comprising the above-mentioned iron ammonium citrate organic acid complex or a salt thereof, preferably the composition being used as a drug, animal feed, or food.

[0016] The present invention further provides a feed composition comprising the above-mentioned iron ammonium citrate organic acid complex or a salt thereof, and one or more of the following: a feed-compatible carrier, excipient, diluent, and vehicle.

[0017] The present invention further provides a food composition comprising the above-mentioned iron ammonium citrate organic acid complex or a salt thereof and a nutritionally acceptable adjuvant.

[0018] The present invention further provides a pharmaceutical composition comprising the above-mentioned iron ammonium citrate organic acid complex or a salt thereof and a pharmaceutically acceptable adjuvant.

[0019] The present invention further provides an application of the ammonium iron citrate organic acid complex or a salt thereof as an animal feed additive or an application in the production of an animal feed additive.

[0020] The present invention further provides an application of the ammonium iron citrate organic acid complex or a salt thereof as a food additive or an application in the production of a food additive.

[0021] The present invention further provides an application of the ammonium iron citrate organic acid complex in the production of a drug for preventing and treating diarrhea in animals.

[0022] The present invention further provides the ammonium iron citrate organic acid complex used as a drug for preventing and treating diarrhea in animals.

[0023] The present invention further provides a method for preventing and treating diarrhea in animals, the method including administering the ammonium iron citrate organic acid complex to an animal.

[0024] The ammonium iron citrate organic acid complex or a salt thereof according to the present invention has beneficial technical effects that the appearance is stable, the hygroscopicity is significantly improved or enhanced, and the stability under light irradiation is clearly improved compared with ammonium iron citrate. Animal breeding tests further show that the ammonium iron citrate organic acid complex or a salt thereof has a breeding effect equivalent to and even better than that of ammonium iron citrate and can be used as an upgraded product to replace ammonium iron citrate.

[0025] Any embodiment of any aspect of the present invention can be combined with other embodiments as long as there is no contradiction. In any embodiment of any aspect of the present invention, any technical feature can be applied to the technical features in other embodiments as long as there is no contradiction.

Brief Description of the Drawings

[0026] [Figure 1] It is the FTIR spectrum diagram of the ammonium iron citrate organic acid complex A. [Figure 2] It is the FTIR spectrum comparison diagram of the ammonium iron citrate organic acid complex B, ammonium iron citrate, and fumaric acid raw materials. [Figure 3] It is the FTIR spectrum diagram of the ammonium iron citrate organic acid complex C. [Figure 4] It is the XRD chart of the ammonium iron citrate organic acid complex A. [Figure 5] It is the XRD chart of the ammonium iron citrate organic acid complex B. [Figure 6] It is the XRD chart of the ammonium iron citrate raw material. [Figure 7] It is the XRD chart of the fumaric acid raw material. [Figure 8] It is the XRD chart of the ammonium iron citrate organic acid complex C. [Figure 9] It is the FTIR spectrum diagram of the raw material mixture of ammonium iron citrate and fumaric acid with a molar ratio of 2:1. [Figure 10] It is the XRD chart of the raw material mixture of ammonium iron citrate and fumaric acid with a molar ratio of 2:1. [Figure 11] It is the DSC curve diagram of the ammonium iron citrate raw material. [Figure 12] It is the DSC curve diagram of the ammonium iron citrate organic acid complex B. [Figure 13] It is the DSC curve diagram of the fumaric acid raw material. [Figure 14] It is the DSC curve diagram of the raw material mixture of ammonium iron citrate and fumaric acid with a molar ratio of 2:1.

[0027] The above-described content only outlines some aspects of the present invention, but is not limited to these aspects. The above-related content and the content of other aspects will be described more specifically and completely below. Detailed Description of the Invention

[0028] The following detailed description is intended to enable those skilled in the art to carry out different embodiments. Specific apparatus, techniques, or applications are described only as examples. The present invention is intended to encompass all alternative, modification, and equivalent technical proposals, all of which fall within the scope of the invention as defined in the claims. Some technical features of the present invention are described individually in several independent embodiments for clarity, but may also be provided in combination in a single embodiment or in any suitable sub-combination.

[0029] The iron ammonium citrate organic acid complex according to the present invention This invention provides an ammonium iron citrate organic acid complex and its salts.

[0030] Here, the organic acid is an organic acid or acidic amino acid that is acceptable for pharmaceutical, food, and feed use, and the organic acid is selected from fumaric acid, maleic acid, succinic acid, malonic acid, oxalic acid, benzoic acid, or sorbic acid, and the acidic amino acid is selected from glutamic acid or aspartic acid, preferably the organic acid is fumaric acid or maleic acid.

[0031] In some specific embodiments, the solution further comprises at least one solvent capable of solvating ammonium iron citrate and an organic acid, preferably the solvent being selected from water, methanol, ethanol, an aqueous methanol solution, or an aqueous ethanol solution.

[0032] In some specific embodiments, the salt of the iron ammonium citrate organic acid complex is selected from a sodium salt, a potassium salt, or an ammonium salt, and preferably the salt of the iron ammonium citrate organic acid complex is the iron ammonium citrate organic acid complex sodium salt.

[0033] In some specific embodiments, the iron ammonium citrate organic acid complex or a salt thereof is used as a drug, feed, or food, and preferably, as a drug, the iron ammonium citrate organic acid complex or a salt thereof is used for the prevention and treatment of diarrhea in animals.

[0034] The aforementioned "acidic amino acid" refers to an amino acid that contains one amino group and two carboxyl groups and has an isoelectric point between 2.8 and 3.2°C.

[0035] The term “pharmaceutical, food and feed acceptable” means that the substance or composition must be chemically or toxicologically appropriate and relevant to the composition of pharmaceuticals, food and feed.

[0036] The term "inclusion" as used in this invention is an open expression and includes the content explicitly meant by this invention, but does not exclude the content of other embodiments.

[0037] A method for producing the aforementioned iron ammonium citrate organic acid complex, Step (1) involves dissolving an organic acid in a solvent to obtain an organic acid solution, Step (2) involves dissolving ammonium iron citrate in a solvent to obtain a solution of ammonium iron citrate, Step (3) involves adding the ammonium iron citrate solution to the organic acid solution to obtain a reaction mixture and stirring it at 25-60°C for 1-4 hours. Step (4) involves stirring the reaction solution after step (3) at room temperature for 4 to 15 hours, The process includes step (4), filtering the reaction solution after step (4), concentrating and drying the filtrate to obtain an ammonium iron citrate organic acid complex containing ammonium iron citrate and an organic acid (step (5)).

[0038] Here, the organic acid is an organic acid or acidic amino acid that is acceptable for pharmaceutical, food, and feed use, and the organic acid is selected from fumaric acid, maleic acid, succinic acid, malonic acid, oxalic acid, benzoic acid, or sorbic acid, and the acidic amino acid is selected from glutamic acid or aspartic acid, and the solvent described in step (1) and step (2) is a solvent that can solvate ammonium iron citrate and the organic acid, and is selected from water, methanol, ethanol, aqueous methanol solution, or aqueous ethanol solution.

[0039] In some specific embodiments, the molar ratio of ammonium iron citrate to the organic acid in the production method is 1:1 to 3:1, preferably 2:1, and more preferably the organic acid is fumaric acid or maleic acid.

[0040] In some specific embodiments, in order to obtain an iron ammonium citrate organic acid complex or a salt thereof with higher chemical purity and lower impurity content, the production of an iron ammonium citrate organic acid complex or a salt thereof according to the present invention further comprises, for the purpose of further removing impurities, placing the iron ammonium citrate organic acid complex, which contains iron ammonium citrate and an organic acid, obtained by concentrating and drying the filtrate obtained in step (5) of the above production method, into methanol, ethanol, an aqueous methanol solution, or an aqueous ethanol solution and subjecting it to a beating treatment.

[0041] In some embodiments, the solubility or bioavailability of the iron ammonium citrate organic acid complex is improved by chemical synthesis to produce a salt. A method for producing the salt of the iron ammonium citrate organic acid complex, Step (1) involves dissolving the organic acid salt in a solvent to obtain an organic acid salt solution, Step (2) involves dissolving ammonium iron citrate in a solvent to obtain a solution of ammonium iron citrate, Step (3) involves adding the ammonium iron citrate solution to the organic acid salt solution to obtain a reaction mixture and stirring it under heating for 1 to 4 hours. Step (4) involves stirring the reaction solution after step (3) at room temperature for 4 to 15 hours, The reaction mixture after step (4) is filtered, the filtrate is concentrated and dried to obtain a salt of an ammonium iron citrate organic acid complex containing ammonium iron citrate and an organic acid salt, which is part of step (5).

[0042] Here, the organic acid salt is a pharmaceutically, food-, and feed-acidically acceptable organic acid salt or acidic amino acid salt, the organic acid is selected from fumaric acid, maleic acid, succinic acid, malonic acid, oxalic acid, benzoic acid, or sorbic acid, the acidic amino acid is selected from glutamic acid, aspartic acid, or γ-aminobutyric acid, and the solvent used in step (1) and step (2) is a solvent capable of solvating ammonium iron citrate and the organic acid salt, and is independently selected from water, methanol, ethanol, aqueous methanol solution, or aqueous ethanol solution. Preferably, the heating conditions are 25 to 60°C.

[0043] In some specific embodiments, the organic acid salt is a sodium organic acid salt, and the product obtained by the method for producing the salt of the iron ammonium citrate organic acid complex is an iron ammonium citrate organic acid complex sodium salt, and the molar ratio of sodium ions to organic acid in the sodium organic acid salt is 1:1 to 1:2. For example, fumaric acid may be used as an example, and monosodium fumarate salt and disodium fumarate salt may be included.

[0044] In some embodiments, the iron ammonium citrate organic acid complex and its salt obtained by the above manufacturing method further comprises at least one solvent capable of solvating the iron ammonium citrate, the organic acid, and its salt, the solvent being selected from water, methanol, ethanol, or a combination thereof.

[0045] In some embodiments, the iron ammonium citrate organic acid complex according to the present invention is wherein the organic acid is selected from fumaric acid or maleic acid.

[0046] Fumaric acid is trans-2-butenioic acid. Maleic acid is cis-butenioic acid and has the same molecular formula, molecular weight, and number of carboxyl groups as fumaric acid, and can be used as a substitute for fumaric acid in the production of iron ammonium citrate organic acid complexes.

[0047] In some embodiments, a solvent capable of solvating ammonium iron citrate and an organic acid is selected from water.

[0048] In one specific example, the iron ammonium citrate organic acid complex according to the present invention comprises iron ammonium citrate and fumaric acid, and the method for producing it is: Step (1) involves dissolving fumaric acid in water to obtain a fumaric acid solution, Step (2) involves dissolving ammonium iron citrate in water to obtain a solution of ammonium iron citrate, Step (3) involves adding the ammonium iron citrate solution to the fumaric acid solution to obtain the reaction mixture and stirring it at 50°C for 1 to 4 hours. Step (4) involves stirring the reaction solution after step (3) at room temperature for 4 to 15 hours, The process includes step (4), filtering the reaction solution after step (4), concentrating and drying the filtrate to obtain an iron ammonium citrate fumarate complex containing iron ammonium citrate and fumaric acid, and step (5).

[0049] In some embodiments, in the method for producing the iron ammonium citrate fumarate complex described above, the molar ratio of iron ammonium citrate to fumarate is 1:1 to 3:1, and the elemental content of the provided iron ammonium citrate fumarate complex is C 23.8 to 25.82%, H 4.09 to 4.29%, N 5.74 to 6.19%, O 45.12 to 48.84%, and Fe 16.13 to 18.8%.

[0050] Furthermore, the iron ammonium fumarate citrate complex according to the present invention further contains a certain amount of water.

[0051] In one specific embodiment, in the method for producing the iron ammonium citrate fumarate complex described above, the molar ratio of iron ammonium citrate to fumarate is 2:1, and the elemental content of the provided iron ammonium citrate fumarate complex is C 25.82%, H 4.09%, N 6.19%, and Fe 18.8%.

[0052] In some manufacturing schemes, with respect to the sodium iron ammonium citrate fumarate salt provided in the present invention by the above method, the process in step (1) of the above manufacturing method is to dissolve the sodium fumarate salt in water to obtain a sodium fumarate salt solution.

[0053] In some specific manufacturing schemes, the sodium fumarate salt is monosodium fumarate salt, and the ammonium iron citrate fumarate complex salt is monosodium iron citrate fumarate salt.

[0054] In some specific manufacturing schemes, the sodium fumarate salt is disodium fumarate salt, and the ammonium iron citrate fumarate complex salt is disodium iron citrate fumarate salt.

[0055] The method for characterizing iron ammonium citrate organic acid complexes and their salts according to the present invention includes, but is not limited to, elemental analysis, Fourier infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC).

[0056] Elemental Analysis Method: Elemental analysis results were obtained using an Elementar Vario EL Cube elemental analyzer. The combustion furnace temperature was 950°C, and the reduction furnace temperature was 600°C. The basis for the data analysis is JY / T 0580-2020 General Rules for Elemental Analysis Methods.

[0057] Fourier Infrared Spectroscopy (FTIR): The FTIR chart was collected using a Fourier infrared spectrometer with model number FT-IR NICOLET 6700, and the absorption wavelength was 400-4000 cm². -1 The test method involves compressing potassium bromide into tablets, and the basis for the test is the GB / T 6040-2019 General Rules for Infrared Spectral Analysis.

[0058] X-ray diffraction (XRD): XRD charts are acquired using an Empyrean X-ray diffractometer. The inspection conditions are as follows: Cu target Kα irradiation, X-ray tube voltage and current are 40kV and 40mA, respectively, divergence slit is 1 / 8°, anti-scattering slit measurement step size is 1 / 4°, anti-scattering slit is 7.5mm, step size is 0.02 o 2θ, and the measurement angle range is 0 o 2θ~90 o The θ value is 2θ, and the dwell time per step is 40 seconds. The basis for the test is the X-ray diffraction method described in Section 4, 0451, of the 2020 edition of the "Pharmacopoeia of the People's Republic of China".

[0059] Differential Scanning Calorimetry (DSC): DSC data is collected using a DSC214 differential scanning calorimetry analyzer from NETZSCH GmbH, Germany. A 0.5-5 mg sample is placed in a pinhole aluminum disk, and the sample is heated from room temperature to 180°C at a rate of 10°C / min while maintaining a 40 mL / min dry nitrogen gas purge. The test basis is differential scanning calorimetry as defined in Part 3 of the General Rules for Thermal Analysis Methods, JY / T 0589.3-2020.

[0060] The stability study tests for the physicochemical properties of the iron ammonium citrate organic acid complex according to the present invention include high humidity stability tests and light irradiation stability tests.

[0061] High humidity stability test: Samples were left in a culture dish, spread into a thin layer of ≤5 mm, and left in a high humidity environment of 25°C and 75±5%RH. Samples were taken and tested on the 5th and 10th day, and two parallel samplings were performed for each sample.

[0062] Light irradiation stability test: Samples were left in a culture dish, spread into a thin layer of ≤5 mm, and left in a light irradiation environment of 4500 Lx ± 500 Lx. Samples were taken and tested on day 0, day 5, and day 10, and two parallel samplings were performed for each sample.

[0063] The iron ammonium citrate organic acid complex or salt thereof according to the present invention has beneficial technical effects compared to iron ammonium citrate, including significantly improved appearance stability under room temperature and high humidity conditions, remarkably improved or enhanced hygroscopicity, and significantly improved stability of chemical properties under light irradiation conditions.

[0064] The biological efficacy studies of the iron ammonium citrate organic acid complex according to the present invention include studies on the effects of the complex and its salts on piglet growth performance and diarrhea, studies on the effects on broiler chicken growth performance, and studies on the application effects in broiler duck feed. The research results showed that when the iron ammonium citrate organic acid complex and its salts are applied to the farming of pigs, chickens, and ducks, they can have a farming effect equivalent to, or even better than, iron ammonium citrate in terms of improving the growth performance of pigs, chickens, and ducks, effectively improving the growth performance or productivity of animals, and can be used as an upgraded product to replace iron ammonium citrate.

[0065] Application of the iron ammonium citrate organic acid complex according to the present invention In food products, ammonium ferric citrate can be used as (1) an iron source used to treat iron deficiency, (2) a food additive used to fortify bread, (3) a dietary iron supplement, and (4) an anti-caking agent applied to the production of complex sweetener-containing products and salt. Ammonium ferric citrate can also be used to prevent or treat iron-induced enteromicrobial disorders in the human body, including controlling the growth of pathogenic bacteria such as Escherichia coli, Enterobacteriaceae, and Streptococcus pneumoniae, or to prevent or treat intestinal dysfunction, including diarrhea, enteritis, or intestinal infections.

[0066] In the animal farming sector, ammonium ferric citrate can be used to reduce H2S production in the rumen. Furthermore, as a nutritional component, ammonium ferric citrate is used in health foods for dogs and cats, promoting their growth, supplementing various trace elements and vitamins necessary for their growth, improving their coat condition, strengthening their immune function, balancing nutrition, regulating estrus, increasing the number of fetuses, and promoting the health of the reproductive system. In addition, as a complex mineral additive in poultry feed, it can supplement the mineral element needs of poultry and promote their growth and development.

[0067] Biological efficacy studies of the ammonium iron citrate organic acid complex and its salts according to the present invention have shown that the ammonium iron citrate organic acid complex and its salts have comparable, and even superior, aquaculture effects compared to ammonium iron citrate in animal studies. Due to their reduced hygroscopicity, the ammonium iron citrate organic acid complex and its salts have improved stability in feeds, foods, and drugs, and their reduced reaction with other components does not decrease the content of other coexisting nutrients or formulation active ingredients, nor their effectiveness in the animal body. Therefore, they can be used in place of ammonium iron citrate in feeds, foods, and drugs. Accordingly, all uses of ammonium iron citrate mentioned above, as well as those not mentioned, are considered to be within the scope of the claims of the present invention.

[0068] The present invention provides applications of the iron ammonium citrate organic acid complex and / or salt thereof as a feed additive or in the manufacture of a feed additive, the feed additive being applicable to animals at each growth stage.

[0069] The animals may be selected from livestock, poultry, aquaculture animals, or pets at each stage of growth.

[0070] Furthermore, the livestock includes, but is not limited to, pigs, cattle, sheep, horses, rabbits, martens, or donkeys; the poultry includes, but is not limited to, chickens, turkeys, ducks, geese, quail, or pigeons; the aquaculture animals include, but are not limited to, fish, shrimp, turtles, crabs, softshell turtles, bullfrogs, swamp eels, or loaches; and the pets include, but are not limited to, dogs or cats of any subspecies.

[0071] In one embodiment, an application of an ammonium iron citrate organic acid complex and / or a salt thereof as an iron supplement or in the manufacture of an iron supplement, wherein the ammonium iron citrate organic acid complex and / or a salt thereof is preferably an ammonium iron citrate fumarate complex and / or a sodium salt thereof.

[0072] In one embodiment, an iron ammonium citrate organic acid complex and / or a salt thereof is used to reduce H2S production in the rumen.

[0073] In one embodiment, an application of an iron ammonium citrate organic acid complex and / or a salt thereof as an animal feed additive or in the manufacture of an animal feed additive, wherein the animal feed additive is used to promote animal growth in aquaculture, and the feed additive is selected from animal iron supplements and / or animal growth promoters.

[0074] In one embodiment, an iron ammonium citrate organic acid complex and / or a salt thereof is applied as a health food for dogs and cats or in the manufacture of a health food for dogs and cats, wherein the health food for dogs and cats promotes the growth of dogs and cats. Preferably, the iron ammonium citrate organic acid complex and / or a salt thereof is used as a nutritional component.

[0075] In one embodiment, the iron ammonium citrate organic acid complex and / or its salt is applied as a nursing feed or in the manufacture of a nursing feed. Furthermore, the nursing feed can reduce the diarrhea rate of weaned piglets, increase the feed intake of weaned piglets, and decrease the feed conversion rate, thereby improving the growth rate of suckling piglets, increasing feed efficiency, and promoting the growth of weaned piglets.

[0076] Another embodiment involves the application of the iron ammonium citrate organic acid complex and / or its salt as a feed for broiler chickens or in the manufacture of broiler chicken feed. Furthermore, the broiler chicken feed can improve the feed intake of broiler chickens, reduce the feed conversion ratio, improve the feed conversion rate, and effectively promote the growth of broiler chickens.

[0077] Another embodiment involves the application of the iron ammonium citrate organic acid complex and its salt as feed for meat ducks or in the manufacture of meat duck feed. Furthermore, the meat duck feed can increase the feed intake of meat ducks and reduce the feed conversion ratio, that is, it can improve the feed conversion rate, thereby increasing the feeding of meat ducks and promoting their growth by improving feed conversion.

[0078] The present invention provides applications of the iron ammonium citrate organic acid complex and / or its salt as a food additive or in the manufacture of a food additive, preferably the food additive being a food iron element fortifier.

[0079] In one embodiment, the iron ammonium citrate organic acid complex and / or its salt is used as an iron source in drugs for treating iron deficiency diseases or in the manufacture of drugs for treating iron deficiency diseases.

[0080] In one embodiment, an iron ammonium citrate organic acid complex and / or a salt thereof is used as an iron source in the treatment of iron deficiency diseases.

[0081] In one embodiment, a method for treating an iron deficiency disease comprises administering an iron ammonium citrate organic acid complex and / or a salt thereof to an animal.

[0082] In one embodiment, the ammonium iron citrate organic acid complex and / or its salt is applied in the production of bread. Furthermore, the ammonium iron citrate organic acid complex and / or its salt is used to enhance the nutritional value of bread.

[0083] One embodiment involves the application of the iron ammonium citrate organic acid complex and / or its salt in the production of dietary iron supplements.

[0084] In one embodiment, the iron ammonium citrate organic acid complex and / or salt thereof is used as an anti-caking agent in the production of products containing complex sweeteners and table salt.

[0085] Research results on the biological efficacy of the iron ammonium citrate organic acid complex and / or its salt according to the present invention have shown that the iron ammonium citrate organic acid complex and / or its salt is similar to iron ammonium citrate and has an effect of improving diarrhea in weaned piglets.

[0086] Therefore, in one embodiment, the iron ammonium citrate organic acid complex and / or salt thereof is used to prevent or treat iron-induced intestinal microbiota disorders in the human body, including controlling the growth of pathogenic bacteria such as Escherichia coli, Intestinal bacteria, and Streptococcus pneumoniae, or to prevent or treat intestinal dysfunction, including diarrhea, enteritis, or intestinal infections, or as a pharmacoactive ingredient in the manufacture of drugs for the prevention and treatment of diarrhea in humans or animals.

[0087] A method for raising animals, the method comprising administering to the animals the aforementioned iron ammonium citrate organic acid complex and / or salt thereof, or the aforementioned composition containing the iron ammonium citrate organic acid complex and / or salt thereof.

[0088] Composition according to the present invention Based on the applications of ammonium iron citrate organic acid complex and / or salts thereof as feed additives, food additives and drugs, or applications in the manufacture of feed additives, food additives and drugs, the present invention provides compositions comprising the ammonium iron citrate organic acid complex and / or salts thereof, the compositions comprising a feed composition, a food composition and a pharmaceutical composition.

[0089] The term "composition" according to the present invention refers to a group or collection comprising one or more compounds according to the present invention.

[0090] The present invention provides a composition comprising the above-mentioned iron ammonium citrate organic acid complex or a salt thereof, and preferably, the composition is used as a drug, animal feed, or food.

[0091] The present invention provides a feed composition comprising the above-mentioned iron ammonium citrate organic acid complex and / or a salt thereof, and one or more of the following: a feed-compatible carrier, excipient, diluent, and vehicle.

[0092] The "carrier" according to the present invention refers to a substance that can carry active ingredients, improve their dispersibility, and is acceptable as a feed, possessing good chemical stability and adsorption properties, and may be selected from organic carriers and inorganic carriers. The organic carrier is a material rich in crude fiber and includes, but is not limited to, corn flour, corn cob powder, wheat bran, rice husk powder, defatted rice bran, rice bran, corn stalk powder, and peanut shell powder. The inorganic carrier is selected from minerals, preferably from calcium salts and silicon oxides, and is used in the production of trace element premixes and includes, but is not limited to, calcium carbonate, silicates, vermiculite, zeolite, and sepiostone.

[0093] The "diluent" according to the present invention refers to a substance that can uniformly distribute additive raw materials into a material and dilute high-concentration additive raw materials to a low-concentration premix or premix, separate trace components from each other, reduce the interaction between active components and improve the stability of active components, without affecting the physical and chemical properties of related substances, and is selected from organic diluents and inorganic diluents. Organic diluents include, but are not limited to, corn flour, deembryonic corn flour, dextrose (glucose), sucrose, bran-containing coarse wheat flour, roasted soybean flour, wheat bran powder, and corn gluten meal, while inorganic diluents include, but are not limited to, limestone, calcium dihydrogen phosphate, seashell powder, kaolin (white clay), salt, and sodium sulfate.

[0094] The "excipient" according to the present invention is a wetting agent that induces viscosity inherent to the substance itself, an adhesive that bonds substances together, a disintegrant that breaks a sheet-like substance into many fine particles, a retaining aid that reduces interparticle friction, or an anti-adhesion agent that prevents materials from adhering together, and includes, but is not limited to, magnesium stearate, talc, vegetable oil, magnesium lauryl sulfate, starch, starch slurry, water, inorganic salts, dextrin, powdered sugar, etc.

[0095] The "vehicle" according to the present invention refers to a solvent necessary for the dissolution or dispersion of a solid, and includes, but is not limited to, water, ethanol, glycerin, etc.

[0096] In some embodiments, the composition further comprises additional animal feed additives and / or animal feed ingredients.

[0097] The "feed additive" according to the present invention refers to a small or trace amount of substance added during feed processing, manufacturing, or use, and includes nutritional feed additives and / or general feed additives.

[0098] The term "animal" in this invention refers to a human or farmed animal that cannot convert inorganic matter into organic matter and uses organic matter as food to carry out life activities such as feeding, digestion, absorption, respiration, circulation, excretion, sensation, movement, and reproduction. "Farmed animal" includes poultry, livestock, aquaculture animals, and other animals legally captured through artificial rearing, including pets such as cats and dogs. "Livestock" is any one of the following, for example, pigs, cattle, horses, goats, sheep, deer, and many useful rodents. "Poultry" includes, for example, chickens, ducks, geese, quail, and pigeons. "Aquaculture animals" includes, for example, fish, shrimp, turtles, and softshell turtles.

[0099] In the present invention, "feed" refers to industrially processed and manufactured food products for animals. Unless otherwise specified, "feed" or "animal feed" includes animal feed ingredients and one or more animal feed additives.

[0100] The "nutritional feed additive" according to the present invention refers to a small or trace amount of substance added to compound feed to balance the feed nutrients, improve the feed utilization rate, and directly provide nutritional effects to animals, and is selected from amino acids, amino acid salts and their analogues, vitamins and retinoid vitamins, mineral elements and their complexes (chelates), microbial enzyme preparations, or non-protein nitrogen.

[0101] The "general feed additives" according to the present invention, also known as "non-nutrient additives," refer to several non-nutrient substances that are added to feed to improve feed utilization and ensure feed quality and grade, and that are beneficial to the health or metabolism of animals. These include growth promoters, insect repellents, flavorings and attractants, feed adjusters, feed compounders, feed preservatives, and herbal medicine additives.

[0102] The "animal feed ingredients" according to the present invention are selected from feed substances such as grains and their processed products, oilseeds and their processed products, leguminous crop seeds and their processed products, tubers, roots and their processed products, other seeds, fruit products and their processed products, fodder, roughage and its processed products, other plants, algae and their processed products, dairy products and their by-products, terrestrial animal products and their by-products, fish, other aquatic organisms and their by-products, minerals, microbial fermentation products and their by-products, and other feed ingredients.

[0103] The present invention provides a food composition comprising the above-mentioned iron ammonium citrate organic acid complex and / or a salt thereof, and a nutritionally acceptable adjuvant. Preferably, the adjuvant is selected from nutritionally acceptable inert carriers, anti-wetting agents, antioxidants, wetting agents, thickeners, stabilizers, polyvalent chelating agents, lubricants, preservatives, sweeteners, and acidity modifiers, or combinations thereof. Preferably, the carrier includes, but is not limited to, maltodextrin, starch, calcium sulfate, magnesium sulfate, calcium carbonate, cellulose derivatives, lactose and its derivatives, or any mixtures and other analogues of such carriers. Preferably, the above-mentioned iron ammonium citrate organic acid complex and / or a salt thereof is the active ingredient.

[0104] The aforementioned anti-wetting agent includes, but is not limited to, calcium carbonate, microcrystalline cellulose, fatty acid salts (Ca, Na, K, and NH4), sodium carbonate, sodium bicarbonate, magnesium carbonate, magnesium hydroxide, magnesium oxide, amorphous silica, silica, calcium silicate, magnesium silicate, talc, sodium aluminum silicate, and aluminum silicate.

[0105] The aforementioned humectants include, but are not limited to, sodium lactate, potassium lactate, sorbitol and sorbitol syrup, mannitol, glycerin, propanetriol, xylitol, and polydextrose.

[0106] The aforementioned antioxidants include, but are not limited to, ascorbic acid, sodium ascorbate, calcium ascorbate, potassium ascorbate, erythorbic acid, sodium erythorbate, lecithin, sodium lactate, citric acid, calcium citrate, tricalcium citrate, esters of citric acid and fatty acids with glycerin, and esters of citric acid with monoglycerides and diglycerides.

[0107] The aforementioned thickening agents include, but are not limited to, gelatin, alginic acid, sodium alginate, potassium alginate, ammonium alginate, calcium alginate, agar, carrageenan and its salts, jatan gum, carob, guar gum, tragacanth, acacia gum, xanthan gum, camphor gum, gellan gum, sorbitol and sorbitol syrup, konjac gum, pectin, amidated pectin, microcrystalline cellulose, methylcellulose, hydroxypropylcellulose, methylethylcellulose, sodium carboxymethylcellulose, polydextrose, and the like.

[0108] The aforementioned stabilizers include sodium caseinate, gelatin, calcium carbonate, calcium acetate, lecithin, monosodium citrate, disodium citrate, sodium citrate, trisodium citrate, potassium citrate, tripotassium citrate, calcium citrate, tricalcium citrate, alginic acid, sodium alginate, potassium alginate, ammonium alginate, calcium alginate, agar, carrageenan and its salts, jatan gum, locust bean, guar gum, tragacanth, acacia gum, xanthan gum, karaya gum, gellan gum, mannitol, This product contains, but is not limited to, konjac gum, pectin, amidated pectin, microcrystalline cellulose, methylcellulose, hydroxypropylcellulose, methylethylcellulose, sodium carboxymethylcellulose, fatty acid salts (Ca, Na, K, and NH4), fatty acid monoglycerides and diglycerides, fatty acid and glycerin, acetate esters of monoglycerides and diglycerides, fatty acid and glycerin, lactic acid esters of monoglycerides and diglycerides, fatty acid and glycerin, citrate esters of monoglycerides and diglycerides, fatty acid and glycerin, tartaric acid esters of glycerin monoesters and diglycerides, fatty acid and glycerin acetate esters, sodium bicarbonate, potassium carbonate, calcium chloride, maltitol and maltitol syrup, polydextrose, etc.

[0109] The polyvalent chelating agent includes, but is not limited to, citric acid, monosodium citrate, disodium citrate, sodium citrate, trisodium citrate, potassium citrate, tripotassium citrate, calcium citrate, tricalcium citrate, sorbitol and sorbitol syrup, acetate esters of fatty acids and monoglycerides and diglycerides, lactic acid esters of fatty acids and glycerin, lactic acid esters of fatty acids and glycerin, citrate esters of fatty acids and glycerin, monoglycerides and diglycerides, tartaric acid esters of fatty acids and glycerin, acetic acid esters of fatty acids and glycerin, calcium sulfate, and the like.

[0110] The aforementioned acidity adjusting agent includes, but is not limited to, calcium carbonate, acetic acid, calcium acetate, lactic acid, malic acid, fumaric acid, sodium lactate, potassium lactate, calcium lactate, citric acid, monosodium citrate, disodium citrate, sodium citrate, trisodium citrate, potassium citrate, tripotassium citrate, calcium citrate, tricalcium citrate, sodium carbonate, sodium bicarbonate, potassium carbonate, ammonium bicarbonate, ammonium carbonate, magnesium carbonate, potassium sulfate, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, magnesium hydroxide, calcium oxide, gluconic acid, gluconolactone, and calcium gluconate.

[0111] The aforementioned sweetener includes, but is not limited to, sucralose, aspartame, acesulfame potassium, sodium saccharin, cyclamate, thaumatin, stevioside, rebaudioside, neohesperidin dihydrochalcone, alitame, or mixtures thereof in any proportion.

[0112] In some embodiments, the food composition further comprises additional dietary supplements and / or food additives.

[0113] Specifically, the food composition contains vitamins, minerals, lycopene, xanthophyll, carnitine, creatine, plant extracts, amino acids, peptides, and proteins, and further contains other nutritional components such as omega-3, omega-6, and omega-9 plants and their derivatives. Examples of minerals include zinc, calcium, magnesium, phosphorus, potassium, selenium, chromium, copper, manganese, cobalt, molybdenum, iodine, germanium, and mixtures thereof. Examples of vitamins include vitamins C, A, D, E, B vitamins, vitamin K, folic acid, and mixtures thereof.

[0114] Furthermore, the food composition further comprises food ingredients.

[0115] The present invention provides a pharmaceutical composition comprising the above-mentioned iron ammonium citrate organic acid complex and / or a salt thereof, and a pharmaceutically acceptable adjuvant. The pharmaceutically acceptable adjuvant is selected from one or more of the following: pharmaceutically acceptable carriers, diluents, excipients, dispersants or suspending agents, surfactants, isotonic agents, thickeners, emulsifiers, preservatives, solid adhesives, lubricants, and vehicles.

[0116] The carrier refers to a pharmaceutically acceptable substance that can carry an active ingredient, improve its dispersibility, and has good chemical stability and adsorption properties, and includes, but is not limited to, formulations that can be applied to pharmaceutically acceptable compositions of different carriers and known methods for producing them.

[0117] The aforementioned "diluent" refers to a substance that can uniformly distribute additive raw materials into the material and dilute high-concentration additive raw materials to a low-concentration premix or premix, thereby separating trace components from each other, reducing the interaction between active ingredients, and improving the stability of the active ingredients, without affecting the physical and chemical properties of the related substances.

[0118] The excipient is selected from one or more of the following: a wetting agent that induces viscosity inherent to the substance itself, an adhesive that bonds substances together, a disintegrant that breaks a sheet-like substance into many fine particles, a retaining aid that reduces interparticle friction, or an anti-adhesion agent that prevents materials from adhering together. It includes, but is not limited to, magnesium stearate, talc, vegetable oil, magnesium lauryl sulfate, starch, starch slurry, water, inorganic salt, dextrin, or powdered sugar.

[0119] The vehicle refers to a solvent necessary for the dissolution or dispersion of a solid, and includes, but is not limited to, water, glycerin, and ethanol.

[0120] Specifically, the above pharmaceutically acceptable adjuvants include ion exchangers, aluminum, aluminum stearate, lecithin, serum proteins, buffers such as phosphates, glycine, sorbic acid, potassium sorbate, a mixture of glycerides of some saturated vegetable fatty acids, water, salts or electrolytes, sodium dihydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silicon, magnesium trisilicate, polyvinylpyrrolidone, polyacrylic acid esters, waxes, polyethylene-polyoxypropylene-barrier polymers, lanolin, sugars such as lactose, glucose and sucrose, starches such as corn starch and potato starch, cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose. This includes, but is not limited to, cellulose and cellulose acetate, plant rubber powder, malt, gelatin, talc, adjuvants such as cocoa butter and suppository waxes, oils such as peanut oil, cottonseed oil, safflower oil, goa oil, olive oil, corn oil and soybean oil, diol compounds such as propylene glycol and polyethylene glycol, ester compounds such as ethyl oleate and ethyl laurate, agar, buffers such as magnesium hydroxide and aluminum hydroxide, alginic acid, water without a heat source, isotonic salts, Ringer's solution, ethanol, phosphate buffer solution and other non-toxic suitable lubricants such as sodium oleate and magnesium stearate, colorants, release agents, coating materials, sweeteners, flavorings, fragrances, preservatives and antioxidants.

[0121] The pharmaceutical composition of the present invention refers to a group or set of compounds comprising one or more compound compositions. The pharmaceutical composition can be used in the manufacture of veterinary drugs and has a remarkable therapeutic effect against diarrhea in animals, particularly livestock in the weaning stage (e.g., weaned pigs).

[0122] In some embodiments, treatment means administering a therapeutic dose of the veterinary drug of the present invention to an animal suffering from a disease to improve the disease or condition (i.e., slow, stop, or reduce the progression of the disease or at least one of its clinical symptoms); in some other embodiments, treatment means administering a therapeutic dose of the veterinary drug of the present invention to an animal suffering from a disease to alleviate or improve at least one physical parameter, including a physical parameter that may not be noticed by the patient; in some other embodiments, treatment means administering a therapeutic dose of the veterinary drug of the present invention to an animal suffering from a disease to modulate the disease or condition physically (e.g., stabilizing noticeable symptoms) or physiologically (e.g., stabilizing physical parameters) or both; in some other embodiments, treatment means administering a therapeutic dose of the veterinary drug of the present invention to an animal suffering from a disease to prevent or delay an attack, onset, or exacerbation of the disease or condition.

[0123] The term "therapeutic dose" refers to the amount of a compound that is sufficiently effective in treating a disease in an animal suffering from the disease, and which can vary depending on the compound, the disease and its severity, and the condition, age, weight, and sex of the animal being treated.

[0124] In some embodiments, the medicinal composition further comprises additional drugs for treating diarrhea in animals.

[0125] The following describes the methods of use of the veterinary drugs according to the present invention. For treating diarrhea in animals, the method of use involves administering a therapeutic dose of ammonium iron citrate organic acid complex and / or a salt thereof, or a composition containing a therapeutic dose of ammonium iron citrate organic acid complex and / or a salt thereof, to the diseased animal. The pharmaceutical compositions of the present invention can be manufactured by the conventional methods of the art as disclosed. The pharmaceutical compositions are specific dosage forms suitable for therapeutic purposes. The ammonium iron citrate organic acid complex is administered in mixture with appropriate drug diluents, excipients, or carriers selected according to the mode of administration and conventional pharmaceutical practice, for example, in an oral dosage form via an appropriate carrier.

[0126] The pharmaceutical composition is used to treat diarrhea in animals, and the oral dosage form includes, but is not limited to, oral enteric-coated tablets, pills, or capsules. Aquaculture farmers or veterinarians administer the oral dosage form containing the pharmaceutical composition of the present invention to animals suffering from the disease in an oral administration form or by mixing it with feed.

[0127] The administration method of the pharmaceutical composition of the present invention varies depending on various known factors, such as the pharmacokinetic characteristics and patterns of a particular reagent and the route of administration, the type, age, and weight of the animal suffering from the disease, the nature and severity of the symptoms, the type of concomitant therapy, the frequency of use of the therapeutic agent, the route of administration, and the expected therapeutic effect. A veterinarian can make a decision and prescribe an effective amount of the drug to prevent, inhibit, reduce, or alleviate the progression of the disease symptoms.

[0128] The pharmaceutical compositions of the present invention are manufactured in dose units according to the formulation to reduce dosage and dose uniformity. Each unit dose of a formulation suitable for administration may contain 1 mg to 100 mg of an iron ammonium citrate organic acid complex and / or its salt. In these dosage forms, the weight of the active ingredient generally accounts for 0.5% to 95% of the total weight of the composition.

[0129] The "unit dose" mentioned above refers to the physical dispersion unit of a drug necessary for a living organism to receive appropriate treatment. [Modes for carrying out the invention]

[0130] To provide a clearer understanding of the object, technical solutions, and advantages of the present invention, the compounds, compositions, and applications of the present invention will be described in more detail below with reference to examples. It should be understood that the specific examples described herein are for illustrative purposes only and are not intended to limit the present invention.

[0131] Example 1: Production scheme for citrate fumarate complex.

[0132] The reagents related to the above manufacturing scheme include the following:

[0133] The ammonium iron citrate, an analytical reagent (AR), was purchased from Shanghai Alading Biotechnology Co., Ltd. (Shanghai, China). Elemental analysis data characterization is C 22.62%, H 4.18%, and N 7.31%. The XRD chart is shown in Figure 6, and the DSC curve is shown in Figure 11.

[0134] Fumaric acid, an analytical reagent (AR), was purchased from Shanghai Aladdin Biotechnology Co., Ltd. (Shanghai, China). The XRD chart is shown in Figure 7, and the DSC curve is shown in Figure 13.

[0135] The raw material mixture (abbreviated as "mixture") of ammonium iron citrate and fumaric acid in a molar ratio of 2:1 has an FTIR spectrum shown in Figure 9, an XRD chart shown in Figure 10, and a DSC curve with a heat dissipation peak at 157.41°C, as shown in Figure 14.

[0136] 1. Preparation of iron ammonium citrate-fumarate complex A The ammonium iron citrate-fumarate complex A (hereinafter abbreviated as "complex A") was a product obtained during manufacturing when the molar ratio of ammonium iron citrate to fumarate was 1:1.

[0137] At room temperature, 150 mL of water and fumaric acid (43.8 g, 377 mmol) were sequentially added to a reaction flask to form a reaction solution. A brown solution obtained by dissolving copper-colored ammonium iron citrate (100.0 g, 377 mmol) in 200 mL of water was then added to the reaction flask and heated. The reaction system was raised to 50°C, and the mixture was stirred for 4.0 hours to allow the reaction to proceed. The reaction solution was then clarified, cooled to room temperature, and stirred for another 4 hours to continue the reaction. The reaction solution was filtered, the filtrate was concentrated and dried, 1000 mL of ethanol was added, and the mixture was stirred and beaten for 3.0 hours before being filtered again. The filtered cake was washed with 500 mL of ethanol, dried at 55°C for 18 hours, and sieved to obtain 104.5 g of complex A, which was a copper-colored solid powder.

[0138] The structural characterization results for complex A are as follows:

[0139] (1) The elemental analysis data characterized the composition as follows: C 25.14%, H 4.15%, N 5.74%, O 48.84%. Based on calculations according to the law of conservation of elements, the iron (Fe) content in composite A was found to be approximately 16.13%.

[0140] (2) The FTIR spectrum is shown in Figure 1.

[0141] (3) The XRD chart is as shown in Figure 4.

[0142] 2. Production of iron ammonium citrate-fumarate complex B The ammonium iron citrate-fumarate complex B (hereinafter abbreviated as "complex B") was a product obtained during manufacturing when the molar ratio of ammonium iron citrate to fumarate was 2:1.

[0143] At room temperature, 50 mL of water and fumaric acid (21.9 g, 189 mmol) were sequentially added to a reaction flask to form a reaction solution. A brown solution obtained by dissolving copper-colored ammonium iron citrate (100.0 g, 377 mmol) in 200 mL of water was then added to the reaction flask and heated. The reaction system was raised to 50°C, and the mixture was stirred and allowed to react for 1 to 1.5 hours to clarify the reaction solution. The mixture was then cooled to room temperature and stirred and allowed to react for 5 hours. The reaction solution was filtered, and the resulting filtrate was concentrated and dried at 55 to 60°C to obtain a hard, copper-colored solid mass. 500 mL of ethanol was added to the obtained solid, and after standing, the solid was scraped off with a scraper. The mixture was then magnetically stirred and beaten for 3.0 hours, and then filtered. The filtered cake was dried overnight at 60°C and sieved to obtain 115 g of copper-colored solid powder. The water content, measured in a moisture dryer, was 2.43%.

[0144] The structural characterization results for complex B are as follows:

[0145] (1) The elemental analysis data characterized the composition as follows: C 25.82%, H 4.09%, N 6.19%, Fe 18.8%. Based on the law of conservation of elements, the oxygen (O) content in complex B was estimated to be approximately 42.69%.

[0146] (2) The comparison results of the FTIR spectral diagrams are shown in Figure 2. The samples corresponding to the spectral diagrams, from top to bottom, are iron ammonium citrate fumarate complex B, iron ammonium citrate, and fumarate raw material. Figure 2 shows that iron ammonium citrate fumarate complex B does not have a characteristic peak for fumarate, indicating that there is no free fumarate in the sample. A comparison of Figure 2 and Figure 9 shows that the material form of iron ammonium citrate fumarate complex B is different from that of the raw material mixture of iron ammonium citrate and fumarate in the same molar ratio (i.e., the input molar ratio is 1:1).

[0147] (3) The XRD chart is shown in Figure 5, which shows that complex B does not have a characteristic peak for fumaric acid, and that there is no free fumaric acid in the sample. A comparison of Figure 5 and Figure 10 shows that the material form of complex B is different from that of the raw material mixture of ammonium iron citrate and fumaric acid in the same molar ratio (i.e., the input molar ratio is 1:1).

[0148] (4) The DSC curve is as shown in Figure 12.

[0149] 3. Production of iron ammonium citrate-fumarate complex C The ammonium iron citrate-fumarate complex C (hereinafter abbreviated as "complex C") was a product obtained during manufacturing when the molar ratio of ammonium iron citrate to fumarate was 3:1.

[0150] At room temperature, 50 mL of water and fumaric acid (20.0 g, 172 mmol) were sequentially added to the reaction flask. A brown solution obtained by dissolving copper-colored ammonium iron citrate (137 g, 517 mmol) in 250 mL of water was then added to the reaction flask and heated. The reaction mixture was raised to 50°C, stirred for 1.5 hours, cooled to room temperature, and continued stirring for 15 hours. The reaction mixture was filtered, the filtrate was concentrated to dry, 1000 mL of ethanol was added, and the mixture was stirred and beaten for 4.0 hours before being filtered again. The filtered cake was washed with 500 mL of ethanol, dried at 55°C for 18 hours, and sieved to obtain 149.5 g of copper-colored solid powder.

[0151] The structural characterization results for complex C are as follows:

[0152] (1) The elemental analysis data characterized the composition as follows: C 23.8%, H 4.29%, N 6.14%, O 48.61%. Based on the law of conservation of elements, the iron content in the solid composite was estimated to be 17.16%.

[0153] (2) The FTIR spectrum is shown in Figure 3.

[0154] (3) The XRD chart is as shown in Figure 8.

[0155] Example 2: Stability study of ammonium iron citrate-fumarate complex 1. Reagents: All are analytical reagents: sulfuric acid, hydroxylamine hydrochloride, phenanthroline, acetic acid, sodium acetate, and the iron ammonium citrate-fumarate complex prepared in Example 1.

[0156] Acetate-sodium acetate buffer solution (pH 4.5): Accurately weigh 18 g of sodium acetate, add 9.8 mL of glacial acetic acid, dilute with water to 1000 mL, and shake well. 5% hydroxylamine hydrochloride solution: Accurately weigh 5 g of hydroxylamine hydrochloride, dissolve in water, add to a 100 mL volumetric flask, and shake well.

[0157] 0.25% phenanthroline solution: Accurately weigh 0.25 g of phenanthroline, add an appropriate amount of water, heat to dissolve, cool, and then pour into a 100 mL volumetric flask and shake well.

[0158] 2. Instruments: Drug stability test boxes, Shimadzu UV-1700 spectrophotometer, etc.

[0159] 3. Test Methods and Conditions Preparation of ammonium iron citrate standard solution: 0.5 g of ammonium iron citrate standard was precisely weighed (to the nearest 0.0001 g), 25 mL of 1% sulfuric acid solution was added, and the solution was ultrasonically dissolved at 65°C until it changed from dark brown to pale yellow. After cooling, the solution was diluted to a volume of 100 mL in a brown volume flask with 1% sulfuric acid and shaken well to prepare a standard storage solution with an iron mass concentration of 1000 μg / mL. 5 mL of the standard storage solution was precisely measured into a 100 mL brown volume flask, diluted to a volume of water, and shaken well to prepare a standard working solution with an iron mass concentration of 50 μg / mL. The solution was stored in a refrigerator at 4°C, away from light, for use.

[0160] Plotting of ammonium iron citrate standard curves: Precisely weigh out 0, 0.2 mL, 0.5 mL, 1 mL, 2 mL, 3 mL, and 4 mL of ammonium iron citrate standard solution, place each into a 50 mL brown volumetric flask, add 2 mL of hydroxylamine hydrochloride solution, 2 mL of phenanthroline solution, and 10 mL of acetic acid-sodium acetate buffer solution, dilute with water to the marked level, shake well to obtain Fe(II) standard solutions with concentrations of 0.00 μg / mL, 0.20 μg / mL, 0.50 μg / mL, 1.00 μg / mL, 2.00 μg / mL, 3.00 μg / mL, and 4.00 μg / mL, respectively. Place in a constant temperature chamber at 37°C and allow to develop color for 80 minutes. The solution with a concentration of 0.00 μg / mL was used as the blank, and the absorbance of the standard solutions was measured at a wavelength of 510 nm. A standard curve was plotted with the Fe(II) solution concentration as the x-coordinate and the absorbance value as the y-coordinate.

[0161] Preparation of the test solution: 50-100 mg of sample was precisely weighed (to the nearest 0.1 mg) and placed in a stoppered Erlenmeyer flask. 50 mL of 1% sulfuric acid solution was precisely added, the flask was stoppered and sealed, and the solution was sonicated at 65°C until it changed from dark brown to pale yellow. After cooling, the flask was immediately tested.

[0162] Preparation of blank test solution: 5.00 mL of the test solution was accurately measured and placed in a brown volumetric flask. 10 mL of acetic acid-sodium acetate buffer solution (pH 3.7) was added, and the solution was diluted with water to the marked level. The flask was shaken well and left in a 37°C constant temperature chamber for 80 minutes.

[0163] Measurement of the test solution: 5.00 mL of the test solution was accurately measured and placed in a brown volumetric flask. 2 mL of phenanthroline solution and 10 mL of acetic acid-sodium acetate buffer solution were added, and the solution was diluted with water to the marked level. The mixture was shaken well, and the flask was placed in a 37°C constant temperature chamber for 80 minutes to allow color development. The blank solution was then used as the blank, and the absorbance was measured at a wavelength of 510 nm. Based on the standard curve, the concentration of Fe(II) in the test solution was determined.

[0164] Stability test at 25°C and 75±5%RH high humidity and results: Samples of ammonium iron citrate, complex A, complex B, and complex C were left in a culture dish, spread into a thin layer of ≤5 mm, and left in a high humidity environment of 25°C and 75±5%RH. Samples were taken and tested on the 5th and 10th day, and two parallel samplings were performed for each sample.

[0165] Light irradiation stability test and results: Samples of ammonium iron citrate, complex A, complex B, and complex C were placed in culture dishes, spread into thin layers of ≤5 mm, and left in a 4500 Lx ± 500 Lx light irradiation environment. Samples were taken and tested on days 0, 5, and 10, and two parallel samplings were performed for each sample. The measurement results were the arithmetic mean of the two parallel measurements, with two decimal places retained, and the percentage change in Fe(II) in the sample was expressed as ΔFe(II)(%). The Fe(II) content (%) expressed as mass percentage was calculated according to formula (1).

[0166]

number

[0167] 4. Results and Conclusions (1) Regarding the physical stability of ammonium iron citrate and its composite B, we mainly examined the weight increase due to moisture absorption and the change in appearance under high humidity conditions of 75±5%RH. The research results are shown in Table 1. The results showed that on the 10th day of the test, the hygroscopicity of the ammonium iron citrate-fumarate composite improved by 41.3% compared to ammonium iron citrate. This value = [(weight increase due to moisture absorption of ammonium iron citrate) - (weight increase due to moisture absorption of ammonium iron citrate-fumarate composite B)] / (weight increase due to moisture absorption of ammonium iron citrate) * 100%. Furthermore, the appearance of the ammonium iron citrate-fumarate composite sample hardly changed during the test period, but the ammonium iron citrate changed from a reddish-brown powder to a black gel-like liquid due to moisture absorption.

[0168] [Table 1]

[0169] (2) Regarding the chemical stability of ammonium iron citrate and ammonium iron citrate-fumarate complex B, we mainly examined the changes in the Fe(II) content of ammonium iron citrate and its complex under light irradiation conditions, and the results are shown in Table 2. The results showed that, under light irradiation conditions, the ΔFe(II) content of ammonium iron citrate-fumarate complex B decreased by approximately 16.25% on the 10th day compared to ammonium iron citrate (this value = [ΔFe(II) of ammonium iron citrate - ΔFe(II) of ammonium iron citrate-fumarate complex] / ΔFe(II) of ammonium iron citrate * 100%), indicating a clear increase in stability.

[0170] [Table 2]

[0171] Example 3: Effects of iron ammonium citrate fumarate complex on piglet growth performance and diarrhea status 140 Duroc-Landrace-Large Yorkshire three-way lean piglets, all 45 days old and of similar weight, were randomly divided into seven treatment groups. Each group consisted of two overlapping groups, with an equal number of males and females, and each overlap comprising 10 piglets. The specific group divisions are shown in Table 3. The pigpens and equipment were disinfected before the experiment. During the experiment period, the pigs were kept in the same pigpens and under the same rearing management conditions, enclosed by fences. During the experiment period, the test pigs were free to eat and drink. Group A was the blank control group, fed only nursing feed. Test groups B and D were fed nursing feed containing different amounts of ammonium ferric citrate, and test groups E and G were fed nursing feed containing different amounts of ammonium ferric citrate fumarate complex B (abbreviated as "complex B"), manufactured in Example 1. Throughout the rearing process, no other antioxidants or growth promoters were added to any of the test groups. The test period was 28 days, and the growth performance of the test pigs was statistically analyzed. The average daily feed intake (ADFI, g / d* head), average daily weight gain (ADG, g / d* head), feed conversion ratio (FCR), and diarrhea rate of the experimental pigs are expressed as "average values" and are shown in Table 3.

[0172] Feed conversion ratio (FCR) = average daily intake / average daily weight gain, Weight gain rate = (Test group ADG - Control group ADG) / Control group ADG * 100% Food intake improvement rate = (test group ADFI - control group ADFI) / control group ADFI * 100%, Feed conversion ratio reduction rate = (Control group FCR - Test group FCR) / Control group FCR * 100% Diarrhea improvement rate = (Diarrhea rate in the test group - Diarrhea rate in the control group) / Diarrhea rate in the control group * 100%.

[0173] [Table 3]

[0174] As can be seen from the above test results, compared to the blank control group, the test group, which was fed a nursing feed containing ammonium iron citrate or its fumarate complex, showed clear improvements in feed intake, average daily weight gain, feed conversion ratio, and diarrhea rate of the test pigs.

[0175] When ammonium ferric citrate was included in the nursing feed, the feed intake of the test pigs increased by 13.62% to 15.29%, body weight increased by 22.68% to 30.33%, the decrease in feed conversion ratio was 7.69% to 11.79%, and the diarrhea rate decreased by 23.37% to 69.04%.

[0176] When the feed for nursing piglets contained ammonium iron citrate fumarate complex, the feed intake of the test pigs increased by 14.31% to 16.41%, body weight increased by 23.50% to 32.79%, the decrease in feed conversion ratio was 6.67% to 13.85%, and the diarrhea rate decreased by 17.40% to 69.16%.

[0177] As can be seen, the effect of the ammonium iron citrate organic acid complex on the growth performance and diarrhea rate of test pigs was equivalent to, and even superior to, ammonium iron citrate in terms of aquaculture effectiveness. In particular, the effect was better when used at concentrations of 500-1000 ppm, and it could be used as an equivalent substitute for ammonium iron citrate in pig feed. Furthermore, compared with the blank control, the results showed that the ammonium iron citrate fumarate complex increased the growth rate of test pigs and improved feed conversion rates, thereby increasing feed profitability, and it can be used as a novel feed additive in pig farming.

[0178] Example 4: Effect of iron ammonium citrate fumarate complex on the growth performance of broiler chickens The study employed a single-factor random design, selecting 240 three-yellow meat chickens with similar ages and average body weights of 50g. These were randomly divided into four treatment groups, with three overlapping groups within each group. Each overlap consisted of 20 three-yellow meat chickens, with an equal number of males and females. The groupings are shown in Table 4. The chicken coops and equipment were disinfected before the study. During the study period, the chickens were kept in cages under the same coop and rearing management conditions. The basal diet consisted mainly of corn-bean meal, and no other antioxidants or growth promoters were added throughout the rearing process. Study A was a blank control group, fed only the basal diet. Studies B-D each received different doses of iron ammonium citrate fumarate complex B in addition to their basal diet, as shown in Table 4. The study period totaled 20 days, during which the test chickens were free to drink and eat, and fed twice a day. Each overlap was used as the unit, and the weight was measured at 21 days of age (feeding was stopped for 12 hours, but drinking water was not stopped). The feed consumption of the test chickens was statistically calculated, and the average daily feed intake (ADFI, g / d* birds), average daily weight gain (ADG, g / d* birds), and feed conversion ratio (FCR) for each group of test chickens were calculated. The calculation formula is as follows.

[0179] Feed conversion ratio (FCR) = average daily intake / average daily weight gain, Weight gain rate = (Test group ADG - Control group ADG) / Control group ADG * 100% Food intake improvement rate = (test group ADFI - control group ADFI) / control group ADFI * 100%, The rate of decrease in feed conversion ratio = (control group FCR - test group FCR) / control group FCR * 100%.

[0180] The test results are shown in Table 4. As the results show, compared to the control group: Compared to the control group, the experimental chickens in the group to which iron ammonium citrate fumarate complex B was added to their basal diet showed improvements of 6.96% to 22.47% and 11.72% to 32.03% in feed intake and average daily body weight gain, respectively, and showed an upward trend with increasing dosage. The feed conversion ratio decreased by approximately 4.45% to 7.29%, and the feed conversion rate increased.

[0181] As can be seen, when applied to broiler chicken feed, iron ammonium fumarate citrate complex B effectively promotes the growth of test chickens, improves feed efficiency, and can be applied to broiler chicken feed as a feed additive that effectively promotes the growth of broiler chickens, thereby improving farming efficiency and profits.

[0182] [Table 4]

[0183] Example 5: Application study of iron ammonium citrate fumarate complex B in meat duck feed A single-factor trial design was employed. 480 Cherry Valley meat ducks, 1 day old, with nearly identical body weight and good health, were selected and randomly divided into four treatment groups, with six overlapping groups, each containing 20 ducks. The control group received a blank feed and was fed a corn meal-type basal diet. The other four treatment groups were sample-added groups, each supplemented with a different dose of iron ammonium citrate organic acid complex B added to their basal diet. The trial lasted a total of 42 days. The specific animal groupings are shown in Table 5. During the trial period, the ducks were free to eat and drink, and immunization was performed according to a standard immunization program. Feeding, feed consumption, and mortality rates of the test ducks in each group were observed and recorded daily. The weight of the ducks was measured on an empty stomach at the start and end of the trial. After the experiment, the average daily weight gain, average daily feed intake, and feed conversion ratio for each treatment group were statistically analyzed using overlapping units, and the results are shown in Table 5.

[0184] As can be seen from the results shown in Table 5, compared to the control group, adding iron ammonium fumarate citrate complex B to the feed of Cherry Valley beef ducks aged 1 to 42 days significantly improved the production performance of the beef ducks. The decrease rates in feed intake, weight gain rate, and feed conversion ratio at the experimentally used doses were 2.40% to 6.24%, 7.64% to 15.72%, and 4.78% to 8.26%, respectively. Thus, iron ammonium fumarate citrate complex B can increase the feed intake and reduce the feed conversion ratio of the test ducks, that is, it can increase the feed conversion rate. By increasing the feed intake and improving feed conversion of the test ducks, it promotes their growth, further improves feed efficiency, and can be used as a feed additive to promote the growth of beef ducks.

[0185] [Table 5]

[0186] The embodiments described above illustrate only a few embodiments of the present invention, and while the descriptions are specific and detailed, they should not be understood as limiting the scope of patent protection of the invention. It should be noted that those skilled in the art can make several further modifications and improvements without departing from the spirit of the invention, all of which fall within the scope of protection. Therefore, the scope of patent protection for the present invention should be based on the appended claims.

Claims

1. An ammonium iron citrate organic acid complex or a salt thereof, wherein the complex comprises ammonium iron citrate and an organic acid, where the organic acid is selected from fumaric acid, maleic acid, succinic acid, malonic acid, oxalic acid, benzoic acid, sorbic acid, or an acidic amino acid, the acidic amino acid is selected from glutamic acid or aspartic acid, preferably the organic acid is fumaric acid or maleic acid, and more preferably the salt of the ammonium iron citrate organic acid complex is a sodium salt of the ammonium iron citrate organic acid complex.

2. The ammonium iron citrate organic acid complex or salt thereof according to claim 1, further comprising at least one solvent capable of solvating ammonium iron citrate and an organic acid, preferably the solvent being selected from water, methanol, ethanol, an aqueous methanol solution, or an aqueous ethanol solution, more preferably the ammonium iron citrate organic acid complex or salt thereof being used as a drug, feed, or food, and even more preferably the ammonium iron citrate organic acid complex or salt thereof being used as a drug for the prevention and treatment of diarrhea in animals.

3. A method for producing an iron ammonium citrate organic acid complex or a salt thereof according to claim 1 or 2, Step (1) to dissolve an organic acid or its salt to obtain a solution of the organic acid or its salt, Step (2) involves dissolving ammonium iron citrate to obtain a solution of ammonium iron citrate, Step (3) involves adding the ammonium iron citrate solution to the organic acid or its salt solution to obtain a reaction mixture and stirring it under heating for 1 to 4 hours. Step (4) involves stirring the reaction solution after step (3) at room temperature for 4 to 15 hours, A method comprising step (4) filtering the reaction solution after step (4), concentrating and drying the filtrate to obtain an iron ammonium citrate organic acid complex or a salt thereof.

4. The manufacturing method according to claim 3, wherein the molar ratio of ammonium iron citrate to organic acid is 1:1 to 3:1, preferably 2:1, the heating temperature is 25 to 60°C, and more preferably the organic acid is fumaric acid or maleic acid.

5. A composition comprising the iron ammonium citrate organic acid complex or a salt thereof described in claim 1 or 2, preferably the composition being used as a drug, animal feed, or food.

6. A feed composition comprising an iron ammonium citrate organic acid complex or a salt thereof as described in claim 1 or 2, and one or more of a feed-acceptable carrier, excipient, diluent, or vehicle, wherein preferably the composition further comprises additional feed additives and / or feed ingredients, and more preferably the feed additives are selected from nutritional feed additives or non-nutritional feed additives.

7. An edible composition comprising an iron ammonium citrate organic acid complex or a salt thereof as described in claim 1 or 2, and a nutritionally acceptable adjuvant, preferably the composition further comprising additional dietary supplements and / or food additives and / or food ingredients.

8. A pharmaceutical composition comprising an iron ammonium citrate organic acid complex or a salt thereof as described in claim 1 or 2, and a pharmaceutically acceptable adjuvant, preferably the composition further comprising an additional drug for treating diarrhea in animals.

9. An application of the iron ammonium citrate organic acid complex or a salt thereof according to claim 1 or 2, or the composition according to any one of claims 5 to 8, as an animal feed additive or in the manufacture of an animal feed additive, wherein the animal feed additive is selected from animal iron supplements and / or animal growth promoters.

10. An application of the iron ammonium citrate organic acid complex or a salt thereof according to claim 1 or 2, or the composition according to any one of claims 5 to 8, as a food additive or in the manufacture of a food additive, wherein the food additive is a food iron element fortifier.

11. Application of the iron ammonium citrate organic acid complex or a salt thereof according to claim 1 or 2, or the composition according to any one of claims 5 to 8, in the manufacture of a drug for the prevention and treatment of diarrhea in animals.

12. A method for raising an animal, comprising administering to the animal an iron ammonium citrate organic acid complex and / or a salt thereof according to claim 1 or 2, or a composition according to any one of claims 5 to 8.

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